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Arthritis Care & Research

Wiley Online Library : Arthritis Care & Research

Published: 2017-09-01T00:00:00-05:00


Changes in physical activity after total hip or knee arthroplasty: A systematic review and meta-analysis of 6 and 12 month outcomes


Objective Little is known about the extent to which physical activity (PA) changes following total knee or hip joint replacement relative to pain, physical function and quality of life. Our objective was to conduct a systematic review and meta-analysis on changes in PA relative to pain, quality of life and physical function after total knee or hip joint replacement. Methods We searched PubMed (Medline), Embase and Cinahl, for peer-reviewed, English-language cohort studies measuring PA with an accelerometer from pre-surgery to post-surgery. Random-effects models were used to produce standardized mean differences (SMDs) for PA, quality of life, pain, and physical function outcomes. Heterogeneity was measured with I2. Results Seven studies (336 participants) met eligibility criteria. No significant increase in PA was found at 6-months (SMD 0.14; 95% CI -0.05 to 0.34; I2=0%) and a small-moderate significant effect was found for increasing PA at 12-months (SMD 0.43; 95% CI 0.22 to 0.64; I2=0%). Large improvements at 6-months in physical function (SMD 0.97; 95% CI 0.12 to 1.82; I2=92.3%), pain (SMD -1.47; 95% CI -2.28 to -0.65; I2=91.6%), and quality of life (SMD 1.02; 95% CI 0.30 to 1.74; I2=83.2%) were found. Conclusions Physical activity did not change at 6-months and a small-moderate improvement was found at 12-months post-surgery, despite large improvements in quality of life, pain, and physical function. Reasons for the lack of increased PA are unknown but may be behavioral in nature as sedentary lifestyle is difficult to change. Changing sedentary behavior should be a future focus among this subgroup. This article is protected by copyright. All rights reserved.

The projected burden of osteoarthritis and rheumatoid arthritis in Australia: A population-level analysis


Objective To forecast the prevalence and direct healthcare costs of osteoarthritis (OA) and rheumatoid arthritis (RA) in Australia to the year 2030. Methods An epidemiological model of the Australian population was developed. Data on the national prevalence of OA and RA were obtained from the Australian Bureau of Statistics (ABS) 2014-2015 National Health Survey. Future prevalence was estimated using ABS population projections for 2020, 2025 and 2030. Available government data on direct healthcare expenditure for OA and RA were modelled to forecast costs (in AUD) for the years 2020, 2025 and 2030, from the perspective of the Australian public healthcare system. Results The number of people with OA is expected to increase nationally from almost 2.2 million in 2015 to almost 3.1 million Australians in 2030. The number of people with RA is projected to increase from 422,309 in 2015 to 579,915 in 2030. Healthcare costs for OA were estimated to be over $2.1 billion in 2015; by the year 2030, these are forecast to exceed $2.9 billion ($970 for every person with the condition). Healthcare costs for RA were estimated to be over $550 million in 2015, including $273 million spent on biological disease-modifying anti-rheumatic drugs. Healthcare costs for RA are projected to rise to over $755 million by the year 2030. Conclusions OA and RA are costly conditions that will impose an increasing healthcare burden at the population level. These projections provide tangible data that can be utilised to map future health service provision to expected need. This article is protected by copyright. All rights reserved.

Combination of capillaroscopic and ultrasonographic evaluations in systemic sclerosis: Results of a cross-sectional study


Objectives To compare microvascular damages on nailfold capillaroscopy (NC) with macrovascular manifestations evaluated by hand power doppler ultrasonography (PDUS) in Systemic Sclerosis (SSc) patients, and to assess the associations of these damages with the main digital manifestations of the disease: digital ulcers (DU), acro-osteolysis and Calcinosis. Methods NC, hand X-Rays and PDUS were systematically performed in 64 unselected SSc patients. PDUS evaluation with assessment of ulnar artery occlusion (UAO) and finger pulp blood flow (FPBF) was performed blinded for the results of X-Rays and NC. Results UAO and pathologic FPBF were associated with severe capillary loss (<4 capillaries/mm) on NC (respectively OR=4.04 (1.23-13.29); p<0.05 and OR=3.38 (1.03-11.05); p<0.05). DU history was associated with UAO (OR=10.71 (3.36-34.13); p<0.0001), pathologic FPBF (OR=7.67 (2.52-23.28); p<0.0001), late pattern (OR=6.33 (2.03-19.68; p=0.001) and severe capillary loss (OR=8.52 (2.15-33.78); p=0.001). Acro-osteolysis was also associated with UAO (OR=15.83 (3.95-63.54); p<0.0001), pathologic FPBF (5.52 (1.71-17.90) p=0.003), late NC pattern (OR=6.86 (2.18-21.53); p=0.001) and severe capillary loss (OR=7.20 (2.16-24.02), p=0.001). Calcinosis on X-rays were associated with late NC pattern (OR=5.41 (1.82-16.12); p=0.002), severe capillary loss (OR=12.69 (3.14-51.26); p<0.0001) and UAO (OR=3.19 (1.14-8.92); p=0.025). Combination of UAO and severe capillary loss in a same patient was especially associated with DU history (OR=18.60 (2.24-154.34); p=0.001) and acro-osteolysis (OR=10.83 (2.56-45.88); p=0.001). Conclusions Microvascular damages evaluated by NC and macrovascular features like UAO assessed by PDUS show concordant associations with the main digital manifestations of the disease. This article is protected by copyright. All rights reserved.

A 55-Year-Old Male Presenting with Altered Mental Status - A Complicated Case of Intracranial Aneurysm


A 55-year-old African American male was in good health 5 months back when he underwent colonoscopy as part of a routine colon cancer screening. After the procedure, he developed colitis and was treated with antibiotics for 5 days with resolution of his symptoms. 1 month after this episode he was admitted at an outside hospital for constellation of fever, bilateral ankle swelling and petechial pruritic rash on his lower extremities. This article is protected by copyright. All rights reserved.

Methotrexate still works


Every time we discuss rheumatoid arthritis (RA), we talk about early diagnosis, treat-to-target therapy, cost-effectiveness between biological and non-biological therapies, the role of disease activity meters, and when and how a biological therapy should be discontinued. Amidst this whirlwind of information, where yesterday's evidence is not the same as today, methotrexate (MTX) remains the cornerstone therapy for patients with RA. This article is protected by copyright. All rights reserved.

Dyslipidemia, Alcohol Consumption and Obesity are the Main Factors Associated with Poor Control of Urate Levels in Patients Receiving Urate-Lowering Therapy


Objective In real life, in a substantial proportion of gouty patients receiving urate-lowering therapy (ULT), urate levels are not maintained below the target of 6 mg/dL. We aimed to search for factors associated with poor control of serum urate levels (sUA) in a large population of gouty patients receiving ULT. Methods This cross-sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments and laboratory data were compared in well-controlled gout (sUA ≤ 6 mg/dL) versus poorly-controlled gout (sUA > 6 mg/dL) on univariate and multivariate analyses. Results Among the 1995 patients receiving ULT, only 445 (22.3%) had reached the target of 6 mg/dL sUA. Such patients had a lower rate of gout flares within the previous year than patients without the target (1.7±1.4 vs. 2.1±1.4, p < 0.0001). The main factors associated with poor sUA level control in multivariate analysis were low high-density lipoprotein-cholesterol level (adjusted odds ratio 0.5, 95% confidence interval 0.26 to 0.96; p=0.04), high total cholesterol level (1.83, 1.29 to 2.60; p=0.0007), increased waist circumference (1.55, 1.11 to 2.13; p=0.008) and alcohol consumption (1.52, 1.15 to 2.00; p=0.003). Conclusion Dyslipidaemia, abdominal obesity and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level. This article is protected by copyright. All rights reserved.

Morphology of the toe flexor muscles in older people with toe deformities


Objective Despite suggestions that atrophied, or weak toe flexor muscles are associated with the formation of toe deformities, there has been little evidence to support this theory. This study aimed to determine whether the size of the toe flexor muscles differed in older people with and without toe deformities. Methods Forty-four older adults (>60 years) were recruited for the study. Each participant had their feet assessed for the presence of hallux valgus or lesser toe deformities. Intrinsic and extrinsic toe flexor muscles were imaged with an ultrasound system using a standardised protocol. Assessor blinded muscle thickness and cross-sectional area was measured using Image J software. Results Participants with lesser toe deformities (n=20) were found to have significantly smaller quadratus plantae (p=0.003), flexor digitorum brevis (p=0.013), abductor hallucis (p=0.004) and flexor halluces brevis (p=0.005) muscles than the participants without any toe deformities (n=19). Female participants with hallux valgus (n=10) were found to have significantly smaller abductor hallucis (p=0.048) and flexor halluces brevis (p=0.013) muscles than the female participants without any toe deformities (n=10; p<0.05). Conclusion This is the first study to use ultrasound to investigate the size of the toe flexor muscles in older people with hallux valgus and lesser toe deformities compared to otherwise healthy older adults. The size of the abductor hallucis and flexor hallucis brevis muscles were decreased in participants with hallux valgus whereas the quadratus plantae, flexor digitorum brevis, abductor hallucis and flexor halluces brevis muscles were smaller in those participants with lesser toe deformities. This article is protected by copyright. All rights reserved.



We would like to thank Drs Moura, Barreto and Moura for their pertinent comments on our paper (1) and clearly agree with them on almost everything they have said. They have correctly noted that our study was confined to the United States but we agree that the underuse of methotrexate is clearly a problem worldwide at least in the developed countries. They make the important point that RA trials have consistently defined suboptimal users of methotrexate as patient who have often seen as little as 15 mg/week and have never been exposed to subcutaneous (SC) MTX. This article is protected by copyright. All rights reserved.

MTX use in Japanese patients with rheumatoid arthritis


We appreciate the letter from Dr. Carlos Antonio Moura and Dr. Carlos Geraldo Moura for their interest in our article [1]. As they noticed, that study was intended to evaluate the concordance of patient-reported joint symptoms, physician-examined arthritic signs, and ultrasound-detected synovitis in rheumatoid arthritis (RA), but not to evaluate the use of MTX. Although we described the median and range of RA duration (months) as 31 and 0-608, we should have clearly stated that 11 of 50 patients enrolled in that study were treatment-naïve. This article is protected by copyright. All rights reserved.

Risk of Hepatitis B Reactivation in Inflammatory Arthritis Patients Receiving Disease Modifying Anti-Rheumatic Drugs (DMARDs): a Systematic Review and Meta-analysis


Objectives To assess hepatitis B (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving Disease Modifying Anti-Rheumatic Drugs (DMARDs) and with or without antiviral prophylaxis. Methods We conducted a systematic review and meta-analysis. Electronic searches were conducted in Pubmed, Medline and EMBASE using OVID through 12/31/2015. A search strategy was developed for each database using the following inclusion criteria: participants (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, resolved, or chronic HBV infection), interventions (TNF inhibitors, non-TNF biologic or non-biologic DMARDs), and outcomes (hepatitis B reactivation). Four reviewers independently extracted study data and assessed study quality with the Newcastle-Ottawa scales. To determine the pooled hepatitis B reactivation rate, the variances of the raw proportions were stabilized using a Freeman-Tukey-type arcsine square root transformation, using a random-effects model. Results Twenty-five studies met the inclusion criteria. The overall pooled rate of hepatitis B reactivation was 1.6% (95% CI, 0.8-2.6%) in patients with resolved hepatitis B. Similar rates were observed in resolved patients on TNF inhibitors (1.4%, 95% CI, 0.5-2.6%), non-TNF biologics (6.1%, 95% CI, 0.0-16.6%) and non-biologic DMARDs (1.7%, 95% CI, 0.2-4.2%). We also found the reactivation rate was lower in chronic HBV infection patients who received antiviral prophylaxis (9.0%, 95% CI, 4.1-15.5%), than those who did not (14.6%, 95% CI, 4.3-29.0%). Conclusion We found the hepatitis B reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in chronic HBV infection patients. Further, lower rates were observed in chronic HBV infection patients using antiviral prophylaxis. This article is protected by copyright. All rights reserved.

Radiographic progression is less in psoriatic arthritis achieving a good response to treatment: data using newer composite indices of disease activity


Objectives The purpose of this study was to compare radiographic outcomes according to the magnitude of the response utilizing three new psoriatic composite disease activity measures (the Psoriatic Arthritis Disease Activity Score (PASDAS), the GRAPPA Composite Exercise (GRACE), and the Disease Activity in PsA (DAPSA). The data were taken from the GO-REVEAL dataset, a large randomised, double-blind, study which evaluated the safety and efficacy of 2 doses of the TNF inhibitor golimumab in subjects with active PsA. Methods Response criteria at 24 weeks were applied across the whole dataset, irrespective of treatment group. Radiographic scores at baseline and 24 weeks were assessed using the Sharp van der Heijde method, modified for PsA. Results Overall, for each measure, radiographic progression was significantly greater in subjects with a moderate or poor outcome, and absent in those with a good outcome. The proportion of subjects without radiographic progression in the good outcome group was: PASDAS, 83%, χ2 = 7.9, p = 0.02; GRACE, 80%, χ2 = 5.8, p = 0.05; DAPSA, 76% χ2 = 3.4, p = 0.19. Conclusions Response criteria for disease specific composite measures enable separation between groups in terms of radiographic progression and may therefore be used as suitable targets for interventional studies, as well as in the clinic. This article is protected by copyright. All rights reserved.

Implementation of Treat to Target for Rheumatoid Arthritis in the US: Analysis of Baseline Data from the TRACTION Trial


Background A treat to target (TTT) strategy is recommended in rheumatoid arthritis (RA). However healthcare providers’ adherence to TTT in clinical practice remains unclear. We examined adherence to TTT for RA in US rheumatology sites. Methods We used baseline information from the randomized controlled TRACTION trial, which recruited 641 patients from 46 providers practicing at 11 US sites. We obtained data on implementation of TTT, patient covariates, provider characteristics, and site variables. We examined the implementation of TTT using four cardinal features: recording a disease target, recording a disease activity measure, engaging in shared decision-making, and changing treatment if not at disease target. These features were assessed across sites and providers. We calculated a “TTT implementation score” as the percentage of features noted. We examined the association between patient, provider, and site covariates and TTT implementation score using proportional odds models. Results Implementation of TTT at baseline was sub-optimal: 64.3% of visits had none of the TTT components present, 33.1% had one component, 2.3% had two components, and 0.3% had all components. Implementation of TTT was significantly different across providers and sites (P-values < 0.0001). In the multivariable model, we observed that longer experience as a rheumatologist was associated with having higher implementation score (P-trend=0.01). Compared with fellows, providers with >20 years of practice were more likely to have more TTT components recorded (OR 7.68, 95% CI 1.46-40.52). Conclusions Our study indicated that adherence to a TTT strategy in RA was sub-optimal, and it differed across providers and sites. This article is protected by copyright. All rights reserved.

Towards Establishing a Standardized Magnetic Resonance Imaging Scoring System for Temporomandibular Joints in Juvenile Idiopathic Arthritis


Objectives The temporomandibular joints (TMJs) are frequently affected in children with juvenile idiopathic arthritis (JIA). Early detection is challenging, as major variation is present in scoring TMJ pathology on Magnetic Resonance Imaging (MRI). Consensus-driven development and validation of a MRI scoring system for TMJs has important clinical utility in timely improvement of diagnosis, and serving as an outcome measure. We report on a multi-institutional collaboration towards developing a TMJ MRI scoring system for JIA. Methods Seven readers independently assessed MRI scans from 21 patients (42 TMJs, age range 6-16y) using three existing MRI scoring systems from American, German, and Swiss institutions. Reliability scores, scoring system definitions and items were discussed among 10 JIA experts through two rounds of Delphi surveys, nominal group voting, and subsequent consensus meetings to create a novel TMJ MRI scoring system. Results Average-measure intraclass correlation coefficients (avICC) for the total scores of all three scoring systems were highly reliable at 0.96 each. Osteochondral items showed higher reliability than inflammatory items. An additive system was deemed preferable for assessing minor joint changes over time. Eight items were considered sufficiently reliable and/or important for integration into the consensus scoring system: bone marrow edema and enhancement (avICC=0.57-0.61; %SDD=±45-63% prior to re-defining), condylar flattening (0.95-0.96; ±23-28%), effusions (0.85-0.88; ±25-26%), erosions (0.94; ±20%), synovial enhancement and thickening (previously combined; 0.90-0.91; ±33%), and disk abnormalities (0.90; ±19%). Conclusion A novel TMJ MRI scoring system was developed by consensus. Further iterative refinements and reliability testing are warranted in upcoming studies. This article is protected by copyright. All rights reserved.

