A randomised double-blind placebo-controlled crossover trial of HUMira (adalimumab) for erosive hand OsteoaRthritis - the HUMOR trial.

OBJECTIVE: To assess the efficacy of adalimumab in patients with erosive hand osteoarthritis (OA). METHOD: Patients >50 years old, meeting the American College of Rheumatology (ACR) criteria for hand OA, with pain >50 on 100 mm visual analogue scale (VAS), morning stiffness >30 min and ≥1 erosive joint on X-ray with synovitis present on magnetic resonance imaging (MRI) were included in a randomised double-blind placebo-controlled crossover trial. Patients were randomised to adalimumab (40 mg subcutaneous injections every other week) or identical placebo injections for 12 weeks followed by an 8-week washout and then crossed over treatment groups for another 12 weeks. The primary outcome was change in VAS hand pain over 12 weeks. Secondary outcomes included change in Australian/Canadian Hand OA Index (AUSCAN) pain, function and stiffness subscales from baseline to 4, 8 and 12 weeks, change in MRI-detected synovitis and bone marrow lesions (BMLs) from baseline to 12 weeks and change in VAS from baseline to 4 and 8 weeks. RESULTS: We recruited 51 patients and 43 were randomised to either Group 1 (N = 18, active then placebo) or Group 2 (N = 25, placebo then active). At 12 weeks there was no difference between the groups on the primary outcome measure (mean decrease in VAS pain of 3.2 mm standard deviation (SD 16.7) for adalimumab vs 0.8 mm (SD 29.6) for placebo). The adjusted treatment effect was -0.7 mm (95% confidence interval (CI) -9.3 to 8.0), P = 0.87. No statistically significant differences were found for any secondary outcomes. CONCLUSION: Adalimumab did not show any effect on pain, synovitis or BMLs in patients with erosive hand OA with MRI-detected synovitis as compared to placebo after 12 weeks. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12612000791831.

Improvement in condition-specific and generic quality of life outcomes in patients with knee osteoarthritis following single-injection Synvisc: results from the LOBRAS study.

OBJECTIVE: To evaluate the effectiveness of viscosupplementation with single-injection hylan G-F20 (Synvisc-One) in knee osteoarthritis (OA), during routine clinical care, in a 52 week observational study. RESEARCH DESIGN AND METHODS: The LOBRAS study involved a 1 year long, multi-center, quasi-experimental, repeated measures, observational study. Consenting patients in Australia fulfilling inclusion/exclusion criteria under the care of a medical specialist in routine clinical practice were enrolled. Prior to, and for 52 weeks following, intra-articular single-injection hylan G-F20, patients were repeatedly evaluated using the WOMAC NRS4.1 Index and the SF-36 questionnaire. The WOMAC NRS4.1 was administered by mobile phone (with paper back-up), and the SF-36 was administered on paper. Patients were monitored for adverse events. MAIN OUTCOME MEASURES: Western Ontario and McMaster (WOMAC) OA Index, and the Short Form 36 questionnaire (SF-36 v2). RESULTS: A total of 131 patients with knee OA were enrolled, of whom 119 provided both pre- and post-intervention WOMAC data. Statistically significant improvements (with a maximum of p ≤ .025) from baseline to Week 12, Month 6 and Week 52 were detected, by intention-to-treat (ITT) and per-protocol (PP) analyses, in WOMAC Pain, Stiffness, Function, PGA, and Total Score, SF-36 PCS, and WOMAC-derived HUI3. Adverse event (AE) monitoring detected treatment-related AEs in 5.3% of patients. CONCLUSIONS: The effectiveness of single-injection hylan G-F20 in routine clinical care is supported by the detection of statistically significant, clinically important improvements in WOMAC Pain, Stiffness, Function, Total, and PGA outcomes, and statistically significant improvements in SF-36 PCS and WOMAC-derived HUI3 outcomes at multiple time points. Limitations of this study include lack of a control group or blinding. No predictive indicators of the response to treatment were identified. In general single-injection hylan G-F20 was well tolerated with very few patients experiencing any treatment-related adverse events. Collectively, these observations attest to the effectiveness of single-injection hylan G-F20 and complement previous observations in routine clinical care.

