The safety and efficacy of intraarticular hyaluronan with/without corticosteroid in knee osteoarthritis: 1-year, single-blind, randomized study. Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomized, controlled trial. A randomized placebo-controlled trial of arthroscopic lavage versus lavage plus intra-articular corticosteroids in the management of symptomatic osteoarthritis of the knee. Intra-articular treatment with hyaluronic acid in osteoarthritis of the knee joint: a controlled clinical trial versus mucopolysaccharide polysulfuric acid ester. Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee. Effects of different hyaluronic acid products on synovial fluid levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in knee osteoarthritis. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response. Intra-articular hyaluronic acid compared to intra-articular triamcinolone hexacetonide in inflammatory knee osteoarthritis. Comparison of two hyaluronan drugs in patients with advanced osteoarthritis of the knee. A prospective, randomized, double-blind study with long term follow-up. A randomized, single-blind comparison of the efficacy and tolerability of hylan G-F 20 and triamcinolone hexacetonide in patients with osteoarthritis of the knee. Intra-articular steroids in knee osteoarthritis: a comparative study of triamcinolone hexacetonide and methylprednisolone acetate. Intra-articular hyaluranic acid compared with progressive knee exercises in osteoarthritis of the knee: a prospective randomized trial with long-term follow-up. Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee. A prospective, randomized trial. Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis. The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan. The effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized clinical trial.
The goal of this study was to assess the safety and efficacy of hyaluronan (HA) with/without corticosteroid in patients with knee osteoarthritis (OA). In a 1-year, randomized, single-blind trial, 24 patients were treated with HA weekly for 3 weeks, then three injections on the 6th month for a total of six injections. Sixteen patients were treated the same but with the addition of 1 ml triamcinolone acetonide prior to the first and fourth HA injection. The treatment was repeated at the sixth month. The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the visual analog pain scale (VAS). After 1 year, progression of OA was evaluated with magnetic resonance imaging (MRI). During the study, pain relief was marked in patients who received combined treatment with respect to WOMAC pain and VAS (p<0.05). At the first year, no progression was observed in either treatment group. Although all patients had improvement for both pain and function, HA together with corticosteroid was superior to HA alone for early pain relief. The MRI findings showed that neither treatment showed a progression on the damage of the cartilage. To evaluate the efficacy of joint lavage and intraarticular steroid injection, alone and in combination, in the treatment of patients with symptomatic knee osteoarthritis (OA).
                Ninety-eight patients with painful tibiofemoral OA were enrolled in a prospective, randomized, controlled, 2 x 2 factorial-design trial of 6 months' duration. The 4 treatment groups consisted of 1) intraarticular placebo (1.5 ml of 0.9% normal saline), 2) intraarticular corticosteroids (3.75 mg of cortivazol in 1.5 ml), 3) joint lavage and intraarticular placebo, and 4) joint lavage and intraarticular corticosteroid. Outcome measures evaluated at baseline, week 1, week 4, week 12, and week 24 included severity of pain (100-mm visual analog scale [VAS]), global status (100-mm VAS), and Lequesne's functional index.
                No interaction between steroid injection and joint lavage was demonstrated. Patients who had undergone joint lavage had significantly improved pain VAS scores at week 24 (P = 0.020). In contrast, corticosteroid injection had no long-term effect (P = 0.313); corticosteroid injection was associated with a decrease in pain only at week 1 (P = 0.003) and week 4 (P = 0.020). After week 4, Lequesne's functional index was not significantly improved regardless of the assigned treatment.
                Compared with placebo, both treatments significantly relieved pain but did not improve functional impairment. The effects of the 2 treatments were additive. Cortivazol provided short-term relief of pain (up to week 4). The effects of joint lavage persisted up to week 24. To assess the efficacy of intra-articular steroid injections following arthroscopy and joint lavage in symptomatic OA of the knee.
