Philip G Conaghan

University of Oxford, Oxford, England, United Kingdom

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Publications (245)1211.14 Total impact

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    ABSTRACT: Osteoarthritis (OA) is the fastest growing cause of disability worldwide. Current treatments for OA are severely limited and a large proportion of people with OA live in constant, debilitating pain. There is therefore an urgent need for novel treatments to reduce pain. Synovitis is highly prevalent in OA and is associated with pain. In inflammatory arthritides such as rheumatoid arthritis, methotrexate (MTX) is the gold standard treatment for synovitis and has a well-known, acceptable toxicity profile. We propose that using MTX to treat patients with symptomatic knee OA will be a practical and safe treatment to reduce synovitis and, consequently, pain. Pain Reduction with Oral Methotrexate in knee Osteoarthritis, a pragmatic phase III trial of Treatment Effectiveness (PROMOTE) is an investigator-initiated, multi-centre, randomized, double-blind, pragmatic placebo-controlled trial. A total of 160 participants with symptomatic knee OA will be recruited across primary and secondary care sites in the United Kingdom and randomized on a 1:1 basis to active treatment or placebo, in addition to usual care, for 12 months. As is usual practice for MTX, dosing will be escalated over six weeks to 25 mg (or maximum tolerated dose) weekly for the remainder of the study. The primary endpoint is change in average knee pain during the past week (measured on an 11-point numerical rating scale) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures. A health economics analysis will also be performed. A magnetic resonance imaging substudy will be conducted to provide an explanatory mechanism for associated symptom change by examining whether MTX reduces synovitis and whether this is related to symptom change. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. The PROMOTE trial is designed to examine whether MTX is an effective analgesic treatment for OA. The MRI substudy will address the relationship between synovitis and symptom change. This will potentially provide a much needed new treatment for knee OA. Current Controlled Trials identifier: ISRCTN77854383 (registered: 25 October 2013).
    Trials 12/2015; 16(1):602. DOI:10.1186/s13063-015-0602-8 · 1.73 Impact Factor
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    ABSTRACT: Objective: To assess the current state of reporting of pain outcomes in Cochrane reviews on chronic musculoskeletal painful conditions and to elicit opinions of patients, healthcare practitioners, and methodologists on presenting pain outcomes to patients, clinicians, and policymakers. Methods: We identified all reviews in the Cochrane Library of chronic musculoskeletal pain conditions from Cochrane review groups (Back, Musculoskeletal, and Pain, Palliative, and Supportive Care) that contained a summary of findings (SoF) table. We extracted data on reported pain domains and instruments and conducted a survey and interviews on considerations for SoF tables (e.g., pain domains, presentation of results). Results: Fifty-seven SoF tables in 133 Cochrane reviews were eligible. SoF tables reported pain in 56/57, with all presenting results for pain intensity (20 different outcome instruments), pain interference in 8 SoF tables (5 different outcome instruments), and pain frequency in 1 multiple domain instrument. Other domains like pain quality or pain affect were not reported. From the survey and interviews [response rate 80% (36/45)], we derived 4 themes for a future research agenda: pain domains, considerations for assessing truth, discrimination, and feasibility; clinically important thresholds for responder analyses and presenting results; and establishing hierarchies of outcome instruments. Conclusion: There is a lack of standardization in the domains of pain selected and the manner that pain outcomes are reported in SoF tables, hampering efforts to synthesize evidence. Future research should focus on the themes identified, building partnerships to achieve consensus and develop guidance on best practices for reporting pain outcomes.
    The Journal of Rheumatology 10/2015; DOI:10.3899/jrheum.141423) · 3.19 Impact Factor
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    ABSTRACT: Objective: There are unique challenges to designing and carrying out high-quality trials testing therapeutic devices in OA and other rheumatic diseases. Such challenges include determining the mechanisms of action of the device and the appropriate sham. Design of device trials is more challenging than that of placebo-controlled drug trials. Our aim was to develop recommendations for designing device trials. Methods: An Arthritis Research UK study group comprised of 30 rheumatologists, physiotherapists, podiatrists, engineers, orthopaedists, trialists and patients, including many who have carried out device trials, met and (using a Delphi-styled approach) came to consensus on recommendations for device trials. Results: Challenges unique to device trials include defining the mechanism of action of the device and, therefore, the appropriate sham that provides a placebo effect without duplicating the action of the active device. Should there be no clear-cut mechanism of action, a three-arm trial including a no-treatment arm and one with presumed sham action was recommended. For individualized devices, generalizable indications and standardization of the devices are needed so that treatments can be generalized. Conclusion: A consensus set of recommendations for device trials was developed, providing a basis for improved trial design, and hopefully improvement in the number of effective therapeutic devices for rheumatic diseases.
