Showing papers in "Arthritis Care and Research in 2016"

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis: ACR RA Treatment Recommendations

Abstract: To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA).

Number of Persons With Symptomatic Knee Osteoarthritis in the US: Impact of Race and Ethnicity, Age, Sex, and Obesity.

Abstract: Objective The prevalence of symptomatic knee osteoarthritis (OA) has been increasing over the past several decades in the US, concurrent with an aging population and the growing obesity epidemic. We quantify the impact of these factors on the number of persons with symptomatic knee OA in the early decades of the 21st century. Methods We calculated the prevalence of clinically diagnosed symptomatic knee OA from the National Health Interview Survey 2007–2008 and derived the proportion with advanced disease (defined as Kellgren/Lawrence grade 3 or 4) using the Osteoarthritis Policy Model, a validated simulation model of knee OA. Incorporating contemporary obesity rates and population estimates, we calculated the number of persons living with symptomatic knee OA. Results We estimate that approximately 14 million persons had symptomatic knee OA, with advanced OA comprising more than half of those cases. This includes more than 3 million persons of racial/ethnic minorities (African American, Hispanic, and other). Adults younger than 45 years of age represented nearly 2 million cases of symptomatic knee OA and individuals between 45 and 65 years of age comprised 6 million more cases. Conclusion More than half of all persons with symptomatic knee OA are younger than 65 years of age. As many of these younger persons will live for 3 decades or more, there is substantially more time for greater disability to occur, and policymakers should anticipate health care utilization for knee OA to increase in the upcoming decades. These data emphasize the need for the deployment of innovative prevention and treatment strategies for knee OA, especially among younger persons.

Epidemiology of Chronic Low Back Pain in US Adults: Data From the 2009–2010 National Health and Nutrition Examination Survey

Abstract: Objective To describe epidemiologic characteristics and associations with increased healthcare utilization in US adults with chronic low back pain (cLBP).

Global Prevalence of Spondyloarthritis: A Systematic Review and Meta-Regression Analysis.

Abstract: Objective To summarize the prevalence of spondyloarthritis (SpA) and its subtypes in the general population, and to identify demographic and methodologic characteristics that might explain heterogeneity in prevalence estimates. Methods A systematic literature search was performed to identify relevant articles. Risk of bias was assessed and data were extracted. Pooled prevalences were calculated. Potential sources of heterogeneity were explored by subgroup analysis and meta-regression analysis. Results The prevalence of SpA ranged from 0.20% (95% confidence interval [95% CI] 0.00–0.66) in South-East Asia to 1.61% (95% CI 1.27–2.00) in Northern Arctic communities; the prevalence of ankylosing spondylitis (AS) from 0.02% (95% CI 0.00–0.21) in Sub-Saharan Africa to 0.35% (95% CI 0.24–0.48) in Northern Arctic communities; and the prevalence of psoriatic arthritis (PsA) from 0.01% (95% CI 0.00–0.17) in the Middle East to 0.19% (95% CI 0.16–0.32) in Europe. The following characteristics were significantly associated with variation in prevalence of SpA, AS, and/or PsA: proportion of females, mean age of the sample, geographic area and setting (demographic characteristics), year of data collection, case finding, and case ascertainment (methodologic characteristics). For the other SpA subgroups, too few studies were available to conduct a meta-analysis, but prevalence estimates of reactive arthritis (range 0.0–0.2%), SpA related to inflammatory bowel disease (range 0.0–0.1%), and undifferentiated SpA (range 0.0–0.7%) were generally low. Conclusion SpA is a common disease, but with large variation in reported prevalence estimates, which can partly be explained by differences in demographic and methodologic characteristics. Particularly, geographic area as well as case finding account for a substantial part of the heterogeneity.

Alternative Methods for Defining Osteoarthritis and the Impact on Estimating Prevalence in a US Population-Based Survey.

Abstract: Osteoarthritis (OA) is the most common joint disorder in the US (1), affecting an estimated 12% of US adults aged 25 to 74 years. This prevalence estimate, based on clinical examinations conducted forty years ago (1971 to 1975) as part of the first National Health and Nutrition Survey (NHANES I) (2), may be an underestimate of current prevalence for at least two reasons. First, symptomatic knee OA prevalence tripled among men and doubled among women from the 1980s to the 2000s (3). Second, obesity, which is a risk factor for another common type of OA, hand OA (4, 5), has increased dramatically since NHANES I (6) (7). We therefore generated an updated estimate of OA prevalence using data from the nationally representative Medical Expenditure Panel Survey (MEPS), which provides estimates of conditions with current adverse health impact (i.e., leading to healthcare utilization, disability, or that bothers the individual). Because it is healthcare utilization and disability that primarily drive the societal costs associated with OA, estimating the prevalence of OA with such adverse health impacts is important to public health practice.

Anti-Melanoma Differentiation-Associated Gene 5 Is Associated With Rapidly Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and Myopathic Dermatomyositis.

Abstract: Objective Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti–melanoma differentiation–associated gene 5 (anti–MDA-5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti–MDA-5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM.

Prevalence of Post-Chikungunya Infection Chronic Inflammatory Arthritis: A Systematic Review and Meta-Analysis.

