Subscribe: Arthritis Care & Research
Added By: Feedage Forager Feedage Grade B rated
Language: English
article protected  article  disease  pain  patient  patients  protected rights  protected  reserved  rights reserved  study  treatment 
Rate this Feed
Rate this feedRate this feedRate this feedRate this feedRate this feed
Rate this feed 1 starRate this feed 2 starRate this feed 3 starRate this feed 4 starRate this feed 5 star

Comments (0)

Feed Details and Statistics Feed Statistics
Preview: Arthritis Care & Research

Arthritis Care & Research

Wiley Online Library : Arthritis Care & Research

Published: 2017-11-01T00:00:00-05:00


Education mitigates the effect of poverty on total knee arthroplasty outcomes


Objective TKA outcomes are worse for patients from poor neighborhoods, but whether education mitigates the effect of poverty is not known. We assessed the interaction between education and poverty on 2-year WOMAC pain and function. Methods Patient level variables from an institutional registry were linked to US Census Bureau data (census tract (CT) level). Statistical models including patient and CT level variables were constructed within multilevel frameworks. Linear mixed effect models with separate random intercepts for each CT were used to assess the interaction between education and poverty at the individual and community level on WOMAC scores. Results Of 3970 TKA patients, 2438 (61%) had some college or more. Having no college was associated with worse pain and function at baseline and 2 years (p = 0.0001). Living in a poor neighborhood (>20% below poverty) was associated with worse 2-year pain (p = 0.02) and function (p = 0.006). There was a strong interaction between individual education and community poverty with WOMAC scores at two years. Patients without college living in poor communities had pain scores that were ~10 points worse than those with some college (83.4% vs. 75.7%, p < 0.0001); in wealthy communities, college was associated with 1 point difference in pain. Function was similar. Conclusion In poor communities, those without college attain 2-year WOMAC scores that are 10 points worse than those with some college; education has no impact on TKA outcomes in wealthy communities. How education protects those in impoverished communities warrants further study. This article is protected by copyright. All rights reserved.

A young child with fever, alopecia, and skin nodules: a clinicopathological conference


The illness started as a continuous high-grade fever noted up to 103°F.. Subsequently, he also developed red painful skin nodules that initially appeared over shins and later progressed to involve thighs, trunks, upper extremities, and face. The nodules also appeared over scalp and there was a was a progressive loss of scalp hair. This article is protected by copyright. All rights reserved.

A multi-national qualitative research study exploring the patient experience of Raynaud's phenomenon in systemic sclerosis


Objectives Raynaud's phenomenon (RP) is the commonest manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self-report. A thorough understanding of the patient experience of SSc-RP is essential to ensuring patient-reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc-RP. Methods Focus groups (FGs) of SSc patients were conducted across 3 scleroderma centers in the US and UK, using a topic guide and a priori purposive sampling framework devised by qualitative researchers, SSc patients and SSc experts. FGs were audio recorded, transcribed, anonymised and analysed using inductive thematic analysis. FGs were conducted until thematic saturation was achieved. Results Forty SSc patients participated in 6 focus groups conducted in Bath (UK), New Orleans (US) and Pittsburgh (US). Seven major themes were identified that encapsulate the patient experience of SSc-RP: physical symptoms, emotional impact, triggers & exacerbating factors, constant vigilance & self-management, impact on daily life, uncertainty and adaptation. The inter-relationship of the 7 constituent themes can be arranged within a conceptual map of SSc-RP. Conclusion We have explored the patient experience of SSc-RP in a diverse and representative SSc cohort and identified a complex interplay of experiences that result in significant impact. Work to develop a novel PRO instrument for assessing the severity and impact of SSc-RP, comprising domains/items grounded in the patient experiences of SSc-RP identified in this study is underway. This article is protected by copyright. All rights reserved.

Treating Early Undifferentiated Arthritis: A Systematic Review and Meta-Analysis of Direct and Indirect Trial Evidence


Objective We undertook a systematic review and meta-analysis of direct and indirect trial evidence to evaluate the efficacy of treatments for patients with undifferentiated arthritis (UA). Methods We searched four electronic databases from inception to January 2016, clinicaltrials. gov, and bibliographies of relevant articles. Two reviewers independently screened and evaluated the studies. The primary outcome was development of rheumatoid arthritis (RA). Results Nine studies were included. Interventions included methotrexate, abatacept, infliximab, intra-articular or intramuscular glucocorticoids, and radiation synovectomy. Treating patients resulted in lower rates of RA at 12 months compared to placebo or no treatment (odds ratio (OR) 0.49; 95% confidence interval (CI) 0.26-0.90). From direct meta-analysis, patients treated with methotrexate were less likely to develop RA at 12 months compared to patients treated without methotrexate (OR 0.13, 95% CI 0.03-0.48). This difference was no longer significant at 30 or 60 months. From indirect comparisons, most interventions showed decreased risk of developing RA compared to placebo at 12 months, reaching statistical significance for methotrexate (OR 0.16, 95% CI 0.08-0.33), and intramuscular methylprednisolone (OR 0.72, 95% CI 0.53-0.99). Limitations Most individual interventions included a limited number of studies. Conclusions Treating patients with UA resulted in a statistically significant delay in the development of RA, with the largest effect observed for methotrexate. These findings suggest that there is a window of opportunity to treat patients with UA early, to delay subsequent progression to RA. This article is protected by copyright. All rights reserved.

Peer-to-peer mentoring for African American women with lupus: A feasibility pilot


Objective To examine the feasibility and potential benefits of peer mentoring to improve the disease self-management and quality of life of individuals with systemic lupus erythematosus (SLE). Methods Peer mentors were trained and paired with up to three mentees to receive self-management education and support by telephone over 12 weeks. This study took place at an academic teaching hospital in Charleston, South Carolina. Seven quads consisting of one peer mentor and three mentees were matched based on factors such as age, area of residence, marital and work status. Mentee outcomes of self-management, health-related quality of life, and disease activity were measured using validated tools at baseline, mid-intervention, and post-intervention. Descriptive statistics and effect sizes were calculated to determine clinically important (>0.3) changes from baseline. Results Mentees showed trends toward lower disease activity (p=0.004) and improved health-related quality of life, in the form of decreased anxiety (p=0.018) and decreased depression (p=0.057). Other improvements in health-related quality of life were observed with effect sizes exceeding 0.3, but did not reach statistical significance. In addition, both mentees and mentors gave very high scores for perceived treatment credibility and service delivery. Conclusion The intervention was well received. Training, peer mentoring program, and outcome measures were demonstrated to be feasible with modifications. This provides preliminary support for the efficacy, acceptability, and perceived credibility of a peer mentoring approach to improve disease self-management and health-related quality of life in African American women with SLE. Peer mentoring may augment current rheumatological care. This article is protected by copyright. All rights reserved.

The perspectives of medical specialists from different disciplines on the management of systemic lupus erythematosus: an interview study


Objectives Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can affect multiple organ systems, with specialists from many disciplines often involved, which may lead to inconsistent care. We aimed to describe the attitudes and perspectives of specialists from different medical disciplines on the management of people with SLE. Methods Face-to-face, semi-structured interviews were conducted with rheumatologists (n=16), nephrologists (n=16), and immunologists (n=11) providing care to adults with SLE from 19 centers across Australia in 2015. All interviews were transcribed and analyzed thematically. Results Five themes were identified: uncertainties in judgments (hampered by unknown and unclear etiology, inapplicable evidence, comprehending information dispersion); reflexive responses (anchoring to specialty training, anticipating outcomes, avoiding disaster, empathy for the vulnerable); overarching duty to patients (achieving patient priorities, maximizing adherence, controlling the disease, providing legitimate information, having adequate and relevant expertise); safeguarding professional opportunities (diversifying clinical skills, protecting colleagues’ interests); and optimizing access to treatment (capitalizing on multidisciplinary care, acquiring breakthrough therapies). Conclusions Specialists strive to deliver evidence-informed patient-centered care, but recognize they are anchored by their training. To overcome uncertainties in clinical management due to lack of high-quality evidence and specialty silo structures, specialists translated evidence from other disease settings and collaborated with other specialists in routine care. Developing robust evidence, tools to support evidence informed decisions, and multidisciplinary shared-care pathways may improve the management of people with this complex disease. This article is protected by copyright. All rights reserved.

A loss of sensation


The patient was in her usual state of good health until one week prior to presentation when she developed low back pain and numbness and tingling around her abdomen and lower back. Over the next several hours the numbness spread distally to involve her legs and feet, and it became difficult to walk. The following day she developed constipation and urinary retention. This article is protected by copyright. All rights reserved.

Profiling Response to TNF-Inhibitor Treatment in Axial Spondyloarthritis


Objectives Lack of response to TNF inhibitory (TNFi) agents is not uncommon, encountered during the treatment of axial spondyloarthritis (AxSpA) patients and can be classified as primary (PLR) or secondary (SLR) lack of response. The primary aim of this study was to evaluate factors associated with TNFi failure types and their characteristics in AxSpA. Methods Adult AxSpA patients who were TNFi naive at the time of baseline evaluation and started on their first biologics for active axial disease were identified. Based on the clinical response to the first TNFi, patients were then stratified into the three groups: PLR, SLR, and responders. Clinical, demographic and laboratory data were collected and analyzed. Results There were a total of 249 (70.7% male [M], 37.3±12.4 years of age) axial SpA patients in the study, which included PLR (n=62), SLR (n=93) and responders (n=94). PLR patients tended to be older, with a lower HLA-B27 rate, a higher percentage of nr-AxSpA patients and a higher baseline BASDAI score compared to SLR or responders. In multiple regression analysis, increasing age, negative HLA-B27, higher baseline BASDAI, and treatment with the soluble TNF receptor protein were the independent predictors of PLR. Conclusions Primary lack of response accounted nearly 40% of the TNFi failures in AxSpA patients. Older age, negative HLA-B27, higher baseline disease activity and treatment with sTNFR were the independent predictors of the primary non-response to TNFi. This article is protected by copyright. All rights reserved.

Demographic and Clinical Factors Associated with Non-Surgical Osteoarthritis Treatment Use Among Patients in Outpatient Clinics


Objective To identify patient demographic and clinical characteristics associated with osteoarthritis (OA) treatment use. Methods This was a secondary data analysis of three clinical trials among patients with hip or knee OA conducted in 1) Duke Primary Care practices, 2) the Durham Veterans Affairs Health Care System (DVAHCS), and 3) the University of North Carolina-Chapel Hill (UNC). At baseline, participants reported socio-demographic characteristics, OA-related pain and function, and OA treatment use including oral analgesia, topical creams, joint injections and physical therapy. Separate, multivariable logistic models (adjusted for clustering of clinics and providers for Duke and VA cohorts) were used to estimate odds ratios and 95% confidence intervals (OR, 95% CI) for the associations between participant characteristics and each type of OA treatment. Results Oral analgesic use was reported by 70-82% of participants across the three cohorts. Physical therapy, knee injections, and topical creams were used by 39%-52%, 55-60%, and 25-39% of participants, respectively. In multivariable models, worse pain, stiffness, and function, per 5-unit increase, were associated with greater odds of using any oral analgesic for the Duke (OR=1.18 (1.08, 1.28)) and UNC (OR=1.14 (1.05, 1.24)) cohorts but not for the VA cohort (OR=1.04 (0.95, 1.14)). For all three cohorts, Non-Whites had higher odds of use of topical creams compared to Whites. Conclusion Results suggest potential under-utilization of therapies other than oral analgesia. Patient characteristics may affect OA treatment use, and understanding the relationship between these factors and OA treatment preferences may improve adherence to OA treatment guidelines. This article is protected by copyright. All rights reserved.

Arthritis after cancer immunotherapy: symptom duration and treatment response


Objective Musculoskeletal manifestations of immune related adverse events (irAEs) after checkpoint inhibitor immunotherapy for cancer remain incompletely characterized and poorly understood. A recently published case series suggested that immunotherapy-induced arthritis is an aggressive process requiring high dose corticosteroids. Methods This was a retrospective chart review of all patients with musculoskeletal irAEs first seen by one of the authors between 2014 and 2016. All patients had been treated for a malignancy with immune checkpoint inhibitors targeting PD-1 (nivolumab, pembrolizumab), PD-L1 (durvalumab) and/or CTLA-4 (ipilimumab, tremelimumab) at Memorial Sloan Kettering Cancer Center. Results We identified 10 patients with a mean (± standard deviation) age 63.2 (± 9.7) years. Seven were treated with a combination of checkpoint inhibitors and three with nivolumab monotherapy. Four developed inflammatory polyarthritis, four oligoarthritis and two tenosynovitis. Six were ANA positive and two had anti-CCP antibodies. Mean time from the first dose of immunotherapy until joint involvement was 6.3 (± 4.3) months. All 10 patients were treated with systemic corticosteroids, but 6/10 required ≤ 20 mg per day of prednisone. Five patients received steroid-sparing agents. Mean time until resolution of joint symptoms after the last dose of immunotherapy was 9.2 (± 6.1) months. Conclusion Musculoskeletal irAEs can manifest as an RA-like polyarthritis, oligoarthritis, tenosynovitis, or PMR. Musculoskeletal symptoms can last more than a year, but they can generally be managed with low to moderate doses of corticosteroids. This article is protected by copyright. All rights reserved.

Early Rheumatoid Arthritis Presentation, Treatment and Outcomes in Aboriginal Patients in Canada: A Canadian Early Arthritis Cohort Study Analysis


Objective Health inequities exist in chronic diseases for Aboriginal people. This study compared early rheumatoid arthritis (ERA) presentation, treatment and outcomes between Aboriginal and Caucasian patients in a large Canadian cohort study. Methods Longitudinal data from the Canadian early ArThritis CoHort (CATCH), a prospective multicenter ERA study, were analyzed for participants who self-identified as Aboriginal or Caucasian ethnicity. Disease characteristics at presentation, prognostic factors, frequency of remission and disease-modifying therapy strategies were contrasted between population groups. Linear mixed-models were used to estimate rates of change for disease activity measures up to five years. Results At baseline, 2173 participants (Aboriginal n=100, Caucasian n=2073) had similar mean (SD) symptom duration (179 (91) days), DAS28 (4.87 (1.48)) and HAQ (0.88 (0.68)) scores. Factors associated with poor prognosis were more frequently present in Aboriginal participants, but disease-modifying therapy selection and frequency of therapy escalation was similar between groups. DAS28 remission was achieved less frequently in Aboriginal than Caucasian participants (adjusted OR 0.39, 95%CI 0.25 to 0.62). Results were primarily driven by slower improvement in swollen joint counts and non-significant improvement in patient global scores in Aboriginal participants. Pain levels remained higher in Aboriginal patients. Conclusions Aboriginal ERA patients experienced worse disease outcomes. This may reflect unmeasured biological differences and/or disparities in prognostic factors informed by inequities in determinants of health. The appropriateness of current treatment strategies applied in different contexts should be considered. This article is protected by copyright. All rights reserved

Efficacy of hydroxychloroquine in hand osteoarthritis: a randomized, double blind, placebo-controlled trial


Objective To determine the symptom modifying effect of hydroxychloroquine (HCQ) in hand osteoarthritis (OA). Methods In this randomized, double blind, multicenter trial, patients with symptomatic hand OA received either HCQ 400 mg once a day or placebo during 24 weeks. The primary outcome was change of pain measured on a 100 mm VAS at 24 weeks. Secondary outcomes included decrease of pain at week 6 and 12 and change in AUSCAN and AIMS2-SF total scores. Results 196 patients were included (placebo n=98, HCQ n=98). Mean (SD) age was 58.0 (7.6) years; 86% were female. Baseline mean pain VAS (standard deviation) was 44.9 (22.9) mm in the placebo group and 43.2 (22.3) mm in the HCQ group. At 24 weeks, change in pain VAS was not significantly different between both groups (imputed mean VAS 42.7 in the HCQ group versus 45.3 in the placebo group after 24 weeks), as was the case in pain VAS at week 6 and 12. Changes in AUSCAN total score and AIMS2-SF total score in both groups were similar between the groups. 24 patients in the placebo group and 21 patients in the HCQ group reported ≥ 1 adverse events (AE). In the HCQ group, 3 patients reported a severe allergic reaction. Fifteen patients withdrew from the study (5 placebo, 10 HCQ group) due to adverse events. Conclusions Treatment with HCQ (24 weeks) is not effective in reducing the symptoms of hand OA compared to placebo. This article is protected by copyright. All rights reserved.