                Seventy-seven patients with OA of the knee were randomized to receive either 120 mg methylprednisolone acetate (MPA) or placebo following arthroscopy. Clinical assessments included severity of pain on movement and at rest, stiffness, the presence of joint effusions, range of movement, WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and Lequesne functional assessment. The outcome measures were evaluated at baseline and 2, 4, 8, 12 and 24 weeks. Further arthroscopies and synovial biopsies were performed at the time of clinical response and at relapse.
                An intention-to-treat analysis was performed on 71 patients (38 MPA, 33 placebo). Using the OARSI (Osteoarthritis Research Society International) response criteria, 58% of the steroid group vs 33% of the placebo group (adjusted relative risk = 2.38) (P = 0.004) responded at 4 weeks. At other time points, there were no significant differences between the treatment groups. There were no significant differences between the two treatment groups for pain, stiffness or WOMAC or Lequesne assessments at any time point.
                The response to intra-articular corticosteroids following joint lavage is short-lived (2-4 weeks), achievement of an OARSI response criterion being the only difference between the two groups. In a single-blind, randomized clinical trial, both the efficacy and safety of hyaluronic acid (HA) were compared with that of mucopolysaccharide polysulfuric acid ester (MPA) in patients with osteoarthritis of the knee joint. Both agents were administered intra-articularly over six weeks. Patients received either seven injections of HA or 13 injections of MPA. Joint function, range of motion, severity of pain, the general condition of the bony structure and soft tissue of the joint area, and the global clinical efficacy and safety of the medication were assessed. The mean improvement in the modified total Larson rating score was 22% (SD = 28) after HA treatment and 7% (SD = 17) after treatment with MPA (analysis of variance: p = 0.02). This change was mainly caused by a reduction of pain. The onset of pain relief was more rapid in the HA group. The therapeutic effect increased in both treatment groups during the follow-up period. During this interval, lasting six months after the start of treatment, a further reduction of pain and an improvement of knee joint function could be observed. At the end of the study, 25 out of 33 (76%) patients in the HA group and 11 out of 24 (46%) patients in the MPA group were symptom-free or markedly improved (Chi-square test: p = 0.02). Both agents were tolerated very well. Non-animal stabilized hyaluronic acid (NASHA) is a novel hyaluronan (HA) preparation with a 4-week intra-articular half-life. This study compared the efficacy of a single injection of NASHA with placebo in patients with osteoarthritis (OA) of the knee.
                This was a 26-week randomized, double-blind, multicenter study of a single intra-articular knee injection with either NASHA or placebo (saline). Assessments included the Western Ontario McMasters Universities osteoarthritis index (WOMAC, Likert Scale) and patients' overall global disease status. A positive response was defined as a reduction in WOMAC pain score for the study knee of 40% from baseline with a minimum improvement of > or =5 points.
                A total of 346 (NASHA 172; placebo 174) patients were treated. WOMAC scores and quality of life were improved in both the NASHA and placebo groups. For the overall population, there were no statistically significant between-group differences in response rates for any efficacy parameters. In patients with OA confined to the knee (N=216), a greater response to NASHA than placebo was observed at week 6 (P=0.025). There were few treatment-related events.
                NASHA was not superior to placebo for the primary efficacy analysis. However, these data may be confounded by the inclusion of patients with OA at other sites, as significant benefits over placebo were found among patients with OA confined to the knee. Future trials of OA that examine a local therapy might need to consider restricting the study population to those patients having OA of only the signal joint. The aim of this study was to evaluate the effects of different hyaluronic acid (HA) forms on synovial fluid levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the treatment of patients with knee osteoarthritis (OA). Forty patients were randomly assigned to 2 groups that were treated with native sodium hyaluronate (group I) or cross-linked hylan G-F 20 (group II). Clinical evaluations and synovial fluid aspirations were performed before the 1st injection (baseline), the 2nd injection (week 1), the 3rd injection (week 2), and at 1 week after the 3rd injection (week 3). Synovial fluid levels of both ICAM-1 and VCAM-1 were significantly reduced at weeks 1 to 3, compared to the baseline values. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index was used for clinical evaluations; the WOMAC pain score and physical function score were progressively improved at weeks 1 to 3 in both groups; the WOMAC stiffness score was significantly improved at week 3 in both groups. No significant differences were noted between the 2 treatment groups in respect to ICAM-1 levels, VCAM-1 levels, WOMAC pain score, stiffness score, or physical function score at any time. The decreased ICAM-1 and VCAM-1 levels after intra-articular HA injection may help to explain the anti-inflammatory effects of HA therapy in knee OA. To evaluate the safety and efficacy of long-term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA).
