[Show abstract][Hide abstract] ABSTRACT: Ultrasonography is an imaging modality that has been utilised in clinical medicine since the 1950s. However, application to joints and rheumatic disease was delayed until appropriate advances in technology made it feasible. Since the 1990s, rheumatologists have embraced ultrasonography as a useful clinical tool and it has increasingly been applied in routine practice. Initial criticism correctly focused on a lack of validity data, recognition that this modality is highly user-dependent and that reliability was not established. In response, the rheumatological community identified relevant pathologies to study, starting with synovitis in rheumatoid arthritis, and set about defining the ultrasound abnormalities, followed by demonstrating the validity, reproducibility and responsiveness of these measures. Much work is now ongoing in the areas of enthesitis, gout and osteoarthritis. Additionally, the evidence base for ultrasonography in clinical practice is being investigated, in order to understand its appropriate place. Given the sensitivity of ultrasonography over clinical examination for detection of inflammation, this work will focus on its role in optimising diagnosis, directing therapy through accurate assessment of disease activity and understanding the optimal selection of joints for feasible disease monitoring. This review summarises the work undertaken to date, ongoing work and future challenges of optimising the role of ultrasonography in rheumatology.
[Show abstract][Hide abstract] ABSTRACT: Background
Radiographic measures of osteoarthritis (OA) are based upon two dimensional projection images. Active appearance modelling (AAM) of knee magnetic resonance imaging (MRI) enables accurate, 3D quantification of joint structures in large cohorts. This cross-sectional study explored the relationship between clinical characteristics, radiographic measures of OA and 3D bone area (tAB).
Clinical data and baseline paired radiographic and MRI data, from the medial compartment of one knee of 2588 participants were obtained from the NIH Osteoarthritis Initiative (OAI). The medial femur (MF) and tibia (MT) tAB were calculated using AAM. ‘OA-attributable’ tAB (OA-tAB) was calculated using data from regression models of tAB of knees without OA. Associations between OA-tAB and radiographic measures of OA were investigated using linear regression.
In univariable analyses, height, weight, and age in female knees without OA explained 43.1%, 32.1% and 0.1% of the MF tAB variance individually and 54.4% when included simultaneously in a multivariable model. Joint space width (JSW), osteophytes and sclerosis explained just 5.3%, 14.9% and 10.1% of the variance of MF OA-tAB individually and 17.4% when combined. Kellgren Lawrence (KL) grade explained approximately 20% of MF OA-tAB individually. Similar results were seen for MT OA-tAB.
Height explained the majority of variance in tAB, confirming an allometric relationship between body and joint size. Radiographic measures of OA, derived from a single radiographic projection, accounted for only a small amount of variation in 3D knee OA-tAB. The additional structural information provided by 3D bone area may explain the lack of a substantive relationship with these radiographic OA measures.
Osteoarthritis and Cartilage 10/2014; 22(10):1703–1709. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sensitive biomarkers are needed to understand synovial response to therapy in osteoarthritis (OA). Dynamic, contrast-enhanced magnetic resonance imaging (DCE MRI) provides quantitative, novel measures of synovial inflammation. This exploratory study examined DCE-assessed synovial response to intra-articular corticosteroid (IACS).
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 10/2014; 22(10):1614-8.
[Show abstract][Hide abstract] ABSTRACT: Peripheral joint osteoarthritis (OA) is predominantly a clinical diagnosis, though imaging may provide confirmation and aid with differential diagnosis where there is clinical doubt. Whilst radiographs (X-rays (XR)) are usually the first-line imaging modality selected, magnetic resonance imaging (MRI), ultrasound and computed tomography (CT) may all have a valuable role in assessing a person with OA, although each has its particular advantages and disadvantages. MRI is of particular use for diagnosing bone conditions that may cause a rapid increase in symptoms, such as avascular necrosis (AVN) or a subchondral insufficiency fracture (SIF), while providing concomitant soft tissue assessment. Ultrasound offers rapid assessment of peripheral joints and can easily assess for features of inflammatory arthritis. CT is faster to perform than MRI and can also image the subchondral bone, but does involve ionising radiation. Selecting the correct imaging modality, in the context of its advantages when visualising a specific joint (e.g., hand vs knee) and with clinical context in mind, will enhance the added value of imaging in clinical practice.
