Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses.

BACKGROUND: The gangliosidoses (Tay-Sachs disease, Sandhoff disease, and GM1-gangliosidosis) are progressive neurodegenerative diseases caused by lysosomal enzyme activity deficiencies and consequent accumulation of gangliosides in the central nervous system (CNS). The infantile forms are distinguished from the juvenile forms by age of onset, rate of disease progression, and age of death. There are no approved treatments for the gangliosidoses. In search of potential biomarkers of disease, we quantified 188 analytes in CSF and serum from living human patients with longitudinal (serial) measurements. Notably, several associated with inflammation were elevated in the CSF of infantile gangliosidosis patients, and less so in more slowly progressing forms of juvenile gangliosidosis, but not in MPS disease. Thirteen CSF and two serum biomarker candidates were identified. Five candidate biomarkers were distinguished by persistent elevation in the CSF of patients with the severe infantile phenotype: ENA-78, MCP-1, MIP-1α, MIP-1ß, and TNFR2. Correspondence of abnormal elevation with other variables of disease-i.e., severity of clinical phenotype, differentiation from changes in serum, and lack of abnormality in other neurodegenerative lysosomal diseases-identifies these analytes as biomarkers of neuropathology specific to the gangliosidosis diseases.

Comparison of provider satisfaction with specialty pharmacy services in integrated health-system and external practice models: A multisite survey.

PURPOSE: The purpose of this study is to obtain insight into providers' satisfaction with services offered by health-system integrated specialty pharmacies and to determine whether providers' perceptions of services offered under an integrated model differ from perceptions of external specialty pharmacy services. METHODS: A multi-site, cross-sectional, online survey of specialty clinic healthcare providers at 10 academic health systems with integrated specialty pharmacies was conducted. The questionnaire was developed by members of the Vizient Specialty Pharmacy Outcomes and Benchmarking Workgroup and was pretested at 3 pilot sites prior to dissemination. Prescribers of specialty medications within each institution were identified and sent an email invitation to participate in the study that included a link to the anonymous questionnaire. Respondents were asked to rate their agreement with 10 statements regarding quality of services of integrated and external specialty pharmacies on a 5-point scale (1 = strongly disagree, 5 = strongly agree). An analysis to determine differences in providers' overall satisfaction with the integrated and external specialty pharmacy practice models, as well as differences in satisfaction scores for each of the 10 statements, was performed using paired-samples t tests. RESULTS: The mean (SD) score for overall satisfaction with integrated specialty pharmacies was significantly higher than the score for satisfaction with external specialty pharmacies: 4.72 (0.58) vs 2.97 (1.20); 95% confidence interval, 1.64-1.87; P < 0.001. Provider ratings of the integrated specialty pharmacy model were also higher for all 10 items evaluating the quality of services (P < 0.05 for all comparisons). CONCLUSION: The study results confirm that the health-system integrated specialty pharmacy practice model promotes high rates of provider satisfaction with services and perceived benefits.

Comparative performance of two methods that assess the quality of international normalized ratio measures.

OBJECTIVES: Two methods, Petersen's error grid analysis and Shermock's method to detect clinically important differences, were recently developed to advance the assessment of analytic performance of point-of-care INR devices. Both methods predict when alternate INR measures lead to different clinical decisions. Our goal was to compare their performance characteristics. DESIGN AND METHODS: Performance characteristics were assessed by comparing the models' predictions to clinical decisions that were directly measured in a previous experiment. RESULTS: Shermock's method (82% of predictions correct) demonstrated superior predictive performance compared with the error grid analysis (75% of predictions correct, p=0.008). Shermock's method was particularly superior at identifying the clinical decisions that actually disagreed (79% for Shermock's method vs. 47% for error grid). Consequently, Shermock's method was superior at identifying a POC device with poor performance (79% accuracy vs. 70%, p=0.006). CONCLUSION: Shermock's method had superior performance characteristics and should be integrated into analytic strategies to assess POC INR devices.