                In a randomized, double-blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50-foot walking time. Clinical symptoms were assessed just before each injection.
                At the 1-year and 2-year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid-injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline-injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2-year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05).
                Our findings support the long-term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long-term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long-term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease. To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide (THA) in knee osteoarthritis (OA) and examine factors which may relate to treatment efficacy.
                Eighty four patients with clinical and radiographic evidence of knee OA were recruited and randomly allocated to receive either THA (20 mg in 1 ml) or placebo (0.9% normal saline, 1 ml). Follow up assessments evaluated the following outcome variables: patient opinion of overall change in the treated knee, visual analogue pain score (VAS), distance walked in one minute (WD), and Health Assessment Questionnaire modified for lower limb function (HAQ).
                Seventy eight percent of THA and 49% of placebo treated patients reported overall improvement at week 1 (p < 0.05). At week 6, improvement was reported in 57% and 55% of patient groups, respectively. VAS improved in both groups at week 1 (THA, p < 0.001; placebo, p < 0.05) and week 6 (both p < 0.01). Improvement in VAS was significantly greater among THA treated patients at week 1 only (p < 0.01). Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion (p < 0.05), and those who had synovial fluid successfully aspirated at the time of injection (p < 0.01). WD improved in THA treated patients at week 1 (p < 0.001), and in both groups at week 6 (THA, p < 0.001; placebo, p < 0.01). Improvements in HAQ were seen in THA patients only at weeks 1 and 6 (p < 0.05). Regression analysis did not identify any additional clinical, radiographic, or synovial fluid characteristics which influenced the response.
                THA provided short term pain relief in knee OA. Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection. The aim of this study was to determine the comparative efficacy and safety of intra-articular (i/a) triamcinolone. hexacetonide (TH) and i/a hyaluronic acid (HA) in inflammatory knee osteoarthritis. A randomized double-blind comparative trail was carried out in a rheumatology outpatient department. There were 63 patients (24 male, 39 female, mean age 70.5 years) with bilateral symptomatic knee osteoarthritis with effusion. Each was given five HA injections at weekly intervals; or 20 mg TH followed by four placebo (saline) injections. Patients were examined weekly during the treatment period and then at monthly intervals for a further 6 months. Assessment included recording of: visual analog scores (VAS) for pain; duration of stiffness; range of movement; joint effusion; local heat; synovial thickening; joint-line and periarticular tenderness. The principal outcome measure was pain on a self-selected activity assessed by Vas. The two groups were comparable at entry and no significant differences between the groups developed at any time during the treatment period. However, there was a high drop-out rate and intention to treat analysis failed to demonstrate statistically significant differences between the groups. In patients remaining in the study, significantly less pain was experienced by the HA group during the 6 month follow-up period. Other parameters showed a similar trend in favor of experienced by the HA group during the 6 month follow-up period. Other parameters showed a similar trend in favor of HA. We could not, however, demonstrate significant differences between the placebo and active treatments. HA may therefore be a useful additional therapy for symptomatic knee osteoarthritis and may have a long duration of action. To compare the long-term effects of high and low molecular weight hyaluronic acid (HA) applications in severe (Kellgren Lawrence stage III) osteoarthritis (OA) of the knee.
                In a prospective clinical trial 184 knees (92 patients) with radiographic Kellgren Lawrence stage III OA were randomized to receive either 3 intra-articular high molecular weight HA (Hylan G-F 20) injections or 3 low molecular weight HA (Orthovisc) injections at one-week intervals. Patients were evaluated by the Hospital for Special Surgery (HSS) Knee Score and were followed-up for 12 months.
