[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA) is currently diagnosed using clinical and radiographic findings. In recent years magnetic resonance imaging (MRI) use in OA has increasingly been studied. This study was conducted to determine the diagnostic utility of MRI in OA through a meta-analysis of published studies.
A systematic literature search was undertaken to include studies that used MRI to evaluate or detect OA. MRI was compared to various reference standards: histology, arthroscopy, radiography, CT, clinical evaluation, and direct visual inspection. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) area under the curve (AUC) were calculated. Random-effects models were used to pool results.
Of 20 relevant studies identified from the literature, 16 reported complete data and were included in the meta-analysis, with a total of 1220 patients (1071 with OA and 149 without). Overall sensitivity from pooling data of all the included studies was 61% [95% confidence interval (CI) 53-68], specificity was 82% (95% CI 77-87), PPV was 85% (95% CI 80-88), and NPV was 57% (95% CI 43-70). The ROC showed an AUC of 0.804. There was significant heterogeneity in the above parameters (I(2)>83%). With histology as the reference standard, sensitivity increased to 74% and specificity decreased to 76% compared with all reference standards combined. When arthroscopy was used as the reference standard, sensitivity increased to 69% and specificity to 93% compared with all reference standards combined.
MRI can detect OA with an overall high specificity and moderate sensitivity when compared with various reference standards, thus lending more utility to ruling out OA than ruling it in. The sensitivity of MRI is below the current clinical diagnostic standards. At this time standard clinical algorithm for OA diagnosis, aided by radiographs appears to be the most effective method for diagnosing OA.
Osteoarthritis and Cartilage 10/2011; 20(1):13-21. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite a growing body of Magnetic Resonance Imaging (MRI) literature in osteoarthritis (OA), there is little uniformity in its diagnostic application. We envisage in the first instance the definition requiring further validation and testing in the research setting before considering implementation/feasibility testing in the clinical setting. The objective of our research was to develop an MRI definition of structural OA.
We undertook a multistage process consisting of a number of different steps. The intent was to develop testable definitions of OA (knee, hip and/or hand) on MRI. This was an evidence driven approach with results of a systematic review provided to the group prior to a Delphi exercise. Each participant of the steering group was allowed to submit independently up to five propositions related to key aspects in MRI diagnosis of knee OA. The steering group then participated in a Delphi exercise to reach consensus on which propositions we would recommend for a definition of structural OA on MRI. For each round of voting, ≥60% votes led to include and ≤20% votes led to exclude a proposition. After developing the proposition one of the definitions developed was tested for its validity against radiographic OA in an extant database.
For the systematic review we identified 25 studies which met all of our inclusion criteria and contained relevant diagnostic measure and performance data. At the completion of the Delphi voting exercise 11 propositions were accepted for definition of structural OA on MRI. We assessed the diagnostic performance of the tibiofemoral MRI definition against a radiographic reference standard. The diagnostic performance for individual features was: osteophyte C statistic=0.61, for cartilage loss C statistic=0.73, for bone marrow lesions C statistic=0.72 and for meniscus tear in any region C statistic=0.78. The overall composite model for these four features was a C statistic=0.59. We detected good specificity (1) but less optimal sensitivity (0.46) likely due to detection of disease earlier on MRI.
We have developed MRI definition of knee OA that requires further formal testing with regards their diagnostic performance (especially in datasets of persons with early disease), before they are more widely used. Our current analysis suggests that further testing should focus on comparisons other than the radiograph, that may capture later stage disease and thus nullify the potential for detecting early disease that MRI may afford. The propositions are not to detract from, nor to discourage the use of traditional means of diagnosing OA.
Osteoarthritis and Cartilage 05/2011; 19(8):963-9. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To summarize literature on the concurrent and predictive validity of MRI-based measures of osteoarthritis (OA) structural change.