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 10/2014; 22(10):1692-1702.
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission.
Annals of the Rheumatic Diseases 08/2014; · 9.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To estimate the prevalence of inadequate pain relief (IPR) among patients with symptomatic knee OA prescribed analgesic therapy and to characterize patients with IPR.
[Show abstract][Hide abstract] ABSTRACT: Greater body mass index (BMI) has been associated with less radiographic progression in rheumatoid arthritis (RA). We evaluated the association between BMI and joint damage progression as measured by X-ray and MRI.
[Show abstract][Hide abstract] ABSTRACT: Background
Lack of standardization of outcome measures limits the usefulness of clinical trial evidence to inform health care decisions. This can be addressed by agreeing on a minimum core set of outcome measures per health condition, containing measures relevant to patients and decision makers. Since 1992, the Outcome Measures in Rheumatology (OMERACT) consensus initiative has successfully developed core sets for many rheumatologic conditions, actively involving patients since 2002. Its expanding scope required an explicit formulation of its underlying conceptual framework and process.
Literature searches and iterative consensus process (surveys and group meetings) of stakeholders including patients, health professionals, and methodologists within and outside rheumatology.
To comprehensively sample patient-centered and intervention-specific outcomes, a framework emerged that comprises three core “Areas,” namely Death, Life Impact, and Pathophysiological Manifestations; and one strongly recommended Resource Use. Through literature review and consensus process, core set development for any specific health condition starts by identifying at least one core “Domain” within each of the Areas to formulate the “Core Domain Set.” Next, at least one applicable measurement instrument for each core Domain is identified to formulate a “Core Outcome Measurement Set.” Each instrument must prove to be truthful (valid), discriminative, and feasible. In 2012, 96% of the voting participants (n = 125) at the OMERACT 11 consensus conference endorsed this model and process.
The OMERACT Filter 2.0 explicitly describes a comprehensive conceptual framework and a recommended process to develop core outcome measurement sets for rheumatology likely to be useful as a template in other areas of health care.
Journal of clinical epidemiology 07/2014; · 5.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA) is the fastest growing cause of disability worldwide. The aim of this study was to understand the impact of OA on individuals and to explore current treatment strategies. An online UK-wide survey of people with self-reported OA was conducted, composed of 52 questions exploring the impact of OA, diagnosis and treatment, the role of health professionals and self-management. Four thousand forty-three people were invited with 2,001 respondents (49 % response, 56 % women; mean age 65 years). Fifty-two percent reported that OA had a large impact on their lives. Fifteen percent of respondents had taken early retirement on average 7.8 years earlier than planned. In consultations with general practitioners, only half reported a discussion on pain; fewer reported discussing their fears (21 %) or management goals (15 %). Nearly half (48 %) reported not seeking medical help until pain was frequently unbearable. Oral analgesics (62 %), topical therapies (47 %), physiotherapy (38 %) and steroid injections (28 %) were commonly used. The majority (71 %) reported varying degrees of persistent pain despite taking all prescribed medication. Although 64 % knew that increasing exercise was important, only 36 % acted on this knowledge; 87 % who increased exercise found it beneficial. Over half had future concerns related to mobility (60 %), maintaining independence (52 %) and coping with everyday activities (51 %). OA had significant individual economic impact especially on employment. Current treatment strategies still leave most people in pain with significant fears for the future. There is considerable opportunity to improve the holistic nature of OA consultations especially in provision of information and promotion of self-management strategies.