    Rheumatology (Oxford, England) 09/2015; DOI:10.1093/rheumatology/kev328 · 4.48 Impact Factor
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    ABSTRACT: To evaluate the interreader reliability of change scores and the responsiveness of the OMERACT Hand Osteoarthritis (OA) Magnetic Resonance Image (MRI) Scoring System (HOAMRIS). Paired MRI (baseline and 5-yr followup) from 20 patients with hand OA were scored with known time sequence by 3 readers according to the HOAMRIS: Synovitis, erosive damage, cysts, osteophytes, cartilage space loss, malalignment, and bone marrow lesions (BML; 0-3 scales with 0.5 increments for synovitis, erosive damage, and BML). Interreader reliability for status and change scores were assessed by intraclass correlation coefficients (ICC), percentage exact agreement and percentage close agreement (PEA/PCA), and smallest detectable change (SDC). Responsiveness was assessed by standardized response means (SRM). Cross-sectional interreader ICC were good to very good (≥ 0.74) for all features except synovitis, cysts, and malalignment (ICC 0.50-0.58). The range of change values was small, leading to low ICC for change scores. The SDC values for sum scores (total range 0-24) varied between 1.97-3.05 (except 1.08 for malalignment). For status scores, PEA/PCA on scores in individual joints across the readers were 8.1-50.0 and 43.8-78.1, respectively. Similarly, PEA/PCA for change scores were 20.6-63.8 and 66.3-93.1, respectively. All features except cysts and BML demonstrated good responsiveness with higher SRM for sum scores (range 0.46-1.62) than for scores in individual joints (range 0.24-0.73). Good to very good interreader ICC values were found for cross-sectional readings, whereas the longitudinal reliability was lower because of a smaller range of change scores. All features, except cysts and BML, showed good responsiveness.
    The Journal of Rheumatology 09/2015; DOI:10.3899/jrheum.140983 · 3.19 Impact Factor
  • Rheumatology (Oxford, England) 08/2015; DOI:10.1093/rheumatology/kev308 · 4.48 Impact Factor
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    ABSTRACT: Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. PROSPERO registration number: CRD 42013005009.
    Arthritis research & therapy 08/2015; 17(1):228. DOI:10.1186/s13075-015-0735-x · 3.75 Impact Factor
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    ABSTRACT: The aim was to systematically review the literature describing the prevalence, impact and current management of musculoskeletal pain in older people living in care homes. Published literature (AMED, CINAHL, EMBASE, psycINFO, MEDLINE, Cochrane Library) and unpublished literature (OpenGrey, the WHO International Clinical Trials Registry Platform, Current Controlled Trials, UK National Research Register Archive) were searched on 1 March 2015. All studies assessing the prevalence, impact and management of musculoskeletal disorders in older people living in care homes were included. Literature was appraised using the CASP cohort and qualitative critical appraisal tools. Data were analysed using descriptive statistical approaches, meta-analysis and meta-ethnography techniques. Twenty-four papers reporting the results of 263,775 care home residents in 12 countries were identified. The evidence base was moderate in quality. Prevalence of musculoskeletal pain for people in care homes was 30.2 % (95 % confidence intervals 29.9-30.5 %; n = 105,463). Care home residents reported that musculoskeletal pain had a significant impact on their perceived independence and overall ability to participate in everyday activities of daily living. Three papers which presented data on interventions demonstrated that whilst multi-component assessment and management packages did not significantly change clinical outcomes, these empowered care home staff to feel more confident in managing these patients. Musculoskeletal pain is a common problem in care homes worldwide, and residents report significant impact on their lives. However, there is uncertainty regarding how to assess and manage such pain. PROSPERO Registration Number: CRD42014009824.