Development, linguistic and clinimetric validation of the WOMAC VA3.01 Bangla for Bangladesh Index.

The aim of this study was to develop and to validate a Bengali version of the Western Ontario and McMaster Osteoarthritis (WOMAC) index in Bangladesh. The WOMAC was translated into the local language of Bangladesh (Bengali) and adapted in the local sociocultural context, following the standard guidelines by Beaton et al. Content validity of the preliminary Bengali version was assessed by using the index of content validity (ICV) and floor and ceiling effects. Patients were assessed at the Department of Rheumatology of Bangabandhu Sheikh Mujib Medical University and were diagnosed to have knee OA by American College of Rheumatology criteria and recruited according to the requirements of the validation study. Convergent and divergent validity were measured by comparing with Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36), and internal consistency was assessed using Cronbach's alpha coefficient. The questionnaire was readministered to 40 patients within a week for assessing reliability by using intra-class correlation coefficient (ICC) and Spearman's rank correlation coefficient. In addition, factor analysis of Bengali WOMAC questionnaire was performed to examine the number of factors influencing a common set of items. A Bengali version was developed with changes in three items to suit local practices. The ICV of the content validity was 1 for all items. The Bengali WOMAC had similar construct validity when compared to the HAQ (ρ 0.74, n = 70) and SF-36 bodily pain and physical functioning. It had dissimilar construct validity to SF-36 mental health domain except WOMAC pain. Factor analysis revealed five factors with eigenvalues of more than 1.0. Cronbach's alpha and ICC exceeded 0.7 in all domains. In the test-retest reliability testing, Spearman's ρ for all items exceeded 0.4 (n = 40). This study has demonstrated that the Bengali version of WOMAC is a valid tool for assessing quality of life of patients with knee osteoarthritis in Bangladesh and is reliable.

Minimum clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: Results from a prospective multinational study.

OBJECTIVE: To estimate the minimum clinically important improvement (MCII) and patient acceptable symptom state (PASS) values for 4 generic outcomes in 5 rheumatic diseases and 7 countries. METHODS: We conducted a multinational (Australia, France, Italy, Lebanon, Morocco, Spain, and The Netherlands) 4-week cohort study involving 1,532 patients who were prescribed nonsteroidal antiinflammatory drugs for ankylosing spondylitis, chronic back pain, hand osteoarthritis, hip and/or knee osteoarthritis, or rheumatoid arthritis. The MCII and PASS values were estimated with the 75th percentile approach for 4 generic outcomes: pain, patient global assessment, functional disability, and physician global assessment, all normalized to a 0-100 score. RESULTS: For the whole sample, the estimated MCII values for absolute change at 4 weeks were -17 (95% confidence interval [95% CI] -18, -15) for pain; -15 (95% CI -16, -14) for patient global assessment; -12 (95% CI -13, -11) for functional disability assessment; and -14 (95% CI -15, -14) for physician global assessment. For the whole sample, the estimated PASS values were 42 (95% CI 40, 44) for pain; 43 (95% CI 41, 45) for patient global assessment; 43 (95% CI 41, 44) for functional disability assessment; and 39 (95% CI 37, 40) for physician global assessment. Estimates were consistent across diseases and countries (for subgroups ≥20 patients). CONCLUSION: This work allows for promoting the use of values of MCII (15 of 100 for absolute improvement, 20% for relative improvement) and PASS (40 of 100) in reporting the results of trials of any of the 5 involved rheumatic diseases with pain, patient global assessment, physical function, or physician global assessment used as outcome criteria.

Severity in irritable bowel syndrome: a Rome Foundation Working Team report.