Microvascular Abnormalities Assessed by Nailfold Capillaroscopy In Juvenile Dermatomyositis After Medium to Long-Term Follow-Up


Objective In juvenile dermatomyositis (JDM), microvascular abnormalities measured by nailfold capillaroscopy (NFC) are common early in disease course. We aimed to compare the presence of NFC abnormalities in patients with medium- to longstanding JDM with that of controls, and to explore associations between NFC abnormalities and disease activity and other disease characteristics. Methods Fifty-eight JDM patients clinically examined median 16.8 (2-38) years after disease onset were compared with matched controls. By NFC, we assessed nailfold capillary density (NCD), giant capillaries, scleroderma and neovascular pattern (defined as scleroderma active or late pattern). NFC was analyzed blinded to patient/control identity and disease characteristics. We measured disease activity and damage by validated tools, and patients were divided into active and inactive disease according to the PRINTO criteria. Results Compared to controls, patients had decreased NCD, mean 6.4/mm (2.1) vs 7.6/mm (0.8), (p=0.001); and showed more abnormalities in all other NFC parameters; 36% of patients vs. 4% of controls had NCD<6/mm, (p <0.001). Giant capillaries, scleroderma and neovascular pattern were found in 9%, 84% and 41% of patients, respectively. Patients with active disease (n=30) presented more frequently neovascular pattern than inactive patients (n=28) (p =0.041). Decreased NCD and neovascular pattern were associated with higher disease activity and impaired muscle function. Conclusion After medium to long-term follow-up, JDM patients had decreased NCD and often neovascular pattern; both were associated with higher disease activity and impaired muscle function. This suggests that NFC can have a role as a biomarker for disease activity also in longstanding JDM. This article is protected by copyright. All rights reserved.

Patterns of Systemic Treatment for Psoriatic Arthritis in the United States: 2004-2015


Objective To examine trends in use of systemic disease-modifying antirheumatic drugs (DMARD) among patients with psoriatic arthritis (PsA) in the U.S. Methods Using claims data (2004-2015) from a large U.S. commercial healthplan, we identified patients with PsA who initiated DMARDs. We examined baseline patient characteristics and initial treatment patterns. We then assessed changes in the DMARD regimen over the 12-month period after the 1st DMARD initiation date. Poisson regression estimated age- and sex-adjusted incidence rates of treatment changes in each calendar year. Results We identified 9,222 PsA patients who initiated DMARDs (42.8% biologic and 57.2% conventional synthetic). Biologic DMARD (bDMARD) initiators were younger than conventional synthetic DMARD (csDMARD) initiators (mean age±sd: 48±13 vs. 52±14 years) and had generally fewer comorbidities, but a higher proportion of bDMARD initiators received non-systemic treatments for psoriasis at baseline. Methotrexate was the most frequently used DMARD, constituting 80.6% of csDMARD initiation. Etanercept (49.1%) was the most commonly prescribed bDMARD followed by adalimumab (34.4%). During the 12-month followup after the 1st DMARD initiation, 20.1% bDMARD and 31.1% csDMARD initiators had their initial DMARD regimen modified, with an increasing trend in treatment modifications over the 11-year study period (p=0.03). Overall, 5.3% of patients had treatment discontinuation, but the rates decreased over time (p<0.001). Conclusions In this large cohort of PsA patients initiated on DMARDs, over 40% were treated with a bDMARD. We found an increasing trend in treatment modification after the initial DMARD use and a decreasing trend in complete DMARD discontinuation over the past decade. This article is protected by copyright. All rights reserved.

Pain catastrophizing is strongly associated with subjective outcomes, but not with inflammatory assessments in rheumatoid arthritis patients


Objectives Pain catastrophizing is conceptualized as a negative cognitive–affective response to anticipated or actual pain and has been associated with important pain-related outcomes. The objective of this prospective study of established rheumatoid arthritis (RA) patients was to explore how pain catastrophizing was related to patient-reported outcomes (PROs), composite scores and assessments of inflammatory activity. Methods RA patients starting bDMARD were examined at baseline and after 1, 2, 3, 6 and 12 months with PROs (joint pain/patient's global VAS, MHAQ, RAID score), clinical and laboratory assessments (tender/swollen joint count, assessor's global VAS, ESR/CRP), ultrasound (US) (grey scale/power Doppler of 36 joints and 4 tendons) and pain catastrophizing. The composite scores DAS28, CDAI and SDAI were calculated. Statistical calculations included independent samples T-test, paired samples T-test, one-way ANOVA, Pearson's correlations, linear and logistic regression. Results Of 209 patients included, 152 (72.7%) completed 12 months follow-up. Pain catastrophizing, PROs, clinical and inflammatory assessments decreased significantly (p<0.001). Pain catastrophizing was strongly correlated with the PROs and composite scores (p<0.001) but not with the inflammatory parameters (swollen joint count, CRP, GS/PD US). Patients with higher levels of pain catastrophizing had higher PROs and composite scores during the study (p<0.001) but not inflammatory assessments. Baseline pain catastrophizing was negatively associated with achievement of remission at 6 and 12 months (p<0.05). Conclusions Pain catastrophizing was strongly associated with PROs and composite measures, but not markers of inflammation. High levels of pain catastrophizing reduced the likelihood of achieving composite score remission and should be a factor to consider in a treat to target strategy. This article is protected by copyright. All rights reserved.

Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population-Based Case-Control Study


Objective: Environmental factors are of importance for the etiology of rheumatoid arthritis (RA), but much remains unknown concerning the contributions from distinct occupational hazards. We explored the association between occupation and the risk of anti-citrullinated protein antibody (ACPA) + RA or ACPA- RA. Methods: We analyzed 3,522 cases and 5,580 controls from the Swedish population-based EIRA case-control study. A questionnaire was used to obtain information on work history and lifestyle factors. Blood samples were taken for serologic analyses. Unconditional logistic regression was used to calculate the odds ratio (OR) of RA associated with the last occupation before study inclusion. Analyses were performed with adjustments for known environmental exposures and lifestyle factors, including pack years of cigarette smoking, alcohol use, body mass index (BMI) and education. Results: Among men, bricklayers and concrete workers (OR: 2.9, 95% CI: 1.4-5.7), material handling operators (OR: 2.4, 95% CI: 1.3-4.4) and electrical and electronics workers (OR: 2.1, 95% CI: 1.1-3.8), had an increased risk of ACPA+ RA. For ACPA- RA, bricklayers and concrete workers (OR: 2.4, 95% CI: 1.0-5.7) and electrical and electronics workers (OR: 2.6, 95% CI: 1.3-5.0) had an increased risk. Among women, assistant nurses and attendants had a moderately increased risk of ACPA+ RA (OR: 1.3, 95% CI: 1.1-1.6). No occupations were significantly associated to ACPA- RA among women. Conclusion: Mainly occupations related to potential noxious airborne agents were associated with an increased risk of ACPA+ or ACPA- RA, after adjustments for previously known confounders. This article is protected by copyright. All rights reserved.

Musculoskeletal Ultrasound Instruction in Adult Rheumatology Fellowship Programs


Objectives Musculoskeletal ultrasound (MSUS) in rheumatology in the United States has advanced through promotion of certification, standards of use, and core fellowship curriculum inclusion requiring exposure. In order to inform endeavors for curricular integration, the study objectives are to assess current program needs for curricular incorporation, and teaching methods being employed. Methods A needs assessment survey (S1) was sent to 113 rheumatology fellowship program directors. For programs that taught MSUS, a,curriculum survey (S2) was sent to lead faculty. Programs were stratified according to program size and use of a formal written curriculum. Results S1 (108/113; response rate 96%) revealed 94% of programs taught MSUS, with 41% having a curriculum. Curricular implementation was unaffected by program size. Formal curricular adoption of MSUS was favored by 103 (95.3%) directors, with 65.7% preferring it to be optional. S2 (74/101, response rate 73%) noted 41% of programs utilized a formal curriculum. Multiple teaching strategies were used, with common content in general. Use of external courses including USSONAR course was prevalent. Fewer barriers were noted but inadequate time, funding and number of trained faculty still remained. Lack of divisional interest (p = 0.046) and fellow interest (p = 0.012) were noted among programs without a formal curriculum. Conclusion MSUS is taught by a significantly larger number of rheumatology fellowship programs today. Multiple teaching strategies are used with common content. Barriers still remain for some programs. Most program directors favor inclusion of a standardized MSUS curriculum with many favoring it to be optional. This article is protected by copyright. All rights reserved.

Age-related vascularization and ossification of joints in children: an international pilot study to test multi-observer ultrasound reliability


Objective To determine the intra- and inter-observer reliability of ultrasound (US)-detected age-related joint vascularization and ossification grading in healthy children. Methods Following standardized image acquisition and machine setting protocols, 10 international US experts examined four joints (wrist, second metacarpophalangeal joint, knee, and ankle) in 12 healthy children (divided into four age groups: 2–4, 5–8, 9–12, and 13–16 years). Grey-scale was used to detect the ossification grade, and power Doppler (PD) US was used to detect physiological vascularization. Ossification was graded from grade 0 (no ossification) to grade 3 (complete ossification). A positive PD signal was defined as any PD signal inside the joint. Kappa statistics were applied for intra- and inter-observer reliability. Results According to the specific joint and age, up to four solitary PD signals (mean, 1.5) were detected within each joint area with predominant localization of the physiological vascularization in specific anatomic positions: fat pad, epiphysis, physis, and short bone cartilage. The kappa values for ossification grading were 0.87 (range, 0.85–0.91) and 0.58 for intra- and inter-observer reliability, respectively. The bias-adjusted kappa values for intra- and inter-observer reliability were 0.71 (range, 0.44–1.00) and 0.69, respectively. Conclusion Detection of normal findings (i.e., grading of physiological ossification during skeletal maturation and identification of physiological vessels) can be highly reliable by using clear definitions and a standardized acquisition protocol. These data will permit development of a reliable and standardized US approach for evaluating paediatric joint pathologies. This article is protected by copyright. All rights reserved.

Joint distribution and 2-year outcome in 347 patients with monoarthritis of less than 16 weeks’ duration


Objective To study the joint distribution and 2-year outcome of patients with recent-onset monoarthritis. Methods Adult patients with clinically apparent monoarthritis of ≤16 weeks’ duration were included in a multi-center 2-year longitudinal study. Clinical characteristics, joint distribution, development of chronic inflammatory rheumatic disease (CIRD), as well as classification according to the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (2010 RA criteria) were studied. Predictors for development of CIRD were analyzed by multivariable logistic regression analyses. Results The knee (49.3%), ankle (16.7%) and wrist (14.1%) were the most frequently affected joints among the 347 included patients. Ninety-one patients (26.2%) developed CIRD during follow-up; 21 (6.1%) were diagnosed with rheumatoid arthritis and 16 (4.6%) with psoriatic arthritis. Longer duration of joint swelling, joint localization, and ACPA- and RF positivity were independent predictors of CIRD. Six of 58 (10.3%) patients with ankle monoarthritis and 21 of 49 (42.9%) patients with wrist monoarthritis developed CIRD during follow-up. The 2010 RA criteria captured all patients diagnosed with seropositive RA at an early stage, mostly within three months. Conclusion Approximately one-fourth of patients with recent-onset monoarthritis developed CIRD over 2 years. Patients presenting with ankle arthritis rarely developed CIRD, whereas patients presenting with wrist arthritis more frequently did so. Longer duration of joint swelling and ACPA- and RF positivity were also predictive of CIRD. Our findings facilitate early identification of monoarthritis patients with unfavorable prognosis. This article is protected by copyright. All rights reserved.

The impact of disease severity, illness beliefs and coping strategies on outcomes in psoriatic arthritis


Objectives Little is known about how people with psoriatic arthritis (PsA) cope and manage their condition, but data show psychological problems are under-recognised and under-treated. The Common Sense - Self-Regulatory Model (CS-SRM) suggests illness beliefs, mediated by coping, may influence health outcomes. The study aimed to investigate the roles of disease severity, illness beliefs and coping strategies in predicting depression, anxiety and QoL in people with PsA. Additionally, we aimed to assess the role of depression and anxiety in predicting QoL. Methods A cross-sectional observational study where adults with PsA (N = 179) completed validated measures of predictor (illness beliefs, coping strategies, disease severity) and outcome variables (depression, anxiety, QoL) using an online survey distributed via social media. Results The participants were a community sample of 179 adults with PsA aged 20 to 72 (77.1% female). After controlling for disease severity, hierarchical multiple regression models indicated that more negative beliefs about consequences and behavioural disengagement as a coping method predicted levels of depression and self-blame predicted anxiety. Beliefs about consequences and the presence of depression predicted quality of life scores after controlling for disease severity. Conclusions This study offers support for the use of the CS-SRM in explaining variation on psychological outcomes in individuals with PsA. The illness beliefs and coping strategies identified as predictors in this paper are potential targets for interventions addressing PsA-related distress and QoL. This article is protected by copyright. All rights reserved.

Trends and Determinants of Osteoporosis Treatment and Screening in Patients with Rheumatoid Arthritis Compared to Osteoarthritis


Objective To profile osteoporosis (OP) care in patients with rheumatoid arthritis (RA) over the past decade. Methods Patients with RA or osteoarthritis (OA) were followed from 2003 through 2014. OP care was defined as receipt of OP treatment (with exception of calcium/vitamin D) or screening (OPTS). Adjusted trends over follow-up, and the factors associated with OP care were examined using the multivariable Cox proportional hazards. Results OPTS was reported in 67.4% of 11,669 RA and 64.6% of 2,829 OA patients during a median (IQR) 5.5 (2-9) years follow-up. In patients for whom treatment was recommended by the 2010 ACR glucocorticoid-induced OP (GIOP) guidelines (48.4% of RA and 17.6% of OA patients), ~55% overall reported OP medication use. RA patients were not more likely to undergo OPTS compared to OA patients, HR (95%CI) 1.04 (0.94-1.15). Adjusted models showed a stable trend for OPTS between 2004 and 2008 compared to 2003 with a significant downward trend after 2008 both in RA and OA patients. Factors associated with receipt of OP care in RA patients were older age, postmenopausal state, prior fragility fracture or diagnosis of OP, any duration of glucocorticoid treatment, and biologic use. Conclusion About half of RA patients for whom treatment was indicated never received a OP medication. OP care in RA patients was not better than OA patients, and the relative risk of application of this care has been decreasing in RA and OA patients since 2008 without improvement after the release of the 2010 ACR GIOP guideline. This article is protected by copyright. All rights reserved.

Accuracy of Magnetic Resonance Imaging for Grading of Subglottic Stenosis in Patients with Granulomatosis with Polyangiitis: Correlation with Pulmonary Function Tests and Laryngoscopy


Objectives To compare magnetic resonance imaging (MRI)-based and laryngoscopy-based subglottic stenosis (SGS) grading with pulmonary function tests (PFT) in patients with granulomatosis with polyangiitis (GPA). Methods In this retrospective study we included 118 examinations of 44 patients with GPA and suspected SGS. All patients underwent MRI, laryngoscopy, and PFT. Stenosis was graded on a 4-point scale by endoscopy and MRI using the Meyer-Cotton (MC)-Score (score1: ≤50%; 2: 51-70%; 3: 71-99%; 4: 100%) and as percentage by MRI. Results were compared with peak expiratory flow (PEF) and maximum inspiratory flow (MIF) from PFT, serving as objective functional reference. Results In MRI, 112/118 examinations (95%) were rated positive for SGS (n=82: grade1; n=26: grade2; n=4: grade3) whereas in laryngoscopy 105/118 examinations (89%) were rated positive for SGS (n=73: grade1; n=24: grade2; n=8: grade3). MRI and laryngoscopy agreed in 75 of 118 examinations (64%). MRI determined higher scores in 20 (17%) and lower scores in 23 (19%) examinations compared to laryngoscopy. MC-scores as determined by both MRI and laryngoscopy showed comparable correlations with PEF (r=-0.363, p=0.016 and r=-0.376, p=0.012, respectively) and MIF (r=-0.340, p=0.024 and r=-0.320, p=0.034, respectively). Highest correlation was found between MRI-based stenosis grading in percentage with PEF (r=-0.441, p=0.003) and MIF (r=-0.413, p=0.005). Conclusions MRI and laryngoscopy provide comparable results for grading of SGS in GPA and correlate well with PFT. MRI is an attractive non-invasive and radiation free alternative for monitoring the severity of SGS in patients with GPA. This article is protected by copyright. All rights reserved.

