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.

Evaluation of Melanotaenia duboulayi (Atheriniformes : Melanotaeniidae), Hypseleotris galii (Perciformes : Eleotridae), and larvicide Vectolex (R) WG (Bacillus sphaericus) for integrated control of Culex annulirostris

Australian freshwater fish species Melanotaenia duboulayi and Hypseleotris galii were selected for a small plot field evaluation of an integrated pest management strategy using native fish and VectoLex® WG (Bacillus sphaericus) for the control of Culex annulirostris Skuse, the principal freshwater vector of arbovirus Ross River virus in Australia. When tested alone, the level of control afforded by M. duboulayi and H. galii was highly dependent on the prerelease density of mosquito larvae; and even when stocking rates as high as 10 g per pond (>30 kg/ha) were used, larval abundance was too high to attain adequate control from fish alone. In contrast, treatment with VectoLex WG at 500 g/ha resulted in 100% mortality of Cx. annulirostris immatures, but no residual activity was evident. The delayed reduction of Cx. annulirostris immatures in ponds stocked with fish alone, and the recolonization by Cx. annulirostris in ponds after treatment with B. sphaericus, did not occur when both treatments were combined.

The makings of maleness: towards an integrated view of male sexual development

As the mammalian embryo develops, it must engage one of the two distinct programmes of gene activity, morphogenesis and organogenesis that characterize males and females. In males, sexual development hinges on testis determination and differentiation, but also involves many coordinated transcriptional, signalling and endocrine networks that underpin the masculinization of other organs and tissues, including the brain. Here we bring together current knowledge about these networks, identify gaps in the overall picture, and highlight the known defects that lead to disorders of male sexual development.