The effectiveness of high molecular weight hyaluronic acid for knee osteoarthritis in patients in the working age: a randomised controlled trial.

BACKGROUND: High molecular weight (HMW) hyaluronic acid (HA) is a treatment option for knee osteoarthritis (OA). The efficacy of HMW-HA in knee OA is investigated extensively, but the effectiveness in patients in the working age is unknown. Nevertheless, the number knee OA patients in the working age is increasing. Surgical treatment options are less eligible in these patients and productivity losses are high. In this study the effectiveness of intra-articular HMW-HA added to regular non-surgical usual care in everyday clinical practice (UC) compared to UC over 52 weeks in symptomatic knee OA patients in the working age was investigated. METHODS: In this open labelled randomized controlled trial, subjects aged between 18 and 65 years with symptomatic knee OA (Kellgren and Lawrence I-III) were enrolled and randomized to UC + 3 weekly injections with HMW-HA (intervention) or UC only (control). The primary outcome was the between group difference in responders to therapy according to OMERACT-OARSI criteria after 52 weeks. These criteria include the domains pain, knee related function and patient's global assessment (PGA). Function was evaluated with the KOOS questionnaire. Pain was assessed with the Numeric Rating Scale. Secondary outcome comprised the between group difference on the individual responder domains, as analysed with a random effects model. Odds Ratios (OR) were calculated by logistic regression analysis. Sensitivity analyses were performed. RESULTS: In total, 156 subjects were included (intervention group 77, control group 79). Subjects in the intervention group (HMW-HA + UC) were more often responder compared to the controls (UC). Depending on whether pain during rest or pain during activity was included in the responder domains, 57.1% versus 34.2% (p = 0.006) and 54.5% versus 34.2% (p = 0.015) was responder to therapy respectively. The results of the secondary outcome analyses show that scores on individual responder domains over all follow-up moments were statistically significant in favour of the intervention group in the domains pain during rest (δ 0.8, 95%CI 0.2; 1.4, p = 0.010), knee related function (δ - 6.8, 95%CI -11.9; - 1.7, p = 0.010) and PGA (δ - 0.7, 95%CI -0.9; - 0.4, p < 0.0001). CONCLUSIONS: Intra-articular HMW-HA added to usual care is effective for knee OA in patients in the working age. TRIAL REGISTRATION: www.trialregister.nl , NTR1651, registered 2009-3-3.

Does this patient with shoulder pain have rotator cuff disease?: The Rational Clinical Examination systematic review.

IMPORTANCE: Rotator cuff disease (RCD) is the most common cause of shoulder pain seen by physicians. OBJECTIVE: To perform a meta-analysis to identify the most accurate clinical examination findings for RCD. DATA SOURCES: Structured search in MEDLINE, EMBASE, and CINAHL from their inception through May 2013. STUDY SELECTION: For inclusion, a study must have met the following criteria: (1) description of history taking, physical examination, or clinical tests concerning RCD; (2) detailing of sensitivity and specificity; (3) use of a reference standard with diagnostic criteria prespecified; (4) presentation of original data, or original data could be obtained from the authors; and (5) publication in a language mastered by one of the authors (Danish, Dutch, English, French, German, Norwegian, Spanish, Swedish). MAIN OUTCOMES AND MEASURES: Likelihood ratios (LRs) of symptoms and signs of RCD or of a tear, compared with an acceptable reference standard; quality scores assigned using the Rational Clinical Examination score and bias evaluated with the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: Twenty-eight studies assessed the examination of referred patients by specialists. Only 5 studies reached Rational Clinical Examination quality scores of level 1-2. The studies with quality scores of level 1-2 included 30 to 203 shoulders with the prevalence of RCD ranging from 33% to 81%. Among pain provocation tests, a positive painful arc test result was the only finding with a positive LR greater than 2.0 for RCD (3.7 [95% CI, 1.9-7.0]), and a normal painful arc test result had the lowest negative LR (0.36 [95% CI, 0.23-0.54]). Among strength tests, a positive external rotation lag test (LR, 7.2 [95% CI, 1.7-31]) and internal rotation lag test (LR, 5.6 [95% CI, 2.6-12]) were the most accurate findings for full-thickness tears. A positive drop arm test result (LR, 3.3 [95% CI, 1.0-11]) might help identify patients with RCD. A normal internal rotation lag test result was most accurate for identifying patients without a full-thickness tear (LR, 0.04 [95% CI, 0.0-0.58]). CONCLUSIONS AND RELEVANCE: Because specialists performed all the clinical maneuvers for RCD in each of the included studies with no finding evaluated in more than 3 studies, the generalizability of the results to a nonreferred population is unknown. A positive painful arc test result and a positive external rotation resistance test result were the most accurate findings for detecting RCD, whereas the presence of a positive lag test (external or internal rotation) result was most accurate for diagnosis of a full-thickness rotator cuff tear.