The impact of comorbidities on tumor necrosis factor inhibitor therapy in psoriatic arthritis: A population-based cohort study


Objective The objective of this population-based cohort study was to investigate the impact of comorbidities on disease activity, treatment response and persistence with the first-tried tumor necrosis factor inhibitor (TNFi) in patients with psoriatic arthritis (PsA). Methods Data on patient characteristics, disease activity and treatment response and persistence was obtained from the DANBIO registry. Information on comorbidities according to the Charlson Comorbidity Index (CCI) was obtained through linkage with the Danish National Patient Register. Kaplan-Meier plots and Cox proportional hazard regression analyses were performed. Percentages of patients achieving relevant clinical responses were calculated. Results We identified 1750 patients eligible for analyses. Patients with higher CCI had higher disease activity measures at baseline and increased occurrence of depression and/or anxiety. Kaplan–Meier curves showed shorter persistence with treatment for patients with ≥ 2 CCI (log-rank: p < 0.001) and for patients with depression and/or anxiety (p = 0.027) compared to patients without comorbidities. In multivariate analysis a CCI score ≥ 2 was associated with reduced TNFi persistence compared with patients without comorbidities (hazard ratio 1.72, [1.26 to 2.37], p = 0.001). A smaller proportion of patients with a CCI score ≥ 2 achieved European League Against Rheumatism (EULAR) good response (p < 0.001) and EULAR good-or-moderate response (p < 0.001) at 6 months compared with patients without comorbidities. Conclusion Presence of comorbidities was associated with higher baseline disease activity, shorter TNFi persistence and reduced clinical response rates in a cohort of Danish patients with PsA. This article is protected by copyright. All rights reserved.

Prevalence of Sacroiliitis in Inflammatory Bowel Disease Using a Standardized CT Scoring System


Objectives: There is an increasing emphasis on early identification and treatment of ankylosing spondylitis (AS) of which the hallmark is sacroiliitis. Patients with inflammatory bowel disease (IBD) are at increased risk of AS and often receive CT scans of their abdomen affording clinicians the opportunity to determine the presence of sacroiliitis. Previous studies using CT have relied only on radiologist's gestalt or a non-validated adaptation of the mNY criteria. Our aim is to assess the prevalence of sacroiliitis in IBD using a validated screening tool and to determine how frequently these patients are referred for rheumatologic evaluation. Methods: Patients with IBD were recruited from an IBD clinic. Control patients were recruited from a urology clinic and were confirmed to be without back pain, spondylitis, psoriasis, colitis, or uveitis by chart review. CT scans were read by two blinded readers and sacroiliitis was defined by the presence of ankylosis or total erosion score (TES) of ≥3. Results: CT scans were available in 233 Crohn's disease, 83 ulcerative colitis, and 108 control patients and sacroiliitis was seen in 15%, 16.9%, and 5.6% patients respectively. The prevalence was higher in IBD than controls (p=0.007) with no significant difference between CD and UC patients. Of the 49 IBD patients found to have sacroiliitis by CT scan, only 5 had been referred to a rheumatologist. Conclusion: There is a three-fold higher prevalence of sacroiliitis in IBD compared with controls. Despite a growing awareness of this increased prevalence, many patients are not referred to a rheumatologist. This article is protected by copyright. All rights reserved.

Patients' attitudes and experiences of disease-modifying anti-rheumatic drugs in rheumatoid arthritis and spondyloarthritis: A qualitative synthesis


Objectives: Non-adherence to disease-modifying anti-rheumatic drugs (DMARDS) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) results in increased disease activity and symptoms and poorer quality of life. We aimed to describe patients' attitudes and experiences of DMARDs in RA and SpA to inform strategies to improve medication adherence. Methods: Databases (MEDLINE, Embase, PsycINFO, CINAHL) were searched to January 2016. Thematic synthesis was used to analyze the findings. Results: From 56 studies involving 1383 adult patients (RA [n=1149], SpA [n=191], not specified [n=43]), we identified 6 themes (with subthemes): intensifying disease identity (severity of sudden pharmacotherapy, signifying deteriorating health, daunting lifelong therapy); distressing uncertainties and consequences (poisoning the body, doubting efficacy, conflicting and confusing advice, prognostic uncertainty with changing treatment regimens); powerful social influences (swayed by others' experiences, partnering with physicians, maintaining roles, confidence in comprehensive and ongoing care, valuing peer support); privilege and right of access to biologics (expensive medications must be better, right to receive a biologic, fearing dispossession); maintaining control (complete ownership of decision, taking extreme risks, minimizing lifestyle intrusion); and negotiating treatment expectations (miraculous recovery, mediocre benefit, reaching the end of the line). Conclusions: Patients perceive DMARDs as strong medications with alarming side effects that intensify their disease identity. Trust and confidence in medical care, positive experiences with DMARDS among other patients, and an expectation that medications will help maintain participation in life can motivate patients to use DMARDs. Creating a supportive environment for patients to voice their concerns may improve treatment satisfaction, adherence and health outcomes. This article is protected by copyright. All rights reserved.

Physical Functioning, Pain and Health-Related Quality of Life in Adults with Juvenile Idiopathic Arthritis: A Longitudinal 30-Year Follow-Up Study


Objectives: To describe physical functioning, pain, and health-related quality of life (HRQOL) in adults with Juvenile idiopathic arthritis (JIA), investigate changes over time, and identify predictors of poorer HRQOL after 30 years of disease duration. Methods: Patients (N=176) clinically examined after 15 years were reassessed with the Health Assessment Questionnaire Disability Index (HAQ-DI), Visual Analogue Scale Pain (VAS pain) and Medical Outcome Study 36-item Short Form (SF-36) after 23 and 30 years. Patients with signs of active disease after a minimum of 15 years were clinically examined again at 30 years. Patients were compared to matched controls. Results: At 30-year follow-up, 82 patients (47%) had HAQ-DI score >0 and median VAS pain score in patients was 0.6 (range 0-10). Patients had lower physical component summary scores (PCS) compared with controls (p<0.001), and this was evident for patients both with and without clinical remission (p≤0.01). No group differences were found in mental component summary scores. Patients also scored worse than controls on all SF-36 subscales (p≤0.01) except mental health. PCS scores worsened significantly between the 15 and 30-year follow-ups (p=0.001). Worse HAQ-DI, VAS pain, and patient's global assessment of wellbeing scores, and receiving disability/social living allowance at 30 years were correlates of lower PCS. Worse HAQ-DI, patient's global assessment of wellbeing, and VAS fatigue at 15-year follow-up predicted lower PCS at 30-year follow-up. Conclusion: JIA had a detrimental effect on physical HRQOL as measured by PCS. The strongest correlates were physical disabilities, pain, fatigue, wellbeing and receiving disability/social living allowance. This article is protected by copyright. All rights reserved.

Financial incentives and health coaching to improve physical activity following total knee replacement: a randomized controlled trial


Objective: Most persons who undergo total knee replacement (TKR) do not increase their physical activity following surgery. We assessed whether financial incentives and health coaching would improve physical activity in persons undergoing TKR. Methods: We designed a factorial randomized controlled trial among persons undergoing TKR for osteoarthritis. Subjects underwent normal perioperative procedures, including post-operative physical therapy, and were assigned to one of four arms: attention control, telephonic health coaching (THC), financial incentives (FI), or THC+FI. We objectively measured step counts and minutes of physical activity with a commercial accelerometer (Fitbit Zip) and compared the changes from pre-TKR to 6 months post-TKR across the four study arms. Results: Of the 202 randomized subjects, 150 (74%) provided both pre-TKR and 6 months post-TKR accelerometer data. Among completers, the average daily step count at 6 months ranged from 5619 (SD 381) in the THC arm to 7152 (SD 407) in the THC+FI arm (adjusting for baseline values). Daily step count 6 months post-TKR increased by 680 (95% CI: -94 – 1,454) in the control arm, 274 (95% CI: -473 – 1021) in the THC arm, 826 (95% CI: 89 – 1563) in the FI arm, and 1808 (95% CI: 1010 – 2606) in the THC+FI arm. Physical activity increased by 14 (SD 10), 14 (SD 10), 16 (SD 10), and 39 (SD 11) minutes in the control, THC, FI, and THC+FI arms, respectively. Conclusions: A dual THC+FI intervention led to substantial improvements in step count and physical activity following TKR. This article is protected by copyright. All rights reserved.

Trends of hospitalization for serious infections in patients with rheumatoid arthritis in the US between 1993 and 2013


Background/Objective: Epidemiology of hospitalizations with infection among patients with rheumatoid arthritis (RA) is unknown despite an increase in RA treatments that confer infection risk. Methods: We examined National Inpatient Sample data from 1993-2013. We identified adults RA hospitalizations, defined by having ICD-9-CM codes (714.xx) in any secondary diagnosis field. We evaluated 5 infections as the primary diagnosis: pneumonia, sepsis, urinary tract infection (UTI), skin and soft tissue infections (SSTI), and opportunistic infections (OIs). The primary outcome was the proportion of hospitalizations for each infection, among all hospitalizations with a secondary diagnosis of RA. Results: There were 792,921 hospitalizations for infection with a secondary diagnosis of RA, with the rates increasing from 90 to 206 per 100,000 persons from 1993-2013. The proportion of hospitalizations decreased for pneumonia (5.4% to 4.6%), UTI (0.4% to 0.38%), and OIs (0.44% to 0.26%). The proportion for SSTI increased slightly (2.3% to 2.5%), while hospitalizations for sepsis more than tripled (1.9% to 6.4%). Conclusions: Between 1993 and 2013, the proportion of hospitalizations for infections among RA patients appeared to decline for pneumonia and OIs, with a slight decrease in UTI, a slight increase in SSTI, and a substantial increase in hospitalizations with sepsis. Our results are consistent with previous reports that the sensitivity of sepsis coding has increased over time. This article is protected by copyright. All rights reserved.

Anti-TIF1-gamma antibodies are not associated with other paraneoplastic rheumatic syndromes than dermatomyositis


Objectives: An association between cancer and dermatomyositis (DM) is well recognized. The high frequency of malignancies detected close to DM diagnosis suggests that DM can be a paraneoplastic syndrome. Recently anti-TIF1-gamma has been discovered to be associated with cancer and DM. A meta-analysis claimed pooled sensitivity of anti-p155 for diagnosing cancer-associated DM to be 78% and specificity to be 89%. Thus anti-TIF1-gamma has shown promising results as a marker forcancer-associated DM . However, none of the studies evaluated anti-TIF1-gamma association with cancer with or without other rheumatic disorders than DM. To clarify the specificity of anti-TIF1-gamma antibodies as a biomarker for cancer-associated DM we analyzed frequency of anti-TIF1-gamma antibodies in other cancer associated rheumatic syndromes as well as in cancer patients and healthy controls. Methods: Sera from patients with paraneoplastic rheumatic syndrome (n=91), patients with solid cancer (n=95) and healthy controls (n=80) were analyzed for the frequency of anti-TIF1-gamma IgG by ELISA using a commercially available recombinant TIF1-gamma protein as coating antigen. The cut-off value was calculated by adding 2SD to the mean OD value of 80 healthy controls. Results: Positivity for anti-TIF1-gamma IgG was 3,3% (n=3) in patients with paraneoplastic rheumatic syndrome, 3,1% (n=3) in cancer patients and 1,3% (n=1) in healthy controls. There was no significant difference in positivity between the groups (p>0,05). Conclusion: AntiTIF1-gamma antibodies are rarely present in patients with solid cancers or paraneoplastic rheumatic syndromes. This finding strengthens the approach to use anti-TIF1-gamma IgG as marker for cancer-associated DM. This article is protected by copyright. All rights reserved.

Relationship between knee pain and infra-patellar fat pad morphology - A within- and between-person analysis from the Osteoarthritis Initiative


Objective: Inflammation is known to be strongly associated with knee pain in osteoarthritis. The infra-patellar fat pad represents a potential source of pro-inflammatory cytokines. Yet, the relationship between infra-patellar fat pad morphology and osteoarthritis symptoms is unclear. Methods: Here we investigate quantitative imaging parameters of infra-patellar fat pad morphology between: a) painful vs. contralateral pain-free limbs of subjects with unilateral pain; and b) knees of patients with chronic knee pain vs. those of matched pain-free control subjects. 46 subjects with strictly unilateral frequent knee pain and bilateral radiographic osteoarthritis (Kellgren-Lawrence grade [KLG] 2/3) were drawn from the Osteoarthritis Initiative. Further, 43 subjects with chronic knee pain over 4 years and 43 matched pain-free controls without pain over this period were studied. Infra-patellar fat pad morphology (volume, surface area, depth) was determined by manual segmentation of sagittal magnetic resonance images. Results: No significant differences in infra-patellar fat pad morphology were observed between painful vs. painless knees of persons with strictly unilateral knee pain (mean difference -0.7%; 95% confidence interval (CI) -0.6,0.9%; p=0.64) or between chronically painful knees vs. matched painless controls (-2.1%; 95% CI -2.2,1.1%; p=0.51). Conclusion: Independent of the ambiguous role of the IPFP in knee OA (a potential source of pro-inflammatory cytokines or a mechanical shock absorber), the size of the infra-patellar fat pad does not appear to be related to knee pain. This article is protected by copyright. All rights reserved.

From Childhood to Adulthood: Disease Activity Trajectories in Childhood-Onset Systemic Lupus Erythematosus


No previous study has studied the longitudinal disease course of childhood-onset SLE (cSLE). Objectives: 1) To assess distinguishable differences in disease activity trajectories in cSLE patients; 2) To determine baseline factors predictive of disease trajectory membership and 3) To assess if the different disease activity trajectories are associated with different damage trajectories. Methods: This is a retrospective, longitudinal inception cohort of cSLE patients. Patients were followed from diagnosis as children, until they were adults. SLE disease activity (DisAct) was modeled, as a latent characteristic, jointly using the SLE disease activity index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors were tested for membership prediction of the latent classes of disease trajectories. Differences in damage trajectories by DisAct classes were tested using a mixed model. Results: Four hundred and seventy-three patients (82% females) with median age at diagnosis of 14.1 years were studied. We studied 11992 visits (2666 patient years). We identified 5 classes of DisAct trajectories. Baseline major organ involvement, number of ACR criteria and age at diagnosis predicted memberships into different classes. A higher proportion of Asians was in class 2 compared to class 5. Class 1 was associated with the most accrual of damage while class 5 with no significant damage accrual even after 10 years. Conclusions: There are five distinct latent classes of disease trajectory in patients with cSLE. Membership within disease trajectories is predicted by baseline clinical and demographic factors. Membership in different disease activity trajectory classes is associated with different damage trajectories. This article is protected by copyright. All rights reserved.