Abstract: Objective To determine the percentage of patients who would develop chronic inflammatory rheumatism (CIR) following chikungunya (CHIK) virus disease Methods We conducted a systematic review of the literature in 3 databases (PubMed, Science Citation Index, and Scopus) to identify studies assessing the proportion of patients who progress to CHIK-CIR We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence intervals (95% CIs) A 2-tailed alpha level of 5% was used for hypothesis testing Measures of heterogeneity, including Cochran's Q statistic, the I2 index, and the tau-squared test, were calculated and reported Subgroup analyses were conducted by type of study and country, by studies evaluating chronic arthritis, and by studies with ≥200 patients and followup ≥18 months Publication bias was assessed using a funnel-plot Results Up to June 15, 2015, our literature search yielded 578 citations The pooled prevalence of CHIK-CIR in 18 selected studies among 5,702 patients was 4022% (95% CI 3111–4934; τ2 = 00838) From studies derived from India, prevalence was 2727% (95% CI 1566–3888; τ2 = 00411), while from France, prevalence was 5025% (95% CI 2538–7512; τ2 = 01797) The prevalence of CHIK chronic arthritis was 1366% (95% CI 931–1800; τ2 = 00060) Considering just those studies with ≥200 patients assessed, prevalence was 3414% (95% CI 2399–4429; τ2 = 00525) In studies with a followup ≥18 months, prevalence was 3213% (95% CI 2221–4204; τ2 = 00453) Conclusion According to our results in the most conservative scenario, approximately 25% of CHIK cases would develop CHIK-CIR (34% if we just consider the most representative studies), and 14% would develop chronic arthritis

Physical therapist‐delivered pain coping skills training and exercise for knee osteoarthritis: Randomized controlled trial

Abstract: Objective To investigate whether a 12-week physical therapist–delivered combined pain coping skills training (PCST) and exercise (PCST/exercise) is more efficacious and cost effective than either treatment alone for knee osteoarthritis (OA). Methods This was an assessor-blinded, 3-arm randomized controlled trial in 222 people (73 PCST/exercise, 75 exercise, and 74 PCST) ages ≥50 years with knee OA. All participants received 10 treatments over 12 weeks plus a home program. PCST covered pain education and training in cognitive and behavioral pain coping skills, exercise comprised strengthening exercises, and PCST/exercise integrated both. Primary outcomes were self-reported average knee pain (visual analog scale, range 0–100 mm) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, range 0–68) at week 12. Secondary outcomes included other pain measures, global change, physical performance, psychological health, physical activity, quality of life, and cost effectiveness. Analyses were by intent-to-treat methodology with multiple imputation for missing data. Results A total of 201 participants (91%), 181 participants (82%), and 186 participants (84%) completed week 12, 32, and 52 measurements, respectively. At week 12, there were no significant between-group differences for reductions in pain comparing PCST/exercise versus exercise (mean difference 5.8 mm [95% confidence interval (95% CI) −1.4, 13.0]) and PCST/exercise versus PCST (6.7 mm [95% CI −0.6, 14.1]). Significantly greater improvements in function were found for PCST/exercise versus exercise (3.7 units [95% CI 0.4, 7.0]) and PCST/exercise versus PCST (7.9 units [95% CI 4.7, 11.2]). These differences persisted at weeks 32 (both) and 52 (PCST). Benefits favoring PCST/exercise were seen on several secondary outcomes. Cost effectiveness of PCST/exercise was not demonstrated. Conclusion This model of care could improve access to psychological treatment and augment patient outcomes from exercise in knee OA, although it did not appear to be cost effective.

Rheumatoid Arthritis and Mortality Among Women During 36 Years of Prospective Follow-Up: Results From the Nurses' Health Study.

Abstract: Objective To evaluate rheumatoid arthritis (RA) and mortality risk among women followed prospectively in the Nurses’ Health Study (NHS). Methods We analyzed 119,209 women in the NHS who reported no connective tissue disease at enrollment in 1976. Comorbidity and lifestyle data were collected through biennial questionnaires. Incident RA cases were validated by medical records review. Cause of death was determined by death certificate and medical records review. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause, cardiovascular disease (CVD), cancer, and respiratory disease mortality for women with RA compared to those without RA. Results We validated 964 incident RA cases and identified 28,808 deaths during 36 years of prospective follow-up. Of 307 deaths among women with RA, 80 (26%) were from cancer, 70 (23%) were from CVD, and 44 (14%) were from respiratory causes. Women with RA had increased total mortality (HR 1.40, 95% CI 1.25–1.57) compared to those without RA, independent of mortality risk factors, including smoking. RA was associated with significantly increased respiratory disease mortality (HR 2.06, 95% CI 1.51–2.80) and cardiovascular disease mortality (HR 1.45, 95% CI 1.14–1.83), but not cancer mortality (HR 0.93, 95% CI 0.74–1.15). For women with seropositive RA, respiratory disease mortality was nearly 3-fold higher than among non-RA women (HR 2.67, 95% CI 1.89–3.77). Conclusion Women with RA had significantly increased mortality compared to those without RA. Respiratory disease and cardiovascular disease mortality were both significantly elevated for women with RA. The nearly 3-fold increased relative risk of respiratory disease mortality was observed only for those with seropositive RA.

