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1.  Mediterranean diet and incidence of rheumatoid arthritis in women 
Arthritis care & research  2015;67(5):597-606.
We examined the association between Mediterranean dietary pattern as measured by Alternate Mediterranean Diet Score (aMed) and risk of incident rheumatoid arthritis (RA) in US women.
We prospectively followed 83,245 participants from the Nurses’ Health Study (NHS, 1980–2008) and 91,393 participants from NHS II (1991–2009) who were initially free of baseline connective tissue diseases. Dietary information was obtained via validated food frequency questionnaires (FFQ) at baseline and approximately every 4 years during follow-up. The aMed was calculated according to the consumption status of 9 food components using cumulative average value. Time-varying Cox proportional hazards models were used to calculate hazard ratios (HR) for RA, seropositive RA and seronegative RA after adjustment for potential confounding factors. Results from 2 cohorts were pooled by an inverse variance–weighted, fixed-effects model.
During 3,511,050 person-years of follow-up, 913 incident cases of RA were documented in the two cohorts. After adjustment for several lifestyle and dietary variables, in both cohorts, greater adherence to Mediterranean dietary pattern was not significantly associated with altered risk of RA. The pooled HR for women in the highest quartile of aMed score was 0.98 (95% CI: 0.80–1.20) compared with those in the bottom quartile. Similar non-significant results were observed for both seropositive and seronegative RA. We did not find significant associations between each individual food component (except for alcohol) of aMed score and risk of incident RA.
We did not find a significant association between Mediterranean dietary pattern and risk of RA in women.
PMCID: PMC4370793  PMID: 25251857
2.  Self-reported and Objectively Measured Physical Activity in Adults with Systemic Lupus Erythematosus 
Arthritis care & research  2015;67(5):701-707.
Most estimates of physical activity (PA) patterns in systemic lupus erythematosus (SLE) are based on subjective self-report measures prone to error. The aims of this study were to obtain objective measurements of PA using an accelerometer and estimates of energy expenditure based on the self-reported International Physical Activity Questionnaire (IPAQ), and to describe their relationship.
The “Activity in Lupus To Energize and Renew” (ALTER) study, a cross-sectional study of PA, included 129 persons with SLE. Accelerometer measures over 7 days included total daily activity counts and minutes of moderate-vigorous physical activity (MVPA). Each person completed the IPAQ via telephone interview. Spearman correlations (r) and 95% confidence intervals (CIs) assessed associations between accelerometer and IPAQ.
Daily PA means (SD) from accelerometer measures were total daily activity counts, 502,910 (118,755) and MVPA, 40 (30) minutes. The median (interquartile range) MET-min per day for IPAQ intensities were: total 400 (159–693); walking, 83 (26–184); and moderate-vigorous, 231 (77–514), and domains were: work 0 (0–73); active transportation 28 (0–85); domestic and garden 77 (26–231); and leisure 57 (0–213). Associations between accelerometer measures and IPAQ were: 1) total daily count vs. IPAQ total, r=0.21, 95% CI: (0.03, 0.37); and 2) MVPA vs. IPAQ moderate-vigorous, r=0.16, 95% CI: (-0.02, 0.33).
Accelerometer measures and IPAQ energy expenditure estimates were moderately correlated. IPAQ provided descriptive PA data whereas accelerometers captured all daily activities and can help assess guideline attainment. The choice of IPAQ versus accelerometer measure should consider the purpose for which PA is measured.
PMCID: PMC4370811  PMID: 25251755
3.  We Need Better Classification and Terminology for “People at High-risk of or in the Process of Developing Lupus” 
Arthritis care & research  2015;67(5):593-596.
PMCID: PMC4391980  PMID: 25302656
systemic lupus; risk factor; prediction; pre-lupus; natural history; incomplete lupus; undifferntiated connective tissue disease
4.  Infection is the leading cause of hospital mortality in patients with dermatomyositis/polymyositis: data from a population-based study 
Arthritis care & research  2015;67(5):673-680.
Dermatomyositis (DM) and polymyositis (PM) are debilitating inflammatory myopathies associated with significant mortality. We evaluated the relative contribution of infection to hospital mortality in a large population-based study of individuals with DM/PM.
Data derive from the 2007 to 2011 Healthcare Cost and Utilization Project National Inpatient Samples and included all hospital discharges that met a validated administrative definition of DM/PM. The primary outcome was hospital mortality. Variables for infections and comorbidities were generated from discharge diagnoses using validated administrative definitions. Logistic regression was used to investigate the relationship between infection and mortality in individuals with DM/PM, adjusting for sociodemographics, utilization variables, and comorbidities. Relative risks were calculated to compare the overall prevalence of specific infections and associated mortality in DM/PM hospitalizations with those seen in the general hospitalized population.