    Rheumatology International 08/2015; DOI:10.1007/s00296-015-3322-1 · 1.52 Impact Factor
  • Emmert Roberts · Philip G Conaghan
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    ABSTRACT: We thank Drs Schwarz and Mullins for their comments1 on our paper,2 and we agree with many of their points. The absolute risks of the studied adverse events were small, and paracetamol still has a better adverse event profile than traditional non-steroidal anti-inflammatory drugs (NSAIDs) or opioids. However, we would like to highlight that there are also non-pharmacological alternatives for chronic pain conditions, especially those of the musculoskeletal system: muscle strengthening, increased activity and weight loss if overweight.3 … [Full text of this article]
    Annals of the Rheumatic Diseases 08/2015; 74(8). DOI:10.1136/annrheumdis-2015-207691 · 10.38 Impact Factor
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    ABSTRACT: A variety of authorities in pain measurement and outcome methodology met prior to the Outcome Measures in Rheumatology (OMERACT) 12 meeting in May 2014 to develop partnerships for consensus on pain outcomes. Following overview presentations, discussion centered on pain-specific and global constructs in the domain of chronic pain. Practical issues for clinical trial implementation were also discussed. Breakout sessions were completed regarding additional details of domain constructs. A nominal group process involving all workshop participants confirmed that chronic pain outcome measures encompass a broad range of constructs and that existing scales may be inadequate for assessment in clinical trials. Participants endorsed that both pain intensity and pain interference are important constructs to be measured in clinical trials of chronic pain as it pertains to rheumatologic diagnoses. Further work is needed on inclusion of the patient perspective in the development of pain domains as well as Cochrane Collaboration summary of findings tables.
    The Journal of Rheumatology 08/2015; DOI:10.3899/jrheum.141386 · 3.19 Impact Factor
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    ABSTRACT: Immune age-related abnormalities may synergise with osteoarthritis (OA) pathology. We explored whether abnormalities in the blood immune cell composition are present in OA, beyond defects typically associated with ageing. Blood was collected from 121 healthy controls (HC) and 114 OA patients. Synovial biopsies were obtained from another 52 OA patients. Flow cytometry was used to establish the frequencies of lineage subsets, naïve, memory and regulatory T and B-cells, cells with an abnormal phenotype related to inflammation (IRC) and memory-like CD8(+) T-cells. Multivariate analysis of covariance (MANCOVA) was used to determine whether the relative subset frequencies differed between HC and OA, controlling for age. Expected histology and T/B-cell infiltration were observed. Following age adjusted analysis, we confirmed the lack of age association in HC for CD4(+), B, NK and NKT cells but a negative trend for CD8(+) T-cells. In OA, CD4(+) and B-cell frequency were lower compared to HC while CD8(+) frequencies were higher. CD8(+) memory-like cells were more likely to be found in OA (odds ratio=15). Increased CD8(+) IRC frequencies were also present in OA. The relationship between age and CD4(+) or CD8(+) naïve T-cells in HC were changed in OA while the age relationships with memory cells were lost. The increase in CD4(+) Treg with age was also lost in OA. B-cells showed limited evidence of disturbance. Immune dysfunction may be present in OA beyond what appears related to ageing; this requires further investigation. Copyright © 2015. Published by Elsevier Ltd.
    Osteoarthritis and Cartilage 07/2015; 2. DOI:10.1016/j.joca.2015.06.018 · 4.17 Impact Factor
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    ABSTRACT: At the pain workshop held prior to the Outcome Measures in Rheumatology (OMERACT) 12 conference, chronic nonmalignant pain (CP) as a "disease" was discussed, in response to growing interest in this concept and in terms of the effect on the OMERACT Filter 2.0 framework. CP is often assessed as a unidimensional outcome measure; however, if CP is a disease, then outcome measures need to define the disease state and identify all its manifestations as well as its effects, as specified by Filter 2.0. The aim was to write a discussion piece, reflecting the workshop contributions and debate, as an important step in opening a dialogue around future OMERACT Filter 2.0 Framework developments.