[Show abstract][Hide abstract] ABSTRACT: Objectives: To review and synthesize the existing literature on the experience of living with a diagnosis of hip and/or knee osteoarthritis (OA). Method: A systematic review was undertaken using meta-ethnography. A search of both published (AMED, CINAHL, EMBASE, PsychINFO, SportsDisc, MEDLINE, Cochrane Clinical Trials Registry, PubMed) and unpublished/trial registry databases [World Health Organization (WHO) International Clinical Trials Registry Platform, Current Controlled Trials, the United States National Institute of Health Trials Registry, National Institute for Health Research (NIHR) Clinical Research Portfolio Database] was undertaken from their inception to 5 June 2013. Results: Thirty-two studies formed the meta-ethnography of the lived experiences of people with OA. In total, 1643 people with OA were sampled, the majority diagnosed with knee OA. The evidence base was weak to moderate in quality. The majority of studies indicated that people viewed living with OA negatively. Four key factors influenced their attitudes to the condition: the severity of their symptoms; the impact of these symptoms on their functional capability; their attitude towards understanding their disease; and their perceptions of other people's beliefs towards their disease. Conclusions: The current literature suggests that greater knowledge of the pathology of OA, management of symptoms, promotion of functional activity for patients and their family/friends networks, and understanding to better inform OA patient's role in society are all important elements that affect a person's attitude to OA. By better understanding these factors during future consultations, clinicians may forge stronger relationships with their patients to more effectively manage this long-term disabling condition.
[Show abstract][Hide abstract] ABSTRACT: To monitor progression to inflammatory arthritis (IA) in individuals with non-specific musculoskeletal (MSK) symptoms and positive anticyclic citrullinated peptide (anti-CCP) antibodies. To develop a pragmatic model to predict development of IA in this patient group.
In this prospective observational cohort, patients with new non-specific MSK symptoms and positive anti-CCP were recruited from regional primary care and secondary care referrals. Clinical, imaging and serological parameters were assessed at baseline. Cox regression analysis was performed to identify predictors of progression to IA and develop a risk score to stratify patients at presentation.
100 consecutive patients (73 women, mean age 51 years) were followed up for median 19.8 months (range 0.1-69.0); 50 developed IA after a median 7.9 months (range 0.1-52.4), 34 within 12 months. The majority (43/50) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis. A model for progression to IA was devised using four variables: tenderness of hand or foot joints, early morning stiffness ≥30 min, high-positive autoantibodies, and positive ultrasonographic power Doppler signal. None of the five individuals at low risk (score 0) progressed to IA, compared with 31% of 29 at moderate risk (1-2) and 62% of 66 at high risk (≥3). Adding shared epitope increased the number at low risk (score 0-1; 0/11 progressed).
In patients presenting with non-specific MSK symptoms and anti-CCP, the risk of progression to IA could be quantified using data available in clinical practice. The proposed risk score may be used to stratify patients for early therapeutic intervention.
NCT02012764 at ClinicalTrials.gov.
Annals of the rheumatic diseases 04/2014; · 8.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures, in patients with rheumatoid arthritis (RA).
This study was conducted as a secondary study of 2 RA clinical trials, GO-BEFORE (development cohort) and GO-FORWARD (validation cohort). Generalized estimating equations were used to evaluate independent cross-sectional associations of component variables (from all time points) with concurrent MRI measures of synovitis and bone edema in the development cohort. Based on regression coefficients, modified versions of the Disease Activity Score in 28 joints (M-DAS28), Simplified Disease Activity Index (M-SDAI), and Clinical Disease Activity Index (M-CDAI) were generated for each subject in the validation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson's and Spearman's correlations, linear/logistic regression, and receiver operating characteristic analysis.
Four variables were independently associated with MRI-detected synovitis and bone edema in the development cohort: C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), swollen joint count in 28 joints (SJC28), and evaluator's global assessment of disease activity using a visual analog scale (EvGA score). Modified disease activity scores were generated using the regression coefficients obtained in the synovitis models for all subjects in the validation cohort; modified scores were calculated as M-DAS28 = 0.49 × ln(CRP) + 0.15 × SJC28 + 0.22 × EvGA + 1 and M-SDAI = CRP + SJC28 + EvGA. Both modified and conventional disease activity scores correlated significantly with MRI measures of synovitis. Modified scores showed superior correlation with synovitis, as compared to conventional scores, at all time points (P < 0.05). Furthermore, the M-DAS28 and M-SDAI had superior test characteristics for prediction of radiographic progression at 52 weeks (both P < 0.05).