Vitamin D Supplementation in Adolescents and Young Adults With Juvenile Systemic Lupus Erythematosus for Improvement in Disease Activity and Fatigue Scores: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: Objective Vitamin D has an important immunomodulatory effect, but there are no trials that directly address the boosting of serum levels of 25-hydroxyvitamin D (25[OH]D) in juvenile-onset systemic lupus erythematosus (SLE). The aim of this study was to evaluate the effect of vitamin D supplementation on disease activity and fatigue in juvenile-onset SLE. Methods This study was a randomized, double-blind, placebo-controlled, 24-week trial. Forty juvenile-onset SLE patients were randomized (1:1) to receive oral cholecalciferol 50,000 IU/week (juvenile-onset SLE-VitD) or placebo (juvenile-onset SLE-PL). Medications remained stable throughout the study. Serum levels of 25(OH)D were measured using radioimmunoassay. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measurement (ECLAM). Fatigue was assessed using the Kids Fatigue Severity Scale (K-FSS). Results At baseline, groups were similar regarding age, body mass index, organ involvement, glucocorticoid dose, use of immunosuppressive drugs, SLEDAI, ECLAM, K-FSS, and levels of 25(OH)D. After 24 weeks, the mean level of 25(OH)D was higher in the juvenile-onset SLE-VitD group than in the juvenile-onset SLE-PL group (P < 0.001). At the end of the intervention, a significant improvement in SLEDAI (P = 0.010) and in ECLAM (P = 0.006) was observed in the juvenile-onset SLE-VitD group compared to the juvenile-onset SLE-PL group. Regarding fatigue evaluation, a reduction of fatigue related to social life score was found in the juvenile-onset SLE-VitD group compared to the juvenile-onset SLE-PL group (P = 0.008). Cholecalciferol was well tolerated with no serious adverse events. Conclusion This study suggests that cholecalciferol supplementation for 24 weeks is effective in decreasing disease activity and improving fatigue in juvenile-onset SLE patients.

Defining an International Standard Set of Outcome Measures for Patients with Hip or Knee Osteoarthritis: Consensus of the International Consortium for Health Outcomes Measurement Hip and Knee Osteoarthritis Working Group

Abstract: OBJECTIVE: To define a minimum Standard Set of outcome measures and case-mix factors for monitoring, comparing, and improving healthcare for patients with clinically diagnosed hip or knee osteoarthritis (OA) with a focus on defining the outcomes that matter most to patients. METHODS: An international Working Group (WG) of patients, arthroplasty register experts, orthopedic surgeons, primary care physicians, rheumatologists, and physiotherapists representing 10 countries was assembled to review existing literature and practices for assessing outcomes of pharmacological and non-pharmacological OA therapies, including surgery. A series of 8 teleconferences, incorporating a modified Delphi process, were held to reach consensus. RESULTS: The WG reached consensus on a concise set of outcome measures to evaluate patients' joint pain, physical functioning, health-related quality of life, work status, mortality, reoperations, readmissions, and overall satisfaction with treatment result. To support analysis of these outcome measures, pertinent baseline characteristics and risk factor metrics were defined. Annual outcome measurement is recommended for all patients. CONCLUSION: We have defined a Standard Set of outcome measures for monitoring the care of people with clinically diagnosed hip or knee OA that is appropriate for use across all treatment and care settings. We believe this Standard Set provides meaningful, comparable, and easy to interpret measures ready to implement in clinics and/or registries globally. We view this as an initial step that, when combined with cost data, will facilitate value-based healthcare improvements in the treatment of hip and knee OA. (Less)

Quality of Community-Based Osteoarthritis Care: A Systematic Review and Meta-Analysis.

Abstract: Objective To evaluate the state of quality of care for osteoarthritis (OA) by summarizing studies that have assessed the care provided to patients. Methods A systematic review of community-based observational studies of actual clinical practice treating people with OA compared with quality indicators (QIs) was performed. Four databases were searched from January 2000 to November 2015. Two reviewers independently determined study eligibility, assessed risk of bias, and extracted study data. The outcome was adherence to the QIs (pass rate). The overall pass rate (the total number of indicators passed divided by the total number of indicators for which the patients were eligible) was extracted from each study. When at least 50% of the studies had comparable individual QIs, the data were pooled with proportion meta-analyses. Results Fifteen studies comprising 16,103 patients were included, and the median overall pass rate across studies was 41% (range 22-65%). The pooled pass rates for individual QIs were "referral to orthopedic surgeon if no response to other therapy": 59.4% (95% confidence interval [95% CI] 47.5-70.3); "paracetamol or acetaminophen first drug used": 46.0% (95% CI 26.6-66.7); "assessed for pain and/or function": 45.5% (95% CI 33.9-57.6); "referral or recommendation to exercise": 38.7% (28.9-49.5); "offered education and self-management": 35.4% (95% CI 27.8-44.0); and "informed about potential risks if NSAIDs prescribed": 34.1% (95% CI 24.7-44.9). Conclusion There is room for improvement in community-based OA care.

Prognosis of Pain and Physical Functioning in Patients With Knee Osteoarthritis: A Systematic Review and Meta‐Analysis

Abstract: Objective To systematically summarize the literature on the course of pain in patients with knee osteoarthritis (OA), prognostic factors that predict deterioration of pain, the course of physical functioning, and prognostic factors that predict deterioration of physical functioning in persons with knee OA. Methods A search was conducted in PubMed, CINAHL, Embase, Psych-INFO, and SPORTDiscus up to January 2014. A meta-analysis and a qualitative data synthesis were performed. Results Of the 58 studies included, 39 were of high quality. High heterogeneity across studies (I(2) >90%) and within study populations (reflected by large SDs of change scores) was found. Therefore, the course of pain and physical functioning was interpreted to be indistinct. We found strong evidence for a number of prognostic factors predicting deterioration in pain (e.g., higher knee pain at baseline, bilateral knee symptoms, and depressive symptoms). We also found strong evidence for a number of prognostic factors predicting deterioration in physical functioning (e.g., worsening in radiographic OA, worsening of knee pain, lower knee extension muscle strength, lower walking speed, and higher comorbidity count). Conclusion Because of high heterogeneity across studies and within study populations, no conclusions can be drawn with regard to the course of pain and physical functioning. These findings support current research efforts to define subgroups or phenotypes within knee OA populations. Strong evidence was found for knee characteristics, clinical factors, and psychosocial factors as prognostics of deterioration of pain and physical functioning.