    The Journal of Rheumatology 07/2015; DOI:10.3899/jrheum.141328 · 3.19 Impact Factor
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    ABSTRACT: During OMERACT 12, a workshop was held with the aim to endorse a core set of domains for 3 settings: clinical trials of symptom and structure modification and observational studies. Additional goals were to endorse a core set of contextual factors for these settings, and to define preliminary instruments for each core domain. Finally, an agenda for future research in hand osteoarthritis (OA) was to be proposed. Literature reviews of preliminary instruments for each core domain of the proposed core set for hand OA in the settings described above. Literature review of radiographic scoring methods and modern imaging in hand OA were also performed. Proposed contextual factors for a core set were identified through 2 Delphi exercises with participation of hand OA experts, patient partners, and OMERACT participants. Results from Delphi exercises and systematic literature reviews were presented and discussed. It was agreed that a preliminary core domain set for the setting clinical trials of symptom modification should contain at least "pain, physical function, patient global assessment, joint activity and hand strength." The settings clinical trial of structure modification and observational studies would in addition include structural damage. Preliminary instruments for the proposed domains were agreed on. A list of prioritized contextual factors was defined and endorsed for further research. A research agenda was proposed for domain instrument validation according to the OMERACT Filter 2.0. Preliminary core sets for clinical trials of symptom and structure modification and observational studies in hand osteoarthritis, including preliminary instruments and contextual factors, were agreed upon during OMERACT 12.
    The Journal of Rheumatology 07/2015; DOI:10.3899/jrheum.141017 · 3.19 Impact Factor
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    ABSTRACT: Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis. In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with, number NCT01752634. Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6·81, 95% CI 3·42-13·56; p<0·0001), 150 mg (51 [51%] patients; 6·52, 3·25-13·08; p<0·0001), and 75 mg (29 [29%] patients; 2·32, 1·14-4·73; p=0·0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder. Novartis. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet 06/2015; DOI:10.1016/S0140-6736(15)61134-5 · 45.22 Impact Factor
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    ABSTRACT: To evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials. In a randomised trial of early methotrexate-naïve RA (GO-BEFORE), RAMRIS scores were determined from MRIs and van der Heijde-Sharp (vdHS) scores from radiographs, at baseline, week 12, week 24 and week 52. Progression in damage scores was defined as change >0.5. Associations of X-ray and MRI outcomes with clinical features were evaluated for convergent validity. Iterative Wilcoxon rank sum tests and tests of proportion estimated the sample size required to detect differences between combination therapy (methotrexate+golimumab) and methotrexate-monotherapy arms in (A) change in damage score and (B) proportion of patients progressing. Patients with early MRI progression had higher DAS28, C reactive protein (CRP) and vdHS at baseline, and higher 2-year HAQ. Associations were similar to those with 1-year vdHS progression. Differences in change in structural damage between treatment arms achieved significance with fewer subjects when 12-week or 24-week MRI erosion score was the outcome (150 patients; 100 among an enriched sample with baseline-synovitis >5) compared with the 52-week vdHS (275 patients). Differences in the proportion progressing could be detected in 234 total subjects with 12-week MRI in an enriched sample whereas 1-year X-ray required between 468 and 1160 subjects. Early MRI erosion progression is a valid measure of structural damage that could substantially decrease sample size and study duration if used as structural damage end point in RA clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the rheumatic diseases 06/2015; DOI:10.1136/annrheumdis-2014-206934 · 10.38 Impact Factor
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    ABSTRACT: We aimed to evaluate how minimal (clinically) important differences (MCID/MID) were calculated in rheumatology in the past 2 decades and demonstrate how the calculation is compromised by the lack of interval scaling. We conducted a systematic literature review on articles reporting MCID calculation in osteoarthritis (OA) and rheumatoid arthritis (RA) from January 1, 1989, to May 9, 2014. We evaluated the methods of MCID calculation and recorded the ranges of MCID for common patient-reported outcome measures (PROM). Taking data from the Health Assessment Questionnaire (HAQ), we showed the effects of performing mathematical calculations on ordinal data. A total of 330 abstracts were reviewed and 123 articles chosen for full text review. Thirty-six (19 OA, 16 RA and 1 OA-RA) articles were included in the final evaluation. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most frequently reported PROM with relevant calculations in OA, and the HAQ in RA. Sixteen articles used anchor-based methods alone for calculation of MCID, and 1 article used distribution-based methods alone. Nineteen articles used both anchor and distribution-based methods. Only 1 article calculated MCID using an interval scale. Wide ranges in MCID for the WOMAC in OA and HAQ in RA were noted. Ordinal-based derivations of MCID are shown to understate true change at the margins, and overstate change in the mid-range of a scale. The anchor-based method is commonly used in the calculation of MCID. However, the lack of interval scaling is shown to compromise validity of MCID calculation.