                The total HSS score in high molecular weight HA patients improved from 71.8+/-11.6 to 86.7+/-11.6 and in low molecular weight HA patients from 66.7+/-11.0 to 86.6+/-9.1 at the end of the trial (p < 0.01). There were no statistically significant differences between the groups and both had improved in all parameters at the latest follow-up (p = 0.000).
                Three intra-articular injections at intervals of 1 week of both HA preparations resulted in a pronounced reduction in pain and improved function as measured by the HSS score during a period of 52 weeks, without complications. To assess prospectively the efficacy and tolerability of hylan G-F 20 (HG-F 20; Synvisc) and intraarticular triamcinolone hexacetonide (TH; Aristospan) for treatment of osteoarthritis (OA) knee pain in a 26 week, randomized, multicenter, evaluator-blind study.
                Patients with OA were treated with typical regimens of HG-F 20 (n = 113) and TH (n = 102). Primary assessments were the WOMAC question A1 (pain walking on a flat surface), and a 100 mm visual analog scale (VAS) for patient and investigator overall assessments. Total WOMAC and WOMAC domain C (function) scores were also assessed. The intent-to-treat population was analyzed using a last-observation carried forward approach.
                Maximum pain relief occurred at 1-2 weeks for TH and at Week 12 for HG-F 20. At Weeks 12 and 26, HG-F 20 was significantly better than TH for the WOMAC question A1 responses (p = 0.0071 and p = 0.0129, respectively), and patient VAS (p < 0.0001 and p < 0.0001) and investigator VAS (p < 0.0300 and p = 0.0004) assessments. Similar significant (p < 0.01) results were observed at Weeks 12 and 26 for total WOMAC and domain C scores. While 15 TH-treated patients discontinued the study due to lack of efficacy, none did so with HG-F 20 treatment (p < 0.01). Both agents were well tolerated with similar adverse event profiles.
                Viscosupplementation with HG-F 20 resulted in a longer duration of effect than TH with a comparable tolerability profile. These data support the preferential use of HG-F 20 over TH for treatment of chronic OA knee pain. The aim of this study was to compare the effectiveness of triamcinolone hexacetonide (THA) and methylprednisolone acetate (MPA), given via the intra-articular route at equipotent dosage to patients with symptomatic knee OA with effusion, in a double-blind randomized comparative trial. Consecutive hospital-referred patients who fulfilled the American College of Rheumatology criteria for knee OA (clinical and radiographic) were randomly allocated to receive either THA 20 mg (1 ml) or MPA 40 mg (1 ml). All patients had synovial fluid aspirated from their knee joint at the time of injection. Assessments were made at 0, 3 and 8 weeks by a second operator, thus blinding both patient and assessor. Outcomes measured at each visit were: knee pain in the previous 48 h (expressed on a 100 mm visual analog scale; VAS), stair climb time (SCT) and Lequesne index score (LEQ). Changes in VAS, SCT and LEQ were compared between the groups using a Student's paired t test. Fifty-seven patients were studied (44 female, 13 male) with a mean age of 62.5 years. Both steroids gave significant pain relief (VAS) at week 3 ( p<0.01) but only MPA showed an effect on VAS and LEQ scores at week 8 compared to baseline ( p<0.05). THA was more effective than MPA at pain reduction at week 3 ( p<0.01); this difference was lost at week 8 ( p=0.17). There was no significant difference between the two drugs in functional endpoints (SCT, LEQ) at either 3 or 8 weeks. Both THA and MPA offer at least temporary symptomatic benefit in knee OA. THA is more effective than MPA at week 3, but its effect is lost by week 8. MPA still has an effect at week 8. The goal of this study was to determine whether hyaluronic acid (HA) or progressive knee exercises (PE) can improve functional parameters in patients with osteoarthritis (OA) of the knee. In a prospective clinical trial 200 knees (105 patients) with radiographic Kellgren Lawrence grade III OA were randomized and received either three intra-articular injections of hyaluronic acid (Hylan G-F 20) at one-week intervals or PE for 6 weeks. Patients were evaluated by use of the Hospital for Special Surgery (HSS) Knee Score and followed-up for 18 months. Total HSS score for HA