Is There a Dose-Response Relationship Between Weight Loss and Symptom Improvement in Persons With Knee Osteoarthritis?

Abstract: Objective We examined the dose-response relationship between weight reduction and pain/functional improvement in persons with symptomatic knee osteoarthritis (KOA) participating in a community-based weight loss program. Methods Consecutive participants with KOA and enrolled in the 18-week Osteoarthritis Healthy Weight for Life weight-loss program were selected. In this completer-type analysis, participants were assessed at baseline, 6 weeks, and 18 weeks for body weight and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales. The dose-response relationship between weight-change categories (>10%, 7.6–10%, 5.1–7.5%, 2.6–5.0%, and <2.5% of body weight loss) and change in KOOS scores was assessed by repeated-measures analysis of variance, controlling for sex and age, body mass index (BMI), and KOOS. The Western Ontario McMaster Universities Osteoarthritis Index function score derived from the KOOS was used to assess a meaningful clinical functional improvement. Results A total of 1,383 persons (71% females) were enrolled. Mean ± SD age, height, and weight were 64 ± 8.7 years, 1.66 ± 0.09 meters, and 95.1 ± 17.2 kg, respectively. Mean ± SD BMI was 34.4 ± 5.2 kg/m2 with 82% of participants obese at baseline. A total of 1,304 persons (94%) achieved a >2.5% reduction in body weight. There was a significant dose-response relationship between all KOOS subscales and percentage of weight change across all weight-change categories. Participants required ≥7.7% (95% confidence interval 5.2, 13.3) body weight loss to achieve a minimal clinically important improvement in function. Conclusion There is a significant dose-response relationship between percentage of weight loss and symptomatic improvement. This study confirms the feasibility of weight loss as a therapeutic intervention in KOA in a community-based setting.

Enhanced Pain Sensitivity Among Individuals With Symptomatic Knee Osteoarthritis: Potential Sex Differences in Central Sensitization

Abstract: Objective Symptomatic knee osteoarthritis (OA) is a condition commonly associated with increased pain, disability, and functional limitations. Given the poor correspondence between radiographic evidence and clinical pain, central sensitization has been implicated as a potential mechanism underlying pain facilitation in knee OA. Sex may be a moderator of centrally mediated changes in knee OA pain; however, few studies have systematically assessed this. Therefore, the aim of this study was to examine differences in peripheral and central sensitization in men and women with symptomatic knee OA, as well as to determine whether these differences vary across age (middle age versus older age). Methods Participants (n = 288) between the ages of 45 and 85 years completed a battery of quantitative sensory pain procedures assessing sensitivity to contact heat, cold pressor, mechanical pressure, and punctate stimuli. Differences in temporal summation (TS) were examined, as well as measures of clinical pain and functional performance. Results When compared to men, women exhibited greater sensitivity to multiple pain modalities (i.e., lower heat, cold, pressure thresholds/tolerances, greater TS of pain); however, there were no sex differences in clinical pain, with the exception of greater widespread pain observed in women. Although there were select age-related differences in pain sensitivity, sex differences in pain varied minimally across the age cohort. Conclusion Overall, these findings provide evidence for greater overall sensitivity to experimental pain in women with symptomatic knee OA compared to men, suggesting that enhanced central sensitivity may be an important contributor to pain in this group.

Cause-Specific Mortality in Male US Veterans with Rheumatoid Arthritis

Abstract: Objective There has been limited investigation into cause-specific mortality and the associated risk factors in men with rheumatoid arthritis (RA). We investigated all-cause and cause-specific mortality in men with RA, examining determinants of survival. Methods Men from a longitudinal RA registry were followed from enrollment until death or through 2013. Vital status and cause of death were determined using the National Death Index. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all-cause, cardiovascular disease (CVD), cancer, and respiratory mortality. Associations with all-cause and cause-specific mortality were examined using multivariable Cox proportional hazards and competing-risks regression. Results There were 1,652 men with RA and 332 deaths. The leading causes of death were CVD (31.6%; SMR 1.77 [95% confidence interval (95% CI) 1.46–2.14]), cancer (22.9%; SMR 1.50 [95% CI 1.20–1.89]), and respiratory disease (15.1%; SMR 2.90 [95% CI 2.20–3.83]). Factors associated with all-cause mortality included older age, white race, smoking, low body weight, comorbidity, disease activity, and prednisone use. Rheumatoid factor concentration and nodules were associated with CVD mortality. There were no associations of methotrexate or biologic agent use with all-cause or cause-specific mortality. Conclusion Men in this RA cohort experienced increased all-cause and cause-specific mortality, with a 3-fold risk of respiratory-related deaths compared to age-matched men in the general population. Further studies are needed in order to examine whether interventions targeting potentially modifiable correlates of mortality might lead to improved long-term survival in men with RA.