Modified disease activity scores demonstrated superior correlation with MRI detection of synovitis at all time points, and more accurately predicted radiographic progression in patients with RA in a clinical trial setting.
[Show abstract][Hide abstract] ABSTRACT: The "Discrimination" part of the OMERACT Filter asks whether a measure discriminates between situations that are of interest. "Feasibility" in the OMERACT Filter encompasses the practical considerations of using an instrument, including its ease of use, time to complete, monetary costs, and interpretability of the question(s) included in the instrument. Both the Discrimination and Reliability parts of the filter have been helpful but were agreed on primarily by consensus of OMERACT participants rather than through explicit evidence-based guidelines. In Filter 2.0 we wanted to improve this definition and provide specific guidance and advice to participants.
The Journal of Rheumatology 04/2014; · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Outcome Measures in Rheumatology (OMERACT) Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The "Truth" section of the OMERACT Filter requires that criteria be met to demonstrate that the outcome instrument meets the criteria for content, face, and construct validity.
Discussion groups critically reviewed a variety of ways in which case studies of current OMERACT Working Groups complied with the Truth component of the Filter and what issues remained to be resolved.
The case studies showed that there is broad agreement on criteria for meeting the Truth criteria through demonstration of content, face, and construct validity; however, several issues were identified that the Filter Working Group will need to address.
These issues will require resolution to reach consensus on how Truth will be assessed for the proposed Filter 2.0 framework, for instruments to be endorsed by OMERACT.
The Journal of Rheumatology 04/2014; · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Outcome Measures in Rheumatology (OMERACT) Filter provides guidelines for the development and validation of outcome measures for use in clinical research. The "Truth" section of the OMERACT Filter presupposes an explicit framework for identifying the relevant core outcomes that are universal to all studies of the effects of intervention effects. There is no published outline for instrument choice or development that is aimed at measuring outcome, was derived from broad consensus over its underlying philosophy, or includes a structured and documented critique. Therefore, a new proposal for defining core areas of measurement ("Filter 2.0 Core Areas of Measurement") was presented at OMERACT 11 to explore areas of consensus and to consider whether already endorsed core outcome sets fit into this newly proposed framework.
Discussion groups critically reviewed the extent to which case studies of current OMERACT Working Groups complied with or negated the proposed framework, whether these observations had a more general application, and what issues remained to be resolved.
Although there was broad acceptance of the framework in general, several important areas of construction, presentation, and clarity of the framework were questioned. The discussion groups and subsequent feedback highlighted 20 such issues.
These issues will require resolution to reach consensus on accepting the proposed Filter 2.0 framework of Core Areas as the basis for the selection of Core Outcome Domains and hence appropriate Core Outcome Sets for clinical trials.
The Journal of Rheumatology 03/2014; · 3.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA) currently affects over 40 million Europeans, with its associated personal suffering and significant economic burden for health systems set to dramatically escalate in a rapidly ageing Europe. Given the very limited effective therapeutic options for OA, the European League Against Rheumatism (EULAR) created an ad hoc committee of OA researchers, clinicians and patients to consider a research agenda focussed on the areas of epidemiology, pathogenesis, imaging and biomarkers, and therapies. The committee deliberated and listed research needs in these areas and also established some cross-area priority themes: predictors of OA progression, especially where this might enable stratified interventions; understanding mechanisms of OA pain; improved understanding of tissue communication in a process where multiple tissue pathologies are common; developing concepts of, and consequently interventions for, early OA where both pain and structural processes may be more effectively targeted than in typical clinical presentations; and the need for new treatment strategies, with examples discussed on pathology-targeted therapies and optimal combinations of therapies. This research agenda should provide useful guidance for all researchers in this field and hopefully lead to improved OA care.
Annals of the rheumatic diseases 03/2014; · 8.11 Impact Factor