    The Journal of Rheumatology 06/2015; DOI:10.3899/jrheum.141150 · 3.19 Impact Factor
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    Claire Yj Wenham · Michael McDermott · Philip G Conaghan
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    ABSTRACT: Given the paucity of effective therapies and the increasing prevalence of osteoarthritis (OA) with ageing and overweight populations, new therapies for this painful, life-impairing condition are desperately needed, for both symptom relief and structural modification. With a growing understanding that OA involves multiple tissue pathologies including inflammation, many more therapeutic targets have been identified. This review will provide a current overview on the role of biologics in OA, including anti-tumour necrosis factor agents, growth factors and interleukin-1 antagonists.
    Current Pharmaceutical Design 03/2015; 21(17). DOI:10.2174/1381612821666150310144940 · 3.45 Impact Factor
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    ABSTRACT: We conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol. We searched Medline and Embase from database inception to 1 May 2013. We screened for observational studies in English, which reported mortality, cardiovascular, gastrointestinal (GI) or renal AEs in the general adult population at standard analgesic doses of paracetamol. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation. Pooled or adjusted summary statistics were presented for each outcome. Of 1888 studies retrieved, 8 met inclusion criteria, and all were cohort studies. Comparing paracetamol use versus no use, of two studies reporting mortality one showed a dose-response and reported an increased relative rate of mortality from 0.95 (0.92 to 0.98) to 1.63 (1.58 to 1.68). Of four studies reporting cardiovascular AEs, all showed a dose-response with one reporting an increased risk ratio of all cardiovascular AEs from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study reporting GI AEs reported a dose-response with increased relative rate of GI AEs or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Of four studies reporting renal AEs, three reported a dose-response with one reporting an increasing OR of ≥30% decrease in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43). Given the observational nature of the data, channelling bias may have had an important impact. However, the dose-response seen for most endpoints suggests a considerable degree of paracetamol toxicity especially at the upper end of standard analgesic doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the Rheumatic Diseases 03/2015; DOI:10.1136/annrheumdis-2014-206914 · 10.38 Impact Factor
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    ABSTRACT: To increase understanding of how to raise the quality of rheumatology guidelines by reviewing European League Against Rheumatism (EULAR) management recommendations, using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, 10 years after publication of the EULAR standardized operating procedures (SOP) for the production of recommendations. It was hoped that this work could help inform improvements in guideline development by other societies and organizations. The SOP were published in 2004 to ensure the quality of EULAR-endorsed recommendations. We reviewed 27 published EULAR recommendations for management using the AGREE II tool. This provides a framework to assess the quality of guidelines across six broad domains using 23 specific questions. Overall the EULAR recommendations reviewed have been performed to a high standard. There are particular strengths in the methodology and presentation of the guidelines; however, the results indicate areas for development in future recommendations: in particular, stakeholder involvement and applicability of the recommendations. Improvements in quality were evident in recent years, with patient representation in 9 of 15 (60.0%) recommendations published 2010-14 compared with 4 of 12 (33.3%) published 2000-09. In the last 10 years the overall quality of recommendations was good, with standards improving over the decade following publication of the SOP. However, this review process has identified potential areas for improvement, especially in patient representation and provision of implementation tools. The lessons from this work can be applied to the development of rheumatology guidelines by other societies and organizations. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:
    Rheumatology (Oxford, England) 02/2015; 54(8). DOI:10.1093/rheumatology/keu525 · 4.48 Impact Factor
