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Objective. The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set. Methods. Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of "developing RA," complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis. Results. The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach. Conclusion. The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.

Objective. Development of functional limitation is thought to be unrelated to changes in severity of radiographic osteoarthritis (OA) of the knee. We evaluated the relationship of change in radiographic OA to the incidence of severe functional limitation. Methods. Participants of the Multicenter Osteoarthritis Study, a cohort study of persons with or at high risk of knee OA, were evaluated at 0 and 30 months. Subjects were classified as having no, incident, stable, or worsening radiographic OA. Incidence of severe functional limitation was defined by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function scores (>36.1/68) and walking speed (

Objectives:Previous studies suggest that high systemic bone mineral density (BMD) is associated with incident knee osteoarthritis (OA) defined by osteophytes but not with joint space narrowing (JSN), and are inconsistent regarding BMD and progression of existing OA. The association of BMD with incident and progressive tibiofemoral OA was tested in a large prospective study of men and women aged 50–79 years with or at risk for knee OA.Methods:Baseline and 30-month weight-bearing posteroanterior and lateral knee radiographs were scored for Kellgren-Lawrence (K-L) grade, JSN and osteophytes. Incident OA was defined as the development of K-L grade ⩾2 at follow-up. All knees were classified for increases in grade of JSN and osteophytes from baseline. The association of gender-specific quartiles of baseline BMD with risk of incident and progressive OA was analysed using logistic regression, adjusting for covariates.Results:The mean (SD) age of 1754 subjects was 63.2 (7.8) years and body mass index was 29.9 (5.4) kg/m2. In knees without baseline OA, higher femoral neck and whole body BMD were associated with an increased risk of incident OA and increases in grade of JSN and osteophytes (pConclusions:In knees without OA, higher systemic BMD was associated with a greater risk of the onset of JSN and K-L grade ⩾2. The role of systemic BMD in early knee OA pathogenesis warrants further investigation.

Objective By magnetic resonance imaging (MRI), subchondral bone attrition (SBA) can be seen in early osteoarthritis (OA), but the significance of this is unknown. We therefore evaluated whether SBA was associated with cartilage loss within the same subregion of the knee. Methods The Multicenter Osteoarthritis Study is a cohort of individuals who have or are at high risk for knee OA. At baseline and 30 months, participants' knee MRIs were graded using the Whole-Organ Magnetic Resonance Imaging Score in the 10 subregions of the tibiofemoral joint for cartilage morphology and SBA. We conducted analyses within a knee to eliminate between-person confounding, using an M:N (cases:controls) matched case–control approach with the 10 subregions of a person's knee forming a matched set. Cases within a knee were defined as subregions with cartilage loss, while controls were subregions in that same knee without cartilage loss. We evaluated the association of cartilage loss over 30 months with the presence of baseline SBA in the same subregion within that knee using conditional logistic regression. Results SBA was associated with an odds ratio of 7.5 (95% confidence interval 5.6–9.9, P < 0.0001) for cartilage loss in the same subregion compared with subregions without any baseline SBA in our sample of 459 knees from participants, 64% of whom were women, with a mean age of 63 years and a mean body mass index of 30.5 kg/m2. Conclusion SBA is strongly associated with cartilage loss within the same subregion of a knee. SBA may directly influence overlying cartilage loss or serve as a marker of an area undergoing great compressive stress and in which cartilage loss is inevitable.

The past decade has seen a substantial increase in the number and quality of clinical trials of new therapies for vasculitis, including randomized, controlled, multicenter trials that have successfully incorporated measures of disease activity and toxicity. However, because current treatment regimens for severe disease effectively induce initial remission and reduce mortality, future trials will focus on any of several goals including: (a) treatment of mild—moderate disease; (b) prevention of chronic damage; (c) reduction in treatment toxicity; or (d) more subtle differences in remission induction or maintenance. Thus, new trials will require outcome measure instruments that are more precise and are better able to detect effective treatments for different disease states and measure chronic manifestations of disease. The OMERACT Vasculitis Working Group comprises international clinical investigators with expertise in vasculitis who, since 2002, have worked collaboratively to advance the refinement of outcome measures in vasculitis, create new measures to address domains of illness not covered by current research approaches, and harmonize outcome assessment in vasculitis. The focus of the OMERACT group to date has been on outcome measures in small-vessel vasculitis with an overall goal of creating a core set of outcome measures for vasculitis, each of which fulfills the OMERACT filter of truth, discrimination, feasibility, and identifying additional domains requiring further research. This process has been informed by several ongoing projects providing data on outcomes of disease activity, disease-related damage, multidimensional health-related quality of life, and patient-reported ratings of the burden of vasculitis.

