A Cochrane review (update 2004): Hylan G-F 20 vs placebo for knee OA

Aim of study: As part of a Cochrane review of viscosupplementation in knee OA, randomised controlled trials (RCT) were reviewed to evaluate evidence for the efficacy of viscosupplementation with Hylan G-F 20 compared to placebo. Methods: Electronic searches were conducted of MEDLINE, EMBASE, Premedline, Current Contents, and CENTRAL. Human, RCT involving Hylan G-F 20 compared to placebo, published prior to 1Q2004, were included. Trials were selected and data extracted by two independent reviewers. Methodological quality was assessed with the Jadad criteria by two reviewers. Data on the OARSI and OMERACT core set clinical outcome measures were extracted where possible. Weighted mean difference (WMD), based on post-test scores, and 95% confidence intervals (CI) were calculated for continuous outcome measures and relative risk (RR) for dichotomous outcome measures. Results: Seven RCT met the inclusion criteria. Median methodological quality was 4 (range 1–5). A further two studies were only reported in abstract form (Jadad score Z 1) and contained insufficient extractable data for inclusion in the analysis. Nine RCT, which compared Hylan G-F 20 to other interventions such as intra-articular corticosteroid, physiotherapy, NSAID, appropriate care, intra-articular gaseous oxygen and other hyaluronan, are not reported here. Twenty-three studies failed to meet inclusion criteria and were excluded. Hylan G-F 20 was more efficacious than placebo at 1–4 weeks post-injection for pain on weight-bearing WMD (random effects [RE]) 13 mm on a 0–100 mm VAS (P Z 0.002) based on 6 RCT. This difference was even greater at 5–13 weeks post-injection, 22 m (RE) (P Z 0.001) based on 5 RCT, and at 14–6 weeks postinjection, 21 m (RE) (P Z 0.006) based on 4 RCT. Hylan G-F 20 was more efficacious than placebo at 1–4 weeks post-injection for pain at night, WMD 7 mm on a 0–100 mm VAS (P Z 0.003) based on 5 RCT. This difference was even greater at 5–13 weeks post-injection, 11 mm (P Z 0.008) based on 4 RCT, and at 14–26 weeks post-injection, 17 mm (P ! 0.00001) based on 3 RCT. There was no significant difference (WMD 8 mm) between Hylan G-F 20 C oral placebo and arthrocentesis C oral placebo at 5–13 weeks post-injection for WOMAC Pain, but Hylan G-F 20 C oral placebo was more efficacious than arthrocentesis C oral placebo for WOMAC Function, WMD 9 mm on a 0–100 mm VAS (P Z 0.01) (Dickson, 2001). Hylan G-F 20 was more effective than placebo at 1–4 weeks postinjection for the variable designed treatment efficacy, WMD 22 mm on a 0–100 mm VAS (P ! 0.00001) based on improvement in 4 RCT. This difference was even greater at 5–13 weeks post injection, 35 mm (P ! 0.00001). Conclusions: Evidence from this updated Cochrane review supports the superior efficacy of Hylan G-F 20 compared to placebo on weight-bearing pain, night pain, function and treatment efficacy in the treatment of knee OA.

Predictors of osteoarthritis(OA) improvement in patients treated with Hylan G-F for knee OA.

Aim of study: Different criteria for treatment response were explored to identify predictors of OA improvement. Analyses were based on data from a previously reported 1-year randomized controlled trial of appropriate care with or without hylan G-F 20 in patients with knee OA. Methods: Five definitions of ‘‘patient responder’’ from baseline to month 12 were examined: at least 20% reduction in WOMAC pain score; at least 20% reduction in WOMAC pain score and at least 20% reduction in either the WOMAC stiffness or function score; OARSI responder criteria (Propositions A and B) for intra-articular drugs; and OMERACT-OARSI responder criteria (Proposition D). As an a posteriori analysis, multivariable logistic regression models for each definition of patient responder were developed using a forward selection method. The following variables were defined prior to modeling and considered in the model along with two-way interactions: age (O65 years), BMI, gender, X-ray grade (0, I, II vs III, IV), co-morbidity (1 or 2 conditions vs 3 or more), duration of OA in study knee (years), previous surgery of study knee, hylan G-F 20 injection technique, WOMAC pain, stiffness and function, and treatment group. Results: Hylan G-F 20 was a predictor of improvement for all patient responder definitions P ! 0.001; odds of improvement were 2.7 or higher for patients in the hylan G-F 20 group compared to appropriate care without hylan G-F 20. For three of the five patient responder definitions, X-ray grade was a predictor of improvement (P ! 0.10; lower X-ray grade increased the odds of improvement). For four of the five patient responder definitions, duration of OA was a predictor of improvement (P ! 0.10; shorter duration of OA increased the odds of improvement). Conclusion: Analyses showed that appropriate care with hylan G-F 20 is the dominant predictor of patient improvement. While high grade structural damage does not preclude a response, patients who are targeted early in the disease process when less structural damage has occurred, may have a greater chance of improvement.

Automatic segmentation of the knee bones using 3D active shape models

This paper presents an automated segmentation approach for MR images of the knee bones. The bones are the first stage of a segmentation system for the knee, primarily aimed at the automated segmentation of the cartilages. The segmentation is performed using 3D active shape models (ASM), which are initialized using an affine registration to an atlas. The 3D ASMs of the bones are created automatically using a point distribution model optimization scheme. The accuracy and robustness of the segmentation approach was experimentally validated using an MR database of fat suppressed spoiled gradient recall images.