Comorbidities in Spondyloarthritis associate with poor function, work disability and quality of life: Results from the ASAS-COMOSPA study


Objective Comorbidities add to the burden of disease and its complexity, and may prevent the achievement of treat-to-target goals. The objective of this study was to study the relationship between comorbidities and key disease outcomes in Spondyloarthritis, namely function, work ability and quality of life. Methods Patients from the multi-national (22 countries), cross-sectional ASAS-COMOSPA study were included in the analysis provided they fulfilled the ASAS criteria. Data on comorbidities based on both self- and physician-report were collected through questionnaires and were subsequently used to compute the Rheumatic Disease Comorbidity Index (RDCI). Univariable and multivariable (adjusted for relevant confounders) multilevel (with country as a random effect) linear or logistic (as appropriate) regression analyses were conducted to investigate the relationship between the RDCI and: (1) functional ability; (2) work ability; (3) quality of life. Results In total, 3370 of 3984 (85%) patients recruited fulfilled the ASAS criteria: 66% were male, mean (SD) age was 43 (14) years, mean (SD) disease duration was 8.4 (9.5) years and mean (SD) RDCI was 0.7 (1.1). At least one comorbidity was reported in 51% of patients; 9% had ≥3 comorbidities. RDCI was independently associated with higher BASFI (β=0.37;95%CI [0.30,0.43]); lower EuroQol five dimensions questionnaire (EQ5D:β=-0.03; [-0.04,-0.02]); less work employment (OR=0.83; [0.76,0.91]); higher absenteeism (β=1.18; [1.04,1.34]) and higher presenteeism (β=1.42; [1.26,1.61]). Conclusion Comorbidities in SpA adversely influence physical function, work ability and quality of life and are important to take into account in daily clinical practice. This article is protected by copyright. All rights reserved.

Asthma in children of mothers with systemic lupus erythematosus and the role of preterm birth


Objective Systemic lupus erythematosus (SLE) and asthma share inheritable IgE-related pathophysiology, but the association between maternal SLE and asthma in the offspring has not been explored. Our aim was to investigate the association between maternal SLE during pregnancy and childhood asthma and examine the role of preterm birth as a mediator of the association using Swedish register data. Methods Information on 12000 singleton live births (2001–2013) was collected from the Medical Birth Register. Childhood asthma was defined as at least one ICD-coded visit in the National Patient Register. Prevalent maternal SLE at delivery was identified from the Medical Birth Register and the National Patient Register. Risk ratios (RRs) for asthma were estimated while controlling for confounders. Mediation analysis was used to estimate what percentage of the total effect can be explained by preterm birth (defined as either <34 or <37 weeks’ gestation). Results We compared 775 children born to mothers with SLE with 11225 born to mothers without SLE. Ninety seven (13%) children of mothers with SLE were diagnosed with asthma compared to 1211 in the unexposed group (11%). The risk ratio for childhood asthma was 1.46 (95% CI 1.16–1.84). In mediation analysis, 20 to 29% of the total effect of SLE was explained by preterm birth. Conclusion Prevalent maternal SLE during pregnancy is associated with an increased risk of asthma in the offspring. While preterm birth can explain a fair proportion of this association, additional unidentified mechanisms are also likely to play a role. This article is protected by copyright. All rights reserved.

Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Anti-Inflammatory Drugs and/or with Active Spinal Lesions


Objective To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO) to enable comparative effectiveness treatment studies. Methods Virtual and face-to-face discussions and meetings were held within the CNO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to non-steroidal anti-inflammatory drug (NSAID) monotherapy and/or with active spinal lesions. Results Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The three CTPs are: (1) methotrexate or sulfasalazine, (2) tumor necrosis factor (TNF)-alpha inhibitors with optional use of methotrexate, and (3) bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response. Conclusion Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO. This article is protected by copyright. All rights reserved.

The association of femoroacetabular impingement and delayed gadolinium enhanced mri of cartilage (dgemric): a population-based study


Objective 1) To assess the association of FAI and dGEMRIC T1 relaxation values (RV). 2) To evaluate whether subtypes of FAI (cam, pincer, mixed) are associated with region-specific dGEMRIC T1 RVs. Methods A population-based sample of Caucasian subjects with and without hip pain, aged 20-49, was selected through random digit dialing. A sample of 128 subjects underwent hip joint 3T dGEMRIC scans. Radiographic cam FAI was defined as an alpha angle >55°, while pincer FAI was defined by a lateral center edge angle >40° or a positive cross-over sign. Mixed impingement was defined by the presence of both cam and pincer impingement. Overall and region-specific T1 RVs were compared between all FAI subtypes using weighted linear regression analysis to account for sampling design of the study. Results Subjects had mean age of 38 years and 51% were female. We did not find an association of FAI with overall hip T1 RV (mean difference =-15.5, 95% CI -77.23, 47.14). Significant associations of cartilage degeneration in anterior superior and central superior regions were found in subjects with mixed FAI compared to other FAI subtypes and non-FAI subjects. Conclusion Subjects with mixed FAI had reduced T1 RVs compared other FAI subtypes. No substantial cartilage degeneration was found in pure cam or pincer FAI compared to non-FAI hips. These results indicate that the presence of cam or pincer impingements alone does not suggest the beginning of cartilage degeneration. In contrast, the presence of both FAI subtypes is a risk factor for early cartilage damage. This article is protected by copyright. All rights reserved.

Value of RAPID3 in patients with PsA: results from the TICOPA and LOPAS II databases


Objective To analyze RAPID3, a patient-reported, composite index, designed initially for feasibility in clinical care. RAPID3 was developed in rheumatoid arthritis, but has been found useful in many rheumatic diseases. We analysed RAPID3 in patients with psoriatic arthritis (PsA). Methods Post-hoc analyses were performed on two independent datasets, the tight control of PsA (TICOPA) clinical trial, and the long-term outcome in PsA study (LOPAS II), an observational cohort. RAPID3 (0-30) is the total of three 0-10 scores for HAQ-DI (recalculated from 0-3), pain visual analog scale (VAS), and global VAS. RAPID3 scores were compared to the PsA disease activity score (PASDAS) and disease activity in psoriatic arthritis (DAPSA) and other available clinical measures, according to Spearman correlation coefficients, standardised response mean (SRM), standard error of the mean (SEM), smallest detectible difference (SDD), minimally important difference (MID in patients who improved) and receiver-operating characteristic (ROC) curves. RAPID3 remission was compared to criteria for both standard minimal disease activity (MDA) and very low disease activity (VLDA). Results RAPID3 was correlated significantly with PASDAS in TICOPA (r=0.79, p<0.01) and with DAPSA in LOPAS (rho=0.59, p<0.01), and with most other measures in both datasets. RAPID3 discriminated between tight control and standard care in TICOPA at 48 weeks at levels comparable to DAPSA and the PASDAS (p<0.01). RAPID3 remission discriminated treatment groups in TICOPA intermediate between MDA and VLDA criteria. Conclusion RAPID3 appears comparably informative to PASDAS and DAPSA in PsA, with greater feasibility for routine clinical care. This article is protected by copyright. All rights reserved.

Association of High Anti-Cyclic Citrullinated Peptide Seropositivity and Lean Mass Index with Low Bone Mineral Density in Rheumatoid Arthritis


Objective Osteoporotic fractures are associated with high morbidity and mortality. Persons with rheumatoid arthritis (RA) have twice the risk of osteoporosis-related fracture than age-matched controls, the causes for which remain unknown. We investigated contributions of RA characteristics, medication use, and body composition to low bone mineral density (BMD) in patients with RA. Methods Data were from the Arthritis, Body Composition, and Disability Study (n=138; 82 women, 56 men). Demographic, clinical, laboratory and functional variables were collected at study visits. Body composition (fat, lean muscle and BMD) was measured by dual x-ray absorptiometry. Linear regression analyses evaluated the association between predictors and femoral neck BMD. Results Average disease duration was 19 years, 70% of patients were rheumatoid factor positive and 55% were high-positive anti-cyclic citrullinated peptide (CCP). Age and high anti-CCP positivity were negatively associated with BMD after controlling for other variables (β=-0.003 and -0.055, respectively, p<0.05). Appendicular lean mass index (ALMI) was positively associated with BMD (β=0.053, p <0.0001). In high-positive anti-CCP participants, increasing anti-CCP levels were associated with a negative linear trend in BMD (β=-0.011, p=0.026). Conclusion High anti-CCP positivity and ALMI were strongly associated with BMD in patients with RA. The linear relationship of anti-CCP levels with lower BMD supports the hypothesis that processes specific to RA negatively impact BMD. In contrast, ALMI was positively associated with BMD, emphasizing the importance of this potentially modifiable risk factor. Our findings highlight the complicated interplay of RA disease-specific and functional factors and their impact on bone mass. This article is protected by copyright. All rights reserved.

Early High-Intensity Versus Low-Intensity Rehabilitation After Total Knee Arthroplasty (TKA) by Bade et al


Recently, a paper entitled “Early High-Intensity Versus Low-Intensity Rehabilitation After Total Knee Arthroplasty: A Randomized Controlled Trial” was published in Arthritis Care Res by Bade et al. (1). We have read the paper with great interest and noted that the study shows essentially no differences between the two training groups in patient-reported outcomes, functional performance and in muscle strength at neither 3 nor 12 months. Both training interventions seemed to improve the primary outcome (stair climbing) in comparison to historical data on patients following standard post-operative care, although such comparisons should be performed cautiously. This article is protected by copyright. All rights reserved.

A 56-year-old man with visual changes and arthralgias


A 56-year-old white man presented with several months of visual changes and diffuse myalgias. He reported difficulty seeing out of the lower portion of his left eye for several months, which he described as “cigarette smoke clouding [his] vision.” He also reported mild discomfort with movement of the affected eye. He attributed the visual loss to potential injury during his work as a welder. In addition, he complained of several months of diffuse body pain and stiffness and generalized malaise. The pain and stiffness were worse in his shoulders and hips and were worse in the morning, with improvement by the middle of the day. On some days, these symptoms were so severe that he was unable to go to work. He also noted a vague bitemporal headache, worse on the left than the right. This article is protected by copyright. All rights reserved.

Association between dose of glucocorticoids and coronary artery lesions in Kawasaki disease


Objective Several studies revealed the efficacy of glucocorticoids on prevention of CAL in KD patients. However, impacts of different doses of glucocorticoids on clinical outcomes of KD remain unknown. Methods Using the Japanese Diagnosis Procedure Combination inpatient database, we evaluated KD patients who were treated with normal-dose (prednisolone 0.5-4.0 mg/kg/day) or high-dose (methylprednisolone 10-40 mg/kg/day) glucocorticoids. We investigated risks of CAL and readmission, total hospitalization cost, and length of hospital stay in the acute phase of KD using propensity-score matching, stabilized propensity-score inverse probability of treatment weighting, and instrumental variable methods. Results We identified a total of 3,220 patients with KD who were treated with normal-dose (n = 2,453) or high-dose (n = 767) glucocorticoids in addition to intravenous immunoglobulin. One-to-one propensity matched analyses with 744 pairs demonstrated no significant differences between the normal-dose and the high-dose groups in risk of CALs (risk ratio, 0.83; 95% confidence interval (CI), 0.49-1.40) and risk of readmissions (risk ratio 0.85; 95%CI, 0.65-1.11). Stabilized propensity-score inverse probability weighting and instrumental variable analyses showed similar results to the propensity-score matching analyses. Conclusions Risks of CALs and readmissions, and total hospitalization costs were similar between the normal-dose and the high-dose glucocorticoids groups for patients with KD, whereas total length of hospital stay was shorter in the high-dose group than that in the normal-dose group. This article is protected by copyright. All rights reserved.

Low-dose glucocorticoids in rheumatoid arthritis: blurring the line between therapeutic dose and substitution therapy?


We would like to thank Masi and colleagues for their interest in our paper as well as for the interesting comments regarding the potential usefulness of neuroendocrine immune (NEI) testing in patients with rheumatoid arthritis (RA). When the first patient with rheumatoid arthritis (RA) was treated with glucocorticoids (GCs) in 1948, the effect was just overwhelming for that time. This article is protected by copyright. All rights reserved.

Hypothesis: Can neuroendocrine immune (NEI) testing of individual RA patients guide benefits to harms ratio in glucocorticoid therapy?


We compliment and endorse the “Official View” by Palmowsky Y and the multidisciplinary experts on their review of guidelines for glucocorticoid (GC) therapy in rheumatoid arthritis (RA) (1). The guidelines generally agreed that GCs are an appropriate option for RA therapy, especially at low doses and for a short duration (1). However, the recommendations lacked evidence and guidance on doses, timing, and duration of GC use. Authors concluded that high-quality studies of GCs in RA are urgently needed (1). This article is protected by copyright. All rights reserved.

Trial Characteristics as Contextual Factors when Evaluating Targeted Therapies in Patients with Psoriatic Disease: A Meta-Epidemiological Study


Objectives To assess the importance of trial characteristics as contextual factors when evaluating treatment effect of targeted therapies for patients with psoriatic disease. Methods We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the two psoriatic conditions combined by using drug retention as common outcome, and separately by using ACR20 for PsA and PASI75 for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta-regression analyses. Odds ratios (OR) were calculated and compared among the trial eligibility criteria via the Ratio of Odds Ratios (ROR). Results Forty-eight PsA and psoriasis trials (51 comparisons, 17,737 patients) were eligible. Overall retention was OR 2.16 (1.70 to 2.75) with higher odds for PsA trials compared with psoriasis trials (ROR = 2.55 [1.64 to 3.97]). The eligibility criteria “targeted therapy history”, “minimum required disease duration”, “required negative rheumatoid factor”, and “required CASPAR criteria” were of importance for achieving ACR20 in PsA. The eligibility criterion “minimum required disease duration” was of importance for achieving PASI75 in psoriasis. 7 PsA trials had rescue before time point of retention reporting (adaptive trials). Conclusion From this exploratory meta-epidemiological study we now have evidence from RCTs to support that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials. This article is protected by copyright. All rights reserved.

Prevalence and disease-specific risk factors for Lower Urinary Tract symptoms in Systemic Sclerosis: an international multi-centric study


Objective The aim of the present study was to determine the prevalence of lower urinary tract symptoms (LUTS) in systemic sclerosis (SSc), to find specific risk factors and to assess their impact on quality of life (QoL). Methods In a multi-centric study, 334 patients completed a self-administered questionnaire on LUTS and QoL. LUTS were classified into three main categories: storage, voiding, and post micturition symptoms. Digestive symptoms burden was captured by a visual analogic scale, divided into five equal categories. Multivariable logistic regressions were performed to test association between risk factors and LUTS categories. Linear regression adjusted the association between LUTS and QoL. Results LUTS were recorded in 311 SSc patients (96.0%) and classified as severe in 120 (38.0%). The storage category of LUTS was the most prevalent (91.9%) followed by voiding (72.2%) and post micturition symptoms (49.8%). Risk factors identified in the multivariable models were higher than the median HAQ-DI (OR: 4.2; 95%CI: 1.4-12.9) for storage category; higher than the median HAQ-DI (OR: 2.4; 95%CI: 1.2-4.9), digestive symptoms burden (OR: 1.9; 95%CI: 1.3-2.7), and synovitis (OR: 4.8; 95%CI: 1.0-22.6) for voiding category; and digestive symptoms burden (OR: 1.2; 95%CI: 1.0-1.5) for post micturition category of symptoms. These factors also increased the odds to suffer from further severe symptoms. QoL was affected by the three categories of LUTS and decreased progressively with increasing frequency of symptoms. Conclusion Self-reported LUTS are amongst the most frequent symptoms in SSc and are associated with digestive complaints. SSc patients with LUTS have lower QoL. This article is protected by copyright. All rights reserved.