OBJECTIVES: The concept of severity in irritable bowel syndrome (IBS) is clinically recognized and operative in diagnostic decision making and treatment planning. Yet, there is no consensus on its definition, and there are limited data on the prevalence of severity subgroups, its medical and psychosocial determinants, and its association with other health status measures. The aims of the Rome Foundation Working Team Committee were to summarize current research, to develop a consensus of understanding on this concept, and to make recommendations for its use in research and clinical care. METHODS: In 2006, a multinational committee of clinical investigators with expertise in IBS and/or psychometric research methods undertook a systematic review of the literature relating to severity in IBS. Owing to limited data, the Foundation commissioned three clinical studies to better characterize the concept of severity in IBS, and summary information and recommendations for future research and clinical care were developed. RESULTS: The main findings were: (i) severity in IBS is defined as a biopsychosocial composite of patient-reported gastrointestinal and extraintestinal symptoms, degree of disability, and illness-related perceptions and behaviors; (ii) both visceral and central nervous system physiological factors affect severity; as severity increases, the central nervous system provides a greater contribution; (iii) severity is related to and influences health-related quality of life and health behaviors and also guides diagnostic and therapeutic clinical decision making; (iv) severity can be subcategorized into clinically meaningful subgroups as mild (∼40%), moderate (∼35%), and severe (∼25%), and this provides a working model for use in future research and clinical care. CONCLUSIONS: Future work is required to understand more precisely the factors contributing to severity and to develop a valid patient-reported instrument to measure severity in IBS.

Electronic data capture (EDC) using cellular technology: implications for clinical trials and practice, and preliminary experience with the m-Womac Index in hip and knee OA patients.

AIM: The capture, analysis and utilisation of health status information are attended by logistic considerations and interpretation challenges. We report a preliminary evaluation of cellular technology in capturing WOMAC NRS 3.1 Index data. METHODS: A Java midlet for delivering the WOMAC NRS3.1 Index on Nokia-6300, Motorola-V3 and Samsung-A711 mobile phones was developed by Exco InTouch. Following task orientation, patients completed the paper-based WOMAC (p-WOMAC questionnaire, and then the three mobile phonebased WOMAC (m-WOMAC applications, in random order. RESULTS: All 12 patients (age range = 55-82 years) successfully completed the m-WOMAC Index on each of the three phones, and all were found acceptable by patients. With respect to m-WOMAC mean overall rank score, no significant difference was found between the 3 phones (Friedman's chi square (2 df) = 2.2, p = 0.34) however, Motorola V3 was favoured with the best mean rank. Pearson correlation between the average p-WOMAC and average m-WOMAC score was 0.996. CONCLUSIONS: Patient reported ratings indicated the m-WOMAC application performed well on all three phones. EDC provides unique opportunities for using quantitative measurement in both clinical practice and research.

Progression of hand osteoarthritis over 2 years: a clinical and radiological follow-up study.

OBJECTIVES: To investigate the course of hand osteoarthritis over 2 years by currently available outcome measures. METHODS: 189 participants of the Genetics, Arthrosis and Progression (GARP) study with hand osteoarthritis were followed for 2 years. Self-reported hand pain and functional limitations were assessed with the Australian/Canadian osteoarthritis hand index (AUSCAN LK 3.0). Pain intensity upon lateral pressure in the interphalangeal and thumb base joints was graded on a four-point scale. Osteophytes (0-3) and joint space narrowing (JSN) (0-3) was scored at baseline and after 2 years in interphalangeal and thumb base joints. Standardised response means (SRM) were calculated. RESULTS: 172 (91%) patients completed the 2-year follow-up (mean age 60.5 years, 78.5% women). Statistically significant increases in self-reported pain and function scores, in pain intensity scores as well as in osteophyte and JSN total scores were seen over 2 years. SRM were 0.25, 0.23, 0.67, 0.34 and 0.35, respectively, for self-reported pain and function scores, pain intensity scores, osteophyte and JSN total scores. Radiological progression was not associated with changes in self-reported pain and function. Women in an early post-menopausal stage were especially at risk of progressing radiologically. CONCLUSIONS: Currently available outcome measures were able to assess progression over the relatively short time period of 2 years. Radiographic outcomes were more responsive than self-reported outcomes. Pain intensity upon lateral pressure seems to be a responsive measure but needs validation.

Topical diclofenac and its role in pain and inflammation: an evidence-based review.