and PE patients improved from 62.6 +/- 13.8 to 88.8 +/- 11.1 and from 65.4 +/- 12.3 to 88.3 +/- 9.1, respectively, at the end of the trial (P < 0.01). There were no statistically significant differences between the groups. Twenty-one patients of the HA group were excluded from the study because they had received another form of therapy. All patients in the PE group completed the trial. The patients who dropped out had also significant improvement from 57.0 +/- 12.9 to 76.7 +/- 11.9 (P < 0.01). This prospective randomized trial confirmed that both HA injections and PE result in functional improvement. HA injections also increase the levels of satisfaction of the OA patients. Although both corticosteroid and hyaluronic acid injections are widely used to palliate the symptoms of knee osteoarthritis, little research involving a comparison of the two interventions has been done. We tested the hypothesis that there are no significant differences between Hylan G-F 20 (Synvisc) and the corticosteroid betamethasone sodium phosphate-betamethasone acetate (Celestone Soluspan) in terms of pain relief or improvement in function, as determined by validated scoring instruments.
                One hundred patients with knee osteoarthritis were randomized to receive intra-articular injection of either Hylan G-F 20 or the corticosteroid, and they were followed for six months. The patients treated with Hylan G-F 20 received one course of three weekly injections. The patients treated with the corticosteroid received one injection at the time of enrollment in the study, and they could request one more injection any time during the study. An independent, blinded evaluator assessed the patients with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a modification of the Knee Society rating system, and the visual analog pain scale.
                Both the group treated with the corticosteroid and the group treated with Hylan G-F 20 demonstrated improvements from baseline WOMAC scores (a median decrease from 55 to 40 points and from 54 to 44 points, respectively; p < 0.01 for both). The scores according to the Knee Society system did not significantly improve for the patients who received the corticosteroid (median, 58 to 70 points; p = 0.06) or for those who received Hylan G-F 20 (median, 58 to 68 points; p = 0.15). The scores on the visual analog scale improved for patients receiving Hylan G-F 20 (median, 70 to 52 mm; p < 0.01) but not for the patients who received the corticosteroid (median, 64 to 52 mm; p = 0.28). However, no significant differences between the two treatment groups were found with respect to the WOMAC, Knee Society system, or visual analog scale results. Women demonstrated a significant improvement in only one of the six possible outcome-treatment combinations (the WOMAC scale), whereas men demonstrated significant improvements in five of the six outcomes (all measures except the Knee Society rating system).
                No differences were detected between patients treated with intra-articular injections of Hylan G-F 20 and those treated with the corticosteroid with respect to pain relief or function at six months of follow-up. Women demonstrated significantly less response to treatment than men did for both treatments on all three outcome scales. Such significant gender-related differences warrant further investigation. To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) injections of NRD101 in the treatment of symptomatic knee osteoarthritis (OA).
                A 1 year prospective, multicentre, randomised, double blind, placebo controlled study of 301 patients aged >50 years with painful and radiological medial knee OA. Patients were randomly assigned into three groups receiving: (1) three courses of three IA injections of hyaluronic acid (HA) + oral placebo; (2) IA injections of saline solution + diacerein 100 mg/day; (3) IA injections of saline solution + oral placebo. Demographic data and symptomatic criteria-pain, Lequesne's index, patient's global assessment of disease activity, percentage of painful days-were obtained during the study; primary structural criterion was JSW. Efficacy criteria were changes in pain VAS, joint space narrowing (JSN), and percentage of progressors (JSN >0.5 mm). An intention to treat analysis was used for symptomatic variables, and completer analysis for structural variables.