Risk of Incident Chronic Obstructive Pulmonary Disease (COPD) in Rheumatoid Arthritis: A Population Based Cohort Study


Objective Studies have demonstrated a link between COPD and inflammation, raising the question whether chronic inflammatory conditions, such as RA, predispose to COPD. Our objective was to evaluate the risk of incident COPD hospitalization in RA compared to the general population. Methods We studied a population-based incident RA cohort with matched general population controls, using administrative health data.. All incident RA cases in British Columbia (BC) who first met RA definition between 01/1996 and 12/2006 were selected using previously published criteria. General population controls were randomly selected, matched 1:1 to RA cases on birth year, sex, and index year. COPD outcome was defined as hospitalization with a primary COPD code. Incidence rates, 95% Cis, and incidence rate ratios (IRR) were calculated for RA and controls. Multivariable Cox proportional hazard models (PHM) estimated the risk of COPD in RA compared to the general population after adjusting for potential confounders. Sensitivity analyses were performed to test the robustness of the results to the possible confounding effect of smoking, unavailable in administrative data, and to COPD outcome definitions. Results The cohorts included 24,625 RA individuals and 25,396 controls. The incidence of COPD hospitalization was greater in RA than controls [IRR (95%CI):1.58(1.34;1.87)]. After adjusting for potential confounders, RA cases had a 47% greater risk of COPD hospitalization than controls. The increased risk remained significant after modelling for smoking and with varying COPD definitions. Conclusion In our population-based cohort, individuals with RA had a 47% greater risk of COPD hospitalization compared to the general population. This article is protected by copyright. All rights reserved.

Autoantibodies targeting ficolin-2 in systemic lupus erythematosus patients with active nephritis


Objective Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease characterized by production of various autoantibodies. The aim of this study was to investigate the presence of anti-ficolin-2 antibodies in SLE patients and to evaluate the association between the levels of these autoantibodies, clinical manifestations, and disease activity. Methods This is a comparative study using a cohort of 165 SLE patients and 48 healthy subjects. SLE patients were further divided into two groups, with “low disease activity” (SLEDAI score ≤ 4, n = 88) and with “high disease activity” (SLEDAI score > 4, n = 77). Clinical manifestations were defined according to the physician in charge. Active lupus nephritis (LN) was documented by kidney biopsy. Detection of anti-ficolin-2 antibodies was performed by ELISA. Results Levels of the anti-ficolin-2 autoantibodies were significantly higher in SLE patients as compared to healthy subjects and associated with the SLEDAI score. They were found positive in 61/165 (37%) SLE patients. Presence of anti-ficolin-2 antibodies was significantly related only to renal involvement, with a very high prevalence (86%) of anti-ficolin-2 antibodies in SLE patients with active LN. Patients with active proliferative LN had significantly more positive anti-ficolin-2 antibodies than those with non-proliferative LN. The combination of anti-ficolin-2, anti-ficolin-3 and anti-C1q demonstrated a very high specificity (98%) for the diagnosis of active LN. Conclusion Our results support the usefulness of anti-ficolin-2 as a complementary serological biomarker for the diagnosis of active lupus with renal manifestation. This article is protected by copyright. All rights reserved.

Sufficient vitamin K status combined with sufficient vitamin D status is associated with better lower extremity function: a prospective analysis of two knee osteoarthritis cohorts


Objective Vitamins K and D are important for the function of vitamin K-dependent proteins in joint tissues. It is unclear if these nutrients are mutually important to functional outcomes related to knee osteoarthritis (OA). We evaluated the association of vitamin K and D sufficiency with lower-extremity function in the Health, Aging Body Composition Knee OA Sub-study (Health ABC) and conducted a replication analysis in an independent cohort, the Osteoarthritis Initiative (OAI). Methods In Health ABC (60% female, 75±3 years) baseline nutrient status was measured using circulating vitamin K and 25(OH)D. Lower-extremity function was assessed using the short physical performance battery (SPPB) and usual 20-meter gait speed. In the OAI (58% female, 61±9 years), baseline nutrient intake was estimated by food frequency questionnaire. Lower-extremity function was assessed using usual 20-meter gait speed and chair stand completion time. Multivariate mixed models were used to evaluate the association of vitamin K and D status and intake with lower-extremity function over 4-5 years. Results Health ABC participants with sufficient plasma vitamin K (≥1.0 nmol/L) and serum 25(OH)D (≥50 nmol/L) generally had better SPPB scores and faster usual gait speed over follow-up (p≤0.002). In the OAI, sufficient vitamin K and vitamin D intake combined was associated with overall faster usual gait speed and chair stand completion time over follow-up (p≤0.029). Conclusion Sufficient vitamin K status combined with sufficient vitamin D status was associated with better lower-extremity function in two knee OA cohorts. These findings merit confirmation in vitamin K and D co-supplementation trials. This article is protected by copyright. All rights reserved.

Minimum performance on clinical tests of physical function to predict walking 6000 steps/day in knee osteoarthritis: An observational study


Objective Evidence of physical function difficulties, such as difficulty rising from a chair, may limit daily walking for people with knee osteoarthritis (OA). The purpose of this study was to identify minimum performance thresholds on clinical tests of physical function predictive to walk ≥6000 steps/day. This benchmark is known to discriminate people with knee OA who develop functional limitation over time from those who do not. Methods Using data from the Osteoarthritis Initiative, we quantified daily walking as average steps/day from an accelerometer (Actigraph GTM1) worn for >10 hours/day over one week. Physical function was quantified using three performance-based clinical tests: five times sit to stand test, walking speed (tested over 20 meters) and 400-meter walk test. To identify minimum performance thresholds for daily walking, we calculated physical function values corresponding to high specificity (80 to 95%) to predict walking ≥6000 steps/day. Results Among 1925 participants (age [mean±sd] 65.1±9.1 years, BMI 28.4±4.8 kg/m2, 55% female) with valid accelerometer data, 54.9% walked ≥6000 steps/day. High specificity thresholds of physical function for walking ≥6000 steps/day ranged from 11.4 to 14.0 sec on the five times sit to stand test, 1.13 to 1.26 meters/sec for walking speed, or 315 to 349 sec on the 400-meter walk test. Conclusion Not meeting these minimum performance thresholds on clinical tests of physical function may indicate inadequate physical ability to walk ≥6000 steps/day for people with knee OA. Rehabilitation may be indicated to address underlying impairments limiting physical function. This article is protected by copyright. All rights reserved.

Effectiveness of Ultrasound-Guided Compared to Blind Steroid Injections in the Treatment of Carpal Tunnel Syndrome


We read with great interest the article by Evers and colleagues.1 Their data confirms what many of us who utilize ultrasound-guided injections have suspected - that is, improved efficacy and decreased hazard of treatment using ultrasound-guided injection for carpal tunnel (CT) syndrome. The authors did comment about additional potential benefits of ultrasound (US) guidance including decreased risk of median nerve and surrounding tissue damage. In addition they described that ultrasound visualization of structures within the CT contributes to the diagnosis. This article is protected by copyright. All rights reserved.

Disclosure of personalized rheumatoid arthritis risk using genetics, biomarkers, and lifestyle factors to motivate health behavior improvements:A randomized controlled trial


Objective To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions. Methods We performed a randomized controlled trial among first-degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for RA (PRE-RA) group received the web-based PRE-RA tool for RA risk factor education and disclosure of personalized RA risk estimates including genotype/autoantibody results and behaviors (n=158). Subjects assigned to the comparison arm received standard RA education (n=80). The primary outcome was readiness for change based on the transtheoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk-related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline assessed immediately, 6 weeks, and 6 months post-intervention. Subjects reported behavior change at each visit. We performed intention-to-treat analyses using generalized estimating equations for the binary outcome. Results Subjects randomized to PRE-RA were more likely to increase ladder scores over post-intervention assessments (RR 1.23, 95%CI 1.01-1.51) than those randomized to non-personalized education. At 6 months, 63.9% of PRE-RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age-adjusted difference 15.8%, 95%CI 2.8-28.8%). Compared to non-personalized education, more PRE-RA subjects increased fish intake (45.0% vs. 22.1%; p=0.005), brushed more frequently (40.7% vs. 22.9%; p=0.01), flossed more frequently (55.7% vs. 34.8%; p=0.004), and quit smoking (62.5% vs. 0.0% among 11 smokers; p=0.18). Conclusion Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk-related behaviors. Personalized medicine approaches may motivate health behavior improvements for those at risk for RA and provide rationale for larger studies evaluating effects of behavior changes on clinical outcomes such as RA-related autoantibody production or RA development. This article is protected by copyright. All rights reserved.

Association between anti-citrullinated fibrinogen antibodies and coronary artery disease in rheumatoid arthritis


Objective Antibodies against citrullinated fibrinogen (anti-cit-fibrinogen) have been implicated in both rheumatoid arthritis (RA) and cardiovascular (CV) risk in RA. The objective of this study was to examine the association between anti-cit-fibrinogens and coronary artery disease (CAD) outcomes. Methods We performed the study in an RA cohort based in a large academic institution linked with electronic medical record data (EMR) containing data on CAD outcomes from medical record review. Using a published bead assay method, we measured 10 types of anti-cit-fibrinogens. We applied a score test to determine the association between the anti-cit-fibrinogens as a group with CAD outcomes. Principal components analysis (PCA) was performed to assess whether the anti-cit-fibrinogens clustered into groups. Each group was then also tested for association with CAD. Sensitivity analyses were also performed using a published ICD9 code group for ischemic heart disease (IHD) as the outcome. Results We studied 1,006 RA subjects with mean age 61.0 (SD 13.0) years and 72.2% anti-CCP positive. As a group, anti-cit-fibrinogen was associated with CAD (p=1.1x10-4). From the PCA analysis, we observed 3 main groups, of which only one group, containing 7 of the 10 anti-cit-fibrinogens, was significantly associated with CAD outcomes (p=0.015). In the sensitivity analysis, all anti-cit-fibrinogens as a group remained significantly associated with IHD (p=2.9x10-4). Conclusion Anti-cit-fibrinogen antibodies as a group were associated with CAD outcomes in our RA cohort, with the strongest signal for association arising from a subset of the autoantibodies. This article is protected by copyright. All rights reserved.

A Rapid Evaluation of Activity in Lupus (LFA-REAL™) Correlates with More Complex Disease Activity Instruments Whether Evaluated by Clinical Investigators or Real-World Clinicians


Lupus disease measures such as the SLE Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) Index are challenging to interpret. The Lupus Foundation of America–Rapid Evaluation of Activity in Lupus (LFA-REAL) is intended to provide an efficient application of anchored visual analogue scores, each representing the individual severity of active symptoms, with the sum of individual scores deriving an overall disease activity assessment. Objectives To compare the performance of LFA-REAL to SLE disease activity assessments and compare scores between trained lupus clinical investigators and clinicians. Methods Investigators scored the SLEDAI, BILAG, PGA, and LFA-REAL, while the clinicians scored the LFA-REAL. The level of agreement between physicians and instruments was determined. Results The study included 99 patients, 93% women, 31% Caucasian, 43.4 (±13.2) years old. At the first visit, the SLEDAI was 5.5 (±4.5), BILAG 6.7 (±7.8), and PGA 33.6 (±24.5). The investigator REAL was 46.2 (±42.9), and clinician REAL 56.1 (±53.6). At the second visit, the investigator REAL was 41.3 (±36.7), and clinician REAL 48.3 (±42.6). Total REAL scores correlated positively with PGA, SLEDAI, and BILAG (ρ 0.58-0.88, p <0.001). REAL scores produced correlation coefficients ρ > 0.7 for musculoskeletal, mucocutaneous, and renal BILAG domains. The intra-class correlation coefficient between the REAL scores of investigators and clinicians was 0.79 for Visit1 (p < 0.001) and 0.86 for Visit2 (p < 0.001). Conclusion The LFA-REAL provides a reliable surrogate for more complicated disease activity measures when used by lupus clinical investigators or clinicians. This article is protected by copyright. All rights reserved.

A Nationwide Experience With The Off-label Use of Interleukin-1 Targeting Treatment in Familial Mediterranean Fever Patients


Objective Around 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anit-IL1) agents. Herein we report our experience with the off-label use of anti-IL1 agents in a large group of FMF patients. Methods In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL1 treatment for at least 6 months were reviewed. Results In total, 172 FMF patients (83 [48%] female, mean age 36.2 [range, 18–68] years old) were included in the analysis; their mean age at symptom onset was 12.6 (range; 1–48) years, and the mean colchicine dose was 1.7 (0.5–4.0) mg/day. Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL1 treatment was used because of colchicine-resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 (6–98) months of treatment, the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine-resistant FMF patients were attack free. Serum levels of C-reactive protein, ESR, and 24 h urinary protein excretion (5458.7 mg/24 h before and 3557.3 mg/24 h after) were significantly reduced. Conclusion Anti-IL1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients. This article is protected by copyright. All rights reserved.

Prognostic significance of cavitary lung nodules in granulomatosis with polyangiitis – A clinical and imaging study of 225 patients


Background Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis with pulmonary nodules as a common manifestation. Our study examined whether pulmonary nodules, and nodule type (solid versus cavitary), are associated with different disease manifestations and outcomes. Methods Demographic, clinical, biological, radiological data at diagnosis, during follow-up, and treatments of GPA patients followed at the Mount Sinai Hospital (Canada) vasculitis clinic were analyzed. Patients were separated by the absence of lung nodules, presence of solid nodules only, and presence of cavitary nodules (+/- solid nodules). Studied outcomes included follow-up lung imaging, relapses, and deaths. Results Among 225 patients with GPA, 46 had solid only and 44 had cavitary nodules at diagnosis. Demographic and clinical manifestations were similar in the patient subgroups at diagnosis. Cyclophosphamide (CYC) was used for induction after diagnosis in 76.7% of patients with cavitary nodules, compared with 64.7% of patients without nodules and 51.1% of patients with solid nodules (p=0.04). With a mean follow-up after diagnosis of 106.6 ± 92.6 months, 6 patients died. In multivariable analysis, diagnosis before 2000 or pulmonary nodule cavitation at diagnosis were associated with relapse, with an HR of 0.38 (95% CI 0.22, 0.65, p<0.001) and 1.53 (95% CI 1.00, 2.33, p=0.05), respectively and after adjustment for CYC use. Conclusions The presence of cavitary nodules led to increased use of CYC, but had no impact on survival. Relapse occurred more often, however, in patients with cavitary nodules than in those with solid or no nodules, and should be studied in other cohorts. This article is protected by copyright. All rights reserved.