OBJECTIVE: Topical diclofenac is widely used in the treatment of pain and inflammation. This comprehensive review assesses the safety and efficacy of topical diclofenac in a range of painful and inflammatory disorders. METHODS: Double-blind, randomized, placebo- or active-controlled trials (RCT) evaluating topical diclofenac in soft-tissue injuries, soft-tissue rheumatic disorders and osteoarthritis were identified through detailed literature searches. In addition, non-RCT evidence from publications evaluating the pharmacologic characteristics of topical diclofenac were also included in this review to obtain a more complete picture of the drug's profile, its efficacy and safety. RESULTS: Studies demonstrate that the drug preferentially distributes to the target tissues in sufficient concentrations to produce a therapeutic effect. A total of 19 double-blind RCTs in more than 3000 patients, supported by single-blind or open trials, consistently show that topical diclofenac significantly reduces pain and inflammation in acute and chronic conditions compared with placebo and is comparable to other topical non-steroidal anti-inflammatory drugs (NSAIDs) and some oral NSAIDs (diclofenac, ibuprofen, naproxen). Improvements have also been observed in patients' functional capacity and mobility. Topical diclofenac is well tolerated, resulting mostly in mild, easily resolved local skin irritation, and is associated with fewer side-effects than other topical NSAIDs and a lower rate of gastrointestinal complications than oral NSAIDs (diclofenac, ibuprofen, naproxen). CONCLUSION: This evidence-based review shows topical diclofenac to be an effective and well tolerated treatment in painful and inflammatory conditions, at least in the short-term. However, only published RCT studies have been included in this analysis, which may exclude some interesting data from non-RCT studies. Future trials of topical diclofenac need to be of longer duration, be better reported and consider a broader spectrum of acute and chronic pain indications.

Differences between systematic reviews/meta-analyses of hyaluronic acid/hyaluronan/hylan in osteoarthritis of the knee.

OBJECTIVE: To explore reasons for discrepant results between systematic reviews (SR)/meta-analyses (MA) of the efficacy and safety of hyaluronic acid/hyaluronan/hylan (HA) therapy in the treatment of osteoarthritis (OA) of the knee. METHODS: A decision algorithm was utilised to identify reasons for discordance among six SR. Sources of discordance such as clinical question, trial selection and inclusion, data extraction, assessment of study quality, assessment of the ability to combine trials, and statistical methods for data synthesis were examined. RESULTS: A similar question was asked in all six SR. Different trials were selected for inclusion in the reviews mainly because of differences in the search strategies and selection criteria. Although similar methods for data extraction were utilised, differences were found both in the outcome measures and time-points selected for extraction. Methodological quality was not always formally assessed. Different statistical methods for data synthesis resulted in conflicting estimates of therapeutic effect. CONCLUSIONS: Reasons for the inconsistency of results reported in the six SR were identified. Using the principles of the GRADE approach for estimating the therapeutic effect of HA in the treatment of OA of the knee, there is moderate evidence suggesting that further research is unlikely to change our confidence in the estimate of the effect. In the balance of benefit to harm, the trade-off is probable benefit with respect to pain reduction and physical function improvement with low risk of harm.

Speed enforcement detection devices for preventing road traffic injuries.