15,407 hospitalizations with DM/PM met inclusion criteria for this study and inpatient mortality was 4.5% (700 deaths). In adjusted logistic regression analyses, infection (OR 3.4, 95% CI 2.9–4.0) was the strongest predictor of hospital mortality among individuals with DM/PM. Bacterial infection (OR 3.5, 95% CI 3.0–4.1), comprised primarily of pneumonia and bacteremia, and opportunistic fungal infections (OR 2.5, 95% CI 1.5–4.0) were independently associated with hospital mortality. The overall burden of infection in hospitalizations with DM/PM was significantly increased in comparison with the general hospitalized population (RR 1.5, 95% CI 1.4–1.6).
Among hospitalized individuals with DM/PM, infection is the leading cause of mortality. Strategies to mitigate infection risk in both the clinic and hospital settings should be evaluated to improve disease outcomes.
PMCID: PMC4404175  PMID: 25331828
5.  Lower Limb Osteoarthritis and the Risk of Falls in a Community-Based Longitudinal Study of Adults with and without Osteoarthritis 
Arthritis care & research  2015;67(5):633-639.
Knee and hip osteoarthritis (OA) are known risk factors for falls, but whether they together additionally contribute to falls risk is unknown. This study utilizes a biracial cohort of men and women to examine the influence of lower limb OA burden on the risk for future falls.
A longitudinal analysis was performed using data from 2 time points of a large cohort. The outcome of interest was falls at follow up. Covariates included age, sex, race, body mass index, a history of prior falls, symptomatic OA of the hip and/or knee, a history of neurologic or pulmonary diseases, and current use of narcotic medications. Symptomatic OA was defined as patient reported symptoms and radiographic evidence of OA in the same joint. Logistic regression analyses were used to determine associations between covariates and falls at follow-up.
The odds of falling increased with an increasing number of lower limb symptomatic OA joints: those with 1 joint had 53% higher odds, those with 2 joints had 74% higher odds, those with 3–4 OA joints had 85% higher odds. When controlling for covariates, patients who had symptomatic knee or hip OA had an increased likelihood of falling (aOR 1.39 95% CI [1.02, 1.88]; aOR 1.60 95% CI [1.14, 2.24], respectively).
This study reveals the risk for falls increases with additional symptomatic OA lower limb joints and confirms that symptomatic hip and knee OA are important risk factors for falls.
PMCID: PMC4404178  PMID: 25331686
6.  Impact of Biologics With and Without Concomitant MTX and at Reduced Doses in Older Rheumatoid Arthritis Patients 
Arthritis care & research  2015;67(5):624-632.
This study examines whether concomitant methotrexate (MTX) use is associated with better biologic persistence and whether self-administered anti-TNF therapies are used at reduced doses in real-world clinical care settings, not just clinical trials.
We conducted a retrospective cohort study among RA patients using Medicare claims data from 2006 to 2012. Subjects were new initiators of etanercept, infliximab, adalimumab, abatacept and tocilizumab with at least 12 months of continuous medical and pharmacy coverage after treatment initiation. We examined the association between concomitant MTX use and persistence on biologics using Cox proportional hazard regression adjusting for demographics and baseline co-morbidities. We further identified a subgroup of patients who initiated and were adherent on etanercept or adalimumab for at least 12 months and examined the proportion of patients who subsequently used these therapies at reduced doses continuously for an additional 12, 18, and 24 months.
Of 26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall, patients initiated biologic monotherapy were 1.4 (95% CI, 1.3–1.5) times more likely to discontinue at 1-year and 1.8 (95% CI, 1.7–2.0) times more likely if starting infliximab monotherapy. Approximately 10–20% of patients who initiated and adhered to etanercept and adalimumab for ≥ 12 months subsequently used reduced-dose therapy for an 12 additional months and beyond.
In real-world practice, concomitant MTX was associated with improved persistence on biologic therapy, especially for infliximab users; reduced-dose injectable anti-TNF therapy was used by a substantial proportion of RA patients.
PMCID: PMC4412783  PMID: 25370912
Rheumatoid Arthritis; Biologic Persistence; Concomitant Methotrexate; Low-dose Biologic
7.  Hospital Volume Predicts Outcomes and Complications after Total Shoulder Arthroplasty in the United States 
Arthritis care & research  2015;67(6):885-890.
To assess the association of hospital procedure volume for total shoulder arthroplasty (TSA) with patient outcomes and complications.