Role of Sleep Disturbance, Depression, Obesity, and Physical Inactivity in Fatigue in Rheumatoid Arthritis

Abstract: Author(s): Katz, Patricia; Margaretten, Mary; Trupin, Laura; Schmajuk, Gabriela; Yazdany, Jinoos; Yelin, Edward | Abstract: ObjectiveFatigue is a major concern for individuals with rheumatoid arthritis (RA). However, in order to treat fatigue adequately, its sources need to be identified.MethodsData were collected during a single home visit (number of participants = 158). All participants had physician-diagnosed RA. Assessments of self-reported sleep quality, depression, physical activity, RA disease activity, muscle strength, functional limitations, and body composition were made. Information on demographics, medications, and smoking was collected. The Fatigue Severity Inventory (FSI; measuring average fatigue over the past 7 days) was used as the primary outcome. Analyses were first conducted to evaluate bivariate relationships with fatigue. Correlations among risk factors were examined. Multivariate analyses identified independent predictors of fatigue.ResultsThe mean ± SD age was 59 ± 11 years, the mean ± SD disease duration was 21 ± 13 years, and 85% of subjects were female. The mean ± SD FSI rating was 3.8 ± 2.0 (range 0-10). In multivariate analyses, self-reported disease activity, poor sleep, depression, and obesity were independently associated with fatigue. Physical inactivity was correlated with poor sleep, depression, and obesity. Mediation analyses indicated that physical inactivity had an indirect association with fatigue, mediated by poor sleep, depression, and obesity.ConclusionThis cross-sectional study suggests that fatigue may not be solely a result of RA disease activity, but may result from a constellation of factors that includes RA disease activity or pain, but also includes inactivity, depression, obesity, and poor sleep. The results suggest new avenues for interventions to improve fatigue in individuals with RA, such as increasing physical activity or addressing depression or obesity.

Cytosolic 5'-Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases.

Abstract: Objective Prior investigations demonstrated that autoantibodies recognizing cytosolic 5′-nucleotidase 1A (NT5C1A) are found in 33–76% of patients with inclusion body myositis (IBM) but are observed only rarely in patients with polymyositis (PM). Thus, anti-NT5C1A may help distinguish IBM from PM. Although 4–21% of patients with dermatomyositis (DM) were shown to be anti-NT5C1A antibody positive, the clinical features of anti-NT5C1A–positive patients with DM have not been described. Furthermore, the prevalence of anti-NT5C1A antibodies in other rheumatic conditions has not been reported. This study was undertaken to define the prevalence and clinical features of anti-NT5C1A–positive patients with DM, PM, IBM, or other systemic autoimmune diseases. Methods We screened for anti-NT5C1A autoantibodies in patients with IBM, DM, PM, Sjogren's syndrome (SS), or systemic lupus erythematosus (SLE) and in healthy volunteers. Clinical characteristics were compared between patients who were anti-NT5C1A positive and those who were anti-NT5C1A negative. Results Anti-NT5C1A autoantibodies were detected in 71 (61%) of 117 patients with IBM, 2 (5%) of 42 patients with PM, 2 (5%) of 42 healthy volunteers, 24 (15%) of 159 patients with DM, 10 (23%) of 44 patients with SS, and 13 (14%) of 96 patients with SLE. No anti-NT5C1A antibody–positive patients with SS or SLE had muscle involvement. Anti-NT5C1A–positive patients with IBM had a lower prevalence of rimmed vacuoles (62% versus 83% of antibody-negative patients; P = 0.02). No differences in the clinical characteristics of antibody-positive and antibody-negative patients with DM, SS, or SLE were observed. Conclusion Anti-NT5C1A is a common target of circulating autoantibodies, especially in IBM but also in several different autoimmune diseases. In SLE and SS, anti-NT5C1A autoreactivity is not associated with muscle disease.

Post‐Traumatic Stress Disorder and Risk for Incident Rheumatoid Arthritis

Abstract: Objective To examine the association between symptoms of post-traumatic stress disorder (PTSD) and rheumatoid arthritis (RA) risk in a prospective cohort and to characterize the role of smoking in this relationship. Methods A subset (n = 54,224) of the Nurses’ Health Study II, a prospective cohort of female nurses, completed the Brief Trauma Questionnaire and a screen for PTSD symptoms. Participants were categorized based on trauma exposure and number of PTSD symptoms. Incident RA cases (n = 239) from 1989 to 2011 were identified. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) between PTSD symptoms and incident RA. To identify the impact of smoking, secondary and subgroup analyses were performed. In all analyses, PTSD and smoking were lagged 2 years before the development of RA. Results Compared to no history of trauma/PTSD symptoms, the HR for ≥4 PTSD symptoms and incident RA was 1.76 (95% CI 1.16–2.67) in models adjusted for age, race, and socioeconomic status. The risk for RA increased with an increasing number of PTSD symptoms (P = 0.01). When smoking was added to the model, the HR for RA remained elevated (HR 1.60 [95% CI 1.05–2.43]). In a subgroup analysis, excluding women who smoked before PTSD onset, results were unchanged (HR 1.68 [95% CI 1.04–2.70]). Conclusion This study suggests that women with high PTSD symptomatology have an elevated risk for RA, independent of smoking, adding to emerging evidence that stress is an important determinant of physical health.