BACKGROUND: It is estimated that by 2020, road traffic crashes will have moved from ninth to third in the world ranking of burden of disease, as measured in disability adjusted life years. The identification of effective strategies for the prevention of road traffic injuries is of global public health importance. Measures aimed at reducing traffic speed are considered essential to preventing road injuries; the use of speed enforcement detection devices (including speed cameras and radar and laser devices) is one such measure. OBJECTIVES: To assess whether the use of speed enforcement detection devices (SEDs) reduces the incidence of speeding, road traffic crashes, injuries and deaths. SEARCH STRATEGY: We searched the Cochrane Injuries Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, Science (and Social Science) Citation Index, TRANSPORT, PsycINFO, CINAHL, EconLit. We searched the websites of road safety and motoring associations, as well as general internet searches. We handsearched selected journals and conference proceedings, and contacted experts in the field. The searches were conducted during May to November 2004. SELECTION CRITERIA: Randomised controlled trials and controlled before-after studies that assessed the impact of speed enforcement detection devices on speeding, road crashes, injuries and deaths were eligible for inclusion. For studies involving co-interventions, SEDs had to be the major intervention focus of the study to be eligible. DATA COLLECTION AND ANALYSIS: We independently screened search results, assessed studies for inclusion, extracted data and assessed methodological quality. Due to variability between and within included studies, a pooled analysis was not appropriate. MAIN RESULTS: No randomised controlled trials were identified. Twenty-six studies met the inclusion criteria, of which 22 were controlled before-after trials incorporating a distinct control or comparison group(s) and four were interrupted time series designs with a comparison group(s). Fourteen studies reported speed and crash outcomes, seven reported crash outcomes only and five reported speed outcomes only. All but one study reported an absolute reduction in pre/post average speeds. A pre/post reduction in the proportion of speeding vehicles ranged across studies from 5% to 70% depending on the speed threshold set. Pre/post reductions of 50% to 65% were reported in the proportion of speeding vehicles travelling >15 km/h over the speed limit. Compared with controls, the relative improvement was from 1% to 15% for average speed and from 14% to 65% for percent speeding. All studies reporting crash outcomes reported an absolute pre/post reduction in all crashes and injury related crashes. In the vicinity of camera sites these pre/post reductions ranged from 14% to 72% for all crashes, 8% to 46% for injury crashes, and 40% to 45% for crashes resulting in fatalities or serious injuries. More generalised effects over wider areas showed an absolute pre/post crash reduction ranging from 9% to 35%, 7% to 30% for all injury crashes and 13% to 58% for crashes resulting in fatalities alone, or in combination with serious injuries. The studies of longer duration showed that these positive trends were either maintained or improved with time. Compared with controls, the relative improvement in pre/post crash numbers resulting in any type of injury ranged from 5% to 36%. AUTHORS' CONCLUSIONS: Despite the methodological limitations of the studies reviewed, the consistency of reported positive reductions in speed and crash outcomes across all studies suggest that SEDs are a promising intervention for reducing the number of road traffic injuries and deaths. More studies of a scientifically rigorous nature are necessary to provide a stronger evidence base that these interventions are worthwhile. There is a need for international harmonisation of data collection methods, including standards on how best to measure speeds and collect crash data, over lengthy intervention and follow-up periods, as well as some consensus as to the expression of outcomes in studies, so that studies can be compared.

Intraarticular corticosteroid for treatment of osteoarthritis of the knee.

BACKGROUND: Osteoarthritis (OA) is a common joint disorder. In the knee, injections of corticosteroids into the joint (intraarticular (IA)) may relieve inflammation, and reduce pain and disability. OBJECTIVES: To evaluate the efficacy and safety of IA corticosteroids in treatment of OA of the knee. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE (to January (week 1) 2006 for update), EMBASE, PREMEDLINE (all to July 2003), and Current Contents (Sept 2000). Specialised journals, trial reference lists and review articles were handsearched. SELECTION CRITERIA: Randomised controlled trials of IA corticosteroids for patients with OA of the knee: single/double blind, placebo-based/comparative studies, reporting at least one core OMERACT III outcome measure. DATA COLLECTION AND ANALYSIS: Methodological quality of trials was assessed, and data were extracted in duplicate. Fixed effect and random effects models, giving weighted mean differences (WMD), were used for continuous variables. Dichotomous outcomes were analysed by relative risk (RR). MAIN RESULTS: Twenty-eight trials (1973 participants) comparing IA corticosteroid against placebo, against IA hyaluronan/hylan (HA products), against joint lavage, and against other IA corticosteroids, were included.IA corticosteroid was more effective than IA placebo for pain reduction (WMD -21.91; 95% confidence interval (CI) -29.93 to -13.89) and patient global assessment (the RR was 1.44 (95% CI 1.13 to 1.82)) at one week post injection with an NNT of 3 to 4 for both, based on n=185 for pain on 100 mm visual analogue scale (VAS) and n=158 for patient global assessment. Data on function were sparse at one week post injection and neither statistically significant nor clinically important differences were detected. There was evidence of pain reduction between two weeks (the RR was 1.81 (95% CI 1.09 to 3.00)) to three weeks (the RR was 3.11 (95% CI 1.61 to 6.01), but a lack of evidence for efficacy in functional improvement. At four to 24 weeks post injection, there was lack of evidence of effect on pain and function (small studies showed benefits which did not reach statistical or clinical importance, i.e. less than 20% risk difference). For patient global, there were three studies which consistently showed lack of effect longer than one week post injection. However, all were fairly small sample sizes (less than 50 patients per group). This was supported by another study which did not find statistically significant differences, at any time point, on a continuous measure of patient global assessment (100 mm VAS).In comparisons of corticosteroids and HA products, no statistically significant differences were in general detected at one to four weeks post injection. Between five and 13 weeks post injection, HA products were more effective than corticosteroids for one or more of the following variables: WOMAC OA Index, Lequesne Index, pain, range of motion (flexion), and number of responders. One study showed a difference in function between 14 to 26 weeks, but no differences in efficacy were detected at 45 to 52 weeks. In general, the onset of effect was similar with IA corticosteroids, but was less durable than with HA products. Comparisons of IA corticosteroids showed triamcinolone hexacetonide was superior to betamethasone for number of patients reporting pain reduction up to four weeks post injection (the RR was 2.00 (95% CI 1.10 to 3.63). Comparisons between IA corticosteroid and joint lavage showed no differences in any of the efficacy or safety outcome measures. AUTHORS' CONCLUSIONS: 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).