                Baseline characteristics were similar between the three groups. Mean (SD) improvement in pain VAS was clinically relevant (-33.9 (27.3), n = 301), but with no difference between the groups (p = 0.96). JSW deteriorated (-0.09 (0.55) mm, n = 277, p = 0.01), but with no difference between the groups (p = 0.82). Percentages of progressors were 17.7, 18.9, and 20.3% (p = 0.90), in groups 1, 2, and 3, respectively.
                A weak but statistically significant structural deterioration occurred over 1 year, together with clinically relevant symptomatic improvement in patients receiving oral drug and iterative IA injections. Symptomatic and/or structural effects for both this new HA compound and diacerein were not demonstrated. The objective of this 12-week, double-masked, randomized, multicenter study was to compare the elastoviscous properties of a high-molecular-weight viscosupplement, hylan G-F 20 (polymer concentration, 0.8%), with those of a lower-molecular-weight hyaluronan (LMW HA) product (polymer concentration, 1%) and to determine the relationship of elastoviscosity to efficacy in the treatment of patients with osteoarthritis (OA) of the knee. Patients had radiographically confirmed primary idiopathic OA of the knee (Larsen grades I to V) with pain despite other treatments. After a 2-week washout period, 70 patients (73 knees) received three 2-mL intra-articular injections of test solution at 1-week intervals. Thirty-eight patients (38 knees) received hylan G-F 20, and 32 patients (35 knees) received LMW HA. During the 12-week follow-up period, the primary outcome measures assessed by patients (using a visual analogue scale) were weight-bearing pain, most painful knee movement, and overall treatment response; the primary outcome measures assessed by study evaluators were weight-bearing pain and overall assessment of treatment. The dynamic elastoviscous properties of the test solutions were measured on an oscillating Couette-type rheometer. Hylan G-F 20 was more elastoviscous than the LMW HA at all frequencies measured (0.001 to 10 Hz). At the final evaluation, patients who received hylan G-F 20 had significantly better results on all primary outcome measures compared with those who received LMW HA. No systemic adverse events were reported. Local adverse events consisted of pain or swelling, noted in 2 of 38 knees injected with hylan G-F 20, and pain, noted in 1 of 35 knees injected with LMW HA (adverse event rates per injection, 1.8% and 0.9%, respectively). The difference in the incidence of adverse events between groups was not statistically significant. The higher-molecular-weight, more elastoviscous hylan G-F 20 had significantly greater pain-relieving effects than did the lower-molecular-weight, less elastoviscous hyaluronan. To determine the effectiveness of exercise therapy in patients with osteoarthritis (OA) of the hip or knee.
                A randomized single blind, clinical trial was conducted in a primary care setting. Patients with hip or knee OA by American College of Rheumatology criteria were selected. Two intervention groups were compared. Both groups received treatment from the patients' general practitioner, including patient education and medication if necessary. The experimental group also received exercise therapy from a physiotherapist in primary care. The treatment period was 12 weeks. The main outcome measures were pain, medication use (nonsteroidal antiinflammatory drugs, NSAID) and observed disability.
                A total of 201 patients were randomized. Exercise therapy was associated with a reduction of pain in the past week (difference in change -17.0; 95% CI -23.6, -10.4) and observed disability (-0.19; 95% CI -0.38; -0.01). Effect sizes were medium (0.58) and small (0.28), respectively. No effect of exercise therapy was found for the use of NSAID. Additional beneficial effects (p = 0.05) were found for the use of paracetamol (effect size 0.33), global effect as perceived by the patient (effect size 0.68), and muscle strength of the hip (effect size 0.34).
                After 12 weeks, exercise therapy is effective in reducing pain and disability. The size of the effects is medium and small, respectively.
The short-term benefit of IA corticosteroids in treatment of knee OA is well established, and few side effects have been reported. Longer term benefits have not been confirmed based on the RevMan analysis. The response to HA products appears more durable. In this review, some discrepancies were observed between the RevMan 4.2 analysis and the original publication. These are likely the result of using secondary rather than primary data and the statistical methods available in RevMan 4.2. Future trials should have standardised outcome measures and assessment times, run longer, investigate different patient subgroups, and clinical predictors of response (those associated with inflammation and structural damage).