Long-Term Followup of a Multicenter Cohort of 101 Patients With Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss)

Abstract: Objective To assess the long-term outcome in eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA). Methods A total of 101 patients fulfilling the American College of Rheumatology criteria for EGPA were included between 1990 and 2011. Clinical features, antineutrophil cytoplasm autoantibodies (ANCAs), and Five-Factors Score (FFS) were assessed at diagnosis. Overall and cumulative survival rates, relapse-free survival, and sequelae were studied based on ANCA status and FFS. Results The rate of cardiomyopathy did not differ according to ANCA status. A total of 79.6% of patients achieved first remission, but 81.1% relapsed. ANCA-positive patients did not relapse more frequently but exhibited more severe disease with mononeuritis (P = 0.0004) and renal involvement (P = 0.02). Being Italian was the only prognostic factor associated with a higher relapse-free survival (P = 0.01), thanks to a longer maintenance of immunosuppressive drugs, suggesting the need for prolonged low-dose corticosteroids. Overall, survival reached 93.1% after a median followup of 6 years. No factor was associated with mortality, but patients over age 65 years with cardiomyopathy or ANCA positivity had more serious outcomes. Sequelae affected 83.2% of patients. Ear, nose, and throat (ENT) involvement was a protective factor for renal (P = 0.04) and cardiac (P = 0.03) morbidity. ANCA positivity was correlated with chronic kidney disease (P = 0.03) and chronic neurologic disability (P = 0.02). Conclusion The actual challenges of EGPA management concern morbidity prevention and quality of life improvement. Long-term corticosteroid treatment appears to reduce relapse risk. ENT involvement is associated with less renal and cardiac morbidity. ANCA positivity predicts renal and neurologic damage.

Toward Standardized Musculoskeletal Ultrasound in Pediatric Rheumatology: Normal Age‐Related Ultrasound Findings

Abstract: Objective. Musculoskeletal (MS) ultrasound (US) is increasingly being used as an extension of paediatric clinical practice, particularly in the clinical management of children with juvenile idiopathic arthritis (JIA). MSUS is most commonly used in the assessment of effusion and synovial hypertrophy and detection of soft tissue disorders. It can also be used to visualise other structures, such as hyaline cartilage and bone surfaces. Given the unique anatomy of the growing skeleton, many of the difficulties encountered in its use result from misinterpretation of MSUS images. Thus, a detailed knowledge of anatomy in healthy children, both in B-mode and Doppler mode, is mandatory. Additionally, as US is the most operator-dependent imaging modality, the experience and expertise of the examiner will determine the value of the diagnostic information obtained from this technique. Incorrect acquisition and interpretation of images may result in inappropriate disease management. Thus, a systematic scanning method and a standardised evaluation procedure are essential in children.

Hydroxychloroquine serum concentrations and flares of systemic lupus erythematosus: A longitudinal cohort analysis

Abstract: Objective To study the relationship between serum hydroxychloroquine (HCQ) concentrations and flares of systemic lupus erythematosus (SLE) in a longitudinal cohort of patients. Methods Patients who fulfilled ≥4 American College of Rheumatology classification criteria for SLE and had been treated with HCQ for >6 months were studied. Blood was assayed for HCQ levels by tandem mass spectrometry. Patients were serially assessed for disease activity, using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and flares (SELENA flares instrument). Comparison of the mean summated SLEDAI scores over time and rates of flares in groups with different HCQ levels was performed by the Kruskal-Wallis test. Results A total of 276 SLE patients were studied (93% women, mean ± SD age 41.0 ± 13.8 years). The proportion of patients with HCQ levels 500 ng/ml (therapeutic) was 11%, 77%, and 12%, respectively. HCQ levels correlated significantly with the prescribed dose but not with body weight or renal function. The prescribed HCQ dose also correlated significantly with baseline SLEDAI scores, indicating that higher doses were used for more active manifestations. After a mean ± SD observation period of 32.5 ± 5.5 months, the mean summated SLEDAI score and the incidence of SLE flares was not statistically different among patients with different baseline HCQ levels. In a subgroup of 73 patients with serologic and clinical remission and having therapeutic HCQ levels, a trend of lower disease activity and fewer incidences of flares was observed. Conclusion Noncompliance and subtherapeutic serum HCQ levels were seen frequently in these SLE patients, which was partly due to the low prescribed dose. In patients in remission, higher HCQ concentrations were associated with a trend showing fewer flares over time.

Assessment of Sacroiliitis at Diagnosis of Juvenile Spondyloarthritis by Radiography, Magnetic Resonance Imaging, and Clinical Examination

Abstract: Objective To evaluate the prevalence of sacroiliitis at diagnosis of juvenile spondyloarthritis (SpA) and the accuracy of physical examination and back pain to detect sacroiliitis, using imaging as the reference standard. Methods We performed a prospective cross-sectional study of 40 children with newly diagnosed juvenile SpA and 14 healthy controls. Subjects were assessed using physical examination, anteroposterior pelvic radiograph, and pelvic magnetic resonance imaging (MRI). Differences in clinical features between those children with and without sacroiliitis were assessed by Fisher's exact test for categorical variables and Wilcoxon's rank sum test for continuous variables. Accuracy of physical examination and back pain for detection of sacroiliitis was determined using MRI as the reference standard. Predicted probability of sacroiliitis was determined using exact multivariate logistic regression. Results Eight children (20%) with juvenile SpA had active sacroiliitis. Of those subjects with active changes on MRI, 7 of 8 (88%) also had evidence of erosions or sclerosis. Five children (13%) with juvenile SpA and 1 control (7%) had nonperiarticular bone marrow edema. Of the subjects with active sacroiliitis, only 3 (38%) reported a history of back pain or tenderness on palpation of the sacroiliac joints. The positive and negative predictive values of clinical examination features and back pain for detection of sacroiliitis were low. The estimated probability of having sacroiliitis was 0.84 (95% confidence interval 0.40–1.00) in HLA–B27–positive patients with an elevated C-reactive protein (CRP) level. Conclusion Active sacroiliitis by MRI is common at diagnosis in juvenile SpA and is frequently asymptomatic. Children who are HLA–B27–positive and have elevated CRP levels have the highest probability of sacroiliitis.

Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis

Abstract: Objective Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID-axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. Methods The RAPID-axSpA (NCT01087762) trial is double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose-blind phase were re-randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient-years. Results At baseline, 38 of 218 CZP-randomized patients (17.4%) and 31 of 107 placebo-randomized patients (29.0%) had past uveitis history. During the 24-week double-blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6–8.8] per 100 patient-years) than in placebo (10.3 [95% CI 2.8–26.3] per 100 patient-years). All cases observed during the 24-week double-blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5–50.1] per 100 patient-years) than placebo (38.5 [95% CI 10.5–98.5] per 100 patient-years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2–7.4] per 100 patient-years) and were similar between AS (4.4 [95% CI 2.3–7.7] per 100 patient-years) and nr-axial SpA (5.6 [95% CI 2.9–9.8] per 100 patient-years). Conclusion The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti–tumor necrosis factor antibodies.

Radiographic Progression of Patients With Psoriatic Arthritis Who Achieve Minimal Disease Activity in Response to Golimumab Therapy: Results Through 5 Years of a Randomized, Placebo‐Controlled Study

Abstract: Objective To evaluate long-term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in the GO-REVEAL trial. Methods The GO-REVEAL trial was a phase III, randomized, double-blind trial with placebo-control through week 24 followed by an open-label extension of golimumab 50/100 mg treatment up to 5 years. In these post-hoc analyses, MDA was defined by the presence of ≥5 of 7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity score ≤20 [range 0–100], Health Assessment Questionnaire disability index [HAQ DI] ≤0.5, and ≤1 tender enthesis point). Results Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at week 14 (23.5% versus 1.0%; P < 0.0001), week 24 (28.1% versus 7.7%; P < 0.0001), and week 52 (42.4% versus 30.2%; P = 0.037). MDA was achieved at least once by ∼50% of golimumab-treated patients overall. Irrespective of treatment randomization, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ DI) and overall disease activity (patient global assessment of disease activity) at week 256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1-unit higher baseline HAQ DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio 0.514 [95% confidence interval 0.321–0.824]; P = 0.006) and ≥4 (odds ratio 0.480 [95% confidence interval 0.290–0.795]; P = 0.004) consecutive visits. Conclusion Among golimumab-treated PsA patients, better long-term functional improvement, patient global assessment, and radiographic outcomes were observed when patients achieved persistent MDA.

Pain, Fatigue, and Psychological Impact on Health-Related Quality of Life in Childhood-Onset Lupus

Abstract: Objective To evaluate pain, fatigue, and psychological functioning of childhood-onset systemic lupus erythematosus (SLE) patients and examine how these factors impact health-related quality of life (HRQOL). Methods At a tertiary rheumatology clinic, 60 childhood-onset SLE patients completed the following: a visual analog scale (VAS) of pain intensity (0–10), the Pediatric Quality of Life (PedsQL) multidimensional fatigue scale, Pain Coping Questionnaire, Pain Catastrophizing Scale (PCS), Children's Depression Inventory I (CDI-I), the Screen for Child Anxiety Related Emotional Disorders (SCARED) questionnaire, and the PedsQL generic core (GC) scale and rheumatology module (RM). Sociodemographics and multiple disease activity indicators were recorded. Results Fatigue was present in 65% of the patients. Clinically relevant pain (pain-VAS >3), anxiety (SCARED ≥25), and depressive symptoms (CDI-I >12) were observed in 40%, 37%, and 30% of the patients, respectively; 22% had high catastrophizing (PCS ≥26). On average, the PedsQL-GC and -RM scores for childhood-onset SLE were lower than in healthy norms. Reduced PedsQL-GC and -RM scores were highly correlated with greater levels of fatigue, anxiety, and depressive symptoms (Pearson's r > 0.65), but had weak correlation with disease activity (Pearson's r < 0.25). Regression analysis demonstrated HRQOL was most impacted by fatigue, pain, and anxiety when evaluating all factors concurrently (P < 0.001). Conclusion Childhood-onset SLE is associated with decreased HRQOL, and psychological aspects of health contribute substantially to low HRQOL, whereas measures of childhood-onset SLE activity seem less relevant. Fatigue, pain, mood, and anxiety symptoms are present in a large subgroup of patients and need medical attention to achieve optimal health outcomes.

Epidemiology of Mixed Connective Tissue Disease, 1985-2014: A Population-Based Study.