A restrictive use of oral glucocorticoids in systemic lupus erythematosus prevents damage without worsening long-term disease control: An observational study


Objective: To analyse the influence of two different treatment strategies on general and specific damage accrual in patients with SLE. Methods: Two cohorts were identified according to the responsible physicians: 1.-patients treated at the Autoimmune Diseases Unit (ADU); 2.-patients treated by other members of the Internal Medicine Department (IM). Members of the ADU worked with a protocol including the universal prescription of hydroxychloroquine (HCQ), the use of maximum oral prednisone doses ≤30mg/day and maintenance therapy with ≤5mg/day, by using methyl-prednisolone pulses and/or early immunosuppressants (IS). We analysed the influence of these two treatment strategies on damage accrual, both general and domain specific, attributed to glucocorticoids (GCs), cardiovascular disease (CV), SLE and unclassified, since the diagnosis of disease in patients with a follow-up ≥5 years. Results: 74 patients were included in group ADU and 213 in group IM. They were comparable for most demographic and lupus-related variables. ADU patients received prednisone later and at lower doses, more methyl-prednisolone pulses, earlier IS and more HCQ (p<0.05 for all comparisons). The SLEDAI decreased similarly in both cohorts (p=0.4). Patients in group ADU were less likely to accrue any damage (p=0.007). They accrued less GCs-related (adjusted HR 0.23, 95%CI 0.07-0.80), CV (adjusted HR 0.28, 95%CI 0.08-0.95) and unclassified damage (adjusted HR 0.58, 95%CI 0.3-1.1). Both groups accrued similar SLE-related damage (adjusted HR 0.84, 95%IC 0.40-1.75). Conclusion: The use of reduced oral prednisone doses, which was possible by combining different therapies, reduced GCs-related damage and improved cardiovascular prognosis without increasing damage caused by SLE. This article is protected by copyright. All rights reserved.

Comparable Rates of Glucocorticoid Associated Adverse Events in Patients with Polymyalgia Rheumatica and Comorbidities in the General Population


Objective: To investigate the use of glucocorticoids (GC) and related adverse events (AE) in a long-term, geographically-defined cohort of patients with polymyalgia rheumatica (PMR). Methods: Using a population-based inception cohort, details of GC therapy were abstracted from medical records of all patients diagnosed with PMR in 2000-2014. Age- and sex-matched comparators without PMR were identified from the same underlying population. Cumulative and daily dosage of GC, rate of disease relapse, occurrence of GC-related AE, and rate of GC discontinuation were analyzed. Results: The study included 359 patients with PMR and 359 comparators. The median time to taper below 5mg/day for 6 months was 1.44 years (95% confidence interval [CI]:1.36-1.62), while the median time to permanent discontinuation was 5.95 years (95%CI:3.37-8.88). The mean cumulative dose of GC at 2 and 5 years was 4.0 grams (g) (standard deviation [SD] 3.5g) and 6.3g (SD 9.8g), respectively. The mean daily dose of GC at 2 and 5 years was 6.1 mg/day (SD 7.6) and 7.2 mg/day (SD 9.5), respectively. There were no differences in rates of AE between patients with PMR and comparators for diabetes mellitus, hypertension, hyperlipidemia, or hip, vertebral or Colles fractures (p>0.2 for all). Cataracts were more common in patients with PMR than comparators (hazard ratio:1.72; 95%CI:1.23-2.41). Conclusions: Relapse rates in PMR are highest in the early stages of therapy. Despite often protracted therapy, with the exception of cataracts, the rates of studied morbidities linked to GC are not more common in PMR than comparators. This article is protected by copyright. All rights reserved.

Despite Early Improvement, Patients with Rheumatoid Arthritis Still Have Impaired Grip Force 5 Years after Diagnosis


Objective. Objective measures of function are important in rheumatoid arthritis (RA). The objective of this study was to investigate grip strength in patients with early RA. Methods. An inception cohort of 225 patients with early RA was followed according to a structured protocol. Average and peak grip force values (Grippit; AB Detektor, Gothenburg, Sweden) of the dominant hand were evaluated and compared to the expected, based on age- and sex-specific reference values from the literature. Separate analyses were performed for those with limited self-reported disability (Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5) and clinical remission (DAS28<2.6). Results. The mean baseline average grip force was significantly lower than the corresponding expected values (105 N vs 266 N; p<0.001). Observed average and peak grip force values were significantly reduced compared to the expected in women as well as in men over time and at all time points. The average grip force improved significantly from inclusion to the 12 month visit [age-corrected mean change: 34 N; 95% confidence interval 26-43]. At 5 years, the average grip force was still lower than expected overall (mean 139 N vs 244 N; p<0.001), and also among those with HAQ-DI ≤ 0.5, and those in clinical remission. Conclusion. Grip strength improved in early RA, in particular during the first year. It was still significantly impaired 5 years after diagnosis, even among those with limited self-reported disability and those in clinical remission. This suggests that further efforts to improve hand function are important in early RA. This article is protected by copyright. All rights reserved.

Impact of Stopping Tumor Necrosis Factor-inhibitors on Rheumatoid Arthritis Patients' Burden of Disease


Objective: To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability and fatigue in patients with established rheumatoid arthritis (RA). Methods: In the pragmatic 12-month POET trial, 817 RA patients with ≥6 months of remission or stable low disease activity were randomized 2:1 to stopping or continuing TNFi. In case of flare, TNFi was restarted at the discretion of the rheumatologist. PROs were assessed every 3 months. Results: TNFi was restarted within 12 months in 252/531 patients (47.5%) in the stop group. At 3 months, mean PRO scores were significantly worse in the stop group and a larger proportion of patients experienced a minimal clinically important difference (MCID) on all PROs. Effect sizes (ES) were strongest for health utility (ES = -0.24) and pain (ES = -0.30). Mean scores improved again after this point but disability scores remained significantly different at 12 months. After 12 months, the relative risk of experiencing a MCID ranged from 1.16 for mental health status to 1.58 for fatigue. Mean PRO scores for patients restarting TNFi within 6 months were no longer significantly different from those that did not restart TNFi at 12 months. Conclusion: Stopping TNFi had a significant negative short-term impact on a broad range of PROs. Long-term negative consequences appeared to be limited and outcomes in patients needing to restart TNFi within the first 6 months tended to be restored at 12 months. This article is protected by copyright. All rights reserved.

Developing and Refining New Candidate Criteria for SLE Classification: An International Collaboration


Objectives. We aimed to define candidate criteria within multi-phase development of SLE classification criteria, jointly supported by EULAR and ACR. Prior steps included item generation and reduction by Delphi exercise, further narrowed to 21 items in a Nominal Group Technique exercise. Our objectives were to apply an evidence-based approach to the 21 candidate criteria, and to develop hierarchical organization of criteria within domains. Methods. A literature review identified the sensitivity and specificity of the 21 candidate criteria. Data on the performance of ANA as an entry criteria and operating characteristics of the candidate criteria in early SLE patients were evaluated. Candidate criteria were hierarchically organized into clinical and immunologic domains, and definitions were refined in an iterative process. Results. Based on the data, consensus was reached to use a positive ANA of ≥1:80 titer (HEp2 cells immunofluorescence) as an entry criterion and to have seven clinical and three immunologic domains, with hierarchical organization of criteria within domains. Definitions of the candidate criteria were specified. Conclusion. Using a data-driven process, consensus was reached on new, refined criteria definitions and organization based on operating characteristics. This work will be followed by a multicriteria decision analysis exercise to weight criteria and to identify a threshold score for classification on a continuous probability scale. This article is protected by copyright. All rights reserved.

Training physical therapists in person-centred practice for people with osteoarthritis: A qualitative case study


Objective. To explore physical therapists' experiences with, and the impacts of, a training program in person-centred practice to support exercise adherence in people with knee osteoarthritis. Methods. A qualitative case study using semi-structured interviews, nested within a clinical trial. Eight Australian physical therapists were interviewed before, and after, training in person-centred practice for people with knee osteoarthritis. Training involved a two-day workshop, skills practice and audit of eight consultations with four patients (per therapist), and a final single-day workshop for audit feedback and consolidation. Semi-structured interviews were audio-recorded and transcribed verbatim. Data were thematically analysed. Results. Three pre-training themes arose regarding: usual communication style; definitions of person-centred care and; sharing exercise adherence responsibility. Three themes related to the training experience emerged: learning a new language; challenging conceptions of practice and; putting it into practice. Post-training, three themes arose regarding: new knowledge deepening understanding of person-centred care; changing beliefs about sharing responsibilities; and changed conceptions of role. Conclusion. Although physical therapists found training overwhelming initially as they realised the limitations of their current knowledge and clinical practice, they felt more confident and able to provide person-centred care to people with knee osteoarthritis by the end of training. Training in structured person-centred methodology that provides opportunity for skills practice with patients using a restructured consultation framework can change physical therapists' beliefs about their roles when managing patients with osteoarthritis and positively impact their clinical practice. This article is protected by copyright. All rights reserved.



First-line, Non-criterial Antiphospholipid Antibody Testing for the Diagnosis of Antiphospholipid Syndrome in Clinical Practice: a Combination of Anti-beta2-glycoprotein I Domain I and Phosphatidylserine-dependent Antiprothrombin Antibodies


Objective. The aim of this study was to assess the value of a combination of anti-beta2-glycoprotein I domain I antibodies (aDI) and phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) tests for the diagnosis of antiphospholipid syndrome (APS). Methods. This cross-sectional study involved a cohort of the patients who visited our clinic from April 2005 to March 2013. IgG aDI, IgG aPS/PT, and IgM aPS/PT tests, together with criteria-defined antiphospholipid antibodies (aPL) tests, were performed in all patients. The total antiphospholipid scores (aPL-S) was calculated for each patient according to the titers and positivity of aPL. Results. The study enrolled 157 patients (51 patients with APS and 106 with non-APS autoimmune diseases). All 21 patients positive for both IgG aDI and IgG and/or IgM (IgG/M) aPS/PT had APS with a high total aPL-S (median: 46, range: 26-76), as did all of the 10 patients positive for IgG aDI but negative for IgG/M aPS/PT (median: 22, range: 4-39). Of the 14 patients positive for IgG/M aPS/PT but negative for IgG aDI, 11 (79%) had APS; these individuals also had high total aPL-S (median: 23, range: 11-60). In contrast, only 9 (8%) out of 112 patients negative for both IgG aDI and IgG/M aPS/PT had APS. Conclusion. Testing IgG aDI and IgG/M aPS/PT shows a high positive predictive value for the diagnosis of APS and correlation with aPL-S. This combination as the first-line performance of aPL may contribute to the simple and definite identification of APS with a high risk of thrombosis in clinical practice. This article is protected by copyright. All rights reserved.



Affect and Incident Participation Restriction in Adults with Knee Osteoarthritis: The MOST Study


Objective Participation restriction, common among people with knee osteoarthritis (OA), may be influenced by positive and negative affect. We examined the risk of incident participation restriction over 84 months conferred by positive and negative affect among people with knee OA. Methods Participants are from the Multicenter Osteoarthritis Study and had or were at high risk of knee OA. Participation restriction and positive and negative affect were measured with the Late Life Disability Index, Instrumental Role Limitation subscale and the positive affect and depressed mood subscales of the Center for Epidemiological Studies Depression Scale, respectively. Robust Poisson regression was used to calculate risk of incident participation restriction over 84 months conferred by combinations of low and high positive and negative affect, adjusting for covariates. Results Of 1810 baseline participants (mean: 62.1 years, 56% female), 470 (26%) had incident participation restriction over 84 months. Participants with low positive affect had 20% greater risk of incident participation restriction than those with high positive affect; participants with high negative affect had 50% greater risk of incident participation compared to those with low negative affect. Participants with both low positive and high negative affect had 80% greater risk of incident participation restriction compared to other combinations of positive and negative affect. Conclusion Low positive and high negative affect, both alone and in combination, increase risk of participation restriction among adults with knee OA. Efforts aimed at preventing participation restriction in this population should consider these mood states. This article is protected by copyright. All rights reserved.

The relationship between fish consumption and disease activity in rheumatoid arthritis


Objective: To assess whether more frequent fish consumption is associated with lower RA disease activity scores among participants in an RA cohort. Methods: We conducted a cross-sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in RA (ESCAPE-RA) cohort study. Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Multivariable, total energy-adjusted linear regression models provided effect estimates and 95% confidence intervals (CI) for frequency of fish consumption (never to <1/month, 1/month to <1/week, 1/week, and ≥2/week) on baseline DAS28-CRP. We also estimated the difference in DAS28-CRP associated with increasing fish consumption by one serving per week. Results: Among 176 participants, median DAS28-CRP was 3.5 (interquartile range 2.9-4.3). In an adjusted linear regression model, subjects consuming fish ≥2 times/week had a significantly lower DAS28-CRP compared with subjects who ate fish never to <1/month (difference -0.49 [95% CI -0.97, -0.02]). For each additional serving of fish per week, DAS28-CRP was significantly reduced by 0.18 (95% CI -0.35, -0.004). Conclusions: Our findings suggest that higher intake of fish may be associated with lower disease activity in RA patients. This article is protected by copyright. All rights reserved.

Social role participation and satisfaction with life: A study among patients with ankylosing spondylitis and population controls


Objective: Participation in society of persons with chronic diseases receives increasing attention. However, little is known which components of participation are most relevant to life satisfaction. This study examines the association between several aspects of social role participation and satisfaction with life (SWL) in patients with ankylosing spondylitis (AS) compared to population controls. Methods: In a cross-sectional study, participants completed the Social Role Participation Questionnaire (SRPQ) and SWL scale. The SRPQ assesses several dimensions of participation (importance, satisfaction with performance, satisfaction with time and physical difficulty) in 11 roles representing three domains (interpersonal relations, leisure and work). For individuals with AS and controls, the association between role-domains and SWL were examined using linear regression for each participation dimension separately, in the total and the employed population, adjusting for age, gender, education and income. Results: 246 AS patients (age: 51±12 years; 62% males; disease duration: 17±12 years) and 510 controls (age: 42±15 years; 70% males) were included. Patients were more frequently (extremely) dissatisfied with life (17.9% vs 8.6%; p<0.05). In the total and the employed population, less physical difficulty and higher satisfaction with interpersonal relations and leisure were associated with higher SWL and this was somewhat stronger in patients than in controls (p<0.1). In employed controls but not in employed patients, satisfaction with work was independently associated with SWL. Conclusion These findings highlight the importance to support persons with AS in ameliorating social role participation, particularly in areas like close relationships and leisure activities, which are typically ignored in treating AS. This article is protected by copyright. All rights reserved.

“Determinants of perceived health non-improvement in early rheumatoid arthritis patients with favorable treatment outcomes”


OBJECTIVE: The aim of this study was to explore the association between achieving favorable clinical outcomes and patients' perceived change in overall health status after 12 months of treat to target (T2T) in patients with early rheumatoid arthritis and to identify determinants of subjective non-improvement. METHODS: Baseline and 12 month data of patients included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study with at least a moderate EULAR response after 1 year were selected for analysis. Logistic regression analysis was used to identify factors associated with non-improved perceived overall health status at 12 months. RESULTS: At 12 months, 75 of 210 patients (35%) did not consider their health to have improved despite having achieved favorable clinical outcomes. Relative change from baseline in pain (Wald = 20.20, p < 0.01) and fatigue (Wald = 5.58, p = 0.02) was independently associated with non-improved perceived overall health status. Similar results were obtained when only patients with ≤1 swollen joints were analyzed. 55% improvement in VAS pain was found to discriminate reasonably well between patients who considered their health to have improved versus patients who did not, with an area under the receiver operating curve of 0.70 (95% CI: 0.61-0.78). CONCLUSION: These results demonstrate that clinical improvements do not equate with improved subjective health for all patients. The associations of non-improvement with changes in pain and fatigue suggests that it might be worthwhile to monitor and address pain and fatigue in addition to and independently of disease activity in early rheumatoid arthritis. This article is protected by copyright. All rights reserved.