Flares after withdrawal of biologic therapies in juvenile idiopathic arthritis: Clinical and laboratory correlates of remission duration


Objective to assess the time in remission after discontinuing biologic therapy in JIA patients. Methods we enrolled 135 patients followed in three tertiary care centers. Primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann–Whitney U-test, Wilcoxon signed-rank test for paired samples, chi-square, and Fisher's exact test were used to compare data. Pearson and Spearman correlation tests were used to determine correlation coefficients for different variables. In order to identify predictors of outcome Cox regression model and Kaplan–Meier curves were constructed, each one at mean of entered covariates. Results The majority of enrolled patients flared after stopping treatment with biologics (102/135, 75.6%) after a median follow-up time in remission off therapy of 6 months (range 3–109). A higher probability of maintaining remission after discontinuing treatment was present in systemic onset disease compared to the rest of JIA patients (Mantel-Cox χ2 8.31, p<0.004). In analysis limited to JIA children with polyarticular and oligoarticular disease, patients who received biologics > 2 years after achieving remission had a higher probability of maintaining such remission off therapy (18.64 ±3.3 months vs 11.51 ±2.7, p<0.009; Mantel-Cox χ2 9.06, p<0.002). No other clinical variable resulted significantly associated with a long-lasting remission. Conclusion Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal. This article is protected by copyright. All rights reserved.

Airborne Occupational Exposures and Risk of Developing Rheumatoid Arthritis: A Job-Exposure Matrix Approach in a Swedish Population-Based Case–Control Study


Professor Alexis Descatha suggests that we should have used job-exposure matrices (JEM) to understand the underlying increased risks we noted between certain occupations and risk of rheumatoid arthritis (RA) in our study Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population-Based Case-Control Study (1). This article is protected by copyright. All rights reserved.

General and Abdominal Obesity as Risk Factors for Late-Life Mobility Limitation after Total Knee or Hip Replacement for Osteoarthritis among Women


Objective To investigate associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with survival to age 85 with mobility limitation or death before age 85 among older women with total knee (TKR) or total hip (THR) replacement for osteoarthritis. Methods This was a prospective study of women (aged 65-79 years at baseline) from the Women's Health Initiative recruited during 1993-1998 and followed through 2012. Women's Health Initiative data were linked to Medicare claims data to determine TKR (n=1,867) and THR (n=944) for osteoarthritis. Women were followed for up to 18 years after undergoing THR or TKR to determine mobility status at age 85. Results Compared with normal-weight women, overweight, obese I, and obese II women with THR had significantly increased risk of survival to age 85 with mobility limitation (P for linear trend <0.001), with the strongest risk among obese II women (OR = 4.37; 95% CI = 1.96-9.74). Obese II women with THR also had increased risk of death before age 85. Women with THR and WC >88 cm relative to ≤88 cm had increased risk of survival to age 85 with mobility limitation (OR = 1.65; 95% CI = 1.17-2.33) but not death before age 85. High BMI, WC, and WHR were associated with significantly increased risk of late-life mobility limitation and death among women with TKR for osteoarthritis. Conclusion Among older women who underwent THR or TKR for osteoarthritis, baseline general and abdominal obesity were associated with increased risk of late-life mobility limitation. This article is protected by copyright. All rights reserved.

From job title to occupational lifetime exposure assessment: the use of job-exposure matrices


We read with interest the paper by Ilar et al. “ Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population-Based Case-Control Study”. (1) The authors showed in a very interesting and large population-based case-control study the association between some occupations and risk of anti-citrullinated protein antibody ways and without rheumatoid arthritis. This article is protected by copyright. All rights reserved.

Comment on the article titled “Increased Incidence of Amyotrophic Lateral Sclerosis in Polymyositis: A Nationwide Cohort Study”


With interest, I read the recent article in Arthritis Care and Research titled “Increased Incidence of Amyotrophic Lateral Sclerosis in Polymyositis: A Nationwide Cohort Study” (1). Tseng at al (1) conducted a retrospective cohort study in Taiwan, exploring a link between amyotrophic lateral sclerosis (ALS) and polymyositis (PM). This article is protected by copyright. All rights reserved.

Patterns of biologics utilization and discontinuation before and during pregnancy in women with autoimmune diseases: A population-based cohort study


Objectives To characterize the patterns of biologics utilization and discontinuation before and during pregnancy in women with autoimmune diseases in British Columbia, Canada. Methods Women with one or more autoimmune diseases identified by International Classification of Diseases 9th/10th revision codes that had pregnancies ending in deliveries between January 1st, 2002 and December 31st, 2012; and had at least one prescription for a biologic one year before, or during, pregnancy were included. We examined secular trends, patterns of biologics use, and risk of biologics discontinuation before and during pregnancy. Associations between drug discontinuations and various factors were investigated using multilevel logistic regression models, fitted with binomial generalized estimating equations. Results Of 6,218 women (8,431 pregnancies) with autoimmune diseases, 131 women (144 pregnancies) were exposed to a biologic before or during pregnancy. Use of biologics in this cohort increased from 0% in 2002 to 5.7% by 2012 (p<0.001). Within the first trimester of pregnancy, 31% (34/110) of women discontinued their biologic and 38% (30/79) discontinued in the second trimester, while 98% (50/51) of those who were on treatment in the second trimester remained on treatment in the third trimester. Women with rheumatoid arthritis had three times higher odds (OR 3.40 [95%CI 1.33-8.71]) of discontinuing biologics during pregnancy, compared to those with inflammatory bowel disease. Conclusions Given the increased utilization of biologics and high odds of discontinuation during pregnancy in certain populations, more research is needed to improve our understanding of the risks and benefits of biologics on fetal and maternal health. This article is protected by copyright. All rights reserved.

Improved Hand Function, Self-Rated Health and Decreased Activity Limitations - results after a two month hand osteoarthritis group intervention


Introduction Hand Osteoarthritis (hand OA) causes pain, impaired mobility and reduced grip force, which cause activity limitations. Osteoarthritis group interventions in primary care settings are sparsely reported. Purpose To evaluate the effects on hand function, activity limitations and self-rated health of a primary care hand OA group intervention. Method 64 individuals with hand OA agreed to participate, 15 were excluded due to not fulfilling the inclusion criteria. The 49 remaining (90% female) participated in OA group intervention at a primary care unit with education, paraffin wax bath and hand exercise over a six-week period. Data were collected at baseline, end of intervention and after one year. Instruments used were the Grip Ability Test (GAT), the Signals of Functional Impairment (SOFI), the JAMAR (dynamometry), hand pain at rest using Visual Analogue Scale (VAS), the Patient Specific Functional Scale (PSFS), the Quick Disabilities of the Arm, Shoulders and Hand (Quick-DASH) and the EuroQol VAS (EQ VAS). Data were analyzed using nonparametric statistics. Results Hand function, activity limitation and self-rated health significantly improved from baseline to end of intervention, JAMAR (right hand, p<0.001, left hand, p=0.008), SOFI (p=0.011), GAT (p<0.001), hand pain at rest (p<0.001), PSFS (1, p=0.008, 2, p<0.001, 3, p=0.004), Quick- DASH (p=0.001), and EQ VAS (p=0.039)and the effects were sustained after one year. Conclusion The hand OA group intervention in primary care improves hand function, activity limitation and self-rated health. The benefits are sustained one year after completion of the intervention. This article is protected by copyright. All rights reserved.



We appreciate the comments from Dr Parperis. The question raised by Parperis was the possibility of amyotrophic lateral sclerosis (ALS) misdiagnosed as polymyositis (PM) initially. Dr Parperis cited the study of Harrington et al to support his claims (1). However, several points had to be considered. This article is protected by copyright. All rights reserved.

Incremental Costs in Giant Cell Arteritis


Objectives To assess and compare direct costs between giant cell arteritis (GCA) patients and matched-controls and identify incremental cost drivers. Methods We carried out a population-based, retrospective, cohort study using the French National Health Insurance System Database. Cost analysis was performed from the French health insurance perspective and took into account direct medical and non-medical costs (€, 2014). Costs were evaluated according to different cost components and divided into periods of 6 months for the accurate assessment of care consumption. Longitudinal multivariate regression analyses using Generalized Estimating Equations (GEE) were used to adjust the effect of GCA on the mean cost over time. Results Analyses were performed on 96 incident GCA patients and 563 matched-controls. The cumulative incremental cost due to GCA was €6,406 and €7,236 for 3 and 5 years, respectively. Total incremental costs were significant for the first 18 months, amounting to €1,342 for the first 6 months, €1,498 between 6 and 12 months and €1,165 between 12 and 18 months (p=0.012, p=0.065, p=0.029, respectively). The most important cost drivers were paramedical procedures, in-patient stays, medication and medical procedures. Multivariate analysis shows the significant effect of GCA on mean cost during the first 3 years of follow-up (RR=1.72; 95% CI: 1.31-2.27, p<0.001) with significant cost reductions (RR=0.70; 95% CI: 0.49-0.99, p=0.05) at the end of follow-up. Conclusion This study provide an accurate assessment of GCA costs during a five year period and gives useful information for future cost-effectiveness studies based on new expensive biotherapies. This article is protected by copyright. All rights reserved.

The Relationship between Poverty and Mortality in Systemic Lupus Erythematosus


Objectives A prior study established that concurrent poverty, persistent poverty, and exiting poverty were associated with the subsequent extent of damage accumulation in systemic lupus erythematosus (SLE). The present study examines whether concurrent poverty affects mortality after taking extent of damage accumulation into account. Methods Analyses were conducted on 807 persons with SLE participating in the UCSF Lupus Outcomes Study in 2009, stratified by whether they were in households ≤125% of the Federal Poverty Level in that year. We used Cox Proportional Hazards regression to estimate the risk of mortality as a function of poverty status, with and without adjustment for demographics; lupus status, including extent of disease damage; overall health status; health behaviors; and health care characteristics. Results Among 807 individuals interviewed in 2009, 71 (8.8%) had died by 2015, 57 (8.3%) among the non-poor and 14 (12.1%) among the poor (p=.18). With only adjustment for age, poverty in 2009 was associated with an increased risk of mortality (Hazard Ratio (HR) 2.14, 95% CI 1.18, 3.88) through 2015. However, after adjustment for extent of damage and age, poverty was no longer associated with an increased risk of mortality (HR 1.68, 95% CI 0.91, 3.10). Among those who died, the poor lived 13.9 fewer years (95% CI 6.9, 20.8, p < .0001). Conclusions The principal way that poverty results in higher mortality in SLE is by increasing the extent of damage accumulation

Impact of Sustained Remission on the Risk of Serious Infection in Patients With Rheumatoid Arthritis


Objective This retrospective analysis examined how sustained remission impacted risk of serious infections in patients with rheumatoid arthritis (RA) enrolled in a clinical registry. Methods Inclusion criteria included RA diagnosis, ≥18 years old, and ≥2 clinical disease activity index (CDAI) scores followed by a follow-up visit. Index date was the second of 2 visits in which a patient had sustained remission (CDAI ≤2.8), low disease activity (LDA) (2.810). Follow-up extended from the index date until first serious infection (requiring intravenous antibiotics or hospitalization) or last follow-up visit. The crude incidence rate (IR) per 100 patient-years for serious infections was calculated for the sustained remission, LDA, and MHDA groups. The multivariable-adjusted incidence rate ratio (IRR) (adjusted for age, sex, and prednisone dose) compared serious infection rates in various disease groups. Results Most patients were female (>70%); mean age was approximately 60 years. The crude IR (95% confidence interval [CI]) per 100 patient-years for serious infections was 1.03 (0.85-1.26) in the sustained-remission group (N=3355), 1.92 (1.68-2.19) in the sustained-LDA group (N=3912), and 2.51 (2.23-2.82) in the sustained-MHDA group (N=5062). Compared to sustained remission, the serious infection rate was higher in sustained LDA (adjusted IRR [95% CI]=1.69 [1.32-2.15]). Compared to sustained LDA, the serious infection rate was higher in sustained MHDA (adjusted IRR [95% CI]=1.30 [1.09-1.56]). Conclusion In this study, lower RA disease activity was associated with lower serious infection rates. This finding may motivate patients and healthcare providers to strive for remission rather than only LDA. This article is protected by copyright. All rights reserved.

Medical expenditures and earnings losses among US adults with arthritis in 2013


Objective We estimated the economic impact of arthritis using 2013 US Medical Expenditure Panel Survey (MEPS) data. Methods We calculated arthritis-attributable and all-cause medical expenditures for adults age ≥ 18 years and arthritis-attributable earnings losses among those 18-64 years who had ever worked. We calculated arthritis-attributable costs using multi-stage regression-based methods, and conducted sensitivity analyses to estimate costs for two other arthritis definitions in MEPS. Results In 2013, estimated total national arthritis-attributable medical expenditures were $139.8 billion (range= $135.9 - $157.5). Across expenditure categories, ambulatory care expenditures accounted for nearly half of arthritis-attributable expenditures. All-cause expenditures among adults with arthritis represented 51% of the $1.2 trillion national medical expenditures among all US adults in MEPS. Estimated total national arthritis-attributable earning losses were $163.7 billion (range= $163.7 - $170.0). The percentage with arthritis who worked in the past year was 7.2 percentage points lower than those without arthritis (76.8%; 95% CI= 75.0-78.6 and 84.0%; 95% CI= 82.5-85.5, respectively; adjusted for socio-demographics and chronic conditions). Total arthritis-attributable medical expenditures and earnings losses were $303.5 billion (range=$303.5 - $326.9). Conclusion Total national arthritis-attributable medical care expenditures and earnings losses among adults with arthritis were $303.5 billion in 2013. High arthritis-attributable medical expenditures might be reduced by greater efforts to reduce pain and improve function. The high earnings losses were largely attributable to the substantially lower prevalence of working among those with arthritis compared with those without, signaling the need for interventions that keep people with arthritis in the work force. This article is protected by copyright. All rights reserved.

Low Hemoglobin Predicts Radiographic Damage Progression in Early Rheumatoid Arthritis – Secondary Analysis from a Phase III trial


Objective To study low blood hemoglobin concentrations as a predictor of radiographic damage progression in patients with rheumatoid arthritis (RA). Methods Post-hoc analyses were performed in patients from the PREMIER trial with early RA undergoing two years of adalimumab (ADA), methotrexate (MTX), or ADA+MTX combination therapy. Low disease activity was defined by the 28-joint based disease activity score DAS28-CRP <3.2, and clinical response by 20% improvement in the American College of Rheumatology response criteria at week 24. Baseline or mean hemoglobin concentrations over time, or anemia as defined using sex-specific World Health Organization criteria, were analyzed in mixed effect models for longitudinal data in men and women as predictors of progressive joint damage, as measured by modified total Sharp scores (ΔmTSS). Data were adjusted for treatment and other patient characteristics, including the DAS28-CRP. Results Baseline hemoglobin was inversely associated with ΔmTSS in adjusted analyses (P <0.05 for both sexes). Baseline anemia predicted higher ΔmTSS in MTX-treated patients over 104 weeks, and in ADA- and combination-treated patients over 26 weeks. Lower hemoglobin concentrations over time, and ‘time-with-anemia’ were both associated with greater damage progression (P <0.001). The effect of low hemoglobin concentrations on joint damage progression remained significant, even in patients achieving low disease activity. Conclusion Low hemoglobin is a DAS28-CRP-independent predictor of radiographic joint damage progression in MTX-treated patients with early RA. This effect decreases over time in ADA- and in combination-treated patients, and in clinical responders irrespective of treatment modality. This article is protected by copyright. All rights reserved.

