20 research outputs found
Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference
The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18
7 10 124 ) or temporal stage (p = 3.96
7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine
Delayed Administration of Basic Fibroblast Growth Factor (bFGF) Attenuates Cognitive Dysfunction Following Parasagittal Fluid Percussion Brain Injury in the Rat
Effect of Transfer of Erythrocytes to a Nonuremic Medium on Corpuscular Parameters and Red Blood Cell Deformability in Patients Treated with CAPD and Hemodialysis
On the Relationship Between the Renin Receptor and the Vacuolar Proton-Atpase Membrane Sector-Associated Protein (M8-9)
Model-based evaluation of cost-effectiveness of nerve growth factor inhibitors in knee osteoarthritis: impact of drug cost, toxicity, and means of administration
ObjectiveStudies suggest nerve growth factor inhibitors (NGFi) relieve pain but may accelerate disease progression in some patients with osteoarthritis (OA). We sought cost and toxicity thresholds that would make NGFi a cost-effective treatment for moderate-to-severe knee OA.DesignWe used the Osteoarthritis Policy (OAPol) model to estimate the cost-effectiveness of NGFi compared to standard of care (SOC) in OA, using Tanezumab as an example. Efficacy and rates of accelerated OA progression were based on published studies. We varied the price/dose from 1000. We considered self-administered subcutaneous (SC) injections (no administration cost) vs provider-administered intravenous (IV) infusion (433/dose). Strategies were defined as cost-effective if their incremental cost-effectiveness ratio (ICER) was less than 148,700. Adding Tanezumab increased QALYs to 11.42, reduced primary TKR utilization to 63%, and increased costs to between 199,500. In the base-case analysis, Tanezumab at 1000/dose, Tanezumab was not cost-effective in all but the most optimistic scenario. Only at rates of accelerated OA progression of 10% or more (10-fold higher than reported values) did Tanezumab decrease QALYs and fail to represent a viable option.ConclusionsAt 400/dose in all settings except IV hospital delivery