Pain and mortality in older adults: The influence of pain phenotype


Objective Moderate to severe chronic pain affects one in five adults. Pain may increase the risk of mortality but the relationship is unclear. This study investigated whether mortality risk was influenced by pain phenotype, characterised by pain extent or pain impact on daily life. Methods The study population was drawn from two large population cohorts of adults aged ≥50 years; the English Longitudinal Study of Ageing (ELSA) (n=6324) and the North Staffordshire Osteoarthritis Project (NorStOP) (n=10985). Survival analyses (Cox's proportional hazard models) estimated the risk of mortality in participants reporting “any pain” and then separately according to the extent of pain (total number of pain sites; widespread pain according to American College of Rheumatology (ACR) criteria; widespread pain according to Manchester criteria) and pain impact on daily life (pain interference; and often troubled with pain). Models were cumulatively adjusted for age, sex, education and wealth/adequacy of income. Results After adjustments, the report of any pain (MRR 1.06, 95% CI (0.95, 1.19)) or having widespread pain (ACR 1.07 (0.92, 1.23) or Manchester 1.16 (0.99, 1.36)) was not associated with an increased risk of mortality. Participants who were often troubled with pain (1.29 (1.12, 1.49)) and those that reported “quite a bit” (1.38 (1.20,1.59)) and “extreme” (1.88 (1.54, 2.29)) pain interference had an increased risk of all-cause mortality. Conclusion Pain that interferes with daily life, rather than pain per se was associated with an increased risk of mortality. Future studies should investigate the mechanisms through which pain increases mortality risk. This article is protected by copyright. All rights reserved.

Novel serum biomarkers differentiate psoriatic arthritis from psoriasis without psoriatic arthritis


Objectives: There is a high prevalence of undiagnosed psoriatic arthritis (PsA) in psoriasis patients. Identifying soluble biomarkers for PsA will help in screening psoriasis patients for appropriate rheumatology referral. We therefore aimed to investigate whether serum levels of novel markers previously discovered by quantitative mass spectrometric (MS) analysis of synovial fluid and skin biopsies, performs better than CRP in differentiating PsA patients from those with psoriasis without PsA (PsC). Methods: In this case-control study serum samples were obtained from 100 subjects with PsA, 100 with PsC, and 100 healthy controls. Patients with PsA and PsC were group matched for age, sex, psoriasis duration and PASI and were not on treatment with biologics. Using ELISA, four high-priority markers (M2BP, CD5L, MPO, and ITGB5), as well as previously established markers (MMP3 and CRP) were assayed. Data were analyzed using logistic regression. Receiver operating characteristic (ROC) curves were plotted. Results: Compared to controls, CD5L, ITGB5, M2BP, MPO, MMP3 and CRP were independently associated with PsA, while only CD5L, M2BP and MPO were independently associated with PsC alone. Compared to PsC, ITGB5, M2BP, and CRP were independently associated with PsA. ROC analysis of this model shows an AUC of 0.85 (95% CI [0.80, 0.90]). The model that included CRP alone had an AUC of 0.71 (95% CI [0.64, 0.78]). Conclusion: Thus, CD5L, ITGB5, M2BP, MPO, MMP3 and CRP are markers for PsA. Combination of ITGB5, M2BP and CRP differentiate PsA from PsC, and performs better than CRP alone. This article is protected by copyright. All rights reserved.

Improving adherence to exercise: Do people with knee osteoarthritis and physical therapists agree on the behavioural approaches likely to succeed?


Objective To describe: (a) which behaviour change techniques (BCTs) to promote adherence to exercise have been experienced by people with knee OA or used by physical therapists; and (b) patient and physical therapist-perceived effectiveness of a range of BCTs derived from behavioural theory. Methods Two versions of a custom-designed survey were administered in Australia and New Zealand, one completed by adults with symptomatic knee OA and the second by physical therapists who had treated people with knee OA in the past 6 months. Survey questions ascertained: frequency of receiving/prescribing exercise for knee OA; BCTs received/used targeting adherence to exercise; and perceived effectiveness of 36 BCTs to improve adherence to prescribed exercise. Results 230 people with knee OA and 143 physical therapists completed the survey. Education about the benefits of exercise was the most commonly received/used technique by both groups. People with knee OA rated the perceived effectiveness of all BCTs significantly lower than the physical therapists (mean difference (95%CI) = 1.9 (1.8-2.0)). When ranked by group mean agreement score, two BCTs were among the top five for both groups: development of specific goals related to knee pain and function; and review, supervision and correction of exercise technique at subsequent treatment sessions. Conclusion Goal setting techniques related to outcomes were considered to be effective by both respondent groups, and testing of interventions incorporating these strategies should be a research priority. This article is protected by copyright. All rights reserved.

Valuing treatment with infliximab for ankylosing spondylitis using a willingness-to-pay approach


Objective: To investigate willingness to pay (WTP) for treatment with infliximab by patients with ankylosing spondylitis (AS) and explore factors associated with WTP. Methods: Data were used from 85 patients participating in the European AS Infliximab Cohort (EASIC) open-label extension of the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT). WTP was included at baseline of EASIC and comprised a hypothetical scenario exploring whether the patient would be willing to pay for beneficial effects of infliximab and, if so, what amount they would be willing to pay per administration. Factors associated with WTP were explored using zero-inflated negative binomial regressions (ZINB). Results: Sixty-three of 85 patients (74.1%) were willing to pay, and among these the mean amount willing to pay was €275 (median €100) [interquartile range €50-200] per administration. Multivariable ZINB analysis showed that Assessment of SpondyloArthritis international Society 20 (ASAS20) response was associated with a 7-fold lower likelihood to pay zero euros (OR=0.14, 95%-confidence interval [95%CI] 0.03-0.71) and a 3-fold increase in the amount willing to pay (exp(B)=3.32, 95%CI 1.44-7.69). In addition, country of residence was associated with lower likelihood to pay zero euros (OR = 0.07, 95% CI 0.02-0.36), while increased age was associated with the amount willing to pay (exp(B)=1.05, 95%CI 1.01-1.09). Conclusion: In a hypothetical scenario, three quarter of patients with AS on long-term infliximab stated to be willing to pay an out-of-pocket contribution for this treatment. Treatment response contributed to the willingness as well as to the amount patients are willing to pay. This article is protected by copyright. All rights reserved.

Quantifying digital ulcers in systemic sclerosis: Reliability of digital planimetry in measuring lesion size


Objective Digital ulcers (DUs) are a major problem in patients with systemic sclerosis (SSc), causing severe pain, and impairment of hand function. In addition, DUs heal slowly and sometimes become infected, which can lead to gangrene and necessitate amputation, without appropriate intervention. A reliable, objective method for assessing DU healing or progression is needed in both clinical and research arenas. The objectives were: (1) to compare two digital planimetry methods of DU area measurement (ellipse and free hand region-of-interest [ROI]) applied to photographs of DUs, and (2) to assess reliability of photographic calibration and the two area measurement methods. Methods 107 DUs from 36 patients with SSc-spectrum disease were photographed. Three raters assessed the photographs. Custom software allowed raters to calibrate photograph dimensions, and draw ellipse/free-hand ROIs. Shapes/dimensions for ROIs were saved for further analysis. Results Calibration (single rater, 5 repeats/image) produced an intra-class correlation co-efficient (intra-rater reliability) of 0.99. Mean (SD) areas of DUs assessed using ellipse and free-hand ROIs were 18.7 (20.2) mm2 and 17.6 (19.3) mm2, respectively. Intra- and inter-rater reliability of the ellipse ROI was 0.97 and 0.77, respectively. For the free hand ROI, the intra- and inter-rater reliability was 0.98 and 0.76. Conclusion This study shows digital planimetry methods applied to SSc-related DUs can be extremely reliable. Further work is now needed to move towards applying these as outcome measures for clinical trials, and in clinical settings. This article is protected by copyright. All rights reserved.

Rheumatoid arthritis patients' motivations for accepting or resisting disease-modifying antirheumatic drug treatment regimens


Objective: Patient refusal of and nonadherence to treatment with disease-modifying antirheumatic drugs (DMARDs) can adversely affect disease outcomes in rheumatoid arthritis (RA). This qualitative study describes how RA patients' feelings in response to experiences and information affected their decisions to accept (agree to adopt, initiate and implement) or resist (refuse, avoid and discontinue) DMARD treatment regimens. Methods: 48 RA patients were interviewed about their experiences making decisions about DMARDs. The interviews were transcribed, coded, and analyzed for themes related to their internal motivations for accepting or resisting treatment regimens, using a narrative analysis approach. Results: In addition to feelings about the necessity and dangers of medications, patients' feelings towards their identity as an ill person, the act of taking medication, and the decision process itself were important drivers of patient's decisions. For patients' motivations to accept treatment regimens, two themes emerged: 1) desire to return to a "normal" life and 2) fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: 1) fear of medications, 2) maintaining control over health, 3) denial of sick identity, 4) disappointment with treatment, and 5) feeling overwhelmed by the cognitive burden of deciding. Conclusion: Feelings in response to experiences and information played a major role in how patients weighed the benefits and costs of treatment options, suggesting that addressing patients' feelings may be important when rheumatologists counsel about therapeutic options. Further research is needed to learn how best to address patients' feelings throughout the treatment decision making process. This article is protected by copyright. All rights reserved.

Can Patient Navigators Improve Adherence to Disease-Modifying Antirheumatic Drugs? Quantitative Findings from the Med Assist Pilot Study


Objective: Non-adherence to DMARDs is common, worsens during the treatment course, and results in adverse outcomes. We studied whether patient navigators – laypersons trained in care coordination, motivational interviewing, basic pharmacology and disease management- improved oral DMARD adherence. Methods: We enrolled 107 patients aged ≥18 years with systemic rheumatic diseases who initiated an oral DMARD within 6 months. Navigators interacted with patients up to 2-4 times per week for 6 months. Patients completed validated surveys (Morisky Medication Adherence Scale (MMAS-8), Mental Health Inventory (MHI-5), Beliefs about Medicines Questionnaire and Brief Illness Perception Questionnaire) at baseline and at 6 months. We used paired t-tests to compare baseline and 6-month outcomes. We examined the association of age, race/ethnicity, insurance and MHI-5 with change in MMAS-8 score using multivariable linear regression. Results: Among 107 patients enrolled, 69 (64%) completed baseline and 6-month MMAS-8 surveys. Mean age was 55 ±16 years; 93% were female. The mean baseline MMAS-8 score was 6.7 ±1.3 (indicating borderline adherence), and the mean MHI-5 was 60.8 ± 9.1(<68 suggests any depressive symptoms). After 6 months, there were no significant changes in MMAS-8 (p=0.09) or MHI-5 (p=0.83). Patients described fewer medication concerns (p=0.03), but a more threatening perception of illness (p=0.01). Our multivariable model demonstrated a small change in MMAS-8 for each 5-year increase in age (β=0.14, p=0.02). Conclusion: Our intervention resulted in no significant change in adherence from baseline. A multicenter, randomized controlled trial is needed to determine whether patient navigators are effective in maintaining adherence to DMARDs over time. This article is protected by copyright. All rights reserved.

Hydroxychloroquine is Not Associated with Hemolytic Anemia in Glucose-6-Phosphate Dehydrogenase (G6PD) Deficient Patients


Objective: Some sources urge caution when prescribing hydroxychloroquine (HCQ) to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, presumably due to a risk of hemolytic anemia. There is limited published data, however, to support this risk. Additionally, not all patients with G6PD deficiency are at similar risk for hemolysis, and people with the African variant are at particularly low risk. Through a retrospective chart review, we aimed to quantify the frequency of G6PD deficient patients with hemolysis attributed to HCQ. Methods: We identified Duke Rheumatology patients with HCQ usage and a measured G6PD level. A retrospective chart review was performed, recording demographics, G6PD levels, episodes of anemia, laboratory values consistent with hemolysis, and HCQ use. Results: Of the 275 patients reviewed, 84% were female, 46% African American and 48% Caucasian. The leading diagnoses were lupus (32%), rheumatoid arthritis (29%), and inflammatory arthritis (14%). Only 4% of patients were G6PD deficient, all African American. Two G6PD-deficient patients had hemolysis during severe lupus flares that occurred while not taking HCQ. There were no reported episodes of hemolysis in over 700 months of HCQ exposure among the 11 G6PD-deficient patients. Conclusion: This is the largest study to date evaluating G6PD deficiency with concurrent use of HCQ. Among 11 patients with G6PD deficiency, 2 had episodes of hemolysis, but neither occurred during HCQ therapy. These data do not support routine G6PD level measurement or withholding HCQ therapy among African American patients with G6PD deficiency. This article is protected by copyright. All rights reserved.

Performance of Anti-nuclear Antibodies for Classifying Systemic Lupus Erythematosus: a Systematic Literature Review and Meta-regression of Diagnostic Data


Objective: To review the published literature on the performance of indirect immunofluorescence (IIF)-HEp-2 ANA testing for classification of SLE. Methods: A systematic literature search was conducted in the MEDLINE, EMBASE and COCHRANE databases for articles published between January 1990 and October 2015. The research question was structured according to PICO (Population, Intervention, Comparator, Outcome) format rules, and PRISMA recommendations were followed where appropriate. Meta-regression analysis for diagnostic tests was performed, using the ANA titer as independent variable while sensitivity and specificity were dependent variables. Results: Of 4,483 publications screened, 62 matched the eligibility criteria, and another two articles were identified through reference analysis. The included studies comprised 13,080 SLE patients in total, of whom 12,542 (95.9%) were reported to be IIF-ANA positive at various titers. For ANA at titers of 1:40, 1:80, 1:160, and 1:320, meta-regression gave sensitivity values of 98.4% (95% confidence interval [CI] 97.6-99.0%), 97.8% (CI 96.8-98.5%), 95.8% (CI 94.1-97.1%) and 86.0% (CI 77.0-91.9%), respectively. The corresponding specificities were 66.9% (CI 57.8-74.9%), 74.7% (CI 66.7-81.3%), 86.2% (CI 80.4-90.5%) and 96.6% (CI 93.9-98.1%), respectively. Conclusion: The results of this systematic literature review and meta-regression confirm that IIF-ANA have high sensitivity for SLE. ANA at a titer of 1:80 have sufficiently high sensitivity to be considered as an entry criterion for SLE classification criteria, i.e. formally test other classification criteria for SLE only if ANA of at least 1:80 have been found. This article is protected by copyright. All rights reserved.

The cost-effectiveness of tight control of inflammation in early psoriatic arthritis: Economic analysis of the TICOPA trial


Objective: Treat-to-target approaches have proved to be effective in rheumatoid arthritis, but have not been studied in psoriatic arthritis (PsA). This study was undertaken to examine the cost effectiveness of tight control (TC) of inflammation in early psoriatic arthritis compared to standard care (SC). Methods: Cost effectiveness analyses were undertaken alongside a UK-based, open-label, multicentre, randomised controlled trial. Taking the perspective of the healthcare sector, effectiveness was measured using EQ-5D-3L which allows the calculation of quality-adjusted life years (QALYs). Incremental cost effectiveness ratios (ICERs) are presented which represent the additional cost per QALY gained over a 48-week time horizon. Sensitivity analyses are presented assessing the impact of variations in the analytical approach and assumptions on the cost-effectiveness estimates. Results: Mean cost and QALYs were higher in the TC group; £4198 vs. £2000 and 0.602 vs. 0.561. These values yielded an ICER of £53948 per QALY. Bootstrapped uncertainty analysis suggest the TC has a 0.07 probability of being cost effective at a £20,000 threshold. Stratified analysis suggest that with certain costs being controlled, an ICER of £24639 can be calculated for patients with a higher degree of disease severity. Conclusion: A tight control strategy to treat PsA is an effective intervention in the treatment pathway, however this study does not find tight control to be cost-effective in most analyses. Reduced drug prices, targeting polyarthritis patients or reducing rheumatology visit frequencies may improve value for money metrics in future studies. This article is protected by copyright. All rights reserved.