Objective To examine the relation of radiographic features of osteoarthritis to knee pain in people with knees discordant for knee pain in two cohorts. Design Within person, knee matched, case-control study. Setting and participants Participants in the Multicenter Osteoarthritis (MOST) and Framingham Osteoarthritis studies who had knee radiographs and assessments of knee pain. Main outcome measures Association of each pain measure (frequency, consistency, and severity) with radiographic osteoarthritis, as assessed by Kellgren and Lawrence grade (0-4) and osteophyte and joint space narrowing grades (0-3) among matched sets of two knees within individual participants whose knees were discordant for pain status. Results 696 people from MOST and 336 people from Framingham were included. Kellgren and Lawrence grades were strongly associated with frequent knee pain—for example, for Kellgren and Lawrence grade 4 v grade 0 the odds ratio for pain was 151 (95% confidence interval 43 to 526) in MOST and 73 (16 to 331) in Framingham (both P

Objective: To determine whether bone attrition (flattening or depression of the subchondral bone) was associated with the presence and severity of knee pain and to evaluate the coexistence of attrition and other MRI features likely associated with pain. Methods: Participants in the Framingham Osteoarthritis Study, a community cohort unselected for OA, answered questions about knee pain and underwent knee x rays and MRI. Attrition, bone marrow lesions (BMLs) and effusions were scored on MRI using the WORMS scale. We assessed attrition in knees with and without pain, and using logistic regression examined its association with pain adjusting for age, gender, Kellgren–Lawrence (K–L) grade, BMI, BML and effusion. We also explored the relation between attrition, pain severity and nocturnal pain. Results: Attrition (Grade ⩾2) was present in 28% (167/592) of painful knees and in 10% (106/1035) of non-painful knees (adjusted OR 1.6 (95% CI 1.1 to 2.2)). Of knees with OA (n = 368), 74% had pain if attrition was present and 58% if it was absent (adjusted OR 1.2 (95% CI 0.7 to 2.0)). Of knees without OA (n = 1222), pain was reported in 39% of knees with attrition and in 27% without it (adjusted OR 2.1 (95% CI 1.1 to 4.0)). We found no association between either attrition/pain severity or attrition/nocturnal pain. Attrition often co-occurred with other OA features associated with pain such as BMLs and effusions. Conclusions: Attrition was associated independently with knee pain. Unlike knees without OA, the association was lost in OA knees where other pathological features that may cause pain also coexisted.

Objective.To examine the association of serum uric acid (SUA) with a marker of preclinical cardiovascular disease (CVD), carotid atherosclerotic plaques (PLQ), where early evidence of risk may be evident, focusing on individuals without CV risk factors.Methods.The National Heart, Lung, and Blood Institute Family Heart Study is a multicenter study designed to assess risk factors for heart disease. PLQ were assessed with carotid ultrasound. We conducted sex-specific logistic regression to assess the association of SUA with presence of PLQ, including analyses among persons without risk factors related to both CVD and hyperuricemia.ResultsIn total, 4866 participants had both SUA and carotid ultrasound assessed (54% women, mean age 52 yrs, mean body mass index 27.6). The association of SUA with PLQ increased with increasing SUA levels, demonstrating a dose-response relation for men [OR 1.0, 1.29, 1.61, 1.75, for SUA categories < 5 (reference), 5 to < 6, 6 to < 6.8, ≥ 6.8 mg/dl, respectively; p = 0.002]. Similar associations were found in men without CV risk factors. We found no relation of SUA with PLQ in women.Conclusion.In this large study, SUA was associated with carotid atherosclerotic plaques in men. Results were similar in the absence of CV risk factors. These results suggest that SUA may have a pathophysiologic role in atherosclerosis in men.

Objective To assess the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) with respect to its selection and weighting of items. Methods This study used the BVAS/WG data from the Wegener's Granulomatosis Etanercept Trial. The scoring frequencies of the 34 predefined items and any “other” items added by clinicians were calculated. Using linear regression with generalized estimating equations in which the physician global assessment (PGA) of disease activity was the dependent variable, we computed weights for all predefined items. We also created variables for clinical manifestations frequently added as other items, and computed weights for these as well. We searched for the model that included the items and their generated weights yielding an activity score with the highest R2 to predict the PGA. Results We analyzed 2,044 BVAS/WG assessments from 180 patients; 734 assessments were scored during active disease. The highest R2 with the PGA was obtained by scoring WG activity based on the following items: the 25 predefined items rated on ≥5 visits, the 2 newly created fatigue and weight loss variables, the remaining minor other and major other items, and a variable that signified whether new or worse items were present at a specific visit. The weights assigned to the items ranged from 1 to 21. Compared with the original BVAS/WG, this modified score correlated significantly more strongly with the PGA. Conclusion This study suggests possibilities to enhance the item selection and weighting of the BVAS/WG. These changes may increase this instrument's ability to capture the continuum of disease activity in WG.