Viscosupplementation for the treatment of osteoarthritis of the knee.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability. OBJECTIVES: To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum). SEARCH STRATEGY: MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched. SELECTION CRITERIA: RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997). DATA COLLECTION AND ANALYSIS: Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer . Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR). MAIN RESULTS: Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses. AUTHORS' CONCLUSIONS: Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

The WOMAC Knee and Hip Osteoarthritis Indices: development, validation, globalization and influence on the development of the AUSCAN Hand Osteoarthritis Indices.

Clinical measurement in both clinical research and clinical practice requires tools and techniques that are valid, reliable and responsive. Patient-centred self-reported measures provide opportunity to evaluate consequences of osteoarthritis, that are important and relevant to patients with the condition. The WOMAC and AUSCAN Indices are health status measurement questionnaires that are valid, reliable and responsive, easy to complete, simple to score and available in multiple language forms and scaling formats. They provide opportunities to capture patient relevant information, relating to the impact of interventions, in clinical research and clinical practice environments. WOMAC data have also contributed to the development of proposed definitions for responder criteria and state-attainment criteria in osteoarthritis.

Performance of the Norwegian version of AUSCAN--a disease-specific measure of hand osteoarthritis.

OBJECTIVE: To examine the performance of the Norwegian version of the AUSCAN Index as a disease-specific health status measure in patients with hand osteoarthritis (OA). METHODS: One hundred and ninety-nine patients with clinical hand OA (mean (SD) age 61.7 (5.7) years, 18 (9%) males) underwent a comprehensive examination including joint status, examination of grip strength and completion of several self-reported health status questionnaires. The Australian/Canadian OA hand index (AUSCAN) captures three different dimensions of hand OA: pain (5 items), stiffness (1 item), and difficulties with daily activities (9 items). Our pre-study hypothesis was to identify AUSCAN as a specific hand measure with strong correlations to hand measures and lower correlations to other general measures of health. RESULTS: Patient completion of the AUSCAN Index was similar or better than other measures. The internal consistency of the AUSCAN was excellent. The pain and physical dimension of AUSCAN correlated substantially to each other and moderately to the stiffness scale. The AUSCAN physical scale correlated moderately to substantially to other measures, the highest correlation being seen with the Arthritis Impact Measurement Scale (AIMS) 2 hand and finger function scale (r=0.73). The standardised differences between patients with and without radiographic abnormalities were numerically larger for the AUSCAN pain and physical scales than for other measures. CONCLUSION: The Norwegian version of the AUSCAN has an acceptable clinimetric performance and is a suitable tool for assessment of hand OA.

