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The purpose of this study was to assess the efficacy and safety of intraarticular Hylan G-F 20 and triamcinolone acetonide 80 mg (TA) in primary knee osteoarthritis (OA) refractory to standard care in a developing country.After injection of either Hylan or TA, patients were seen at 12 and 26 wk. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, pain, stiffness (100 mm visual analogue score), and European Quality of Life (EQ) score were measured as well as radiographic joint space change and joint severity grade.The 26-week study was completed by 24 patients receiving Hylan (45 knees) and 21 receiving TA (38 knees). The primary outcome (improvement ≥40% of total WOMAC scores) at 12 wk in the Hylan group was 30 (66.7%) and in the TA group 5 (13.2%) (P<0.00) and at 26 wk, 35 (77.8%) and 10 (26.3%), respectively, (P<0.001). All secondary end points (pain, stiffness quality of life) improved significantly after 12 and 26 wk in both groups) but more in the Hylan group. The Kellgren-Lawrence radiographic grade improved more in the Hylan group than the TA group. The joint space improved at 12 wk in the Hylan and TA groups (0.4±0.8 and 0.1±0.5, respectively, P=0.044), and at 26 wk (0.6±1.1 and 0.0±0.5, respectively, P=0.003). No remarkable side effects were observed.In primary knee OA refractory to standard care, pain improved significantly more with Hylan G-F 20 than with TA after 12 and 26 wk as regards function and quality of life. Further studies are needed to assess longer time effects.