An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the kneel

Objective: Five double-blind, randomized, saline-controlled trials (RCTs) were included in the United States marketing application for an intra-articular hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee. We report an integrated analysis of the primary Case Report Form (CRF) data from these trials. Method. Trials were similar in design, patient population and outcome measures - all included the Lequesne Algofunctional Index (LI), a validated composite index of pain and function, evaluating treatment over 3 months. Individual patient data were pooled; a repeated measures analysis of covariance was performed in the intent-to-treat (ITT) population. Analyses utilized both fixed and random effects models. Safety data from the five RCTs were summarized. Results: A total of 1155 patients with radiologically confirmed knee OA were enrolled: 619 received three or five IA-HA injections; 536 received. placebo saline injections. In the active and control groups, mean ages were 61.8 and 61.4 years; 62.4% and 58.8% were women; baseline total Lequesne scores 11.03 and 11.30, respectively. Integrated analysis of the pooled data set found a statistically significant reduction (P < 0.001) in total Lequesne score with hyaluronan (HA) (-2.68) vs placebo (-2.00); estimated difference -0.68 (95% CI: -0.56 to -0.79), effect size 0.20. Additional modeling approaches confirmed robustness of the analyses. Conclusions: This integrated analysis demonstrates that multiple design factors influence the results of RCTs assessing efficacy of intra-articular (IA) therapies, and that integrated analyses based on primary data differ from meta-analyses using transformed data. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Exploring composite acoustic features for efficient music similarity query

Music similarity query based on acoustic content is becoming important with the ever-increasing growth of the music information from emerging applications such as digital libraries and WWW. However, relative techniques are still in their infancy and much less than satisfactory. In this paper, we present a novel index structure, called Composite Feature tree, CF-tree, to facilitate efficient content-based music search adopting multiple musical features. Before constructing the tree structure, we use PCA to transform the extracted features into a new space sorted by the importance of acoustic features. The CF-tree is a balanced multi-way tree structure where each level represents the data space at different dimensionalities. The PCA transformed data and reduced dimensions in the upper levels can alleviate suffering from dimensionality curse. To accurately mimic human perception, an extension, named CF+-tree, is proposed, which further applies multivariable regression to determine the weight of each individual feature. We conduct extensive experiments to evaluate the proposed structures against state-of-art techniques. The experimental results demonstrate superiority of our technique.