We assessed whether individual American College of Rheumatology core set measures (CSM), and the CSM grouped as composite patient-derived (CPD) or composite physician/assessor-derived (CMD), performed differently in rheumatoid arthritis (RA) clinical trials.We used data from 9 RA trials [anti-tumor necrosis factor-alpha (TNF-alpha) and disease modifying antirheumatic drug (DMARD)] in which CSM had been assessed, conducted from the early 1990s to present, with a total of 2969 patients. We grouped the CSM as CPD (pain, patient global assessment, function) and CMD [tender joint count (TJC), swollen joint count (SJC), physician global, inflammatory marker]. Using bootstrap simulation, we estimated the sample size that would be required to distinguish active treatment from placebo with the Wilcoxon rank-sum test in the clinical trials for the outcomes of percentage change of each individual CSM, of the Disease Activity Score (DAS), and average percentage change of the CMD or of the CPD.Comparing the performance of individual CSM relative to one another, the physician and patient global assessments and TJC would require the lowest sample sizes to distinguish active treatment from placebo, while use of the SJC, inflammatory marker, and function would require the highest. The CMD performed similarly to the DAS, requiring similar sample sizes, while the CPD would require 1.7 times greater sample size to distinguish treatment from placebo. The results were similar across DMARD and anti-TNF-alpha trials.Because of their demonstrated sensitivity to change, composite measures assessing RA outcomes in clinical trials should continue to include physician/assessor-derived core set measure assessments.

Background: Bisphosphonates may have chondroprotective effects that could be of relevance in osteoarthritis. Using data from a large fracture prevention trial, we evaluated the effect of alendronate on the progression of radiographic spinal osteophytes (OST) and disc-space narrowing (DSN). Methods: The Fracture Intervention Trial (FIT) evaluated the effectiveness of alendronate at 5 mg/day (first 2 years) followed by 10 mg/day (third year) vs placebo over 3–4 years in preventing osteoporotic fractures. In 200 randomly selected subjects from FIT, we read baseline and follow-up lateral x rays for anterior OST and DSN (both scored 0–3 at each vertebral level) in the thoracic and lumbar spine. We calculated the mean difference in change in the sum of OST and DSN scores at T4 to L5 from baseline to follow-up, respectively, in each treatment arm using linear regression. Results: The participants’ baseline characteristics were similar in the alendronate and placebo arms. The adjusted mean change in summary OST score was less in the alendronate group compared to placebo (3.2 vs 4.7, p = 0.04), indicating that OST progression was less in the alendronate group. The adjusted mean change in summary DSN score was less in the alendronate group vs placebo for the whole spine (0.4 vs 0.7, p = 0.2), particularly when limited to the lumbar spine (0.3 vs 0.6, p = 0.04). Conclusions: In this secondary analysis of data from a randomised controlled trial, alendronate was associated with less spinal OST and DSN progression than placebo. This suggests a role for bisphosphonates in altering the pathological processes seen in osteoarthritis.

Damage denotes the aspects of chronic disease that do not reverse with therapy. This concept is particularly important for the primary systemic vasculitides, since the careful differentiation between activity and damage may help avoid unnecessary exposure to cytotoxic medications. Damage significantly influences both longterm prognosis and quality of life. Because the primary systemic vasculitides have diverse manifestations, the use of a damage assessment instrument is crucial to ensure reproducibility. The Vasculitis Damage Index (VDI) is the only validated measure for damage assessment in vasculitis. Use of the VDI in recent clinical trials has shown that it may not adequately determine the full spectrum of damage experienced by patients with vasculitis of small- and medium-size vessels. We propose reexamining the way in which damage is assessed, focusing on vasculitides of small- and medium-size vessels, and outline an initiative to create a substantially revised and improved damage assessment instrument using data-driven approaches. This initiative is part of a larger international effort to create a unified approach to disease assessment for the primary systemic vasculitides.