Serum levels of HMGB1 and sRAGE are associated to extraglandular involvement and disease activity as defined by ESSDAI in Sjögren's syndrome


Objective To assess serum levels of high mobility group box 1 (HMGB1) and the soluble receptor for advanced glycation endproducts (sRAGE) in patients with Sjögren's Syndrome (SS) and explore correlations with disease activity. Methods Thirty-nine patients with SS and 21 healthy controls (HC) were included in this cross-sectional study. Clinical and laboratory values were obtained from all patients. Disease activity was assessed by European League against Rheumatism (EULAR) SS disease activity index (ESSDAI). Serum samples were collected and HMGB1 and sRAGE levels were measured by ELISA, furthermore HMGB1 concentrations were semiquantified by Western blot (WB). Results In ELISA HMGB1 serum levels did not differ between patients with SS and HC (p=0.783). When measured by semiquantitative WB, HMGB1 levels were increased in patients with SS compared to HC (p=0.012). HMGB1 serum levels detected by WB were higher in patients with extraglandular manifestations (p=0.003), and correlated with disease activity as determined by the ESSDAI (r=0.544, p<0.0001). Furthermore sRAGE was elevated in the sera of patients with SS (p=0.003) compared to HC and also correlated with the ESSDAI (r=0.545, p=0.002). Conclusions Serum levels of total HMGB1 and sRAGE were elevated in patients with SS compared to HC and correlated with disease activity as measured by the ESSDAI. Patients with extraglandular involvement revealed high HMGB1 serum levels. This article is protected by copyright. All rights reserved.

Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program


Background Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We characterized lymphoma events in the tofacitinib RA clinical development program. Methods Lymphoma events (to March 2015) were identified from 19 tofacitinib studies (two Phase 1, nine Phase 2, six Phase 3, and two long-term extension) of patients with moderate to severe RA. Patients in these studies received tofacitinib dosed at 1–30 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic DMARDs. Lymphoma incidence rates (IR; number of patients with events/100 patient-years) and standardized incidence ratios (SIR) were calculated. A descriptive case-matched control analysis (1:4) was performed to identify potential risk factors for lymphoma. Results A total of 6,194 patients received tofacitinib (19,406 patient-years’ exposure; 3.4 years’ median treatment duration). Nineteen lymphomas occurred with IR 0.10 (95% confidence interval: 0.06, 0.15) not increasing with time of exposure. The age- and sex-adjusted SIR of lymphoma was 2.62 (1.58, 4.09) (SEER database). Clinical characteristics of the 19 lymphomas were typical for the RA population. Three lymphomas were positive for Epstein-Barr virus, 8 were negative, 2 were equivocal; 6 were untested. Numerically more lymphoma cases had history of Sjögren's syndrome and were positive for anti-cyclic citrullinated protein and rheumatoid factor at baseline versus matched controls. Mean corticosteroid dose was higher for lymphoma cases versus controls. Conclusions In the tofacitinib RA clinical development program, lymphoma rates were stable over time and there were minimal differences in baseline characteristics of patients with and without lymphoma. This article is protected by copyright. All rights reserved.

Coping strategies, psychological impact and support preferences of men with rheumatoid arthritis: a multicentre survey


Objectives To investigate the existence and distribution of two typologies (termed ‘Factors’) of men with RA identified through our previous Q-methodology study (n=30) in a larger sample of men with RA, and whether differences in psychosocial impact or support preferences exist between the two factors, and between men and women with RA. Methods A postal survey was sent to 620 men with RA from 6 rheumatology units across England, and the support preferences section of the survey was given to 232 women with RA. Results 295 male patients (47.6%) and 103 female patients (44.4%) responded. Fifteen male participants had missing data, thus 280 were included in the analysis. Of these, 61 (22%) were assigned to Factor A (“accept and adapt”), 120 (35%) were assigned to Factor B (“struggling to match up”) and 99 (35%) were unassigned to either factor. The two factors differed significantly with Factor B reporting more severe disease, less effective coping strategies and poorer psychological status. For support, men favoured a question and answer session with a consultant (54%) or specialist nurse (50%), a website for information (69%), a talk from researchers (54%), or a symptom management session (54%). Overall, women reported more interest in support sessions than men, with ≥50% of women reporting interest in nearly every option provided. Conclusions Some men accept and adapt to their RA, but others (43%) report severe disease, less effective coping and poor psychological status. Men's preferences for support take the practical form, with a focus on expanding their knowledge. This article is protected by copyright. All rights reserved.

Efficacy of a Work Disability Prevention Program for People with Rheumatic and Musculoskeletal Conditions: The Work It Study Trial


Objective Work disability rates are high among people with rheumatic and musculoskeletal conditions. Effective disability preventive programs are needed. We examined the efficacy of a modified vocational rehabilitation approach delivered by trained occupational therapists and physical therapists on work limitation and work loss over two years among people with rheumatic and musculoskeletal conditions. Methods Eligibility criteria for this single-blind parallel-arm randomized trial included 21-65 years of age, 15 or more hours/week employment, self-reported doctor-diagnosed rheumatic or musculoskeletal condition, and concern about staying employed. The intervention consisted of a 1.5 hour meeting, an action plan, written materials on employment supports, and telephone calls at 3-weeks and 3-months. Control group participants received the written materials. The primary outcome was the Work Limitations Questionnaire (WLQ), Output Job Demand subscale. The secondary outcome was work loss. Intent to treat analyses were performed. This study is registered with ClinicalTrials. gov number NCT01387100. Results Between October 2011 and January 2014, 652 individuals were assessed for eligibility. 287 participants were randomized: 143 intervention and 144 control participants. 264 participants (92%) completed two-year data collection. There was no difference in the mean WLQ change scores from baseline to two year follow-up (-8.6 ± 1.9 intervention vs. -8.3 ± 2.2 control (p=.93)). Of the 36 participants who experienced permanent work loss at two years: 11 (8%) were intervention participants and 25 (18%) control participants (p=.03). Conclusion The intervention did not have an effect on work limitations but reduced work loss. The intervention can be delivered by trained rehabilitation therapists. This article is protected by copyright. All rights reserved.

Comment on 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis


We have read the recently published 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (1), and applaud the committee's efforts, but have a number of areas of disagreement. Our main concern is that in adults at high risk for fracture, oral and then parenteral bisphosphonates are recommended over teriparatide in selecting drug therapy. This represents a departure from the 2010 ACR GIO Guidelines (2) which avoided rating bisphosphonates (either oral or parenteral) preferentially over teriparatide. This article is protected by copyright. All rights reserved.

Timing and impact of decisions to adjust disease-modifying antirheumatic drug therapy for rheumatoid arthritis patients with active disease


Objective Guidelines recommend that rheumatoid arthritis (RA) patients with moderate to high disease activity (MHDAS) adjust disease-modifying antirheumatic drug (DMARD) therapy at least every 3 months until reaching low disease activity or remission (LDAS). We examined how quickly RA patients with MHDAS adjust DMARD therapy in clinical practice, and whether those who adjust DMARDs within 90 days in response to MHDAS reach LDAS sooner. Methods We identified RA patients with MHDAS in the University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry, and conducted a competing risks regression on time to DMARD therapy adjustment and a Cox regression on time to LDAS. Results We identified 538 eligible subjects with 943.5 patient-years of follow-up. Sixty percent of patients with persistent MHDAS adjusted DMARDs within 90 days. Among all subjects, median times to DMARD adjustment and LDAS were 154 [IQR: 1-706] and 301 [140-706] days, respectively. Being elderly (subdistribution hazard ratio (SHR)=0.61, p=0.02), lower baseline disease activity (SHR=0.72, p<0.01), longer duration of RA (SHR=0.98, p<0.01), and biologic use (SHR=0.71, p<0.01) were significantly associated with longer times to therapy adjustment. African-American race (HR=0.63, p=0.01), higher baseline disease activity (HR=0.75, p<0.01), and not adjusting DMARD therapy within 90 days (HR=0.76, p=0.01) were associated with longer times to LDAS. Conclusion Adjusting DMARDs within 90 days was associated with shorter times to LDAS, but many patients with persistent MHDAS waited more than 90 days to adjust DMARDs. Interventions are needed to address the timeliness of DMARD adjustments for RA patients with MHDAS. This article is protected by copyright. All rights reserved.

Trajectories of fear-avoidance beliefs on physcial activity over two years in people with rheumatoid arthritis


Objective To identify and describe two-year trajectories of fear-avoidance beliefs on physical activity and to identify predictors of these trajectories in people with rheumatoid arthritis (RA). Methods We included 2569 persons with RA (77% women, mean age 58 years). Data on fear-avoidance beliefs (Fear-Avoidance Beliefs Questionnaire - Physical Activity subscale, FABQ-PA, 0-24), sociodemographics, disease-related variables, self-efficacy and health-enhancing physical activity (HEPA) were collected from registers and by questionnaires at baseline, 14 and 26 months. K-means cluster analysis was used to identify fear-avoidance trajectories and multinomial logistic regression was used to identify predictors of trajectory membership. Results Three trajectories of fear-avoidance beliefs were identified: “Low” (n=1,060, mean FABQ-PA=3), “Moderate” (n=1,043, mean FABQ-PA=9), and “High” (n=466, mean FABQ-PA=15). Consistent predictors of being in the “High” fear-avoidance trajectory versus the other two trajectories were: high activity limitation, male gender, income below average, not performing current HEPA and elevated anxiety/depression. Additional, less consistent predictors such as shorter education, more pain and low exercise self-efficacy were also identified. Conclusions Stable trajectories of fear-avoidance beliefs on physical activity exist among people with RA. Fear-avoidance may be targeted more effectively by tailoring physical activity promotion to vulnerable socioeconomic groups, men and those with high activity limitation and anxiety/depression. This article is protected by copyright. All rights reserved.

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis


The Voting Panel recommended oral bisphosphonates as a first choice and parenteral bisphosphonates as a second choice after comparing data about absolute fracture reduction, harms (toxicity and inconvenience of daily injections), and costs. Drs. Maricic, Deal, Dore, and Laster cite the randomized trial of alendronate versus teriparatide in glucocorticoid-treated patients that reported incident fractures as a secondary outcome. This trial found a lower risk of clinical vertebral fractures in the teriparatide compared to alendronate treated patients (0% vs. 2.4% [n=4/169], p=0.037) but no difference in the risk of nonvertebral fracture (7.5% vs. 7.0%, p=0.843) (1). This article is protected by copyright. All rights reserved.

How Well Do Rheumatology Fellows Manage Acute Infusion Reactions? A Pilot Curricular Intervention


Background Infusible DMARDs are commonly prescribed in rheumatology and other fields. There are no published formal educational curricula rheumatology fellowship programs can use to teach infusion reaction management skills to fellows. We aimed to better understand this educational gap, and implement and assess the effectiveness of an experiential curriculum on acute infusion reaction management. Methods We included current rheumatology fellows and recent graduates from five fellowship programs. Using a novel behavioral checklist we assessed fellows’ performance managing an infusion reaction in a simulation, followed by a didactic focused on infusion reactions. Pre and post-surveys assessed experiences to determine relevance, as well as attitudes and knowledge. Results Despite ubiquitous prescribing of infusible biologic DMARDs, >50% of fellows were uncomfortable managing infusion reactions. Only 11% of fellows reported infusion reaction training during fellowship, but 56% reported managing actual patient infusion reactions. In the simulated infusion reaction, fellows managed grade 1 reactions appropriately, but grade 4 reactions poorly, meeting <50% of objectives. All fellows discontinued the infusion in the setting of anaphylaxis, but only 56% administered epinephrine. There was no difference in performance or written knowledge by training year. All fellows felt more prepared to manage infusion reactions post-curriculum and were satisfied with the experience. Conclusion We confirmed an education gap in rheumatology fellowship training regarding infusion reactions, both in knowledge and performance. We developed and implemented a brief experiential curriculum including simulation of a high-risk patient care scenario. This curriculum was well received and is easily exportable to other programs. This article is protected by copyright. All rights reserved.

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.

Identification of Clusters of Foot Pain Location in a Community Sample


Objective To identify foot pain clusters according to pain location in a community-based sample of the general population. Methods This study analyzed data from the North West Adelaide Health Study. Data were obtained between 2004 and 2006, using computer-assisted telephone interviewing, clinical assessment, and self-completed questionnaire. The location of foot pain was assessed using a diagram during the clinical assessment. Hierarchical cluster analysis was undertaken to identify foot pain location clusters, which were then compared in relation to demographics, comorbidities, and podiatry services utilization. Results There were 558 participants with foot pain (mean age 54.4 years, 57.5% female). Five clusters were identified: 1 with predominantly arch and ball pain (26.8%), 1 with rearfoot pain (20.9%), 1 with heel pain (13.3%), and 2 with predominantly forefoot, toe, and nail pain (28.3% and 10.7%). Each cluster was distinct in age, sex, and comorbidity profile. Of the two clusters with predominantly forefoot, toe, and nail pain, one of them had a higher proportion of men and those classified as obese, had diabetes mellitus, and used podiatry services (30%), while the other was comprised of a higher proportion of women who were overweight and reported less use of podiatry services (17.5%). Conclusion Five clusters of foot pain according to pain location were identified, all with distinct age, sex, and comorbidity profiles. These findings may assist in the identification of individuals at risk for developing foot pain and in the development of targeted preventive strategies and treatments.

Fibromyalgia and the Prediction of Two-Year Changes in Functional Status in Rheumatoid Arthritis Patients


Objective Previous cross-sectional studies have shown that rheumatoid arthritis (RA) patients with fibromyalgia (FM) have higher disease activity, greater medical costs, and worse quality of life compared to RA patients without FM. We determined the impact of FM on 2-year changes in the functional status of RA patients in a prospective study. Methods Subjects included participants in the Brigham Rheumatoid Arthritis Sequential Study who were enrolled in a substudy of the effects of pain in RA. Subjects completed questionnaires, including the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) and Polysymptomatic Distress (PSD) scale, semiannually, and underwent physical examination and laboratory tests yearly. Results Of the 156 included RA subjects, 16.7% had FM, while 83.3% did not. In a multivariable linear regression model adjusted for age, sex, race, baseline MDHAQ score, disease duration, rheumatoid factor/cyclic citrullinated peptide antibody seropositivity, disease activity, and psychological distress, RA patients with FM had a 0.14 greater 2-year increase in MDHAQ score than RA patients without FM (P = 0.021). In secondary analyses examining the association between continuous PSD scale score and change in MDHAQ, higher PSD scale scores were significantly associated with greater 2-year increases in MDHAQ score (β coefficient 0.013, P = 0.011). Conclusion Both the presence of FM and increasing number of FM symptoms predicted worsening of functional status among individuals with RA. Among individuals with RA and FM, the magnitude of the difference in changes in MDHAQ was 4- to 7-fold higher than typical changes in MDHAQ score among individuals with established RA.

Clinical and Serologic Features in Patients With Incomplete Lupus Classification Versus Systemic Lupus Erythematosus Patients and Controls


Objective Incomplete lupus erythematosus (ILE) involves clinical and/or serologic manifestations consistent with but insufficient for systemic lupus erythematosus (SLE) classification. Because the nature of ILE is poorly understood and no treatment recommendations exist, we examined the clinical manifestations, medication history, and immunologic features in a diverse collection of ILE and SLE patients. Methods Medical records of subjects enrolled in the Lupus Family Registry and Repository were reviewed for medication history and American College of Rheumatology (ACR) classification criteria to identify ILE patients (3 ACR criteria; n = 440) and SLE patients (≥4 ACR criteria; n = 3,397). Participants completed the Connective Tissue Disease Screening Questionnaire. Anticardiolipin and plasma B lymphocyte stimulator (BLyS) were measured by enzyme-linked immunosorbent assay, antinuclear antibodies (ANAs) by indirect immunofluorescence, and 13 autoantibodies by bead-based assays. Results On average, ILE patients were older than SLE patients (46.2 years versus 42.0 years; P < 0.0001), and fewer ILE patients were African American (23.9% versus 32.2%; P < 0.001). ILE patients exhibited fewer autoantibody specificities than SLE patients (1.3 versus 2.6; P < 0.0001) and were less likely to have ANA titers ≥1:1,080 (10.5% versus 19.5%; P < 0.0001). BLyS levels were intermediate in ILE patients (controls < ILE; P = 0.016; ILE < SLE; P = 0.008). Pericarditis, renal, or neurologic manifestations occurred in 12.5% of ILE patients and were associated with non–European American race/ethnicity (P = 0.012). Hydroxychloroquine use increased over time, but was less frequent in ILE than SLE patients (65.2% versus 83.1%; P < 0.0001). Conclusion Although usually characterized by milder symptoms, ILE manifestations may require immunomodulatory treatments. Longitudinal studies are necessary to understand how ILE affects organ damage and future SLE risk, and to delineate molecular pathways unique to ILE.