We used the U.S. Nationwide Inpatient Sample (NIS) from 1998–2011 to study the association of hospital annual TSA procedure volume with patient characteristics and TSA outcomes, including discharge disposition (home vs. inpatient facility), length of index hospitalization, post-arthroplasty periprosthetic fracture and revision. Annual hospital TSA volume was categorized as <5, 5–9, 10–14, 15–24 and ≥25 TSA procedures annually.
Patients receiving TSA at higher volume hospitals were more likely to be female (p<0.0001) and White (p<0.0001). Compared to low volume hospitals (<5, 5–9, 10–14 procedures annually), patients receiving TSA at higher volume hospitals (15–24, ≥25) had significantly lower likelihood of: (1) being discharged to an inpatient medical facility, 16.5%, 13.4%, 13.0%, 12.7% and 11.5% (p<0.0001); (2) hospital stay >median, 46.6%, 40.4%, 36.6%, 34.4% and 29.2% (p<0.0001); (3) post-arthroplasty fracture, 1.2%, 0.8%, 0.9%, 0.6% and 0.8% (p=0.0004); (4) blood transfusion, 8%, 7.1%, 6.7%, 7.1% and 5.5% (p=0.006); and (5) TSA revision, 0.5%, 0.3%, 0.2%, 0.3%, 0.3% (p=0.045), respectively.
In this study, we found that higher annual hospital TSA volume was associated with better TSA outcomes in the U.S. These findings document the impact of annual hospital TSA volume on TSA outcomes. Patients, surgeons and policy-makers should be aware of these findings and take them into account in decision-making, policy decisions and resource allocation.
PMCID: PMC4418937  PMID: 25370499
hospital volume; total shoulder arthroplasty; TSA; utilization; outcomes; mortality; hospital stay; discharge; fracture; blood transfusion; revision
8.  Epidemiology of Systemic Lupus Erythematosus and Cutaneous Lupus in a Predominantly White Population in the United States 
Arthritis care & research  2015;67(6):817-828.
Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993 to 2005.
SLE cases were identified from review of medical records and fulfilled the 1982 ACR classification criteria. CLE cases included patients with classic discoid LE (CDLE), subacute cutaneous LE (SCLE), lupus panniculitis and bullous LE. Age-and sex-adjusted incidence and prevalence were standardized to 2000 US white population.
The age- and sex-adjusted incidence of SLE (2.9 per 100,000; 95% CI 2.0, 3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1, 5.2, p= 0.10). However, incidence of CLE was three times higher than SLE in males (2.4 versus 0.8 per 100,000, p=0.009). The age- and sex-adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; p<0.001). The prevalence of CLE and SLE in women were similar but the CLE prevalence was higher in men than in women (56.9 versus 1.6 per 100,000, p<0.001). The incidence of CLE rose steadily with age and peaked at 60-69 years.
The incidences of CLE and SLE are similar but CLE is more common than SLE in males and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE.
PMCID: PMC4418944  PMID: 25369985
9.  Factors Associated with Hallux Valgus in a Community-Based Cross-Sectional Study of Adults with and without Osteoarthritis 
Arthritis care & research  2015;67(6):791-798.
To determine whether hallux valgus (HV) was associated with potential risk factors including foot pain in a large, bi-racial cohort of older men and women.
We conducted a cross-sectional analysis of cohort members of the Johnston County Osteoarthritis Project of whom 1,502 had complete clinical and demographic data available (mean age 68 years, mean body mass index [BMI] 31.3 kg/m2, 68% women, 30% African American). The presence of HV was assessed visually using a validated examination. Multivariate logistic regression models with generalized estimating equations for the total sample and for each sex and race subgroup were used to examine the effect of age, BMI, foot pain, pes planus, and knee or hip radiographic osteoarthritis (OA) on HV.
HV was present in 64% of the total sample (African American men=69%, African American women=70%, Caucasian men=54%, Caucasian women=65%). The association between HV and foot pain was elevated but not statistically significant (adjusted odds ratio [aOR] 1.21, 95% confidence interval 0.99, 1.47). Women, African American, older individuals, and those with pes planus or knee/hip OA had significantly higher odds of HV (aORs 1.17–1.48). Participants with higher BMI had lower odds of HV compared to those with normal BMI (aORs 0.54–0.72). Overall, patterns of associations were similar across subgroups.
HV was associated with female sex, African American race, older age, pes planus, and knee/hip OA and inversely associated with higher BMI. Early prevention and intervention approaches may be needed in high-risk groups; longitudinal studies would inform these approaches.
PMCID: PMC4440851  PMID: 25418024
hallux valgus; pes planus; foot pain; epidemiology
10.  Time trends in incidence, clinical features and cardiovascular disease in Ankylosing Spondylitis over 3 decades: a population based study 
Arthritis care & research  2015;67(6):836-841.