An online literature search was conducted of the OVID, EMBASE, CINAHL, PsychInfo and Cochrane databases of articles published up to the time of the search, April 2009. 1338 abstracts obtained with this search were preliminarily screened for relevance by two reviewers. Of these, 243 were selected for data extraction for this analysis on validity as well as separate reviews on discriminate validity and diagnostic performance. Of these 142 manuscripts included data pertinent to concurrent validity and 61 manuscripts for the predictive validity review. For this analysis we extracted data on criterion (concurrent and predictive) validity from both longitudinal and cross-sectional studies for all synovial joint tissues as it relates to MRI measurement in OA.
Concurrent validity of MRI in OA has been examined compared to symptoms, radiography, histology/pathology, arthroscopy, CT, and alignment. The relation of bone marrow lesions, synovitis and effusion to pain was moderate to strong. There was a weak or no relation of cartilage morphology or meniscal tears to pain. The relation of cartilage morphology to radiographic OA and radiographic joint space was inconsistent. There was a higher frequency of meniscal tears, synovitis and other features in persons with radiographic OA. The relation of cartilage to other constructs including histology and arthroscopy was stronger. Predictive validity of MRI in OA has been examined for ability to predict total knee replacement (TKR), change in symptoms, radiographic progression as well as MRI progression. Quantitative cartilage volume change and presence of cartilage defects or bone marrow lesions are potential predictors of TKR.
MRI has inherent strengths and unique advantages in its ability to visualize multiple individual tissue pathologies relating to pain and also predict clinical outcome. The complex disease of OA which involves an array of tissue abnormalities is best imaged using this imaging tool.
Osteoarthritis and Cartilage 03/2011; 19(5):557-88. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The design and execution of prevention trials for OA have methodological issues that are distinct from trials designed to impact prevalent disease. Disease definitions and their precise and sensitive measurement, identification of high-risk populations, the nature of the intervention (pharmaceutical, nutraceutical, behavioral) and its potential pleiotropic impacts on other organ systems are critical to consider. Because prevention trials may be prolonged, close attention to concomitant life changes and co-morbidities, adherence and participant retention in the trial is of primary importance, as is recognition of the potential for "preventive misconception" and "behavioral disinhibition" to affect the ability of the trial to show an effect of the intervention under study. None of these potential pitfalls precludes a successful and scientifically rigorous process and outcome. As technology improves the means to measure and predict the OA process and its clinical consequences, it will be increasingly possible to screen individuals for high-risk phenotypes, combining clinical factors with information from imaging, genetic, metabolic and other biomarkers and to impact this high-risk condition to avoid or delay OA both structurally and symptomatically.
Osteoarthritis and Cartilage 03/2011; 19(5):500-8. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To summarize literature on the responsiveness and reliability of MRI-based measures of knee osteoarthritis (OA) structural change.
A literature search was conducted using articles published up to the time of the search, April 2009. 1338 abstracts obtained with this search were preliminarily screened for relevance and of these, 243 were selected for data extraction. For this analysis we extracted data on reliability and responsiveness for every reported synovial joint tissue as it relates to MRI measurement in knee OA. Reliability was defined by inter- and intra-reader intra-class correlation (ICC), or coefficient of variation, or kappa statistics. Responsiveness was defined as standardized response mean (SRM) - ratio of mean of change over time divided by standard deviation of change. Random-effects models were used to pool data from multiple studies.
The reliability analysis included data from 84 manuscripts. The inter-reader and intra-reader ICC were excellent (range 0.8-0.94) and the inter-reader and intra-reader kappa values for quantitative and semi-quantitative measures were all moderate to excellent (range 0.52-0.88). The lowest value (kappa=0.52) corresponded to semi-quantitative synovial scoring intra-reader reliability and the highest value (ICC=0.94) for semi-quantitative cartilage morphology. The responsiveness analysis included data from 42 manuscripts. The pooled SRM for quantitative measures of cartilage morphometry for the medial tibiofemoral joint was -0.86 (95% confidence intervals (CI) -1.26 to -0.46). The pooled SRM for the semi-quantitative measurement of cartilage morphology for the medial tibiofemoral joint was 0.55 (95% CI 0.47-0.64). For the quantitative analysis, SRMs are negative because the quantitative value, indicating a loss of cartilage, goes down. For the semi-quantitative analysis, SRMs indicating a loss in cartilage are positive (increase in score).