Risk of Autism Spectrum Disorders in Children Born to Mothers With Rheumatoid Arthritis: A Systematic Literature Review


Objective There is recent evidence to suggest that in utero exposure to maternal antibodies and cytokines is an important risk factor for autism spectrum disorders (ASDs). We aimed to systematically review the risk of ASDs in children born to mothers with rheumatoid arthritis (RA) compared to children born to mothers without RA. Methods We conducted a systematic review of original articles using the electronic databases PubMed, Embase, and Web of Science. Results Our literature search yielded a total of 70 articles. Of the potentially relevant studies retrieved, 67 were excluded for lack of relevance and/or because they did not report original data. Three studies were included in the final analysis. A case–control study found no difference in the prevalence of RA in mothers of children with ASDs versus control mothers. Another case–control study showed a statistically significant 8-fold increase in autoimmune disorders, including RA, in mothers of offspring with ASDs compared to controls. Forty-six percent of offspring with ASDs had a first-degree relative with RA, compared to 26% of controls. And in a population-based cohort study, investigators observed an increased risk of ASDs in children with a maternal history of RA compared to children born to unaffected mothers. These studies had methodologic limitations: none controlled for medication exposures, only 1 controlled for obstetric complications and considered the timing of RA diagnosis in relation to pregnancy, and all but 1 used a case–control study design. Conclusion Observational studies suggest a potentially increased risk of ASDs in children born to mothers with RA compared to children born to mothers without RA, although data are limited.

Impact of Obesity and Adiposity on Inflammatory Markers in Patients With Rheumatoid Arthritis


Objective The C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are important disease activity biomarkers in rheumatoid arthritis (RA). This study aimed to determine to what extent obesity biases these biomarkers. Methods Body mass index (BMI) associations with CRP level and ESR were assessed in 2 RA cohorts: the cross-sectional Body Composition (BC) cohort (n = 451), including whole-body dual x-ray absorptiometry measures of fat mass index; and the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA) registry (n = 1,652), using multivariable models stratified by sex. For comparison, associations were evaluated in the general population using the National Health and Nutrition Examination Survey. Results Among women with RA and in the general population, greater BMI was associated with greater CRP levels, especially among women with severe obesity (P < 0.001 for BMI ≥35 kg/m2 versus 20–25 kg/m2). This association remained after adjustment for joint counts and patient global health scores (P < 0.001 in BC and P < 0.01 in VARA), but was attenuated after adjustment for fat mass index (P = 0.17). Positive associations between BMI and ESR in women were more modest. In men with RA, lower BMI was associated with higher CRP levels and ESR, contrasting with positive associations among men in the general population. Conclusion Obesity is associated with higher CRP levels and ESR in women with RA. This association is related to fat mass and not RA disease activity. Low BMI is associated with higher CRP levels in men with RA; this unexpected finding remains incompletely explained but likely is not a direct effect of adiposity.

Fear of Movement and Associated Factors Among Adults With Symptomatic Knee Osteoarthritis


Objective To examine the frequency of and factors associated with fear of movement (FOM) among patients with symptomatic knee osteoarthritis (KOA), using the new Brief Fear of Movement (BFOM) measure. Methods Participants (n = 350) enrolled in a clinical trial completed the BFOM scale prior to randomization. The relationships of BFOM with the following characteristics were examined: age, sex, race, education, pain and activities of daily living (ADL) subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee symptom duration, depressive symptoms (8-item Patient Health Questionnaire [PHQ-8]), history of falls and knee injury, family history of knee problems, self-efficacy for exercise (SEE), and unilateral balance test. A proportional odds logistic regression model examined multivariable associations of participant characteristics with a 3-level BFOM variable (agreement with 0, 1–2, or ≥3 items). Results The majority of participants (77%) agreed with at least 1 item on the BFOM scale, and 36% endorsed 3+ items, suggesting a high degree of FOM. In the multivariable model, the following remained significant after backward selection: age (odds ratio [OR] 0.79 per 10-point increase, 95% confidence interval [95% CI] 0.66–0.95), KOOS ADL (OR 0.86 per 10-point increase, 95% CI 0.76–0.97), PHQ-8 (OR 1.15, 95% CI 1.08–1.22), and SEE (OR 0.87 per 10-point increase, 95% CI 0.78–0.96). Conclusion FOM was common among patients with symptomatic KOA, and this could negatively impact physical activity. Psychological variables were significantly associated with FOM, suggesting behavioral and psychological interventions may decrease FOM and improve outcomes among individuals with symptomatic KOA.

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts


Objective To assess the 5-year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years. Methods Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS) method in the Early Rheumatoid Arthritis Study (ERAS), 1986–2001, and the Early Rheumatoid Arthritis Network (ERAN), 2002–2013. Mixed-effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN, separately. RF, along with age, sex, and baseline markers of disease activity were controlled for. Results A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy-four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF-positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855). Conclusion Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease-modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment.

Effect of Comprehensive Behavioral and Exercise Intervention on Physical Function and Activity Participation After Total Knee Replacement: A Pilot Randomized Study


Objective To test the feasibility of a comprehensive behavioral intervention (CBI) program that combines intense exercises with an education program, to be implemented at a later stage (3 months) following total knee replacement (TKR), and to get a first impression of the effects of the CBI as compared to a standard of care exercise (SCE) program on the outcomes of physical function and physical activity. Methods A total of 44 subjects participated in a 3-month program of either CBI or SCE, followed by 3 months of a home exercise program. Outcomes of physical function and physical activity were measured at baseline and at 6-month followup. Analysis of variance was used to compare statistical differences between groups, whereas responder analyses were used for clinically important differences. Results The CBI was found to be safe and well tolerated. As compared to the SCE group, the CBI group had less pain (P = 0.035) and better physical function based on the Short Form 36 health survey (P = 0.017) and the single-leg stance test (P = 0.037). The other outcome measures did not demonstrate statistically significant differences between the 2 groups. Results from the responder analysis demonstrated that the CBI group had a 36% higher rate of responders in physical function as compared to the SCE group. Also, the CBI group had 23% more responders in the combined domains of physical function and physical activity. Conclusion The CBI program is feasible and improves physical function and physical activity in patients several months after TKR. Larger pragmatic randomized trials are needed to confirm the results of this study.

Impact of Uveitis on Quality of Life in Adult Patients With Juvenile Idiopathic Arthritis


Objective To establish the impact of uveitis on the quality of life (QoL) in adult patients with juvenile idiopathic arthritis (JIA). Methods Adult patients with a history of JIA, both with (n = 31) or without (n = 51) chronic anterior uveitis, were included. Their scores on 3 validated QoL questionnaires (National Eye Institute Visual Functioning Questionnaire [NEI VFQ-25], Medical Outcomes Study 36-Item Short Form health survey [SF-36], and EuroQol 5-domain questionnaire [EQ-5D]) were analyzed to find factors that could influence QoL. Results The median overall composite score (OCS) of the NEI VFQ-25 was significantly worse in the uveitis group compared to the non-uveitis group (respectively, 83.4 [range 15.2–94.7] and 94.9 [range 46.3–100]; P < 0.001). Nearly all subscale scores were lower in patients with uveitis than in patients without uveitis (P < 0.001 for all). After adjusting for duration of arthritis, JIA subtype, arthritis onset before or after 1990, and the use of systemic immunomodulatory medication, the QoL was still worse in patients with uveitis (NEI VFQ-25 OCS regression coefficient = −11.7; P = 0.002). No significant differences were found between the groups for the SF-36 and the EQ-5D. In the total JIA group, the use of systemic medication appeared to negatively influence some general QoL scores. Conclusion Having a history of uveitis has a substantial negative effect on the vision-related QoL in JIA in adulthood, despite good visual acuity. General QoL scores did not differ between uveitis and non-uveitis patients, but the use of systemic immunomodulatory treatment, independent of uveitis, did negatively influence general QoL scores in adult JIA patients.

“Sounds a Bit Crazy, But It Was Almost More Personal:” A Qualitative Study of Patient and Clinician Experiences of Physical Therapist–Prescribed Exercise For Knee Osteoarthritis Via Skype


Objective To explore the experience of patients and physical therapists with Skype for exercise management of knee osteoarthritis (OA). Methods This was a qualitative study. The Donabedian model for quality assessment in health care (structure, process, and outcomes) informed semistructured individual interview questions. The study involved 12 purposively sampled patients with knee OA who received physical therapist–prescribed exercise over Skype, and all therapists (n = 8) who delivered the intervention in a clinical trial were interviewed about their experiences. Interviews were audio recorded and transcribed. Two investigators undertook coding and analysis using a thematic approach. Results Six themes arose from both patients and therapists. The themes were Structure: technology (easy to use, variable quality, set-up assistance helpful) and patient convenience (time efficient, flexible, increased access); Process: empowerment to self-manage (facilitated by home environment and therapists focusing on effective treatment) and positive therapeutic relationships (personal undivided attention from therapists, supportive friendly interactions); and Outcomes: satisfaction with care (satisfying, enjoyable, patients would recommend, therapists felt Skype more useful as adjunct to usual practice) and patient benefits (reduced pain, improved function, improved confidence and self-efficacy). A seventh theme arose from therapists regarding process: adjusting routine treatment (need to modify habits, discomfort without hands-on, supported by research environment). Conclusion Patients and physical therapists described mostly positive experiences using Skype as a service delivery model for physical therapist–supervised exercise management of moderate knee OA. Such a model is feasible and acceptable and has the potential to increase access to supervised exercise management for people with knee OA, either individually or in combination with traditional in-clinic visits.

Bone Mineral Density and the Risk of Hip and Knee Osteoarthritis: The Johnston County Osteoarthritis Project


Objective To address knowledge gaps regarding the relationship between bone mineral density (BMD) and incident hip or knee osteoarthritis (OA); specifically, lack of information regarding hip OA or symptomatic outcomes. Methods Using data (n = 1,474) from the Johnston County Osteoarthritis Project's first (1999–2004) and second (2005–2010) followup of participants ages ≥45 years, we examined the association between total hip BMD and both hip and knee OA. Total hip BMD was measured using dual x-ray absorptiometry, and participants were classified into sex-specific quartiles (low, intermediate low, intermediate high, and high). Radiographic OA (ROA) was defined as development of Kellgren/Lawrence grade ≥2. Symptomatic ROA (sROA) was defined as onset of both ROA and symptoms. Weibull regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results Median followup time was 6.5 years (range 4.0–10.2 years). In multivariate models, and compared with participants with low BMD, those with intermediate high and high BMD were less likely to develop hip sROA (HR 0.52 [95% CI 0.31–0.86] and 0.56 [95% CI 0.31–0.86], respectively; P = 0.024 for trend); high BMD was not associated (HR 0.69 [95% CI 0.45–1.06]) with risk of hip ROA. Compared with participants with low BMD, those with intermediate low and intermediate high total hip BMD were more likely to develop knee sROA (HR 2.15 [95% CI 1.40–3.30] and 1.65 [95% CI 1.02–2.67], respectively; P = 0.325 for trend); similar associations were seen with knee ROA. Conclusion Our findings suggest that higher BMD may reduce the risk of hip sROA, while intermediate levels may increase the risk of both knee sROA and ROA.

Comparative Effectiveness of Mycophenolate Mofetil for the Treatment of Juvenile-Onset Proliferative Lupus Nephritis


Objective Although juvenile-onset proliferative lupus nephritis (PLN) leads to significant morbidity and mortality, there is no clinical trials–based evidence to support the treatment effectiveness of any therapy for juvenile-onset PLN. Marginal structural models enable us to estimate treatment effectiveness using observational data while accounting for confounding by indication. Methods We used prospectively collected data to examine the effect of mycophenolate mofetil (MMF), compared to the use of other therapies, on the long-term outcome of a juvenile-onset PLN cohort (age at PLN onset <18 years). The major outcome variable was the estimated glomerular filtration rate (GFR) using the revised Schwartz formula. Confounding by indication was corrected for marginal structural model. Results A total of 172 subjects with juvenile-onset PLN, with a mean followup duration of approximately 4 years, were included. Overall, MMF was superior to other therapies, with a relative effect estimate for MMF of 1.06, i.e., 6% better estimated GFR on average (95% confidence interval 0.7, 11.3), corrected for potential confounding by indication. We found that beginning in year 4 there was a significant improvement in estimated GFR in the patients who were treated with MMF versus other therapies. This improvement was maintained until the end of the study. Conclusion MMF was more beneficial than other therapies in improving/maintaining long-term renal function in patients with juvenile-onset PLN up to a maximum followup of 7 years. This finding is consistent with evidence from adult PLN clinical trials.

Impact of Moving From a Widespread to Multisite Pain Definition on Other Fibromyalgia Symptoms


Objective To investigate whether associations between pain and the additional symptoms associated with fibromyalgia are different in persons with chronic widespread pain (CWP) compared to multisite pain (MSP), with or without joint areas. Methods Six studies were used: 1958 British birth cohort, Epidemiology of Functional Disorders, Kid Low Back Pain, Managing Unexplained Symptoms (Chronic Widespread Pain) in Primary Care: Involving Traditional and Accessible New Approaches, Study of Health and its Management, and Women's Health Study (WHEST; females). MSP was defined as the presence of pain in ≥8 body sites in adults (≥10 sites in children) indicated on 4-view body manikins, conducted first to include joints (positive joints) and second without (negative joints). The relationship between pain and fatigue, sleep disturbance, somatic symptoms, and mood impairment was assessed using logistic regression. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Results There were 34,818 participants across the study populations (adults age range 42–56 years, male 43–51% [excluding WHEST], and CWP prevalence 12–17%). Among those reporting MSP, the proportion reporting CWP ranged between 62% and 76%. Among those reporting the symptoms associated with fibromyalgia, there was an increased likelihood of reporting pain, the magnitude of which was similar regardless of the definition used. For example, within WHEST, reporting moderate/severe fatigue (Chalder fatigue scale 4–11) was associated with a >5-fold increase in likelihood of reporting pain (CWP OR 5.2 [95% CI 3.9–6.9], MSP–positive joints OR 6.5 [95% CI 5.0–8.6], and MSP–negative joints OR 6.5 [95% CI 4.7–9.0]). Conclusion This large-scale study demonstrates that regardless of the pain definition used, the magnitude of association between pain and other associated symptoms of fibromyalgia is similar. This finding supports the continued collection of both when classifying fibromyalgia, but highlights the fact that pain may not require to[...]

Perioperative Timing of Infliximab and the Risk of Serious Infection After Elective Hip and Knee Arthroplasty


Objective The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after elective hip or knee arthroplasty. Methods A retrospective cohort study evaluated US Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty from 2007 to 2013. Propensity-adjusted analyses examined whether infliximab stop timing (time between the most recent infusion and surgery) was associated with hospitalized infection within 30 days or prosthetic joint infection (PJI) within 1 year. Results Hospitalized infection within 30 days occurred after 270 of 4,288 surgeries (6.3%). Infliximab stop timing <4 weeks versus 8–12 weeks was not associated with an increase in infection within 30 days (propensity-adjusted odds ratio [OR] 0.90 [95% confidence interval (95% CI) 0.60–1.34]). The rate of PJI was 2.9 per 100 person-years and was not increased in patients with stop timing <4 weeks versus 8–12 weeks (hazard ratio [HR] 0.98 [95% CI 0.52–1.87]). Glucocorticoid dosage >10 mg/day was associated with increased risk of 30-day infection (OR 2.11 [95% CI 1.30–3.40]) and PJI (HR 2.70 [95% CI 1.30–5.60]). Other risk factors for infection included elderly age, comorbidities, revision surgery, and previous hospitalized infection. Conclusion Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short- or long-term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially >10 mg/day, was associated with an increased infection risk.

