Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee: a randomized controlled trial

OBJECTIVE: To compare the efficacy and safety of intraarticular hylan and 2 hyaluronic acids (HAs) in osteoarthritis (OA) of the knee. METHODS: This was a multicenter, patient-blind, randomized controlled trial in 660 patients with symptomatic knee OA. Patients were randomly assigned to receive 1 cycle of 3 intraarticular injections per knee of 1 of 3 preparations: a high molecular weight cross-linked hylan, a non-cross-linked medium molecular weight HA of avian origin, or a non-cross-linked low molecular weight HA of bacterial origin. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 6 months. Secondary outcome measures included local adverse events (effusions or flares) in injected knees. During months 7-12, patients were offered a second cycle of viscosupplementation. RESULTS: Pain relief was similar in all 3 groups. The difference in changes between baseline and 6 months between hylan and the combined HAs was 0.1 on the WOMAC pain score (95% confidence interval [95% CI] -0.2, 0.3). No relevant differences were observed in any of the secondary efficacy outcomes, and stratified analyses provided no evidence for differences in effects across different patient groups. There was a trend toward more local adverse events in the hylan group than in the HA groups during the first cycle (difference 2.2% [95% CI -2.4, 6.7]), and this trend became more pronounced during the second cycle (difference 6.4% [95% CI 0.6, 12.2]). CONCLUSION: We found no evidence for a difference in efficacy between hylan and HAs. In view of its higher costs and potential for more local adverse events, we see no rationale for the continued use of hylan in patients with knee OA.

Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review and meta-analysis

OBJECTIVE: To compare the effectiveness and safety of intraarticular high-molecular hylan with standard preparations of hyaluronic acids in osteoarthritis of the knee. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials comparing hylan with a hyaluronic acid in patients with knee osteoarthritis. Trials were identified by systematic searches of Central, Medline, EMBase, Cinahl, the Food and Drug Administration, and Science Citation Index supplemented by hand searches of conference proceedings and reference lists (last update November 2006). Literature screening and data extraction were performed in duplicate. Effect sizes were calculated from differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled standard deviation. Trials were combined using random-effects meta-analysis. RESULTS: Thirteen trials with a pooled total of 2,085 patients contributed to the meta-analysis. The pooled effect size was -0.27 (95% confidence interval [95% CI] -0.55, 0.01), favoring hylan, but between-trial heterogeneity was high (I(2) = 88%). Trials with blinded patients, adequate concealment of allocation, and an intent-to-treat analysis had pooled effect sizes near null. The meta-analyses on safety revealed an increased risk associated with hylan for any local adverse events (relative risk [RR] 1.91; 95% CI 1.04, 3.49; I(2) = 28%) and for flares (RR 2.04; 95% CI 1.18, 3.53; I(2) = 0%). CONCLUSION: Given the likely lack of a superior effectiveness of hylan over hyaluronic acids and the increased risk of local adverse events associated with hylan, we discourage the use of intraarticular hylan in patients with knee osteoarthritis in clinical research or practice.

Meta-analysis: chondroitin for osteoarthritis of the knee or hip

BACKGROUND: Previous meta-analyses described moderate to large benefits of chondroitin in patients with osteoarthritis. However, recent large-scale trials did not find evidence of an effect. PURPOSE: To determine the effects of chondroitin on pain in patients with osteoarthritis. DATA SOURCES: The authors searched the Cochrane Central Register of Controlled Trials (1970 to 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and conference proceedings; checked reference lists; and contacted authors. The last update of searches was performed on 30 November 2006. STUDY SELECTION: Studies were included if they were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip. There were no language restrictions. DATA EXTRACTION: The authors extracted data in duplicate. Effect sizes were calculated from the differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled SD. Trials were combined by using random-effects meta-analysis. DATA SYNTHESIS: 20 trials (3846 patients) contributed to the meta-analysis, which revealed a high degree of heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials. When the authors restricted the analysis to the 3 trials with large sample sizes and an intention-to-treat analysis, 40% of patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13 to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of 0.99 (CI, 0.76 to 1.31) for any adverse event. LIMITATIONS: For 9 trials, the authors had to use approximations to calculate effect sizes. Trial quality was generally low, heterogeneity among the trials made initial interpretation of results difficult, and exploring sources of heterogeneity in meta-regression and stratified analyses may be unreliable. CONCLUSIONS: Large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged.