Abstract: Objective To characterize the epidemiology of mixed connective tissue disease (MCTD) from 1983 to 2014. Methods An inception cohort of patients with incident MCTD in 1985–2014 in Olmsted County, Minnesota was identified based on comprehensive individual medical record review. Diagnosis of MCTD required fulfillment of at least 1 of the 4 widely accepted diagnostic criteria without fulfillment of classification criteria for other connective tissue diseases. Data were collected on demographic characteristics, clinical presentation, laboratory investigations, and mortality. Results A total of 50 incident cases of MCTD were identified (mean age 48.1 years and 84% were female). The annual incidence of MCTD was 1.9 per 100,000 population. Raynaud's phenomenon was the most common initial symptoms (50%), followed by arthralgia (30%) and swollen hands (16%). The diagnosis was frequently delayed with the median time from first symptom to fulfillment of criteria of 3.6 years. At fulfillment of criteria, arthralgia was the most prevalent manifestation (86%), followed by Raynaud's phenomenon (80%), swollen hands (64%), leukopenia/lymphopenia (44%), and heartburn (38%). Evolution to other connective tissue occurred infrequently with a 10-year rate of evolution of 8.5% and 6.3% for systemic lupus erythematosus and systemic sclerosis, respectively. The overall mortality was not different from the general population with a standardized mortality ratio of 1.1 (95% confidence interval 0.4–2.6). Conclusion This study was the first population-based study of MCTD to provide a complete picture of epidemiology and clinical characteristics of MCTD. MCTD occurred in about 2 persons per 100,000 per year. Evolution to other connective diseases occurred infrequently and the mortality was not affected.

Patient‐Physician Discordance in Global Assessment in Rheumatoid Arthritis: A Systematic Literature Review With Meta‐Analysis

Abstract: Objective The integration of the patient in therapeutic decision-making is important in the management of rheumatoid arthritis (RA), but the patient opinion regarding disease status may differ from the physician's opinion. The aim of this study was to assess in the published literature the frequency and drivers of patient-physician discordance in global assessment in RA. Methods A systematic literature review of all articles published up to January 2015 in Medline or Embase, reporting discordance in RA, was conducted by 2 investigators. Discordance was defined based on the absolute difference of patient global (PGA) and physician global assessments (PhGA) on 0–10-cm scales. The frequency of discordance and its predictors were collected in each study. Frequencies of discordance were pooled by meta-analysis using random effect. Results In all, 12 studies were selected (i.e., 11,879 patients): weighted mean ± SD age was 55.1 ± 13.9 years, weighted mean ± SD disease duration was 10.4 ± 9.3 years, and 80.7% were women. The value of the difference |PGA − PhGA| defining discordance varied between ≥0.5 cm (n = 2 studies) to ≥3 cm (n = 5 studies); the weighted mean value was 2.7 cm. The pooled percentage of patients with discordance was 43% (95% confidence interval 36%–51%; range 25%–76%). PGA was usually higher than PhGA. The drivers of PGA were pain and functional incapacity, whereas drivers of PhGA were joint counts and acute-phase reactants. Conclusion Discordance in global assessment was most frequently defined as a difference of 3 points or more; even with such a stringent definition, up to half the patients were found to be discordant. The long-term consequences of this discordance remain to be determined.

Prevalence of Gout in the Adult Population of France.

Abstract: OBJECTIVE: To estimate adult gout prevalence in France. METHODS: We used a previously established phone questionnaire that allowed for classifying patients as gouty or non-gouty by 2 logistic regression models and 1 Classification and Regression Tree (CART) method, the sensitivity and specificity of which were all more than 80%. The full questionnaire was administered by phone to subjects who acknowledged present or past non-traumatic acute pain in a peripheral joint, the others being classified as non-gouty. A random sample of adults residing in France was derived from the national telephone (home and mobile) directory by the quota method and further redressed to match the French population. The target size for the interview survey conducted in March and June 2013 was 10,000 participants. RESULTS: We interviewed 10,026 participants. All three models (2 logistic regression and CART models) converged to an estimated gout prevalence of 0.9%. This was lower than that estimated by self-reporting only (3.7%; 95% CI: 3.3-4.1). The prevalence was higher for males than females and increased with age but did not differ by area of France. CONCLUSION: Gout prevalence in the adult population of France in 2013 was estimated at 0.9%. Studies using self-reporting only might overestimate the prevalence. This article is protected by copyright. All rights reserved

Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials.

Abstract: Objective To assess the efficacy, tolerability, and safety of cannabinoids (phyto- and syntheto-) in the management of rheumatic diseases. Methods Multiple databases, including Medline, Embase, and CENTRAL, were searched. Randomized controlled trials with outcomes of pain, sleep, quality of life, tolerability (dropouts due to adverse events), and safety (serious adverse events), with comparison of cannabinoids with any type of control, were included. Study methodology quality was evaluated with the Cochrane risk of bias tool. Results In 4 short-term studies comprising 203 patients (58 with rheumatoid arthritis, 71 with fibromyalgia, and 74 with osteoarthritis [OA]), cannabinoids had a statistically significant effect on pain in 2, sleep in 2, and improved quality of life in 1, with the OA study prematurely terminated due to futility. The risk of bias was high for all 3 completed studies. Dizziness, cognitive problems, and drowsiness, as well as nausea, were reported for almost half of the patients. No serious adverse events were reported for cannabinoids during the study duration. No studies of herbal cannabis were identified. Conclusion Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions. Pain relief and effect on sleep may have some potential therapeutic benefit, but with considerable mild to moderate adverse events. There is currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases pending further study.