Cutaneous and Systemic Findings Associated With Nuclear Matrix Protein 2 Antibodies in Adult Dermatomyositis Patients


Objective To characterize the cutaneous and systemic clinical phenotype of dermatomyositis patients with antinuclear matrix protein 2 (anti–NXP-2) antibodies. Methods We conducted a retrospective cohort analysis of 178 dermatomyositis patients seen at the Stanford University Clinic. An electronic chart review employing a keyword search strategy was performed to collect clinical and laboratory data. Anti–NXP-2 antibodies were assayed by immunoprecipitation using NXP-2 produced by in vitro transcription/translation. Results Antibodies to NXP-2 were detected in 20 of the 178 patients (11%). Anti–NXP-2 antibodies were associated with male sex (50% versus 25%; P = 0.02), dysphagia (74% versus 39%; P = 0.006), myalgia (89% versus 52%; P = 0.002), peripheral edema (35% versus 11%; P = 0.016), and calcinosis (37% versus 11%; P = 0.007). These patients were less likely to be clinically amyopathic (5% versus 23%; P = 0.08). Five of the 20 patients with anti–NXP-2 antibodies (25%) had an associated internal malignancy. No other cutaneous characteristics were associated with anti–NXP-2 antibodies, except a decreased frequency of Gottron's sign (44% versus 75%; P = 0.012) and a greater likelihood of having mild skin disease. Conclusion Dermatomyositis patients with anti–NXP-2 antibodies have a distinct and often severe systemic phenotype that includes myalgia, peripheral edema, and significant dysphagia, despite having milder inflammatory skin disease.

Population-Based Study of Changes in Arthritis Prevalence and Arthritis Risk Factors Over Time: Generational Differences and the Role of Obesity


Objective To investigate cohort effects in arthritis prevalence across 4 birth cohorts: World War II (born 1935–1944), older and younger baby boomers (born 1945–1954 and 1955–1964, respectively), and Generation X (born 1965–1974), and to determine whether birth cohort effects in arthritis prevalence were associated with differences in risk factors over time or period effects. Methods Analysis of biannually collected data from the longitudinal Canadian National Population Health Survey, 1994–2011 (n = 8,817 at baseline). Data included self-reported arthritis diagnosed by a health professional, risk factors (years of education, household income, smoking, physical activity, sedentary behavior, body mass index [BMI]), and survey year as an indicator of period. We used hierarchical age–period–cohort analyses to compare the age trajectory of arthritis by birth cohort and to examine the contribution of changes in risk factors and period to cohort differences. Results More recent cohorts had successively a greater prevalence of arthritis. Risk factors were significantly associated with arthritis prevalence independently of cohort differences. The effects of increasing education and income over time on potentially reducing the arthritis prevalence were almost counter-balanced by effects of increasing BMI. Significant cohort–BMI and age–BMI interactions indicated an earlier age of arthritis onset for obese individuals than those of normal weight. Conclusion Projections that only take into account the changing age structure of the population may underestimate future trends. Our understanding of the impact of BMI on arthritis is likely an underestimate. Cohort differences focus attention on the need to target arthritis management education to young and middle-aged adults.

Issue Information


Serious Infection Rates Among Children With Systemic Lupus Erythematosus Enrolled in Medicaid


Objective To investigate the nationwide prevalence and incidence of serious infections among children with systemic lupus erythematosus (SLE) enrolled in Medicaid, the US health insurance program for low-income patients. Methods From Medicaid claims (2000–2006) we identified children ages 5 to <18 years with SLE (≥3 International Classification of Diseases, Ninth Revision [ICD-9] codes of 710.0, each >30 days apart) and lupus nephritis (LN; ≥2 ICD-9 codes for kidney disease on/after SLE codes). From hospital discharge diagnoses, we identified infection subtypes (bacterial, fungal, and viral). We calculated incidence rates (IRs) per 100 person-years, mortality rates, and hazard ratios adjusted for sociodemographic factors, medications, and preventive care. Results Among 3,500 children with identified SLE, 1,053 serious infections occurred over 10,108 person-years; the IR was 10.42 per 100 person-years (95% confidence interval [95% CI] 9.80–11.07) among all those with SLE and 17.65 per 100 person-years (95% CI 16.29–19.09) among those with LN. Bacterial infections were most common (87%, of which 39% were bacterial pneumonias). In adjusted models, African Americans and American Indians had higher rates of infections compared with white children, and those with comorbidities or receiving corticosteroids had higher infection rates than those without. Males had lower rates of serious infections compared to females. The 30-day postdischarge mortality rate was 4.4%. Conclusion Overall, hospitalized infections were very common in children with SLE, with bacterial pneumonia being the most common infection. Highest infection risks were among African American and American Indian children, those with LN, comorbidities, and those taking corticosteroids.

From Childhood to Adulthood: The Trajectory of Damage in Patients With Juvenile-Onset Systemic Lupus Erythematosus


Objective To determine the longitudinal damage trajectory of patients with juvenile-onset systemic lupus erythematosus (SLE), and to identify baseline and disease course predictors of damage trajectory. Methods This is a retrospective inception cohort. Longitudinal pediatric-age data were obtained from a juvenile-onset SLE research database, while adult-age data were obtained from either a research database or patients' charts. Baseline factors were tested as predictors. Time-varying factors were lagged 6–24 months before a visit for testing their predictive effects. The longitudinal damage trajectory was modeled using a weighted generalized estimating equation. Results This study cohort consisted of 473 subjects, with followup to 26 years. A total of 65% of patients were ages >18 years at last followup. Cataracts (14%), avascular necrosis (10%), and osteoporosis (5%) were the most common items of damage. Two patients had myocardial infarctions. Baseline features, self-reported ethnicity (Afro-Caribbean), earlier time periods of diagnosis, and the presence of a life-threatening major organ manifestation (lupus nephritis class III–V, cerebrovascular accidents, major organ vasculitis, pulmonary hemorrhage, or myocarditis), were associated with greater damage. Throughout the disease course, an acute confusional state, lupus headache, and fever predicted subsequent increases in the damage trajectory. A higher prednisone dose and exposure to cyclophosphamide also predicted subsequent increases in the damage trajectory. Antimalarial exposure was protective against an increase in damage trajectory. Conclusion Patients with juvenile-onset SLE accrue damage steadily into adulthood. Baseline factors predict greater damage and/or influence the evolution of the damage trajectory. Additionally, SLE clinical features and therapies during the course of di[...]

Clinical Profiles of Young Adults With Juvenile-Onset Fibromyalgia With and Without a History of Trauma


Objective To examine the differential presentation(s) of psychological and health-related outcomes in young adults with juvenile-onset fibromyalgia (FM) with and without a history of trauma, compared to healthy controls. Methods In total, 110 participants (86 with juvenile-onset FM and 24 healthy controls, with a mean age of 23.4 years) completed a structured clinical interview to assess for trauma and psychological comorbidities, as well as self-report questionnaires on pain, physical functioning, and health care utilization. Results Of the juvenile-onset FM participants, 37% (n = 32) reported a history of trauma. Three group comparisons (i.e., juvenile-onset FM with trauma versus juvenile-onset FM with no trauma versus healthy controls) revealed that juvenile-onset FM participants significantly differed from healthy controls on all psychological and health-related outcomes. Further, although juvenile-onset FM participants with and without a history of trauma did not significantly differ on pain and physical functioning, juvenile-onset FM participants with a history of trauma were significantly more likely to have psychological comorbidities. Conclusion This is the first controlled study to examine the differential outcomes between juvenile-onset FM participants with and without a history of trauma. Group comparisons between juvenile-onset FM participants and healthy controls were consistent with previous research. Further, our findings indicate that juvenile-onset FM participants with a history of trauma experience greater psychological, but not physical, impairment than juvenile-onset FM participants without a history of trauma.

Additional Value of Different Radiographic Views on the Identification of Early Radiographic Hip and Knee Osteoarthritis and Its Progression: A Cohort Study


Objective To investigate the prevalence and progression of early radiographic osteoarthritis (OA) of the hip and knee on different radiographic views, to determine whether different radiographic views have additional value in detecting early hip and knee radiographic OA cases or progression. Methods In the Cohort Hip and Cohort Knee (CHECK) study (n = 1,002), 5 different radiographs were obtained: an anteroposterior and faux profile view of the hips, and posteroanterior, mediolateral, and skyline views of the knees. The prevalence of radiographic OA was estimated based on each view separately and in combinations. We determined whether different radiographic views have additional value in detecting and determining the progression of radiographic OA cases, compared to standard projections. Results In the hip, we found 22.9% more cases when we combined both views. In the knee, we detected 79.7% more radiographic OA cases when we combined information from all 3 different radiographic views than when using only the posteroanterior view. Progression was seen in 33.1% more cases when using 2 hip radiographs, and in 65.1% more cases when using 3 knee radiographs. Conclusion The use of different radiographic views increased the number of participants classified as having radiographic OA in an early OA cohort, both at baseline and at followup. The progression of early radiographic OA is demonstrated more frequently when multiple different radiographic views are used.

Association of Chondrocalcinosis in Knee Joints With Pain and Synovitis: Data From the Osteoarthritis Initiative


Objective To evaluate the relationship between chondrocalcinosis and pain or synovitis in knee joints by examining data from the Osteoarthritis Initiative (OAI). Methods Data were obtained from the OAI public-use data sets. The relationship between chondrocalcinosis on baseline knee radiograph and pain at baseline and at 4 years was examined. Analyses were adjusted for age, sex, body mass index, and Kellgren-Lawrence (K/L) grade and the correlation between 2 knees in a subject was controlled using generalized estimating equations. The relationship between chondrocalcinosis and synovitis on magnetic resonance imaging (MRI) was examined by comparing knees with chondrocalcinosis at baseline and age, sex, and K/L grade–matched knees with no chondrocalcinosis. We read MRIs of a subset of knees for synovitis using the MRI Osteoarthritis Knee Score (MOAKS) on baseline and 4-year MRI. Results Knees with chondrocalcinosis (n = 162) more often had pain compared to knees without chondrocalcinosis (n = 2,030) at baseline and had higher Western Ontario and McMaster Universities Osteoarthritis Index pain scores, both at baseline (mean 2.4 [95% confidence interval (95% CI) 1.9, 2.9]) versus mean 1.8 [95% CI 1.7, 1.9]) and at 4 years (mean 2.5 [95% CI 1.9, 3.1] versus mean 1.6 [95% CI 1.5, 1.8]), as well as higher Intermittent and Constant Osteoarthritis Pain intermittent pain scores at 4 years. There was no difference in MOAKS synovitis scores at baseline and at 4 years between the chondrocalcinosis group (n = 102) and the control group (n = 99). Conclusion Knees with chondrocalcinosis had increased pain and did not have higher synovitis scores on MRI compared to knees without chondrocalcinosis. The mechanisms by which chondrocalcinosis is associated with increased pain remain[...]

Lifetime Risk of Primary Total Hip Replacement Surgery for Osteoarthritis From 2003 to 2013: A Multinational Analysis Using National Registry Data


Objective To compare the lifetime risk of total hip replacement (THR) surgery for osteoarthritis (OA) between countries, and over time. Methods Data on primary THR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway, and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of THR was calculated for 2003 and 2013 using registry, life table, and population data. Results In 2003, lifetime risk of THR ranged from 8.7% (Denmark) to 15.9% (Norway) for females, and from 6.3% (Denmark) to 8.6% (Finland) for males. With the exception of females in Norway (where lifetime risk started and remained high), lifetime risk of THR increased significantly for both sexes in all countries from 2003 to 2013. In 2013, lifetime risk of THR was as high as 1 in 7 women in Norway, and 1 in 10 men in Finland. Females consistently demonstrated the highest lifetime risk of THR at both time points. Notably, lifetime risk for females in Norway was approximately double the risk for males in 2003 (females 15.9% [95% confidence interval (95% CI) 15.6–16.1], males 6.9% [95% CI 6.7–7.1]), and 2013 (females 16.0% [95% CI 15.8–16.3], males 8.3% [95% CI 8.1–8.5]). Conclusion Using representative, population-based data, this study found statistically significant increases in the lifetime risk of THR in 5 countries over a 10-year period, and substantial between-sex differences. These multinational risk estimates can inform resource planning for OA service delivery.

Current Risk Adjustment and Comorbidity Index Underperformance in Predicting Post-Acute Utilization and Hospital Readmissions After Joint Replacements: Implications for Comprehensive Care for Joint Replacement Model


Objective To compare the performances of 3 comorbidity indices, the Charlson Comorbidity Index, the Elixhauser Comorbidity Index, and the Centers for Medicare & Medicaid Services (CMS) risk adjustment model, Hierarchical Condition Category (HCC), in predicting post-acute discharge settings and hospital readmission for patients after joint replacement. Methods A retrospective study of Medicare beneficiaries with total knee replacement (TKR) or total hip replacement (THR) discharged from hospitals in 2009–2011 (n = 607,349) was performed. Study outcomes were post-acute discharge setting and unplanned 30-, 60-, and 90-day hospital readmissions. Logistic regression models were built to compare the performance of the 3 comorbidity indices using C statistics. The base model included patient demographics and hospital use. Subsequent models included 1 of the 3 comorbidity indices. Additional multivariable logistic regression models were built to identify individual comorbid conditions associated with high risk of hospital readmissions. Results The 30-, 60-, and 90-day unplanned hospital readmission rates were 5.3%, 7.2%, and 8.5%, respectively. Patients were most frequently discharged to home health (46.3%), followed by skilled nursing facility (40.9%) and inpatient rehabilitation facility (12.7%). The C statistics for the base model in predicting post-acute discharge setting and 30-, 60-, and 90-day readmission in TKR and THR were between 0.63 and 0.67. Adding the Charlson Comorbidity Index, the Elixhauser Comorbidity Index, or HCC increased the C statistic minimally from the base model for predicting both discharge settings and hospital readmission. The health conditions most frequently associated with hospital read[...]

Association Between Menopausal Factors and the Risk of Seronegative and Seropositive Rheumatoid Arthritis: Results From the Nurses’ Health Studies


Objective To investigate whether menopausal factors are associated with the development of serologic rheumatoid arthritis (RA) phenotypes. Methods Data were analyzed from the Nurses’ Health Studies (NHS; 1976–2010 and NHSII 1989–2011). A total of 120,700 female nurses ages 30–55 years in the NHS, and a total of 116,430 female nurses ages 25–42 years in the NHSII, were followed via biennial questionnaires on lifestyle and disease outcomes. In total, 1,096 incident RA cases were confirmed by questionnaire and chart review. Seropositive RA was defined as rheumatoid factor positive (RF) or antibodies to citrullinated protein antigen (ACPA) positive, and seronegative RA was defined as RF negative and ACPA negative. We used Cox proportional hazards models to obtain multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) of seropositive/seronegative RA associated with menopausal status, age at menopause, type of menopause, ovulatory years, and postmenopausal hormone therapy (PMH) use. Results Postmenopausal women had a 2-fold increased risk of seronegative RA, compared with premenopausal women (NHS: HR 1.8 [95% CI 1.1–3.0], NHSII: HR 2.4 [95% CI 1.4–3.9], and pooled HR 2.1 [95% CI 1.4–3.0]). Natural menopause at early age (≤44 years) was associated with an increased risk of seronegative RA (pooled HR 2.4 [95% CI 1.5–4.0]). None of the menopausal factors was significantly associated with seropositive RA. We observed no association between PMH use and the risk of seronegative or seropositive RA, except that PMH use of ≥8 years was associated with increased risk of seropositive RA (pooled HR 1.4 [95% CI 1.1–1.9]). Conclusion Postmenopause and [...]