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    ABSTRACT: Assessment of the synovium in patients with knee OA is of great potential value for clinical trials. Ultrasonography could provide this but few data exist on its ability to assess synovial response to therapies. The aim of this study was to examine whether US can detect synovial response to IA corticosteroid (IACS) therapy and to explore associations between synovial characteristics and symptoms. A total of 35 people with ACR radiographic knee OA were included, including those who required an injection of 80 mg of IA methylprednisolone. All participants completed a visual analogue scale for pain and underwent US of the knee at baseline, 1 and 4 weeks. Minimum clinically important improvement (MCII) in pain was ≥20 mm. One week of data were available for 33 patients (19 received IACS and 14 others). Synovial thickness (ST) decreased in 16 IACS patients and 2 others [mean between-group difference 4.7 mm (95% CI 1.1, 8.2), P = 0.012]. Absolute reduction was not associated with absolute reduction in pain (r = 0.20, P = 0.289), but decreased ST was substantively associated with reduction in pain greater than or equal to the MCII (52.9% vs 23.1%, P = 0.098, φ = 0.30). The power Doppler score decreased in 13 IACS patients and 3 others {median change in IACS patients -1.0 [interquartile range (IQR) -5.0-0.0], others 0.0 [-0.3-1.3], P = 0.004}. Absolute changes in pain and power Doppler score were weakly associated (ρ = 0.36, P = 0.049) and a decreased power Doppler score was associated with reduction in pain greater than or equal to the MCII (64.3% vs 18.8%, P = 0.011, φ = 0.46). Ultrasonography can detect short-term synovial response in knee OA. In particular, power Doppler score may be both responsive to and associated with pain, warranting further investigation. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:
    Rheumatology (Oxford, England) 02/2015; 54(8). DOI:10.1093/rheumatology/keu529 · 4.48 Impact Factor
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    ABSTRACT: Objective: To assess the intrareader and interreader agreement and sensitivity to change of the Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Joint Space Narrowing (RAMRIS-JSN) score in the rheumatoid arthritis (RA) wrist in a longitudinal multireader exercise. Methods: Coronal T1-weighted MR image sets of 1 wrist from 20 patients with early RA were assessed twice for JSN at 17 sites at baseline and after 36 or 60 months by 4 readers blinded to patient data but not time order. The joints were scored 0-4 according to the OMERACT RAMRIS-JSN score. Intraclass correlation coefficients (ICC), smallest detectable change (SDC), percentage exact/close agreement (PEA/PCA), and standardized response mean (SRM) were calculated. Results: Median baseline and change score was 10.3 and 1.9, respectively. Intrareader ICC for baseline and change scores was good (≥ 0.50) to very good (≥ 0.80) for all and 3 of 4 readers, respectively. Interreader ICC was very good for change (0.93), while poor for baseline score if all 4 readers were included (0.36), but very good if 1 reader was excluded (0.87). Intrareader and interreader SDC was low (2.34-3.18), except for the intrareader SDC for 1 reader (6.75). The mean PEA/PCA was high for baseline and change scores both within and between the readers (51.5-99.2), except for interreader baseline PEA (14.4). SRM was moderate for all readers (0.55-0.77). Conclusion: The OMERACT RAMRIS-JSN score showed high overall intrareader and interreader reliability, and moderate sensitivity to change, supporting inclusion of the measure as part of the OMERACT RAMRIS system.
    The Journal of Rheumatology 02/2015; DOI:10.3899/jrheum.141009 · 3.19 Impact Factor

Publication Stats

6k Citations
1,211.14 Total Impact Points


  • 2015
    • University of Oxford
      Oxford, England, United Kingdom
  • 1999–2015
    • University of Leeds
      • • Leeds Institute of Rheumatic and Musculoskeletal Medicine
      • • Section of Clinical Musculoskeletal Disease
      • • Leeds Institute of Molecular Medicine (LIMM)
      Leeds, England, United Kingdom
  • 2014
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
  • 2009–2014
    • Leeds Teaching Hospitals NHS Trust
      Leeds, England, United Kingdom
    • University of Cambridge
      • School of Clinical Medicine
      Cambridge, ENG, United Kingdom
    • St George's Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2012
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2010
    • Institute of Genetics and Molecular Medicine
      Edinburgh, Scotland, United Kingdom
  • 2008
    • Stanford University
      Palo Alto, California, United States
  • 2007
    • St George Hospital
      Sydney, New South Wales, Australia
    • University of Auckland
      • Department of Molecular Medicine and Pathology
      Окленд, Auckland, New Zealand
    • Sørlandet Hospital
      Arendal, Aust-Agder county, Norway
  • 2006–2007
    • University of Copenhagen Herlev Hospital
      Herlev, Capital Region, Denmark
  • 1994
    • St. Vincent Hospital
      Green Bay, Wisconsin, United States
  • 1993–1994
    • St. Vincent's Hospital Sydney
      • Clinical Pharmacology and Toxicology
      Sydney, New South Wales, Australia