Background New classification criteria for inclusion of gout patients in clinical studies are being devised based on a points system. The question is what threshold to use for defining an eligible subject for inclusion in a study for gout. Misclassification will occur almost inevitably. However, in studies (interventions) with low risk and low costs, misclassification is less a problem than in studies (interventions) with high risk and high costs. Therefore, preferred cut points for classification criteria may differ by study type. Objectives To determine the acceptable level of positive predictive value (PPV) and negative predictive value (NPV) for classification criteria for gout, given the type of study. Methods We held an international web-based survey with 91 general practitioners and rheumatologists, comfortable with the diagnosis and treatment of gout. Conjoint analysis was used as the framework for devising and analyzing questions. Panel members were anonymously given 20 pairs of two profiles describing a study type and a positive predictive value and a negative predictive value. The panelists were asked to make a choice which of the 2 study profiles they would prefer to enroll a patient. There were 5 study types presented: a phase 3 RCT of an NSAID versus prednisone for acute gout; a phase 3 RCT of a biologic agent for acute gout; a phase 2 RCT of a novel uricosuric drug of unknown efficacy and limited toxicity data; a case-control genome-wide-association (GWAS) study of gout; a cohort study examining long term outcomes of gout. PPV and NPV both had five levels: 60%, 70%, 80%, 90%, 99%. The data were analyzed using Sawtooth software. A binary logit model was used to calculate the relative importance of study type, PPV and NPV. Importance of each level of NPV given a specific study type and PPV was plotted in a line-graph to read the point at which the function crosses the x-axis (i.e. utility =0) above which there is preference. By varying the level of NPV and study type one can see whether this cut point is dependent on study type and NPV. Results There were 91 panellists: 35% female; 7% trainees; 93% rheumatologists and 5% general practitioners; with an average of 19 years of practice and mostly seeing 5 to 60 gout patients monthly. PPV was most highly weighted in decision making: the relative importance was 59% for PPV; 29% for NPV and 13% for study type. Although the overall (“univariate”) minimal preferred NPV was 90%, this depended on PPV and study type. The minimal preferred NPV was 60% or 70% if PPV is 90% (figure) and similar for several study types. NPV should be at least 80% if PPV is 80% for a phase 3 RCT on NSAIDS, and NPV should be at least 70% for a cohort study if PPV is 80% (not shown). Conclusions A positive predictive value of 90% with a negative predictive value of 70% was preferred for most study types; the cut point in the classification criteria for gout should not produce PPV and NPV lower than these values. While it has been hypothesized that different cut-points may be needed based on study type, a single cut-point can be a reasonable approach for all study types if the cut point approximates a PPV of 90% and NPV of 80%. Disclosure of Interest None declared

Background Arthrocentesis is a common procedure in rheumatology clinical practice, usually to obtain synovial fluid for diagnostic purposes or as a therapeutic procedure for glucocorticoid intra-articular injection. There is a generally held belief amongst rheumatologists that needle arthrocentesis is a safe and well-tolerated procedure. Previous reports of the safety of needle arthrocentesis have been in the context of glucocorticoid injection (1). The safety of diagnostic arthrocentesis has not been previously studied systematically. Objectives To determine the frequency of adverse events of diagnostic arthrocentesis in patients suspected to have gout. Methods Consecutive patients with recent joint swelling or possible tophus underwent arthrocentesis or nodule tissue aspiration as part of a cross-sectional diagnostic study for gout. All patients were evaluated at 6 weeks by telephone or in the clinic to determine any adverse events (AE) following the arthrocentesis. The 95% confidence intervals for the percentage frequency of AE were obtained by bootstrapping. Results Arthrocentesis was performed in 910 patients and 887 of these patients (97.5%) were evaluated for AE. Any adverse event was observed in 12 participants (1.4%, 95%CI 0.6 to 2.1). The commonest AE was pain (5 events), nearly all of which were rated as mild. Other non-serious AE reported were bruising (2 events), and joint swelling (4 events). There was 1 case (0.1%, 95% CI 0 to 0.34) of septic arthritis subsequent to the arthrocentesis who required hospitalization and antibiotics. Conclusions Diagnostic arthrocentesis is safe and associated with a very low frequency of adverse events, which are generally mild. However, septic arthritis rarely occurs with an estimated (bootstrapped 95% CI) frequency of between 0 and 3.4 per 1000 patient-procedures. Acknowledgements This study was supported by the American College of Rheumatology, European League against Rheumatism, Arthritis New Zealand, Association Rhumatisme et Travail, and Asociaciόn de Reumatόlogos del Hospital de Cruces. Disclosure of Interest None declared

Objective Chondrocalcinosis, which can promote joint inflammation and cartilage degeneration, is highly prevalent in elderly white subjects. Data on its prevalence are scarce in other ethnic populations. This study was undertaken to compare the prevalence of chondrocalcinosis in Chinese subjects with that in white subjects. Methods We recruited a random sample of Beijing residents ages ≥60 years. Participants underwent standard weight-bearing anteroposterior knee radiography and posteroanterior hand radiography using the protocols developed in the Framingham Osteoarthritis Study. Radiographic chondrocalcinosis was defined as present in a knee or wrist when there was evidence of definite linear cartilage calcification. We compared the prevalence of chondrocalcinosis in Chinese subjects with that in white subjects using age-standardized prevalence ratios. We used identical methods to collect samples of tap water from 2 cities and measured their levels of calcium, magnesium, and phosphate in the same laboratory. Results Chinese subjects had a much lower prevalence of knee chondrocalcinosis (1.8% in men, 2.7% in women) than did white subjects (6.2% in men, 7.7% in women), with the age-standardized prevalence ratio being 0.34 (95% confidence interval [95% CI] 0.20–0.54) and 0.43 (95% CI 0.31–0.59) in men and women, respectively. Wrist chondrocalcinosis was rare in elderly Chinese subjects (prevalence 0.3% in men and 1.0% in women), with the age-standardized prevalence ratio being 0.06 (95% CI 0.01–0.18) in Chinese men and 0.18 (95% CI 0.10–0.30) in Chinese women. Calcium levels in the tap water in Beijing were 15-fold higher than in Framingham, whereas no difference was found in magnesium and phosphate levels. Conclusion Knee chondrocalcinosis and wrist chondrocalcinosis are far less common in Chinese subjects in Beijing than in US white subjects in Framingham, Massachusetts. Given the current lack of understanding of the etiology of chondrocalcinosis, further epidemiologic studies of the impact of genetic and environmental factors on occurrence of chondrocalcinosis are indicated.