Clinical Enthesitis in a Prospective Longitudinal Psoriatic Arthritis Cohort: Incidence, Prevalence, Characteristics, and Outcome


Objective To evaluate the incidence, prevalence, characteristics, disease associations, risk factors, and outcome of clinical enthesitis in patients with psoriatic arthritis (PsA). Methods The study included patients with PsA followed prospectively. Enthesitis was defined as the presence of at least 1 tender enthesis at 1 of the 18 entheseal sites of the Spondyloarthritis Research Consortium of Canada enthesitis index. Results Between 2008 and 2014, 281 of 803 patients had enthesitis, providing a prevalence of 35%. A total of 192 patients developed enthesitis during the course of followup, with an annual incidence of 0.9%. Most of the patients had 1 (48.4%) or 2 (32.2%) tender entheseal sites, and the mean ± SD number of sites per visit was 2.03 ± 1.6. The 3 most common sites were at the insertions of the Achilles tendon, plantar fascia on the calcaneus, and the lateral epicondyles (24.2%, 20.8%, and 17.2%, respectively). More active disease (higher actively inflamed joint count, tenosynovitis, and dactylitis), more pain, and less clinical damage were associated with enthesitis. Higher body mass index, more actively inflamed joints, and younger age were risk factors for developing this condition. Enthesitis resolved in most patients without changing treatment. Conclusion Clinical enthesitis is common, with a period prevalence of 35% of PsA patients. It usually involves only 1 or 2 sites simultaneously. The most common tender sites are at the insertions of the Achilles tendon, plantar fascia, and the lateral epicondyles. More active disease and more pain are associated with enthesitis.

Clinical Characteristics, Disease Activity, and Patient-Reported Outcomes in Psoriatic Arthritis Patients With Dactylitis or Enthesitis: Results From the Corrona Psoriatic Arthritis/Spondyloarthritis Registry


Objective To characterize psoriatic arthritis (PsA) patients with dactylitis or enthesitis and evaluate the associations of these manifestations with disease activity and patient-reported outcomes. Methods Using the Corrona PsA/Spondyloarthritis Registry, patient characteristics, disease activity, and patient-reported outcomes at registry enrollment were assessed for PsA patients ages ≥18 years with or without dactylitis or enthesitis. Regression models were used to evaluate associations of dactylitis and enthesitis with outcomes, including minimal disease activity, Health Assessment Questionnaire scores, patient-reported pain and fatigue, and work productivity (Work Productivity and Activity Impairment questionnaire). Adjustments were made for age, sex, race, body mass index, disease duration, and history of biologic agent, disease-modifying antirheumatic drug, and prednisone use. Results This analysis included 1,567 PsA patients (420 with enthesitis; 228 with dactylitis). Patients with versus without dactylitis or enthesitis had greater disease activity and were less likely to be in minimal disease activity (P < 0.05). Patients with versus without enthesitis had poorer functional status as assessed by the Health Assessment Questionnaire (adjusted P = 4.15 x 10−5), greater patient-reported pain and fatigue (adjusted P < 0.0001), and greater likelihood of any impairment while working (adjusted odds ratio [OR] 1.57, P = 0.027), overall work impairment (OR 1.85, P = 0.006), and activity impairment (OR 1.77, P = 0.008). Dactylitis was associated with similar numerical trends, but differences versus patients without dactylitis did [...]

Sensitivity and Specificity of Radiographic Scoring Instruments for Detecting Change in Axial Psoriatic Arthritis


Objective There is no widely recognized method used to assess axial disease in psoriatic arthritis (PsA). We aimed to determine the sensitivity to change of the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s), the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), the Radiographic Ankylosing Spondylitis Spine Score (RASSS), and the PsA Spondylitis Radiology Index (PASRI) in axial PsA. Methods Radiographs of 105 patients with axial PsA were retrieved for 2 time points at least 2 years apart and subsequently anonymized. All radiographs were scored by 3 rheumatologists blinded to name and order of examination using an electronic application that allowed recording of disease manifestations specific to axial PsA and automatically calculated the BASRI-s, mSASSS, RASSS, and PASRI scores. An independent expert determined whether there was true radiographic progression from an overall impression after viewing the radiographs with knowledge of chronologic order. The sensitivity, specificity, and odds ratios for every 1-unit increase in the scores were determined to identify true change. Results Of the patients studied, 25 (24%) showed progression, as determined by the independent expert. The respective sensitivity and specificity values for an increase in score to detect true change were as follows: 0.48 and 0.78 (BASRI-s), 0.52 and 0.84 (mSASSS), 0.44 and 0.84 (RASSS), and 0.52 and 0.74 (PASRI). Logistic regression analyses showed that an increase of 1 point in the respective scores was associated with the following odds ratios for identifying true progression: BASRI-s 3.0, mSASSS 5.27[...]

Medication Nonadherence in Systemic Lupus Erythematosus: A Systematic Review


Objective Medication nonadherence has not been well characterized in systemic lupus erythematosus (SLE). Our objective was to a conduct a systematic review of the literature, examining the burden and determinants of medication nonadherence in SLE. Methods We conducted a systematic search of Medline (1946–2015), Embase (1974–2015), and Web of Science (1900–2015) databases and selected original studies of SLE patients that evaluated nonadherence to SLE therapies as the primary study outcome. We extracted information on study design, sample size, length of followup, data sources, type of nonadherence problem examined, adherence measures and reported estimates, and determinants of adherence reported in multivariable analyses. Results After screening 4,111 titles, 11 studies met the inclusion criteria. Study sample sizes ranged from 32 to 246 patients, and studies were categorized according to data source: self-report (5), electronic monitoring devices (1), clinical records from rheumatology clinics (3), and refill information from pharmacy records (2). Overall, the percentage of nonadherent patients ranged from 43% to 75%, with studies consistently reporting that over half of patients are nonadherent. Studies also showed that up to 33% of patients discontinue therapy after 5 years. Determinants of nonadherence included having depression, rural residence, lower education level, and polypharmacy. Conclusion Overall, synthesis of current evidence suggests that the burden of medication nonadherence is substantial in SLE. Findings highlight the importance of developing interventi[...]

Subjective and Objective Measures of Dryness Symptoms in Primary Sjögren's Syndrome: Capturing the Discrepancy


Objective To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a sensitivity scale) and to explore predictors of dryness sensitivity. Methods Archive data from the UK Primary Sjögren's Syndrome Registry (n = 688) were used. Patients were classified on a scale from −5 (stoical) to +5 (sensitive) depending on the degree of discrepancy between their objective and subjective symptoms classes. Sensitivity scores were correlated with demographic variables, disease-related factors, and symptoms of pain, fatigue, anxiety, and depression. Results Patients were on average relatively stoical for both types of dryness symptoms (mean ± SD ocular dryness −0.42 ± 2.2 and −1.24 ± 1.6 oral dryness). Twenty-seven percent of patients were classified as sensitive to ocular dryness and 9% to oral dryness. Hierarchical regression analyses identified the strongest predictor of ocular dryness sensitivity to be self-reported pain and that of oral dryness sensitivity to be self-reported fatigue. Conclusion Ocular and oral dryness sensitivity can be classified on a continuous scale. The 2 symptom types are predicted by different variables. A large number of factors remain to be explored that may impact symptom sensitivity in primary Sjögrenʼs syndrome, and the proposed method could be used to identify relatively sensitive and stoical patients for future studies.

Gout Self-Management in African American Veterans: A Qualitative Exploration of Challenges and Solutions From Patients' Perspectives


Objective To explore gout self-management and associated challenges and solutions in African Americans. Methods We conducted semistructured interviews with 35 African American veterans with gout, who received health care at Birmingham or Philadelphia Veterans Affairs (VA) medical centers, had filled urate-lowering therapy (ULT; most commonly allopurinol) for at least 6 months, and had a ULT medication possession ratio ≥80%. The interview protocol was constructed to explore key concepts related to gout self-management, including initial diagnosis of gout, beginning medical care for gout, the course of the gout, ULT medication adherence, dietary strategies, comorbidity and side effects, and social support. Results Thirty-five African American male veterans with gout who had ≥80% ULT adherence (most commonly, allopurinol) were interviewed at Birmingham (n = 18) or Philadelphia (n = 17) VA medical centers. Mean age was 65 years, mean body mass index was 31.9 kg/m2, 97% had hypertension, 23% had coronary artery disease, and 31% had renal failure. The main themes motivating African American veterans to better gout self-management were fear of pain, adherence to medications, self-discipline, lifestyle changes, information gathering, and developing a positive outlook. Birmingham participants more frequently revealed skipping gout medications. More Philadelphia participants discussed lifestyle/diet changes to prevent gout flares, indicated limiting social activities that involved drinking, and sought more information about gout s[...]

“It's Not Me, It's Not Really Me.” Insights From Patients on Living With Systemic Sclerosis: An Interview Study


Objective Patients with systemic sclerosis (SSc) experience severe physical limitations and psychological morbidity, but their lived experience remains underrepresented and is reflected in the scarcity of evidence-based patient-centered interventions. We aimed to describe patients’ perspectives of SSc to inform strategies to improve their care. Methods Face-to-face semistructured interviews were conducted with 30 adult patients with limited cutaneous or diffuse cutaneous SSc in Australia. Transcripts were thematically analyzed using HyperRESEARCH software. Results Six themes were identified: bodily malfunction (restrictive pain, debilitating physical changes, pervasive exhaustion), deprivation of social function (loss of work and career, social isolation, threat to traditional roles, loss of intimacy), disintegration of identity (stigmatizing physical changes, disassociated self-image, extinguished hopes, alone and powerless, invisibility of illness), insecurity of care (unrecognized disease, ambiguity around diagnosis and cause, information insufficiency, resigning to treatment limitations, seeking reassurance, fear of progression), avoiding the sick role (evading thoughts of sickness, protecting family, favorable comparison), and perseverance and hope (positive stoicism, optimism about treatment and monitoring, taking control of own health, pursuing alternative treatments, transcending illness through support). Conclusion SSc inflicts major bodily and social restrictions that crush patients[...]

Predictors of Reduced Health-Related Quality of Life in Adult Patients With Idiopathic Inflammatory Myopathies


Objective Extensive studies on health-related quality of life (HRQoL) in idiopathic inflammatory myopathies (IIMs) are lacking. Our objective was to document HRQoL and to identify factors associated with a reduced HRQoL in patients with IIM. Methods A total of 1,715 patients (median age 49.9 years, 70% female, 87% white) who met probable or definite Bohan and Peter criteria or Griggs criteria for myositis were included from the Myovision registry. HRQoL was ascertained using the Short Form 12 (SF-12) health survey questionnaire. HRQoL physical component summary (PCS) and mental component summary (MCS) scores in relation to different patient and disease characteristics were compared to scores from matched normative data from the US general population and rheumatoid arthritis (RA) patients. Bivariate and multiple linear regression analyses were performed to assess the association between HRQoL and patient and disease parameters. Results The mean SF-12 summary scores were significantly lower in IIM patients than in the normative and RA populations. A diagnosis of inclusion body myositis, older age, patient-reported negative effect of disease on work, presence of another co-occurring autoimmune disease, polypharmacy, and IIM-associated lung disease and joint involvement were significantly associated with lower PCS scores. Lower MCS scores were associated with joint involvement and a negative effect of disease on work. Conclusion In this large study of patient-reported outc[...]

Rheumatic and Musculoskeletal Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors: A Systematic Review of the Literature


Objective Immune checkpoint inhibitors (ICIs) are improving prognoses in advanced stage cancers, but they also lead to immune-related adverse events (IRAEs). IRAEs targeting many organ systems have been reported, but musculoskeletal and rheumatic IRAEs have not been well-characterized. We systematically reviewed published literature on musculoskeletal and rheumatic IRAEs to better understand prevalence and clinical characteristics. Methods Medline and CENTRAL databases were searched for articles reporting rheumatic and musculoskeletal IRAEs secondary to ICI treatment. After screening abstracts and full texts in duplicate, clinical features, prevalence, and treatment data were extracted and summarized. Results A total of 1,725 unique abstracts were screened; 231 contained original data and were about ICIs and went to full-text screening. Fifty-two of these contained information about musculoskeletal or rheumatic IRAEs or about treatment with ICIs in preexisting autoimmune disease. Of these, 33 were clinical trials, 3 were observational studies, and 16 were case reports or series. Arthralgia prevalence in clinical trials ranged 1–43%, and myalgia was reported in 2–20%. Arthritis was reported in 5 of 33 clinical trials, and vasculitis was reported in only 2. One observational study and 3 case reports described patients with preexisting autoimmune disease treated with ICIs. Case reports included development of inflammatory arthritis, vasculitis[...]

Association of Fibrosing Myopathy in Systemic Sclerosis and Higher Mortality


Objective To determine if a unique subtype of scleroderma muscle disease exists by comparing the clinical features of systemic sclerosis (SSc; scleroderma) patients with predominant fibrosis on muscle biopsy to those with inflammatory muscle histopathology. Methods This retrospective, cross-sectional study included SSc patients with muscle weakness and an available muscle biopsy. Biopsies with fibrosis but without inflammation/necrosis were designated as “fibrosing myopathy,” and those with inflammation and/or necrosis were assigned a category of “inflammatory myopathy.” Clinical data, including features of SSc, serum creatine kinase (CK) levels, electromyography, autoantibody profile, and survival, were compared between the 2 groups. Results The study population consisted of 37 weak SSc patients, 8 with fibrosing myopathy and 29 with inflammatory myopathy. Compared to those with inflammatory myopathy, patients with fibrosing myopathy were more likely to have diffuse SSc skin subtype (87% versus 62%; P = 0.18), African American race (62.5% versus 37.9%; P = 0.20), and a lower mean ± SD forced vital capacity (55.5 ± 31.9 versus 66.4 ± 17.6; P = 0.23). They also had lower mean ± SD CK values (516 ± 391 versus 2,477 ± 3,511 IU/liter; P = 0.007) and lower aldolase values (13.8 ± 4.7 versus 27.3 ± 4.7; P = 0.01). Patients with fibrosing myopathy had a significantly higher mortality (5 of 8 [62.5%] versus 4 [...]

Antinuclear Matrix Protein 2 Autoantibodies and Edema, Muscle Disease, and Malignancy Risk in Dermatomyositis Patients


Objective Dermatomyositis (DM) patients typically present with proximal weakness and autoantibodies that are associated with distinct clinical phenotypes. We observed that DM patients with autoantibodies recognizing the nuclear matrix protein NXP-2 often presented with especially severe weakness. The aim of this study was to characterize the clinical features associated with anti–NXP-2 autoantibodies. Methods There were 235 DM patients who underwent testing for anti–NXP-2 autoantibodies. Patient characteristics, including muscle strength, were compared between those with and without these autoantibodies. The number of cancer cases observed in anti–NXP-2-positive subjects was compared with the number expected in the general population. Results Of the DM patients, 56 (23.8%) were anti–NXP-2-positive. There was no significant difference in the prevalence of proximal extremity weakness in patients with and without anti–NXP-2. In contrast, anti–NXP-2-positive patients had more prevalent weakness in the distal arms (35% versus 20%; P = 0.02), distal legs (25% versus 8%; P < 0.001), and neck (48% versus 23%; P < 0.001). Anti–NXP-2-positive subjects were also more likely to have dysphagia (62% versus 35%; P < 0.001), myalgia (46% versus 25%; P = 0.002), calcinosis (30% versus 17%; P = 0.02), and subcutaneous edema (36% versus 19%; P = 0.01) than anti–NXP-2-negative patients. Five an[...]