Viscosupplementation for the treatment of osteoarthritis of the knee.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability. OBJECTIVES: To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), NRD-101, Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum). SEARCH STRATEGY: MEDLINE, EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to April 2004 were handsearched. SELECTION CRITERIA: RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997). DATA COLLECTION AND ANALYSIS: Each trial was assessed independently by two reviewers (NB, JC) for its methodological quality using a validated tool. All data were extracted by one reviewer (JC) and verified by a second reviewer (VR). Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). Dichotomous outcomes were analyzed by relative risk (RR). MAIN RESULTS: Sixty-three trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and one year. Thirty-seven trials included comparisons of hyaluronan/hylan and placebo, nine trials included comparisons of intra-articular (IA) corticosteroids, and five trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs). The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 11 to 54% for pain and 9 to 15% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses. AUTHORS' CONCLUSIONS: Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that based on non-randomised groups, the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.1 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.1 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

Intraarticular corticosteroid for treatment of osteoarthritis of the knee.

BACKGROUND: Osteoarthritis (OA) is a common joint disorder. In the knee, injections of corticosteroids into the joint (intra-articular (IA)) may relieve inflammation, and reduce pain and disability. OBJECTIVES: To evaluate the efficacy and safety of IA corticosteroids in treatment of OA of the knee. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE, EMBASE, PREMEDLINE (all to July 2003), and Current Contents (Sept 2000). Specialised journals, trial reference lists and review articles were handsearched. SELECTION CRITERIA: Randomised controlled trials of IA corticosteroids for patients with OA of the knee: single/double blind, placebo-based/comparative studies, reporting at least one core OMERACT III outcome measure. DATA COLLECTION AND ANALYSIS: Methodological quality of trials was assessed, and data were extracted in duplicate. Fixed effect and random effects models, giving weighted mean differences (WMD), were used for continuous variables. Dichotomous outcomes were analysed by relative risk (RR). MAIN RESULTS: Twenty-six trials (1721 participants) comparing IA corticosteroid against placebo, against IA hyaluronan/hylan (HA products), against joint lavage, and against other IA corticosteroids, were included.IA corticosteroid was more effective than IA placebo for pain reduction (WMD -17.79; 95% confidence interval (CI) -25.02 to -10.55) and patient global assessment (the RR was 1.44 (95% CI 1.13 to 1.82)) at one week post injection with an NNT of 3 to 4 for both, based on n=185 for pain on 100 mm visual analogue scale (VAS) and n=158 for patient global assessment. Data on function were sparse at one week post injection and neither statistically significant nor clinically important differences were detected. There was evidence of pain reduction between two weeks (the RR was 1.81 (95% CI 1.09 to 3.00)) to three weeks (the RR was 3.11 (95% CI 1.61 to 6.01), but a lack of evidence for efficacy in functional improvement. At four to 24 weeks post injection, there was lack of evidence of effect on pain and function (small studies showed benefits which did not reach statistical or clinical importance, i.e. less than 20% risk difference). For patient global, there were three studies which consistently showed lack of effect longer than one week post injection. However, all were fairly small sample sizes (less than 50 patients per group). This was supported by another study which did not find statistically significant differences, at any time point, on a continuous measure of patient global assessment (100 mm VAS). In comparisons of corticosteroids and HA products, no statistically significant differences were in general detected at one to four weeks post injection. Between five and 13 weeks post injection, HA products were more effective than corticosteroids for one or more of the following variables: WOMAC OA Index, Lequesne Index, pain, range of motion (flexion), and number of responders. One study showed a difference in function between 14 to 26 weeks, but no differences in efficacy were detected at 45 to 52 weeks. In general, the onset of effect was similar with IA corticosteroids, but was less durable than with HA products. Comparisons of IA corticosteroids showed triamcinolone hexacetonide was superior to betamethasone for number of patients reporting pain reduction up to four weeks post injection (the RR was 2.00 (95% CI 1.10 to 3.63). Comparisons between IA corticosteroid and joint lavage showed no differences in any of the efficacy or safety outcome measures. AUTHORS' CONCLUSIONS: 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 4.1 analysis and the original publication. These are likely the result of using secondary rather than primary data and the statistical methods available in RevMan 4.1. 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).

Science of assessment.