Incidence and Prevalence of Cardiovascular Risk Factors Among Patients With Rheumatoid Arthritis, Psoriasis, or Psoriatic Arthritis


Objective To estimate prevalence and incidence of cardiovascular (CV) risk factors of hypertension, diabetes mellitus, hyperlipidemia, and obesity in patients with rheumatoid arthritis (RA), psoriasis, or psoriatic arthritis (PsA). Methods Patients with RA, psoriasis, or PsA were identified based on medical and pharmacy claims from the MarketScan claims databases from January 1, 2002 through December 31, 2014. Primary outcomes included age- and sex-standardized prevalence of CV risk factors during the 12 months preceding diagnosis date and incidence rates per 1,000 patient-years, with 95% confidence intervals (95% CIs) during followup. Results Prevalence for RA, psoriasis, and PsA cohorts for hypertension was 18.6% (95% CI 18.3–18.8), 16.6% (95% CI 16.3–17.0), and 19.9% (95% CI 19.4–20.4), respectively; for diabetes mellitus 6.2% (95% CI 6.1–6.4), 6.3% (95% CI 6.0–6.5), and 7.8% (95% CI 7.4–8.2); for hyperlipidemia 9.9% (95% CI 9.7–10.1), 10.4% (95% CI 10.2–10.7), and 11.6% (95% CI 11.2–12.0); and for obesity 4.4% (95% CI 4.2–4.6), 3.8% (95% CI 3.5–4.0), and 6.0% (95% CI 5.6–6.5). Incidence rates per 1,000 patient-years during followup for RA, psoriasis, and PsA cohorts, respectively, for hypertension were 74.0 (95% CI 72.5–75.5), 68.2 (95% CI 65.9–70.4), and 79.8 (95% CI 76.3–83.3); for diabetes mellitus 10.6 (95% CI 10.1–11.1), 13.0 (95% CI 12.1–13.8), and 14.7 (95% CI 13.5–16.0); for hyperlipidemia 40.3 (95% CI 39.4–41.3), 47.1 (95% CI 45.4–48.7), and 52.0 (95% CI 49.6–54.3); and for obesity 24.4 (95% CI 23.4–25.4), 26.4 (95% CI 25.0–27.8), and 32.9 (95% CI 30.6–35.2). Conclusion Patients with RA, psoriasis, and PsA have high prevalence and incidence of CV risk factors, suggesting the need for risk factor monitoring of these patients.

Treatment of Rheumatoid Arthritis With Anti–Tumor Necrosis Factor or Tocilizumab Therapy as First Biologic Agent in a Global Comparative Observational Study


Objective To compare clinical effectiveness between tocilizumab and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional synthetic disease-modifying antirheumatic drugs initiating biologic therapy. Methods Patients prescribed tocilizumab (intravenous) or TNFi were prospectively observed in routine clinical practice for 52 weeks across 158 sites in 26 countries. The primary observation was the change from baseline in Disease Activity Score based on 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) at week 24 using analysis of covariance for between-groups comparison. Secondary end points included Clinical Disease Activity Index (CDAI) and patient-reported outcomes at weeks 24 and 52. Results Of 1,216 patients, 35% initiated tocilizumab and 65% initiated TNFi. RA duration was shorter, and disease activity and corticosteroid use were higher in tocilizumab patients. Tocilizumab-treated patients had greater improvement in DAS28-ESR at weeks 24 and 52 (week 24 difference [95% confidence interval] in adjusted means: −0.831 [−1.086, −0.576]; P < 0.001). Change from baseline in CDAI was also greater with tocilizumab (adjusted means difference: week 24, −3.48; week 52, −4.60; both P < 0.001). Tocilizumab-treated patients had more improvement in the Health Assessment Questionnaire disability index than TNFi-treated patients (P < 0.05). The cumulative probability of drug discontinuation at week 52 was lower with tocilizumab (15%) than TNFi (27%; P < 0.001, unadjusted analysis). Unadjusted frequencies (events per 100 patient-years) for tocilizumab and TNFi were 6.44 and 11.99 for serious adverse events, 1.98 and 5.03 for serious infections, and 0.74 and 0.77 for deaths, respectively. Conclusion Patients initiating tocilizumab experienced greater effectiveness and drug survival than those initiating TNFi in an observational setting.

Rheumatoid Arthritis Treatment After Methotrexate: The Durability of Triple Therapy Versus Etanercept


Objective Although it is common for rheumatologists to initiate biologic agents after failure of methotrexate monotherapy in rheumatoid arthritis (RA), ample data support the initial use of combinations of conventional therapies in this clinical scenario. Our study explores the durability of triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) versus methotrexate-etanercept in RA. Methods RA patients with suboptimal response to methotrexate (n = 353) were randomized to either triple therapy or methotrexate-etanercept therapy in a 48-week, double-blinded, noninferiority trial. Patients without clinical improvement at 24 weeks were switched to the alternative treatment. Of the total, 289 participated in followup. We report treatment durability, Disease Activity Score in 28 joints (DAS28), and other measures during an open-label extension for an additional period up to 72 weeks. Results Mean ± SD duration of open-label followup was 11 ± 6 months. The likelihood of continuing conventional therapy at 1 year was 78% for triple therapy versus 63% for methotrexate-etanercept, with most treatment changes occurring at the start of followup. More patients changed from methotrexate-etanercept to triple therapy than from triple therapy to methotrexate-etanercept (P = 0.005). DAS28 scores and other disease activity measures were not different for the 2 treatments and were stable during followup. Conclusion In RA patients with suboptimal methotrexate response randomized to receive triple therapy or methotrexate-etanercept, the former was found to be significantly more durable. Given cost differences and similar outcomes, the variable durability demonstrated provides additional evidence supporting conventional combinations over biologic agent combinations as the first choice after methotrexate inadequate response.

Patients' Perceptions of Their Relatives' Risk of Developing Rheumatoid Arthritis and of the Potential for Risk Communication, Prediction, and Modulation


Objective To understand the perspectives of patients with rheumatoid arthritis (RA) about the risk of their relatives developing RA in the future, and about communicating with their relatives concerning risk and its modulation. Methods Twenty-one RA patients took part in semistructured interviews. Results Participants reported willingness to communicate with relatives about their risk of developing RA, but described choosing which relatives to communicate with, on the basis of the relatives' perceived receptivity to such risk information. Participants described the potential for risk information to cause negative emotions. Some participants did not consider RA to be hereditable, and few reported smoking as a risk factor. Patients described a lack of public awareness about the causes of RA and the negative impact that RA has on the quality of life. Awareness of this negative impact was identified as an important driver for predictive and preventive strategies. Participants held positive perceptions of predictive testing for RA, though the results of predictive tests were conceptualized as having a high degree of accuracy. Negative views of predictive testing were associated with an appreciation of the probabilistic nature of risk information. Participants felt that their relatives would prefer lifestyle modification over medication as a risk reduction strategy. Conclusion Information about risk factors for RA, and the potential impact of RA on the quality of life, is needed to support family communication about RA risk. Management of expectations is needed in relation to the probabilistic nature of risk information, and appropriate support should be provided for negative psychological outcomes.

Associations Between Five Important Domains of Health and the Patient Acceptable Symptom State in Rheumatoid Arthritis and Psoriatic Arthritis: A Cross-Sectional Study of 977 Patients


Objective To explore the link between a patient acceptable symptom state (PASS) and patient-perceived impact in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Methods This was a cross-sectional study of unselected patients with definite RA or PsA. Pain, functional capacity, fatigue, coping, and sleep disturbance were assessed using a numeric rating scale (0–10) and compared between patients in PASS or not (Cohen's effect sizes). The domains of health associated with PASS status were assessed by multivariate forward logistic regression, and PASS thresholds were determined using the 75th percentile method and receiver operating characteristic analyses. Results Among 977 patients (531 with RA, 446 with PsA), the mean ± SD age was 53.4 ± 13.2 years, mean ± SD disease duration was 11.2 ± 10.0 years, and 637 (65.8%) were women. In all, 595 patients (60.9%) were in PASS; they had lower symptom levels, and all domains of health except sleep disturbance discriminated clearly between patients in PASS or not (effect sizes 0.73–1.45 in RA and 0.82–1.52 in PsA). In multivariate analysis, less pain and better coping were predictive of being in PASS. Odds ratios were: RA pain 0.80 (95% confidence interval [95% CI] 0.67–0.96), PsA pain 0.63 (95% CI 0.52–0.75), RA coping 0.84 (95% CI 0.74–0.96), and PsA coping 0.83 (95% CI 0.71–0.97). The cutoffs of symptom intensity (range 0–10), corresponding to PASS for the 5 domains of health and the 2 diseases were similar, i.e., approximately 4–5. Conclusion In RA and PsA, PASS was associated with the 5 domains of health analyzed, and in particular with less pain and better coping.

Determinants of Patient-Physician Discordance in Global Assessment in Psoriatic Arthritis: A Multicenter European Study


Objective Patient-physician discordance in global assessment of disease activity concerns one-third of patients, but what does it reflect? We aimed to assess patient-physician discordance in psoriatic arthritis (PsA) and patient-reported domains of health (physical and psychological) associated with discordance. Methods We analyzed the PsAID (Psoriatic Arthritis Impact of Disease), a cross-sectional, multicenter European study of patients with PsA according to expert opinion. Patient global assessment (PGA) and physician global assessment (PhGA) were rated on a 0–10 numeric rating scale. Discordance was defined as the difference (PGA−PhGA) and as the absolute difference |PGA−PhGA| ≥3 points. Determinants of PGA−PhGA were assessed by a stepwise multivariate linear regression among 12 physical and psychological aspects of impact: pain, skin problems, fatigue, ability to work/leisure, functional incapacity, feeling of discomfort, sleep disturbance, anxiety/fear, coping, embarrassment/shame, social participation, and depressive affects. Results In 460 patients (mean ± SD age 50.6 ± 12.9 years, 52.2% female, mean ± SD disease duration 9.5 ± 9.5 years, mean ± SD Disease Activity Index for Psoriatic Arthritis score 30.8 ± 32.4, and 40.4% undergoing treatment with biologic agents), the mean ± SD PGA was higher than the mean PhGA, with a mean absolute difference of 1.9 ± 1.8 points. Discordance defined by |PGA−PhGA| ≥3 of 10 concerned 134 patients (29.1%), and 115 patients (85.8% of the patients with discordance) had PGA>PhGA. Higher fatigue (β = 0.14), lower self-perceived coping (β = 0.23), and impaired social participation (β = 0.16) were independently associated with a higher difference (PGA−PhGA). Conclusion Discordance concerned 29.1% of these patient/physician dyads, mainly by PGA>PhGA. Factors associated with discordance were psychological rather than physical domains of health. Discordance was more frequent in patients in remission, indicating more work is needed on the patient perspective regarding disease activity.

Yearly Trends in Elective Shoulder Arthroplasty, 2005–2013


Objective To evaluate the change in incidence rate of shoulder arthroplasty, the utilization of shoulder arthroplasty for specific indications, and the surgeon volume trends associated with these procedures between 2005 and 2013. Methods A population-based cohort study was conducted using the more than 7 million members of an integrated health care system in California. Cases of shoulder arthroplasties performed between 2005 and 2013 were identified using a shoulder arthroplasty registry. Annual shoulder arthroplasty incidence rates per 100,000 patients were determined, and adjusted yearly changes in rates were estimated using incidence rate ratios (IRRs). Changes in surgeon volumes by year and number of surgeons performing different procedures were also compared. Results The incidence of shoulder arthroplasty per 100,000 members increased from 6.1 (95% confidence interval [95% CI] 5.5–6.7) in 2005 to 13.4 (95% CI 12.5–14.2) in 2013. In patients with osteoarthritis, there was increasing utilization of total shoulder arthroplasty (IRR 1.12 [95% CI 1.11–1.14]) and decreasing utilization of hemiarthroplasty (IRR 0.91 [95% CI 0.89–0.94]). For patients with rotator cuff tear arthropathy, there was an increase in utilization of reverse total shoulder arthroplasty (IRR 1.33 [95% CI 1.29–1.37]) but no change in hemiarthroplasty (IRR 0.99 [95% CI 0.92–1.05]). The average surgeon yearly volume increased for total shoulder arthroplasty (P < 0.001) and for reverse total shoulder arthroplasty (P = 0.020). Conclusion Shoulder arthroplasty is being used with greater frequency in this population. Surgeons are performing a greater yearly volume of total shoulder arthroplasty and reverse total shoulder arthroplasty.

Prevalence of Primary Sjögren's Syndrome in a US Population-Based Cohort


Objective To report the point prevalence of primary Sjögren's syndrome (SS) in the first US population-based study. Methods Cases of all potential primary SS patients living in Olmsted County, Minnesota, on January 1, 2015, were retrieved using Rochester Epidemiology Project resources, and ascertained by manual medical records review. Primary SS cases were defined according to physician diagnosis. The use of diagnostic tests was assessed and the performance of classification criteria was evaluated. The number of prevalent cases in 2015 was also projected based on 1976–2005 incidence data from the same source population. Results A total of 106 patients with primary SS were included in the study: 86% were female, with a mean ± SD age of 64.6 ± 15.2 years, and a mean ± SD disease duration of 10.5 ± 8.4 years. A majority were anti-SSA positive (75%) and/or anti-SSB positive (58%), but only 22% met American–European Consensus Group or American College of Rheumatology criteria, because the other tests required for disease classification (ocular dryness objective assessment, salivary gland functional or morphologic tests, or salivary gland biopsy) were rarely performed in clinical practice. According to the physician diagnosis, the age- and sex-adjusted prevalence of primary SS was 10.3 per 10,000 inhabitants, but according to classification criteria, this prevalence was only 2.2 per 10,000. The analysis based on previous incidence data projected a similar 2015 prevalence rate of 11.0 per 10,000. Conclusion The prevalence of primary SS in this geographically well-defined population was estimated to be between 2 and 10 per 10,000 inhabitants. Physicians rarely used tests included in the classification criteria to diagnose the disease in this community setting.

Meta-Regression of a Dose-Response Relationship of Methotrexate in Mono- and Combination Therapy in Disease-Modifying Antirheumatic Drug–Naive Early Rheumatoid Arthritis Patients


Objective To investigate a possible short-term dose-response relationship of initial treatment with methotrexate (MTX) in monotherapy and combination therapy in recent-onset rheumatoid arthritis (RA) patients. Methods A systematic literature search was performed on trials and cohorts, including early, disease-modifying antirheumatic drug (DMARD)–naive RA patients treated with MTX, with data on clinical results within 6 months from treatment start. Cohen's effect sizes were calculated for the Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) level, and/or Disease Activity Score (DAS)/in 28 joints (DAS28) in 4 treatment groups: MTX monotherapy, or MTX in combination with synthetic (cs) DMARDs, biologic (b) DMARDs, or glucocorticoids. Random-effects meta-regression analyses were performed for each outcome, with treatment group as the predictor corrected for baseline HAQ or disease activity and assessment point. Results Thirty-one studies including 5,589 patients were included. The meta-regression did not support higher effectiveness of increasing MTX dose in monotherapy. The number of treatment groups using combination therapy with csDMARDs was too small to perform meta-regression analyses. In combination therapy with glucocorticoids, a higher MTX dose was associated with higher (worse) outcome HAQ, but not with DAS/DAS28 or ESR/CRP level. In combination therapy with bDMARDs, a higher MTX dose was associated with higher outcome HAQ and DAS/DAS28, but not with ESR/CRP level. All effect sizes were small. Conclusion In DMARD-naive, early RA patients who start MTX, either as monotherapy or in combination with bDMARDs or glucocorticoids, a higher initial dose of MTX was not associated with better clinical outcomes. This finding suggests that there is little short-term gain from starting with high compared to low MTX doses.

Effects of Long-Term Etanercept Treatment on Clinical Outcomes and Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: 104-Week Results From a Randomized, Placebo-Controlled Study


Objective To evaluate the long-term clinical and imaging efficacy of etanercept in patients with early, active nonradiographic axial spondyloarthritis (SpA). Methods Adult patients who satisfied the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA (but not the modified New York radiographic criteria), with symptom duration >3 months to <5 years, and who were unresponsive to ≥2 nonsteroidal antirheumatic drugs (NSAIDs) received double-blind etanercept 50 mg/week or placebo for 12 weeks, followed by open-label etanercept 50 mg/week to week 104. Clinical, magnetic resonance imaging (MRI; Spondyloarthritis Research Consortium of Canada [SPARCC] scores), and safety outcomes at 104 weeks were analyzed. Results Of 215 randomized patients (etanercept: n = 106; placebo: n = 109), 205 entered the study (etanercept/etanercept: n = 100; placebo/etanercept: n = 105) and 169 completed the open-label period (etanercept/etanercept: n = 83; placebo/etanercept: n = 86). At week 104, 61 of 81 (75%), 49 of 81 (61%), 48 of 80 (60%), and 57 of 81 (70%) patients who received etanercept throughout the trial achieved ASAS20, ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease, and Bath Ankylosing Spondylitis Disease Activity Index criteria for 50% improvement (BASDAI 50) scores, respectively (observed). From baseline to week 104, continued improvements in clinical outcomes (ASDAS–C-reactive protein: −1.5 and −1.7; BASDAI: −3.3 and −3.8 [last observation carried forward]), and SPARCC MRI scores (sacroiliac joint: −6.0 and −3.4; spinal: −2.1 and −0.8 [observed]) were seen in patients receiving etanercept/etanercept and placebo/etanercept. During the study, 8% in the etanercept/etanercept group and 7% in the placebo/etanercept group had serious adverse events; no new safety signals were seen. Conclusion Patients with early, active nonradiographic axial SpA and an inadequate response to at least 2 NSAIDs demonstrated improvement in clinical and imaging outcomes that were sustained through 104 weeks of etanercept treatment.