To determine the degree of correlation between Farr and ELISA methods of detecting anti-dsDNA antibodies in patients with systemic lupus erythematosus (SLE), and their association with measures of disease activity.Anti-dsDNA antibodies were assayed using the Farr and ELISA methods in patients followed between January 1, 2000, and December 31, 2002. Statistical correlations between Farr and ELISA were determined. Relationships between the 2 assays and measures of disease activity [SLE Disease Activity Index 2000 (SLEDAI-2K-DNA), renal, central nervous system (CNS), and vasculitis] were determined for the same clinic visit.550 patients with 2940 clinic visits met the inclusion criteria. Correlation between Farr and ELISA levels was 0.46 using the first visit for each patient. When the Farr was abnormal, the ELISA was equally likely to be normal or abnormal. Abnormal Farr results were associated with higher SLEDAI-2K scores than normal Farr results (6.2 vs 4.3, respectively; p0.0001). There was less of a distinction with ELISA results (5.9 vs 4.8; p = 0.04). Farr levels were significantly associated with the presence of renal disease and vasculitis, while ELISA levels were not. Neither Farr nor ELISA results correlated with the presence of active CNS involvement.Farr and ELISA techniques for the detection of anti-dsDNA antibodies in patients with SLE are poorly correlated. The Farr is superior to the ELISA in correlating with measures of global disease activity, as well as renal and vasculitis involvement. The Farr technique should continue to be used in clinical practice. The ELISA adds no additional information.

Objective To evaluate the relationship between chondrocalcinosis and the progression of knee osteoarthritis (OA) using longitudinal magnetic resonance imaging (MRI) assessments. Methods Longitudinal knee MRIs were obtained in the Boston OA Knee Study (BOKS) and in the Health, Aging and Body Composition (Health ABC) Study. Chondrocalcinosis was determined as present or absent on baseline knee radiographs. Cartilage morphology was graded on paired longitudinal MRIs using the Whole-Organ Magnetic Resonance Imaging Score in 5 cartilage subregions of each of the medial and lateral tibiofemoral joints. Cartilage loss in a subregion was defined as an increase in the cartilage score of ≥1 (0–4 scale). The risk for change in the number of subregions with cartilage loss was assessed using Poisson regression, with generalized estimating equations to account for correlations. Analyses were adjusted for age, sex, body mass index, baseline cartilage score, and presence of damaged menisci. Results In BOKS, 23 of the 265 included knees (9%) had chondrocalcinosis. In Health ABC, 373 knees were included, of which 69 knees (18.5%) had chondrocalcinosis. In BOKS, knees with chondrocalcinosis had a lower risk of cartilage loss compared with knees without chondrocalcinosis (adjusted risk ratio [RR] 0.4, 95% confidence interval [95% CI] 0.2–0.7) (P = 0.002), and there was no difference in risk in Health ABC (adjusted RR 0.9, 95% CI 0.6–1.5) (P = 0.7). Stratification by intact versus damaged menisci produced similar results within each cohort. Conclusion In knees with OA, the presence of chondrocalcinosis was not associated with increased cartilage loss. These findings do not support the hypothesis that chondrocalcinosis worsens OA progression.

The complexity of assessing disease activity, disease status, and damage in the vasculitides reflects the multisystemic pathologic manifestations of these often chronic illnesses. Major progress has been made in the past decade in the development of validated and widely accepted outcome measures for use in clinical trials. Over time, these tools have been regularly revised, expanded, and supplemented with new measures of disease prognosis and damage. As a result clinical research in this area has become increasingly complex. This article critically reviews the current status of tools for assessing disease activity and damage in "ANCA-associated" vasculitides (Wegener's granulomatosis and microscopic polyangiitis), summarizes the current level of validation of each measure, addresses central problems and controversies to be considered during development of new vasculitis assessment tools, and proposes a series of research agendas for consideration by the vasculitis research community.