Psoriatic arthritis is a multisystem disorder which, from a measurement standpoint, demands consideration of its cutaneous manifestations and both axial and peripheral musculoskeletal involvement. Measurements of various aspects of impairment, ability/disability, and participation/handicap are feasible using existing measurement techniques, which are for the most part valid, reliable, and responsive. Nevertheless, there remain opportunities for the further development of consensus around core set measures and responder criteria, as well as for instrument development and refinement, standardised assessor training, cross-cultural adaptation of health status questionnaires, electronic data capture, and the introduction of standardised quantitative measurement into routine clinical care.

Effectiveness and safety of repeat courses of hylan G-F 20 in patients with knee osteoarthritis.

OBJECTIVE: To compare the effectiveness and safety of repeat treatment with hylan G-F 20 based on data from a randomized, controlled trial [Raynauld JP, Torrance GW, Band PA, Goldsmith CH, Tugwell P, Walker V, et al. A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results. Osteoarthritis Cartilage 2002;10:506-17]. The hypotheses tested were whether the single-course and repeat-course subgroups would be superior to appropriate care and not different from each other. METHOD: A total of 255 patients with knee osteoarthritis were randomized to "appropriate care with hylan G-F 20" or "appropriate care without hylan G-F 20". The hylan G-F 20 group was partitioned into two subgroups: (1) patients who received a single course of hylan G-F 20; and (2) patients who received two or more courses of hylan G-F 20. RESULTS: For the primary effectiveness measure, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score as a percent of baseline, the single-course subgroup improved by 41%, the repeat-course subgroup by 35%, and the appropriate care group by 14%. Both subgroups improved significantly more than the appropriate care group (P<0.05), and were not statistically significantly different from each other (70% power to detect a 20% difference). Secondary effectiveness measures showed similar results. In the repeat-course subgroup, no statistically significant differences were found in the number of local adverse events, the number of patients with local adverse events, or arthrocentesis rates between the first and repeat courses of treatment. CONCLUSIONS: Although the study was neither designed nor powered to examine repeat treatment, this a posteriori analysis provides support for a favorable effectiveness and safety profile of hylan G-F 20 in repeat course patients.

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement.

BACKGROUND: In clinical trials, at the group level, results are usually reported as mean and standard deviation of the change in score, which is not meaningful for most readers. OBJECTIVE: To determine the minimal clinically important improvement (MCII) of pain, patient's global assessment of disease activity, and functional impairment in patients with knee and hip osteoarthritis (OA). METHODS: A prospective multicentre 4 week cohort study involving 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. Patients assessed their response to treatment on a five point Likert scale at the final visit. An anchoring method based on the patient's opinion was used. The MCII was estimated in a subgroup of 814 patients (603 with knee OA, 211 with hip OA). RESULTS: For knee and hip OA, MCII for absolute (and relative) changes were, respectively, (a) -19.9 mm (-40.8%) and -15.3 mm (-32.0%) for pain; (b) -18.3 mm (-39.0%) and -15.2 mm (-32.6%) for patient's global assessment; (c) -9.1 (-26.0%) and -7.9 (-21.1%) for WOMAC function subscale score. The MCII is affected by the initial degree of severity of the symptoms but not by age, disease duration, or sex. CONCLUSION: Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients.

Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state.

BACKGROUND: The patient acceptable symptom state (PASS) is the value beyond which patients can consider themselves well. This concept can help in interpreting results of clinical trials. OBJECTIVE: To determine the PASS estimate for patients with knee and hip osteoarthritis (OA) by assessing pain, patient's global assessment of disease activity, and functional impairment. METHODS: A 4 week prospective multicentre cohort study of 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment of disease, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. The patients assessed their satisfaction with their current state at the final visit. An anchoring method based on the patient's opinion was used. RESULTS: For patients with knee and hip OA, the estimates of PASS were, respectively, 32.3 and 35.0 mm for pain, 32.0 and 34.6 mm for patient global assessment of disease activity, and 31.0 and 34.4 points for WOMAC function score. The PASS varied moderately across the tertiles of baseline scores but not across age, disease duration, or sex. CONCLUSION: The use of PASS in clinical trials would provide more meaningful results expressed as a proportion of patients in an acceptable symptom state.