Physical Activity and Correlates of Physical Activity Participation Over Three Years in Adults With Rheumatoid Arthritis


Objective To characterize physical activity participation (moderate-to-vigorous physical activity [MVPA], ≥150 minutes of moderate physical activity or 75 minutes of vigorous physical activity per week), to examine associations between disease activity and MVPA, and to identify MVPA correlates in adults with rheumatoid arthritis (RA) over 3 years. Methods This study included 573 RA patients (94% white, 83% female, mean age 61 years, mean RA duration 19.5 years) with ≥1 annual registry visit and who completed the physical activity questionnaire. Baseline and annual measures included demographics/medical history, self-efficacy for disease management, quality of life, patient/physician global assessment, physical function, and self-reported physical activity. A logistic repeated-measures model using the generalized estimating equation examined the relationship between disease activity and MVPA. Results Average disease activity (from the 3-variable Disease Activity Score in 28 joints using the C-reactive protein level) was mean ± SD 3.1 ± 1.4, 36% were physically inactive, and 29% met MVPA recommendations. There was a negative borderline association with disease activity (odds ratio [OR] 0.89 [95% confidence interval (95% CI) 0.79–1.00]). Correlates of meeting MVPA recommendations, adjusting for disease activity, were being white (OR 2.95 [95% CI 1.29–6.75]), older age (ages >69 years OR 0.58 [95% CI 0.36–0.92]), poor mental health (OR 0.63 [95% CI 0.41–0.95]), poor physical function (OR 0.59 [95% CI 0.34–1.01]), overweight/obese (body mass index [BMI] >25–30 OR 0.69 [95% CI 0.50–0.95], BMI >30–39.9 OR 0.60 [95% CI 0.41–0.88], and BMI ≤40 OR 0.24 [95% CI 0.08–0.74]), and patient global assessment (≥10–20 OR 0.57 [95% CI 0.39–0.83]). Conclusion A small proportion of patients met MVPA recommendations despite well-controlled disease. Disease activity was negatively associated with physical activity over time. Physical activity correlates were linked to lifestyle, mental health, and patient perceptions of disease, suggesting[...]

Telerheumatology: A Systematic Review


Objective To identify and summarize the published and gray literature on the use of telemedicine for the diagnosis and management of inflammatory and/or autoimmune rheumatic disease. Methods We performed a registered systematic search (CRD42015025382) for studies using MEDLINE (1946 to July 2015), Embase (1974 to July 2015), Web of Science (1900 to July 2015), and Scopus (1946 to July 2015) databases. We included studies that demonstrated the use of telemedicine for diagnosis and/or management of inflammatory/autoimmune rheumatic disease. Following data extraction, we performed a descriptive analysis. Results Our literature search identified 1,468 potentially eligible studies. Of these studies, 20 were ultimately included in this review. Studies varied significantly in publication type, quality of evidence, and the reporting of methods. Most demonstrated a high risk of bias. Rheumatoid arthritis was the most commonly studied rheumatic disease (42% of patients). Studies demonstrated conflicting results regarding the effectiveness of telemedicine (18 found it effective, 1 found it effective but possibly harmful, and 1 found it ineffective). A limited number of studies included some component of a cost analysis (n = 6; 16% of patients); all of these found telemedicine to be cost-effective. Conclusion Studies identified by this systematic review generally found telemedicine to be effective for the diagnosis and management of autoimmune/inflammatory rheumatic disease; however, there is limited evidence to support this conclusion. Further studies are needed to determine the best uses of telemedicine for the diagnosis and management of these conditions.

Primary Care Screening and Comorbidity Management in Rheumatoid Arthritis in Ontario, Canada


Objective Quality measurement for rheumatoid arthritis (RA) patients has largely focused on care provided by rheumatologists. Our aim was to develop and assess quality measures related to the screening and management of comorbidity in RA patients in primary care. Methods We used the primary care Electronic Medical Record Administrative data Linked Database in Ontario, Canada. We harmonized Canadian general population and RA clinical recommendations to develop and assess screening, process, and outcome measures. For each RA patient, 10 non-RA patients were matched by age and sex. Stratified analyses were performed, comparing patients with RA to those without RA, to assess the performance of quality measures. Results We compared 1,405 RA patients to 14,050 matched non-RA patients (72.8% female; mean age 62.5 years). Compared to non-RA patients, RA patients more frequently had influenza (44.9% versus 40.0%) and pneumococcal (40.4% versus 34.1%) vaccinations and bone mineral density testing (67.4% versus 58.1%). Herpes zoster vaccinations were less frequent among RA patients (13.8% versus 19.5%), as was screening for cervical cancer (58.6% versus 64.0%). No significant differences were observed between RA and non-RA patients in screenings for breast (70.7% versus 73.8%) or colorectal (31.7% versus 34.5%) cancers. Only a quarter of RA patients had a comprehensive cardiovascular risk assessment. No definitive differences were detected in the management of patients who had co-occurring cardiovascular disease or diabetes mellitus. Conclusion For both RA and non-RA patients, compliance with Canadian recommendations for preventive medical services and screening for comorbid conditions in primary care was less than optimal. This indicates key targets for improvement.

Issue Information


Identifying Clinical Factors Associated With Low Disease Activity and Remission of Rheumatoid Arthritis During Pregnancy


Objective To identify a combination of clinical factors associated with low disease activity and remission in the third trimester during pregnancy in women with rheumatoid arthritis (RA). Methods This study is embedded in the Pregnancy-Induced Amelioration of Rheumatoid Arthritis study, a prospective cohort study. There were data available on 190 pregnancies from first trimester until delivery. Multivariate regression analyses were performed on the disease activity (Disease Activity Score in 28 joints [DAS28] using the C-reactive protein [CRP] level) in the third trimester. Independent covariates were the DAS28-CRP-3 in first trimester, prednisone and sulfasalazine use in the first trimester, parity, methotrexate use in the past, autoantibody status, the presence of erosions, and RA disease duration. Results In multivariate regression models, the DAS28-CRP-3, use of prednisone in the first trimester, and the presence of autoantibodies were negatively associated with low disease activity (DAS28-CRP-3 <3.2) in the third trimester (P < 0.05), and the DAS28-CRP-3 and presence of autoantibodies were also associated with remission (DAS28-CRP-3 <2.6) (P < 0.001). Subgroup analysis revealed that the associations of prednisone use and presence of autoantibodies were only present in patients with moderate-to-high disease activity (DAS28-CRP-3 ≥3.2) in the first trimester. Conclusion RA patients who have a low DAS28-CRP-3 in the first trimester (irrespective of autoantibody status or prednisone use) are likely to have low disease activity or remission in the third trimester. Also, women with higher disease activity who are not taking prednisone and who express no autoantibodies still have a fair chance of low disease activity in the last trimester.

Magnetic Resonance Imaging–Detected Myocardial Inflammation and Fibrosis in Rheumatoid Arthritis: Associations With Disease Characteristics and N-Terminal Pro–Brain Natriuretic Peptide Levels


Objective Myocardial dysfunction and heart failure (HF) are increased in rheumatoid arthritis (RA), yet there are few studies of the myocardium in RA. Methods RA patients with no known heart disease or risk factors underwent gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Images were assessed for left-ventricular (LV) structural and functional parameters and for myocardial late gadolinium enhancement (LGE; an indicator of myocardial fibrosis) and T2-weighted imaging (an indicator of active inflammation). We modeled the associations between RA characteristics and N-terminal pro–brain natriuretic protein (NT-proBNP) levels with LGE and T2-weighted imaging. We also assessed whether LGE and/or T2-weighted imaging were associated with abnormal LV structure or dysfunction. Results A total of 60 RA patients were studied. LGE was present in 19 (32%) and T2-weighted imaging in 7 (12%), 5 of whom also had LGE. After adjustment for relevant confounders, higher odds of LGE with each swollen joint (odds ratio [OR] 1.87, P = 0.008), each log unit higher C-reactive protein level (OR 3.36, P = 0.047), and each log unit higher NT-proBNP (OR 20.61, P = 0.009) were found. NT-proBNP was also significantly higher (135%) among those with T2-weighted imaging than in those without T2-weighted imaging or LGE. Higher LV mass index and LV mass:end diastolic volume ratio were observed in those with T2-weighted imaging than in those with no myocardial abnormalities and in those with LGE without T2-weighted imaging; however, ejection fraction was not reduced in those with either LGE or T2-weighted imaging. Conclusion These data suggest that cardiac MRI findings indicating myocardial inflammation/fibrosis are correlated with RA disease activity and alterations in myocardial structure known to precede clinical HF.

Performance of the Patient-Reported Outcomes Measurement Information System 29-Item Profile in Rheumatoid Arthritis, Osteoarthritis, Fibromyalgia, and Systemic Lupus Erythematosus


Objective The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to improve measurement of patient-reported outcomes. We examined performance of the 29-item PROMIS Profile (PROMIS-29) in persons with rheumatoid arthritis (RA), osteoarthritis (OA), fibromyalgia (FM), and systemic lupus erythematosus (SLE). Methods Participants in the National Data Bank for Rheumatic Diseases completed the PROMIS-29, which includes 4-item forms for 7 PROMIS domains. Scales were scored and converted to T scores. Distributions of scale scores were examined, convergent and known-groups validity was tested, and differences in scores from online versus paper questionnaires were examined. Results Sample sizes were 4,346 for RA, 727 for OA, 241 for FM, and 240 for SLE. Participants were predominantly female, with a mean disease duration ≥20 years, and were ages ∼60 years. Large ceiling effects occurred for some PROMIS-29 scales. Correlations of PROMIS-29 scores with scales measuring similar constructs ranged from high to moderate for RA, OA, and SLE; correlations for FM were markedly lower for some scales. Consistent patterns of worsening PROMIS-29 scores with increasing disease severity or declining health status were observed. Differences in scores obtained by online versus paper questionnaires ranged from 0.3 to 2.2 points. Conclusion Results provide guarded support for using the PROMIS-29 in these conditions. The PROMIS-29 4-item static forms appear to identify differences among levels of health and to measure constructs similar to those measured by legacy questionnaires. However, large ceiling effects suggest that measurement may be more precise at the “bad” ends of the scales, which may limit responsiveness, and differences by mode of administration appear to exist.

Self-Management Education Participation Among US Adults With Arthritis: Who's Attending?


Objective Self-management education (SME) programs teach people with chronic conditions skills to manage their health conditions. We examined patterns in SME program participation among US adults with arthritis ages ≥18 years. Methods Respondents with arthritis were those who reported ever being diagnosed with arthritis by a doctor or health care provider. We analyzed 2014 National Health Interview Survey data to estimate the percentage (unadjusted and age-standardized) who ever attended an SME program overall and for selected subgroups, representativeness of SME participants relative to all adults with arthritis, and trends in SME course participation. Results In 2014, 1 in 9 US adults with arthritis (11.3% [95% confidence interval (95% CI) 10.4–12.3]; age-standardized 11.4% [95% CI 10.0–12.9]) had ever participated in an SME program. SME participation (age-standardized) was highest among those with ≥8 health care provider visits in the past 12 months (16.0% [95% CI 13.1–19.4]). Since 2002, the number of adults with arthritis who have ever participated in SME has increased by 1.7 million, but the percentage has remained constant. Conclusion Despite its many benefits, SME participation among US adults with arthritis remains persistently low. By recommending that their patients attend SME programs, health care providers can increase the likelihood that their patients experience SME program benefits.

Dietary Fiber Intake in Relation to Knee Pain Trajectory


Objective Dietary fiber may reduce knee pain, in part by lowering body weight and reducing inflammation. In this study, we assessed whether fiber intake was associated with patterns of knee pain development. Methods In a prospective, multicenter cohort of 4,796 men and women ages 45–79 years with or at risk of knee osteoarthritis, participants underwent annual followups for 8 years. Dietary fiber intake was estimated using a validated food frequency questionnaire at baseline. Group-based trajectory modeling was used to identify Western Ontario and McMaster Universities Osteoarthritis Index pain trajectories, which were assessed for associations with dietary fiber intake using polytomous regression models. Results Of the eligible participants (4,470 persons and 8,940 knees, mean ± SD age 61.3 ± 9.1 years, 58% women), 4.9% underwent knee replacement and were censored at the time of surgery. Four distinct knee pain patterns were identified: no pain (34.5%), mild pain (38.1%), moderate pain (21.2%), and severe pain (6.2%). Dietary total fiber was inversely related to membership in the moderate or severe pain groups (P ≤ 0.006 for trend for both). Subjects in the highest versus those in the lowest quartile of total fiber intake had a lower risk of belonging to the moderate pain pattern group (odds ratio [OR] 0.76 [95% confidence interval (95% CI) 0.61–0.93]) and severe pain pattern group (OR 0.56 [95% CI 0.41–0.78]). Similar results were found with grain fiber and these 2 pain pattern groups. Conclusion Our findings suggest that a high intake of dietary total or grain fiber, particularly the recommended daily fiber average intake of 25 gm per day, is associated with a lower risk of developing moderate or severe knee pain over time.

Associations Between Clinical Evidence of Inflammation and Synovitis in Symptomatic Knee Osteoarthritis: A Cross-Sectional Substudy


Objective Painful knee osteoarthritis (KOA) has been associated with joint inflammation. There is, however, little literature correlating signs of localized inflammation with contrast-enhanced (CE) magnetic resonance imaging (MRI) of synovium. This study examined the relationship between clinical and functional markers of localized knee inflammation and CE MRI–based synovial scores. Methods Patients with symptomatic KOA were enrolled into the randomized, double-blind, Vitamin D Evaluation in Osteoarthritis (VIDEO) trial. In this cross-sectional substudy, associations between validated MRI-based semiquantitative synovial scores of the knee and the following markers of inflammation were investigated: self-reported pain and stiffness, effusion, warmth, joint line tenderness, erythrocyte sedimentation rate, radiographic severity, and functional ability tests. Results A total of 107 patients satisfied the inclusion criteria of complete data and were included in the analysis. Significant associations were found between the number of regions affected by synovitis and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, effusion, and joint line tenderness. Each additional region affected by synovitis was associated with an increase in WOMAC pain (1.82 [95% confidence interval (95% CI) 0.05, 3.58], P = 0.04), and the association with extent of medial synovitis was particularly strong (3.21 [95% CI 0.43, 5.99], P = 0.02). Extent of synovitis was positively associated with effusion (odds ratio 1.69 [95% CI 1.37, 2.08], P [...]

Cross-Cultural and Construct Validity of the Animated Activity Questionnaire


Objective The Animated Activity Questionnaire (AAQ) assesses activity limitations in patients with hip/knee osteoarthritis and consists of video animations; the patients choose the animation that best matches their own performance. The AAQ has shown good validity and reliability. This study aims to evaluate cross-cultural and construct validity of the AAQ. Methods Cross-cultural validity was assessed using ordinal logistic regression analysis to evaluate differential item functioning (DIF) across 7 languages. Construct validity was assessed by testing correlations between the AAQ and a patient-reported outcome measure (PROM) and performance-based tests. Results Data from 1,239 patients were available. Compared to the Dutch language (n = 279), none of the 17 items showed DIF in English (n = 202) or French (n = 193), 1 item showed uniform DIF in Spanish (n = 99) and Norwegian (n = 62), and 2 items showed uniform DIF in Danish (n = 201). In all these languages, the occurrence of DIF did not influence the total score, which remained comparable with the original Dutch version. For Italian (n = 203) versus Dutch, however, 6 items showed uniform DIF, and 1 item showed nonuniform DIF, indicating some problems with the cross-cultural validity between these countries. With regard to construct validity, the correlations with PROM (0.74) and performance-based tests (0.36–0.68) were partly as expected (>0.60). Conclusion The AAQ, an innovative tool to measure activity limitations that can be placed on the continuum between PROMs and performance-based tests, showed a good overall cross-cultural validity, and seems to have great potential for international use in research and daily clinical practice in many European countries.