To evaluate the patterns and determinants of medication use during recurrent gout attacks.We followed participants with documented gout in an online prospective case-crossover study. During an attack, subjects were asked if they had consulted a physician for the attack and what medications they were using. Definitely inappropriate therapy was defined as use of allopurinol or a uricosuric agent acutely without having used it as a prophylactic. Potentially inappropriate therapy was defined as use of analgesics alone, alternative remedies, or no medications. We estimated the risk of havingor= 1 attack in 1 year using life table methods. We examined the relation of various risk factors to the risk of inappropriate therapy using Poisson regression.Among 232 participants (mean age 52 yrs, 81% male) with documented gout, the risk of havingor= 1 attack in a year was 69%. One hundred ten participants consulted a physician for each attack, 49 did so for only some attacks, while 43 never consulted a physician for any attack. Fifty-three participants had definitely (n = 10) or potentially (n = 43) inappropriate therapy for their recurrent attacks. Physician consultation for an attack was associated with increased risk of inappropriate therapy (risk ratio, RR, 2.5, p = 0.006), whereas an increasing number of gout attacks was associated with lower risk of inappropriate therapy (RR 0.8, p = 0.01).Given the high risk of recurrent attacks and the substantial number of persons whose attacks are not appropriately managed, further education about management of gout attacks for both patients and physicians may be warranted.

Background A recent randomized trial demonstrated a 77% reduced risk of myocardial infarction (MI) among adults with known coronary artery disease treated with long-term low dose colchicine.1 Whether colchicine reduces the risk of incident MI in gout patients is unknown. Objectives We examined the association of colchicine use and incident MI among gout patients using data from a general population database (The Health Improvement Network [THIN]). Methods Included were adults aged 18-89 years who had been enrolled in THIN ≥2 years and had no history of MI. We identified persons who developed gout from 2000-2012, and identified MI cases. In a nested case-control analysis, we matched each gout patient with MI, to 5 gout patients without MI based on age and sex. Colchicine use was categorized as current (prescription within 30 days of index date), recent (31-179 days), past (≥180 days) or never. We conducted a conditional logistic regression model to adjust for potential confounders of MI. We also examined the number of colchicine prescriptions issued in the year prior to the index date in a case-control analysis. Results Among 55,509 persons with incident gout, there were 974 cases of MI, matched to 4762 controls. The adjusted ORs for current, recent and past colchicine use (relative to non-use) were 0.96, 1.49, and 1.12 respectively. The adjusted ORs for 1, 2, 3-5, and >6 prescriptions were 1.31 (95% CI 0.97-1.78), 1.50 (0.88-2.55), 1.35 (0.72-2.55) and 0.62 (0.18-2.10) respectively. View this table: Table 1. Case-control studies of the association of colchicine use and myocardial infarction (MI) among gout patients in The Health Improvement Network Conclusions In this large observational general population study, colchicine use was not associated with a reduced risk of MI among persons with gout. However, colchicine use in this population was generally sporadic (likely for gout flares), rather than continuous. We cannot rule out the potential for confounding by indication. Future studies should identify a larger sample of continuous colchicine users to clarify its potential cardioprotective role in gout. References 1. Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61(4):404-10. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1664

Background Ankylosing spondylyitis (AS) and Psoriatic arthritis (PsA) have been associated with increased risk of myocardial infarction (MI). Diclofenac use has been associated with MI in the general population and is commonly used in spondyloarthropathy (SpA) patients. However data on risk of MI with diclofenac use in the SpA population are not available. Objectives To examine the relation between diclofenac use and the risk of MI among SpA patients. Methods Using 1995-2012 data from The Health Improvement Network, a database of medical records from general practitioners in the United Kingdom, we identified patients with incident AS or PsA who had no history of ischemic heart disease or MI. Eligibility criteria included age 18-89 years, >1 year enrollment in THIN prior to SpA diagnosis, and ≥1 prescription for an NSAID (never users excluded to minimize confounding by indication). We identified subjects prescribed diclofenac after SpA diagnosis and generated a diclofenac-exposed cohort. We selected subjects who were not currently exposed to diclofenac for inclusion in the comparator cohort. We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) for incident MI. We conducted the equivalent cohort analyses for naproxen users (a negative control) and rofecoxib users (a positive control). Results Among individuals with incident AS or PsA, we identified 3480, 2176, and 527 incident users of diclofenac, naproxen and rofecoxib, respectively. Within the 3 cohorts studied, AS was present in 28-32% and 44-49% of all subjects were female. Crude incidence rate ratios for MI were 1.25 (0.86, 1.84) in the diclofenac cohort, 1.20 (0.78, 1.85) in the naproxen cohort, and 2.34 (1.24, 4.43) in the rofecoxib cohort relative to non-use. After multivariable adjustment, the hazard ratio for MI was 1.61 (1.08, 2.40) for diclofenac, 1.40 (0.90, 2.19) for naproxen, and 2.60 (1.30, 5.22) for rofecoxib (Table) compared with non-use. Restriction to AS subjects led to similar effect estimates, but did not reach statistical significance due to small numbers. Conclusions Diclofenac use among SpA patients was associated with a 61% increased risk of MI relative to non-use, while naproxen use was not associated with increased risk. Diclofenac use in persons with AS or PsA may increase MI risk beyond that associated with the underlying inflammatory disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1665