MRI has evolved substantially over the last decade and its strengths include the ability to visualize individual tissue pathologies, which can be measured reliably and with good responsiveness using both quantitative and semi-quantitative techniques.
Osteoarthritis and Cartilage 03/2011; 19(5):589-605. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hallux valgus (HV) is common with a standardised prevalence of 28.4% in adults older than 40 years. It has been shown to associate with impaired quality of life (QOL) in small hospital based studies. Previous studies of association between HV, function and disability are based on the presence or absence of regional foot pain which may be due to other foot pathology and is not specific to HV. The objective of this study is to examine the association between self reported HV, big toe pain and impaired QOL in a primary care population. We hypothesise that presence of self-reported HV alone, big toe pain alone and both together will associate with progressively impaired QOL. This hypothesis is based on the known association of concurrent HV and foot pain with impaired physical function and the fact that foot pain and not foot deformity impairs functional status. Our study shows that concurrent HV and big toe pain but not isolated HV associates with impaired overall satisfaction with health and low score on the physical, psychological and social domains of World Health Organization Quality of Life-BREF (WHOQOL-BREF).
Osteoarthritis and Cartilage 07/2010; 18(7):923-6. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009.
A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence.
Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for self-management, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) -0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES=0.77, 95% CI 0.36, 1.17) was no longer significant (ES=0.16, 95% CI -0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES=0.10, 95% CI -0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3g/day have been published (HR=1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo.
Publication of a large amount of new research evidence has resulted in changes in the calculated risk-benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.
Osteoarthritis and Cartilage 02/2010; 18(4):476-99. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess if smoking status at the time of commencing an anti-TNF-alpha agent for rheumatoid arthritis (RA) reduces the likelihood of achieving at least a moderate response on the European League Against Rheumatism (EULAR) response criteria at 3-month assessment.
All patients with RA treated with their first anti-TNF-alpha agent at the Department of Rheumatology, Derby Hospital NHS Trust between April 2001 and October 2008 were included in this retrospective case control study. Information about age, gender, disease duration, body mass index, smoking status (current smoker, ex-smoker, and nonsmoker), comorbidities, oral prednisolone use, and 28 joint 4 variables disease activity score (DAS28) at the time of commencing an anti-TNF-alpha agent was recorded. Details of rheumatoid factor (RF) and past and present disease modifying antirheumatic drugs were recorded. A case control study was carried out to examine possible baseline predictors of treatment effects at the 3-month assessment.
Results were available for 395 patients at 3-month assessment. According to the EULAR response criteria 42 patients failed to show at least a moderate response. After adjusting for confounders using multivariate analysis, current smoking at the time of commencing an anti-TNF-alpha agent reduced the chance of achieving at least a moderate response on the EULAR response criteria when compared with nonsmokers (aOR [95% CI] 0.20 [0.05-0.83], P = 0.03).
RA patients who smoke are less likely to respond to an anti-TNF-alpha agent.
Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 01/2010; 16(1):15-8. · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate the efficacy and safety of diacerein as a pain-reducing agent in the treatment of osteoarthritis (OA), using meta-analysis of published randomized placebo-controlled trials (RCTs).
Systematic searches of the bibliographic databases Medline, Embase, Cinahl, Chemical Abstracts, Cochrane and Web of Science for RCTs concerning diacerein treatment of OA. Inclusion criteria: explicit statement about randomization to either diacerein or placebo, and co-primary outcomes being reduction in pain and improvement in function. Efficacy effect size (ES) was estimated using Hedges's standardized mean difference. Safety was measured via the risk ratio (RR) of patients having at least one episode of diarrhoea, or withdrawal due to adverse events. Trials were combined by using random-effects meta-analysis. Consistency was evaluated via the I-squared index.