Pediatric craniofacial trauma

PURPOSE: Maxillofacial and skull fractures occur with concomitant injuries in pediatric trauma patients. The aim of this study was to determine the causes and distributions of maxillofacial and skull fractures as well as concomitant injuries of pediatric patients in Switzerland. Results were compared with worldwide studies. MATERIALS AND METHODS: A retrospective review was conducted of 291 pediatric patients with maxillofacial and skull fractures presenting to a level-I trauma center over a 3-year span. Data concerning the mechanism of the accident and the topographic location of the injuries were analyzed. RESULTS: The most common causes were falls (64%), followed by traffic (22%) and sports-related accidents (9%). Fifty-four percent of the fractures occurred in the skull vault and 37% in the upper and middle facial third. One third of the patients (n = 95) suffered concomitant injuries, mostly cerebral concussions (n = 94). CONCLUSIONS: The spectrum of craniofacial injuries is related to the specific developmental stage of the craniofacial skeleton. It is probable that national prevention programs will have a positive effect on reducing the incidence of falls. Standardization of studies is needed for international comparison.

Disseminated Tuberculosis Following Total Knee Arthroplasty in an HIV Patient

Skeletal tuberculosis is now uncommon in developed countries. In immunocompromised patients - particularly in the HIV-infected - who present with subacute or chronic joint pain refractory to conventional treatment, osteoarticular tuberculosis should still be included in the differential diagnosis. We report on a lethal case of disseminated tuberculosis in an HIV-infected subject. Dissemination may have resulted from the implantation of an articular prosthesis in a knee joint with unsuspected osteoarticular tuberculosis. The diagnosis was established months later when the patient presented with far-advanced tuberculous meningitis, miliary tuberculosis of the lungs, femoral osteomyelitis and extended cold abscesses along the femoral shaft. Failure to respond to a conventional four-drug regimen is explained by the resistance pattern of his multi-drug resistant strain of Mycobacterium tuberculosis, which was only reported after the patient's death. This case illustrates the diagnostic challenges of osteoarticular tuberculosis and the consequences of a diagnostic delay in an HIV-infected individual.

The value of conservative treatment in ruptures of the anterior cruciate ligament (ACL)

BACKGROUND: Thirty-eight of the 73 consecutive acute ruptures of the anterior cruciate ligament (ACL) proven by a magnetic resonance imaging scan (MRI) in skeletally mature patients (16-55 years old) were classified as suitable for primarily conservative treatment. Patient selection was performed using a preoperative screening protocol based on the structural damage, clinical symptoms, compliance, sportive activity, and the consent of a well-informed patient. METHODS: In 12 of the 38 treated patients, the conservative protocol showed a good to very good outcome, 2 patients had persistent giving-way and were considering ACL reconstruction, 14 patients had a secondary ACL reconstruction in our clinic (average 5.3 months after injury), 9 patients were operated on in other hospitals (average 13.3 months after injury), and 1 patient was lost to follow-up. RESULTS: All patients with successful conservative treatment were able to perform low-risk pivoting sports and two patients are practicing high-risk pivoting sports. The average International Knee Documentation Committee (IKDC) score was 92.5 (82.8-98.9); the subjective overall knee function was 93% (60% to 100%). Of the 12 patients with good and very good results, 6 continued playing the same sports at an unreduced intensity, 4 patients reduced their activities slightly, and 1 patient played more sports than before. CONCLUSIONS: Although the authors performed a preoperative screening to select patients suitable for conservative treatment, almost two-thirds of the primarily conservatively treated ACL ruptures needed an operative reconstruction in the long term. In one-third of the patients, conservative treatment led to a good or very good result. At the endpoint of the study only 12 (16%) of a total of 73 patients with acute injuries of the ACL had successful conservative treatment. Therefore, patients must be comprehensively instructed about the treatment program and the chances of success of conservative ACL treatment.