Background OA may be influenced by a metabolic phenotype, which may increase risk of cardiovascular (CV) disease. Hand OA is especially likely to be related to metabolic as opposed to mechanical causes. Previous studies have suggested conflicting associations between hand OA and mortality and there has been no exploration of hand OA and specific types of CV disease, which may have different etiologies. Objectives To study whether hand OA is associated with increased mortality and cardiovascular events in a population-based cohort. Methods We included participants from the Framingham Heart Study, whose CV events and deaths were adjudicated and subtyped by a panel of cardiologists/neurologists. Subjects were 50-75 years, without rheumatoid arthritis and with available information enabling classification of radiographic (≥1 hand joints with Kellgren Lawrence grade (KLG)>2 without pain) and symptomatic hand OA (≥1 hand joints with KLG≥2 and pain in the same joint). Incident CV events (coronary heart disease, congestive heart failure and/or atherothrombotic brain infarction) were defined among subjects that were free of such events at baseline. We examined whether symptomatic and radiographic hand OA were associated with mortality and incident CV events using Cox proportional hazards models adjusting for age, sex, cohort, body mass index, blood glucose, lipid profile, blood pressure, medication use (lipid-lowering, antihypertensive, antidiabetics, NSAIDs and aspirin), smoking and alcohol (for mortality: also previous cardiovascular events and cancer). We also adjusted for the number of joints in the lower limb with pain as a potential marker for OA related physical inactivity. Results For analyses on mortality, we included 1348 participants (53.8% women) with mean (SD) age of 62.2 (8.2) years at the time of hand OA assessment, of whom 540 (40.1%) and 186 (13.8%) had radiographic and symptomatic hand OA, respectively. Median (interquartile range) time to death or censoring was 191 (172, 203) months. There was no association between hand OA and mortality (table). Although we did not find a significant relation to incident CV events overall, we found a significant association between symptomatic hand OA and coronary heart disease (table). The association remained after additional adjustment for pain in the lower limb (HR 2.00, 95% CI 0.96-4-15). Conclusions Symptomatic hand OA was associated with an increased risk of coronary heart disease events, which remained after adjusting for metabolic factors at baseline as well as pain in the lower limb. The association was non-significant for radiographic hand OA, suggesting an effect of pain, which may be a possible marker of inflammation. Disclosure of Interest None Declared

Background Meniscal damage is a potent risk factor for the development and progression of knee osteoarthritis (OA). However, studies addressing the possible cause(s) of meniscus lesions are sparse. Objectives To gain new insights into whether radiographic hand OA, a possible biomarker of general OA susceptibility, is associated with meniscal damage. Methods We studied 974 subjects (56.9% women, 92.9% Caucasians) between 50 and 90 years of age drawn via census tract data and random-digit dialing from Framingham, MA, USA. Selection was not based on knee, hand, or other joint problems. One reader (IKH) assessed bilateral hand radiographs (distal interphalangeal, first interphalangeal, proximal interphalangeal, metacarpophalangeal, and the first carpometacarpal/scaphotrapezial joint) according to the Kellgren and Lawrence (KL) scale (a total of 30 joints). Another reader (ME) assessed right knee 1.5T MRI scans for meniscal integrity in the anterior horn, body, or posterior horn of the medial and lateral meniscus. A third reader (PA) graded all frontal knee radiographs obtained by semi-flexed weight-bearing fixed-flexion protocol according to the KL scale. All readers were blinded to the other readings and clinical data. We divided the sample into three groups based on the number of finger joints with radiographic OA (KL grade ≥2). We then calculated the odds of having meniscal damage (i.e., tear or maceration/destruction) in at least one subregion of either the medial and (or) the lateral meniscus in those with 1 to 2 and ≥3 OA finger joints, respectively, as compared to those with no OA finger joints (logistic regression with adjustment for age, sex and body mass index). We also evaluated the above association in subjects with KL grade 0 in their right knee (n=749), i.e., excluding all knees with evidence of radiographic structural findings suggesting tibiofemoral OA (KL grade ≥1). Results The proportion of subjects in the study sample (n=974) without radiographic OA in the finger joints was 35.0%, while radiographic OA in 1 to 2, and ≥3 finger joints was present in 27.8% and 37.2%, respectively. The prevalence of a meniscal damage in one or more locations on MRI of the right knee according to number of finger joints with OA (grouping as above) was 24.9%, 31.7%, and 47.2%, respectively. The odds of having meniscal damage was significantly increased if having 3 or more finger joints affected by radiographic OA, and the adjusted estimate remained similar in knees with KL grade 0 (n=749). Conclusions Having multiple finger joints with radiographic OA is associated with meniscal damage of the knee. The results suggest a common systemic/genetic predisposition and (or) a common environmental risk factor for radiographic hand OA and meniscal damage in the middle-aged and elderly. Disclosure of Interest None Declared