Six trials (seven sub-studies; 1533 patients) contributed to the meta-analysis, revealing a large degree of inconsistency among the trials (I(2)=56%) in regard to pain reduction: the combined ES was -0.24 [95% confidence intervals (CI): -0.39 to -0.08, P=0.003], favouring diacerein. The statistically significant improvement in function (P=0.01) was based on a small amount of heterogeneity (I(2)=11%), but presented a questionable clinical effect size (ES=-0.14). Risk of publication bias could not be excluded, and trials with duration of more than 6 months did not favour diacerein. There was an increased risk of diarrhoea with diacerein (RR=3.51 [2.55-4.83], P<0.0001), and some withdrawal from therapy following adverse events (RR=1.58 [1.05-2.36], P=0.03).
Diacerein may be an alternative therapy for OA for patients who cannot take paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) because of adverse effects or lack of benefit. However, it is associated with increased risk of diarrhoea, and the symptomatic benefit after 6 months remains unknown.
Osteoarthritis and Cartilage 10/2009; 18(3):289-96. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To develop concise, patient-focussed, up to date, evidence-based, expert consensus recommendations for the management of hip and knee osteoarthritis (OA), which are adaptable and designed to assist physicians and allied health care professionals in general and specialist practise throughout the world.
Sixteen experts from four medical disciplines (primary care, rheumatology, orthopaedics and evidence-based medicine), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. A systematic review of existing guidelines for the management of hip and knee OA published between 1945 and January 2006 was undertaken using the validated appraisal of guidelines research and evaluation (AGREE) instrument. A core set of management modalities was generated based on the agreement between guidelines. Evidence before 2002 was based on a systematic review conducted by European League Against Rheumatism and evidence after 2002 was updated using MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Library and HTA reports. The quality of evidence was evaluated, and where possible, effect size (ES), number needed to treat, relative risk or odds ratio and cost per quality-adjusted life years gained were estimated. Consensus recommendations were produced following a Delphi exercise and the strength of recommendation (SOR) for propositions relating to each modality was determined using a visual analogue scale.
Twenty-three treatment guidelines for the management of hip and knee OA were identified from the literature search, including six opinion-based, five evidence-based and 12 based on both expert opinion and research evidence. Twenty out of 51 treatment modalities addressed by these guidelines were universally recommended. ES for pain relief varied from treatment to treatment. Overall there was no statistically significant difference between non-pharmacological therapies [0.25, 95% confidence interval (CI) 0.16, 0.34] and pharmacological therapies (ES=0.39, 95% CI 0.31, 0.47). Following feedback from Osteoarthritis Research International members on the draft guidelines and six Delphi rounds consensus was reached on 25 carefully worded recommendations. Optimal management of patients with OA hip or knee requires a combination of non-pharmacological and pharmacological modalities of therapy. Recommendations cover the use of 12 non-pharmacological modalities: education and self-management, regular telephone contact, referral to a physical therapist, aerobic, muscle strengthening and water-based exercises, weight reduction, walking aids, knee braces, footwear and insoles, thermal modalities, transcutaneous electrical nerve stimulation and acupuncture. Eight recommendations cover pharmacological modalities of treatment including acetaminophen, cyclooxygenase-2 (COX-2) non-selective and selective oral non-steroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs and capsaicin, intra-articular injections of corticosteroids and hyaluronates, glucosamine and/or chondroitin sulphate for symptom relief; glucosamine sulphate, chondroitin sulphate and diacerein for possible structure-modifying effects and the use of opioid analgesics for the treatment of refractory pain. There are recommendations covering five surgical modalities: total joint replacements, unicompartmental knee replacement, osteotomy and joint preserving surgical procedures; joint lavage and arthroscopic debridement in knee OA, and joint fusion as a salvage procedure when joint replacement had failed. Strengths of recommendation and 95% CIs are provided.
Twenty-five carefully worded recommendations have been generated based on a critical appraisal of existing guidelines, a systematic review of research evidence and the consensus opinions of an international, multidisciplinary group of experts. The recommendations may be adapted for use in different countries or regions according to the availability of treatment modalities and SOR for each modality of therapy. These recommendations will be revised regularly following systematic review of new research evidence as this becomes available.
Osteoarthritis and Cartilage 03/2008; 16(2):137-62. · 4.26 Impact Factor