Cost-Utility Analysis of High Molecular Weight Hyaluronic Acid for Knee Osteoarthritis in Everyday Clinical Care in Patients at a Working Age: An Economic Evaluation of a Randomized Clinical Trial.

OBJECTIVE: Knee osteoarthritis (OA) is associated with high medical costs and especially with high productivity costs, in particular in patients in their working years. High molecular weight (HMW) hyaluronic acid (HA) is an alternative treatment for nonsteroidal antiinflammatory drugs, which are known for their serious side-effects. The cost-utility of intraarticular HMW-HA treatment in these patients is unknown, however, and was assessed in this study. METHODS: Secondary care patients ages 18-65 years with knee OA were randomized to usual care plus HMW-HA (intervention group) or to usual care only (control group). A cost-utility analysis over 52 weeks from the societal and health care perspective was performed. Uncertainty for costs, effects, and cost-utility ratio was analyzed by nonparametric bootstrapping. Baseline imbalance adjustment was done by inverse probability of treatment weighting. RESULTS: In total, 156 subjects were included (intervention group n = 77, control group n = 79). The total of productivity and medical costs was €475 higher in the intervention group at €7,754 (95% confidence interval [95% CI] 5,426, 10,436) versus €7,270 (95% CI 5,453, 9,262). The amount of quality-adjusted life years (QALYs) gained during followup was also higher in the intervention group (0.779 versus 0.727). This variation resulted in an incremental cost-effectiveness ratio of €9,100/QALY from a societal perspective and €8,700/QALY from a health care perspective. When the maximum willingness to pay for conditions similar to knee OA is considered, the probability on cost-effectiveness is 64% and 86%, respectively. CONCLUSION: Intraarticular HMW-HA added to usual care for knee OA is probably cost-effective in the treatment of knee OA.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) shows no change in cartilage structural composition after viscosupplementation in patients with early-stage knee osteoarthritis.

INTRODUCTION: Viscosupplementation with hyaluronic acid (HA) of osteoarthritic (OA) knee joints has a well-established positive effect on clinical symptoms. This effect, however, is only temporary and the working mechanism of HA injections is not clear. It was suggested that HA might have disease modifying properties because of its beneficial effect on cartilage sulphated glycosaminoglycan (sGAG) content. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a highly reproducible, non-invasive surrogate measure for sGAG content and hence composition of cartilage. The aim of this study was to assess whether improvement in cartilage structural composition is detected using dGEMRIC 14 weeks after 3 weekly injections with HA in patients with early-stage knee OA. METHODS: In 20 early-stage knee OA patients (KLG I-II), 3D dGEMRIC at 3T was acquired before and 14 weeks after 3 weekly injections with HA. To evaluate patient symptoms, the knee injury and osteoarthritis outcome score (KOOS) and a numeric rating scale (NRS) for pain were recorded. To evaluate cartilage composition, six cartilage regions in the knee were analyzed on dGEMRIC. Outcomes of dGEMRIC, KOOS and NRS before and after HA were compared using paired t-testing. Since we performed multiple t-tests, we applied a Bonferroni-Holm correction to determine statistical significance for these analyses. RESULTS: All KOOS subscales ('pain', 'symptoms', 'daily activities', 'sports' and 'quality of life') and the NRS pain improved significantly 14 weeks after Viscosupplementation with HA. Outcomes of dGEMRIC did not change significantly after HA compared to baseline in any of the cartilage regions analyzed in the knee. CONCLUSIONS: Our results confirm previous findings reported in the literature, showing persisting improvement in symptomatic outcome measures in early-stage knee OA patients 14 weeks after Viscosupplementation. Outcomes of dGEMRIC, however, did not change after Viscosupplementation, indicating no change in cartilage structural composition as an explanation for the improvement of clinical symptoms.