Early High-Intensity Versus Low-Intensity Rehabilitation After Total Knee Arthroplasty: A Randomized Controlled Trial


Objective To examine the safety and efficacy of a high-intensity (HI) progressive rehabilitation protocol beginning 4 days after total knee arthroplasty (TKA) compared to a low-intensity (LI) rehabilitation protocol. Methods A total of 162 participants (mean ± SD ages 63 ± 7 years; 89 women) were randomized to either the HI group or LI group after TKA. Key components of the HI intervention were the use of progressive resistance exercises and a rapid progression to weight-bearing exercises and activities. Both groups were treated in an outpatient setting 2 to 3 times per week for 11 weeks (26 total sessions). Outcomes included the stair climbing test (SCT; primary outcome), timed-up-and-go (TUG) test, 6-minute walk (6MW) test, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 12-item Short Form health survey (SF-12), knee range of motion (ROM), quadriceps and hamstring strength, and quadriceps activation. Outcomes were assessed preoperatively and at 1, 2, 3 (primary end point), 6, and 12 months postoperatively. Results There were no significant differences between groups at 3 or 12 months in SCT, TUG, 6MW, WOMAC scores, knee ROM, quadriceps and hamstrings strength, quadriceps activation, or adverse event rates. By 12 months, outcomes on the 6MW, TUG, WOMAC, SF-12, quadriceps and hamstring strength, and quadriceps activation had improved beyond baseline performance in both groups. Conclusion Both the HI and LI interventions were effective in improving strength and function after TKA. HI progressive rehabilitation is safe for individuals after TKA. However, its effectiveness may be limited by arthrogenic muscular inhibition in the early postoperative period.

Disease Outcomes and Care Fragmentation Among Patients With Systemic Lupus Erythematosus


Objective To examine the impact of care fragmentation across multiple health care institutions on disease outcomes in patients with systemic lupus erythematosus (SLE). Methods Using the Chicago HealthLNK Data Repository, an assembly of electronic health records from 6 institutions, we identified patients with SLE, using International Classification of Diseases, Ninth Revision (ICD-9) codes, whose care was delivered at more than 1 organization. We examined whether patients had severe infections or comorbidities (ICD-9 code defined) that indicated SLE-induced damage. T-tests and chi-square tests were used to examine differences between fragmentation groups. Logistic regression was used to assess factors contributing to the occurrence of disease outcomes. Results We identified 4,276 patients with SLE. A total of 856 (20%) received care from more than 1 health care institution. African American patients and patients with public insurance were more likely to experience care fragmentation compared to white and private insurance patients (odds ratio [OR] 1.66, 95% confidence interval [95% CI] 1.44–1.97 and OR 1.63, 95% CI 1.42–1.95). We identified increased risk of infections (OR 1.57, 95% CI 1.30–1.88), cardiovascular disease (OR 1.51, 95% CI 1.23–1.86), end-stage renal disease (OR 1.34, 95% CI 1.05–1.70), nephritis (OR 1.28, 95% CI 1.07–1.54), and stroke (OR 1.28, 95% CI 1.01–1.62) among patients with fragmented care, adjusted for age, sex, race, insurance status, length of followup time, and total visit count. Conclusion In this cross-site cohort of SLE patients, care fragmentation is associated with increased risk of severe infection and comorbidities. These results suggest that improved health info[...]

Variation in the Treatment of Children Hospitalized With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis in the US


Objective There are few reports on the treatment of antineutrophil cytoplasmic antibody–associated vasculitis (AAV) in children. This study characterizes the use of cyclophosphamide, rituximab, and plasma exchange in children hospitalized with AAV in the US. Methods We conducted a retrospective cohort study of children hospitalized with AAV from 2004–2014 utilizing an administrative and billing database from 47 tertiary care pediatric hospitals. All patients had an International Classification of Diseases, Ninth Revision, Clinical Modification discharge code of 446.4 and ≥1 charge for glucocorticoids. Treatment receipt was determined using billing data. Mixed-effects logistic regression was used to evaluate factors associated with the likelihood of receipt of each of the 3 treatments. Results During the 11-year study period there were 1,290 admissions for 393 children. The median age at index admission was 14.6 years, and 61% were female. Dialysis or mechanical ventilation was required by 16% and 17% of the children, respectively. The median length of stay was 9 days. The percentages of children receiving cyclophosphamide, rituximab, or both were 57%, 21%, and 10%, respectively, and 22% received plasma exchange. Mechanical ventilation was associated with the receipt of cyclophosphamide and plasma exchange, but not rituximab. There was an increasing trend in the use of rituximab over time during the study period (P [...]

Takayasu Arteritis and Pregnancy: A Population-Based Study on Outcomes and Mother/Child-Related Concerns


Objective To assess pregnancy outcomes in an unselected Takayasu arteritis (TAK) cohort, and identify pregnancy-related concerns. Methods Consenting female patients with TAK were predominantly recruited from a population-based southeast Norway TAK cohort. Additional cases (n = 8) were recruited at Oslo University Hospital. Data on the number of pregnancies, births, and pregnancy outcomes before and after disease onset were retrieved from medical charts, patient questionnaires, and the Medical Birth Registry of Norway (MBRN). Data on pregnancy-related concerns were gathered from patient questionnaires. Results Altogether, the 58 women in the TAK study cohort had been through 110 pregnancies, 73 (in 33 patients) before disease onset and 37 (in 23 patients) after onset. The frequencies of miscarriages, induced abortions, and maternal complications did not differ between pregnancies occurring before and after TAK onset. Pregnancy-related hypertension was seen in 4.2% of the patients, compared to 1.5% (P = 0.37) in the reference cohort from MBRN, and preeclampsia/eclampsia in 4.5% compared to 3% (P = 0.2). The mean gestational age at delivery in pregnancies after TAK onset was 37.5 weeks, compared to 39.5 weeks in the MBRN references (P [...]

Predictors of Hospitalization, Length of Stay, and Cost of Care Among Adults With Dermatomyositis in the United States


Objective To determine the prevalence and risk factors for hospitalization with dermatomyositis and assess inpatient burden of dermatomyositis. Methods Data on 72,651,487 hospitalizations from the 2002–2012 Nationwide Inpatient Sample, a 20% stratified sample of all acute-care hospitalizations in the US, were analyzed. International Classification of Diseases, Ninth Revision, Clinical Modification coding was used to identify hospitalizations with a diagnosis of dermatomyositis. Results There were 9,687 and 43,188 weighted admissions with a primary or secondary diagnosis of dermatomyositis, respectively. In multivariable logistic regression models with stepwise selection, female sex (logistic regression: adjusted odds ratio 2.05 [95% confidence interval (95% CI) 1.80, 2.34]), nonwhite race (African American: 1.68 [1.57, 1.79]; Hispanic: 2.38 [2.22, 2.55]; Asian: 1.54 [1.32, 1.81]; and multiracial/other: 1.65 [1.45, 1.88]), and multiple chronic conditions (2–5: 2.39 [2.20, 2.60] and ≥6: 2.80 [2.56, 3.07]) were all associated with higher rates of hospitalization for dermatomyositis. The weighted total length of stay (LOS) and inflation-adjusted cost of care for patients with a primary inpatient diagnosis of dermatomyositis was 80,686 days and $168,076,970, with geometric means of 5.38 (95% CI 5.08, 5.71) and $11,682 (95% CI $11,013, $12,392), respectively. LOS and costs of hospitalization were significantly higher in patients with dermatomyositis compared to those without. Notably, race/ethnicity was associated with increased LOS (log-linear regression: adjusted β [95% CI] for African American: 0.14 [0.04, 0.25] and Asian: 0.38[...]

Calcium Pyrophosphate Deposition Disease and Associated Medical Comorbidities: A National Cross-Sectional Study of US Veterans


Objective Calcium pyrophosphate deposition disease (CPDD) is a common cause of acute and chronic arthritis, yet there are few large epidemiologic studies of CPDD. We sought to characterize CPDD in the national Veterans Affairs (VA) population. Methods Using data from the Department of VA Corporate Data Warehouse, patients with International Classification of Diseases, Ninth Revision, codes for CPDD seen at any VA medical center from 2010 through 2014 were matched by age and sex with control patients without CPDD. We used multivariate analysis to compare the prevalence and odds ratios (ORs) of various comorbidities, substance use, medication exposures, and arthroplasties among patients with and without CPDD. Results We identified 25,157 patients with CPDD, yielding a point prevalence of 5.2 per 1,000. The mean ± SD age was 68.1 ± 12.3 years, and 95% were male. The strongest positive associations with CPDD were hyperparathyroidism (OR 3.35 [95% confidence interval (95% CI) 2.96–3.79]), gout (OR 2.82 [95% CI 2.69–2.95]), osteoarthritis (OR 2.26 [95% CI 2.15–2.37]), rheumatoid arthritis (OR 1.88 [95% CI 1.74–2.03]), and hemochromatosis (OR 1.87 [95% CI 1.57–2.24]). Positive associations were also seen with higher odds for osteoporosis (OR 1.26 [95% CI 1.16–1.36]), hypomagnesemia (OR 1.23 [95% CI 1.16–1.30]), chronic kidney disease (OR 1.12 [95% CI 1.07–1.18]), and calcium supplementation (OR 1.15 [95% CI 1.06–1.24). Negative associations were seen with proton-pump inhibitors (OR 0.58 [95% CI 0.55–0.60]) and loop diuretics (OR 0.80 [95% CI 0.76–0.84]). Conclusion Using a large[...]

Disease Severity in Never Smokers, Ex-Smokers, and Current Smokers With Axial Spondyloarthritis: Results From the Scotland Registry for Ankylosing Spondylitis


Objective To examine the relationship between smoking, smoking cessation, and disease characteristics and quality of life (QoL) in spondyloarthritis. Methods The Scotland Registry for Ankylosing Spondylitis collects data from clinically diagnosed patients with spondyloarthritis. Clinical data, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) scores, were obtained from medical records. Mailed questionnaires contained information on smoking status and QoL (Ankylosing Spondylitis QoL questionnaire [ASQoL]). Linear and logistic regression were used to quantify the effect of smoking, and smoking cessation, on various disease-specific and QoL outcomes, with adjustments for age, sex, deprivation, education level, and alcohol use. Results are presented as regression coefficients (β) or odds ratios (ORs) with 95% confidence intervals (95% CIs). Results Data were obtained from 946 participants (73.5% male, mean age 52 years). Current smoking was reported by 22%, and 38% were ex-smokers. Ever smokers had poorer BASDAI (β = 0.5 [95% CI 0.2, 0.9]) and BASFI scores (β = 0.8 [95% CI 0.4, 1.2]), and reported worse QoL (ASQoL β = 1.5 [95% CI 0.7, 2.3]). Compared to current smokers, ex-smokers reported less disease activity (BASDAI β = −0.5 [95% CI −1.0, −0.04]) and significantly better QoL (ASQoL β = −1.2 [95% CI −2.3, −0.2]). They also were more likely to have a history of uveitis (OR 2.4 [95% CI 1.5, 3.8]). Conclusion Smokers with spondyloarthritis experience worse disease [...]

Identifying Axial Spondyloarthritis in Electronic Medical Records of US Veterans


Objective Large database research in axial spondyloarthritis (SpA) is limited by a lack of methods for identifying most types of axial SpA. Our objective was to develop methods for identifying axial SpA concepts in the free text of documents from electronic medical records. Methods Veterans with documents in the national Veterans Health Administration Corporate Data Warehouse between January 1, 2005 and June 30, 2015 were included. Methods were developed for exploring, selecting, and extracting meaningful terms that were likely to represent axial SpA concepts. With annotation, clinical experts reviewed sections of text containing the meaningful terms (snippets) and classified the snippets according to whether or not they represented the intended axial SpA concept. With natural language processing (NLP) tools, computers were trained to replicate the clinical experts' snippet classifications. Results Three axial SpA concepts were selected by clinical experts, including sacroiliitis, terms including the prefix spond*, and HLA–B27 positivity (HLA–B27+). With supervised machine learning on annotated snippets, NLP models were developed with accuracies of 91.1% for sacroiliitis, 93.5% for spond*, and 97.2% for HLA–B27+. With independent validation, the accuracies were 92.0% for sacroiliitis, 91.0% for spond*, and 99.0% for HLA–B27+. Conclusion We developed feasible and accurate methods for identifying axial SpA concepts in the free text of clinical notes. Additional research is required to determine combinations of concepts that will accurately ide[...]

Hallux Valgus, By Nature or Nurture? A Twin Study


Objective To evaluate the contributions of shared but unmeasured genetic and environmental factors to hallux valgus (HV). Methods Between 2011 and 2012, 74 monozygotic (MZ) and 56 dizygotic (DZ) female twin pairs self-reported HV and putative risk factors, including footwear use across their lifespan. Estimates of casewise concordance (PC), correlation (ρ), and odds ratios (ORs) were calculated, adjusting for age and other risk factors, and compared between MZ and DZ pairs using logistic regression, generalized estimating equations, and a maximum likelihood-based method, respectively. Results A total of 70 participants (27%) reported HV, with 12 MZ and 7 DZ pairs being concordant. After adjusting for age, twins were correlated (ρ = 0.27 [95% confidence interval (95% CI) 0.08, 0.46]) and concordant (PC = 0.45 [95% CI 0.29, 0.61]; mean age 58 years), with no difference between MZ and DZ pairs (P = 0.7). HV was associated with regularly wearing footwear with a constrictive toe-box during the fourth decade (adjusted OR 2.73 [95% CI 1.12, 6.67]). This risk factor was correlated in MZ (ρ = 0.38 [95% CI 0.15, 0.60]) but not DZ (ρ = −0.20 [95% CI −0.43, 0.03]) pairs. These correlations were significantly different (P = 0.002). Conclusion Twins are correlated for HV, but we found no evidence that correlation was due to shared genetic factors. We identified an environmental risk factor, footwear with a constrictive toe-box, that is not shared to the same extent by MZ and DZ pairs, contrary to the assu[...]

Dietary and Nondietary Triggers of Oral Ulcer Recurrences in Behçet's Disease


Objective The nature and impact of food and other external triggers in recurrences of Behçet's disease (BD)-related oral ulcers (OUs) remain unknown. This survey investigated dietary and nondietary triggers of BD-related OU recurrences. Methods Patients with BD who were followed in 7 French hospital departments completed a self-administered patient questionnaire. General and specific dietary triggering factors were sought in open questions. The questionnaire also included closed questions, notably to evaluate the effect of 6 general triggering situations and 24 selected foods. The results were expressed as number (percentage) of positive responses. Results Among the 101 questionnaires distributed, 81 were usable. Among the 81 patients, 96% fulfilled the International Criteria for Behçet's Disease classification criteria, and 53% qualified their OU recurrences during the previous 12 months as very discomforting or discomforting. For the 6 general situations suggested, 50 patients (62%) declared ≥1 as a “sure” trigger of OU recurrences. In both open and closed questions, the most frequent triggers were fatigue/stress (37–47% of patients) and food (32–35%). Among the 24 suggested foods, nuts (48%), pineapple (42%), peanuts (32%), Emmental cheese (30%), almonds (23%), lemons (22%), and other cheeses (21%) were the most frequently reported. The corresponding open question gave consistent findings but with lower frequencies. Conclusion Most patients can identify triggers of recurring BD-rel[...]

Illness Perceptions and Mortality in Patients With Gout: A Prospective Observational Study


Objective To examine whether illness perceptions independently predict mortality in early-onset gout. Methods Between December 2006 and January 2014, a total of 295 participants with early-onset gout ([...]

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