Background The gold standard for diagnosing crystal arthritis is aspiration of synovial fluid and subsequent polarized microscopy on the punctured fluid. However, various studies have shown a lack of consistency in results of crystal analysis among different observers. We have proposed to certify dedicated colleagues by confirming skill of crystal identification and to increase our insight in general about expertise with the identification of crystals in synovial fluid. By obtaining these data concerning current microscopical performance, we aim to find areas of crystal recognition which are open for further improvement. Objectives The primary objective is to confirm the expertise of physicians with the identification of crystals in synovial fluid/tissue. An online test prepared for the Study of Updated Gout criteria: acr/eulaR (SugaR) emphasizes the recognition of monosodium urate (MSU) crystals, plus the identification of a predefined set as non-MSU crystals; this online test also includes identification of other crystals, such as calcium pyrophosphate dihydrate (CPP), cholesterol, oxalate and apatite. Our secondary objective is to find out whether observer factors are related to microscopical performance. Methods Diagnosticians from different countries, who are working in the rheumatology field and performing microscopic analysis were asked to participate to qualify for entrance to the SugaR Study. The first part of the test included a number of questions concerning personal/professional data. The second part contained 30 slides with images of crystals and other look-a-likes from synovial fluid: crystals shown were 8 MSU, 5 CPP, 4 cholesterol, 2 oxalate and 1 apatite. The test also included slides with potentially confusing look-a-likes. Results Up to January 1st 2013, 56 persons performed the online test; 46% (n=43) of them identified each one of the 20 crystals correctly. With respect to MSU crystals 77% identified 8 MSU crystals, 91% identified at least 7 out of 8 MSU crystals; 68% of all attendees identified 5 CPP crystals and 91% at least 4 out of 5 CPP crystals. See table. Ability to recognize crystals when they are there (%) Conclusions Almost half of the attendees performed well at identifying a diversity of crystals: MSU crystals appeared easier to identify than CPP. The objective performance regarding crystal identification can be improved in all. There seems to be no clear relationship between confidence of expertise and actual expertise. Disclosure of Interest None Declared

TPS669 Background: A substantial number of breast cancer survivors who are taking aromatase inhibitors (AIs) complain of side effects including arthralgias. Given the efficacy of AIs, it is essential that we identify approaches to mitigate arthralgias. We are conducting an NCI-funded trial is to examine the impact of a year-long exercise intervention in 180 breast cancer survivors taking an AI and experiencing at least mild arthralgias. Outcomes include severity of arthralgias, endocrine-related quality of life, % body fat, bone mass, and serum markers of inflammation. The purpose of this abstract is to present preliminary recruitment and adherence results. Methods: Women are being recruited via the Connecticut Tumor Registry and Rapid Case Ascertainment Shared Resource of Yale Cancer Center into the Hormones and Physical Exercise (HOPE) Study. Participants are randomly assigned to exercise (n = 90) or usual care (n = 90). The exercise intervention includes supervised resistance and unsupervised aerobic exercise sessions over 12 months. Data are collected at baseline, 3-, 6-, 9 and 12-months. Results: Study recruitment began in April 2010 and will continue through December 2012. As of January 1, 2012, we have received 1605 names of potentially eligible women. Of these 1605, 777 women are waiting to be screened (e.g., letter mailed to patient or on hold because recently diagnosed), 244 women could not be screened (e.g., unable to contact by phone), and 584 women have completed a telephone screening. Of the 584 women screened, 24% were ineligible because of discontinuing AIs because of arthralgias or chose not to take AIs primarily because of this potential side effect; another 36% were ineligible for various reasons; 24% were not interested; 11% were randomized (n = 65 women); and 5% are undergoing baseline visits (n = 29). On average, women are 62 yrs old and have been taking an AI for 1.8 yrs. Twenty-three women have completed the trial, with high exercise adherence rates (attendance to supervised sessions = 82% ). Conclusions: A growing number of women are choosing to not take AIs or are discontinuing AIs because of side effects. Our study may prove beneficial for the growing number of women diagnosed with hormone receptor-positive breast cancer each year.