Productivity costs and medical costs among working patients with knee osteoarthritis.

OBJECTIVE: Although the knee joint is one of the joints most affected by osteoarthritis (OA), research on the economic implications of joint disease has generally focused only on OA. The goal of this study was to identify and quantify knee-related productivity and medical costs in knee OA patients with paid employment. Furthermore, we evaluated associations between productivity loss and relevant patient, health, and work characteristics. METHODS: Consecutive knee OA patients with mild to moderate knee OA who were 18-65 years of age, had conservative treatment for ≥6 months, and had paid employment were included. Productivity loss and health care consumption were measured by questionnaires. The associations between productivity loss and patient, health, and work characteristics were explored with regression analyses. RESULTS: In total, 117 knee OA patients with a mean age of 53.2 years and a mean body mass index of 28.8 kg/m(2) were included. Total knee-related productivity costs and medical costs were €871 (median €411, interquartile range [IQR] €107-1,200) per patient per month, with total productivity costs of €722 (median €217, IQR €0-1,041) and total medical costs of €149 (median €137, IQR €72-198). More pain during activity and performing physically intensive work were significantly associated with productivity loss. CONCLUSION: The total knee-related productivity costs and medical costs of conservatively treated symptomatic knee OA patients with paid employment in The Netherlands are €871 per patient per month, with productivity costs accounting for 83% and medical costs for 17%. Productivity loss is associated with having more pain during activity and performing physically intensive work. Developing adequate treatment strategies for knee OA may be cost beneficial.

The most accurate approach for intra-articular needle placement in the knee joint: a systematic review.

INTRODUCTION: Intra-articular needle placement in the knee joint, such as injection or aspirations, are commonly used for therapeutic, diagnostic, and research purposes. Although several approaches can be used to establish an intra-articular injection or aspiration of the knee joint, the accuracy differs per approach. OBJECTIVE: To summarize the evidence concerning the accuracy of different approaches for intra-articular needle placements in the knee. Additionally, to assess whether the accuracy of different approaches is related to factors such as underlying disease, severity of underlying disease, approach-related factors, and/or the rate of local reactions. METHODS: The literature was systemically reviewed until July 2010. Risk of bias of the included studies was assessed by the QUADAS tool. Study characteristics were extracted; accuracy results were pooled per approach. RESULTS: Nine studies were included. The superolateral approach with the leg in extension was studied most (230 injections) and resulted in the highest pooled accuracy of 91% (95% CI 84-99%). The lateral midpatellar approach, the anterolateral approach, and the anteromedial approach resulted in the lowest pooled accuracy rates, 85% (95% CI 68-100%), 67% (95% CI 43-91%) and 72% (95% CI 65-78%), respectively. CONCLUSIONS: The superolateral approach was investigated most and resulted in the highest pooled accuracy rate of 91% (95% CI 84-99%). Nevertheless, this approach still results in a substantial amount of extra-articular needle placements. Guidance of intra-articular needle placements by imaging techniques may enhance the accuracy. The costs and extra time associated with these techniques should be taken into consideration.