To determine trends in the incidence and clinical presentation of ankylosing spondylitis (AS), the incidence of cardiovascular disease (CVD) and cardiovascular (CV) risk factors among patients with AS and compare the observed incidence of CVD with that predicted by the Framingham risk score (FRS).
A population-based inception cohort of residents of Olmsted County, Minnesota ≥18 years who fulfilled modified New York criteria for AS in 1980-2009 was assembled. Clinical features at presentation were recorded. Age and sex adjusted incidence rates and survival were estimated. Incident CVD and CV risk factors were identified. The 10-year CVD risk was calculated using the FRS. Standardized incidence ratios (ratios of observed CVD in AS to that predicted by the FRS) were calculated.
86 patients were diagnosed with AS over the study period with an age and sex-adjusted incidence of 3.1 per 100,000 (95% CI 2.5, 3.8). The mean age at diagnosis was 35 years (range: 19-69). Inflammatory back pain, seen in 90%, was the most common presenting manifestation. The 10-year cumulative incidence of CVD was 15.8% ± 6.1%, three times higher than the predicted events based on the FRS (SIR 3.01; 95% CI 1.35, 6.69; p=0.007). Overall survival was similar to the general population.
AS occurs in about 3 persons per 100,000 per year. Clinical features, extra-articular manifestations and interval from symptom onset to diagnosis have remained constant in this population over the study period. The CVD risk in these patients is higher than expected and underestimated by the FRS.
PMCID: PMC4550091  PMID: 25384671
Arthritis care & research  2015;67(6):776-781.
The patient global assessment (PGA) is intended to provide an integrated summary of all symptoms of arthritis, but it is not clear which disease features most impact patients' assessments of changes in their overall status. We investigated what aspects of rheumatoid arthritis (RA) activity correlated best with prospectively measured changes in the PGA, and with patients’ retrospective judgments of improvement.
We studied 250 patients with active RA in a prospective longitudinal study. Disease activity measures were collected before and after treatment escalation. Prospectively measured changes in PGA and patients' judgments of improvement or worsening at the follow-up visit were tested for correlations with changes in patient-reported measures of symptoms and functioning, joint counts, and laboratory tests.
Patients improved during the study, with the mean (± standard deviation) PGA decreasing from 55.6 ± 25.2 to 37.6 ± 24.0. At the follow-up visit, 167 patients (66.8%) reported improvement in overall arthritis status. Changes in pain severity, stiffness severity, and fatigue were the only significant correlates of changes in PGA. In contrast, changes in the Health Assessment Questionnaire, tender joint count or Disease Activity Score-28 (DAS28), and stiffness severity were associated with retrospective judgments of improvement.
Prospectively measured changes in PGA in RA were related solely to other patient-reported measures, but patients’ retrospective judgments of improvement were related to functional limitations, tender joint count, and DAS28. Patients' subjective judgments of improvement reflect aspects of RA different from the PGA, and may be a simple complementary measure of treatment efficacy.
PMCID: PMC4556344  PMID: 25370806
12.  Alternative Methods for Defining Osteoarthritis and the Impact on Estimating Prevalence in a US Population-Based Survey 
Arthritis care & research  2016;68(5):574-580.
Provide a contemporary estimate of osteoarthritis (OA) by comparing accuracy and prevalence of alternative definitions of OA.
The Medical Expenditure Panel Survey (MEPS) household component (HC) records respondent-reported medical conditions as open-ended responses; professional coders translate these responses into ICD-9-CM codes for the medical conditions files. Using these codes and other data from the MEPS-HC medical conditions files, we constructed three case definitions of OA and assessed them against medical provider diagnoses of ICD-9-CM 715 [osteoarthrosis and allied disorders] in a MEPS subsample. The three definitions were: 1) strict = ICD-9-CM 715; 2) expanded = ICD-9-CM 715, 716 [other and unspecified arthropathies], OR 719 [other and unspecified disorders of joint]); and 3) probable = strict OR expanded + respondent-reported prior diagnosis of OA or other arthritis excluding rheumatoid arthritis (RA).
Sensitivity and specificity of the three definitions were: strict – 34.6% and 97.5%; expanded – 73.8% and 90.5%; and probable – 62.9% and 93.5%.
The strict definition for OA (ICD-9-CM 715) excludes many individuals with OA. The probable definition of OA has the optimal combination of sensitivity and specificity relative to the two other MEPS-based definitions and yields a national annual estimate of 30.8 million adults with OA (13.4% of US adult population) for 2008 – 2011.
PMCID: PMC4769961  PMID: 26315529
13.  Investigations of Potential Phenotypes of Foot Osteoarthritis: Cross‐Sectional Analysis From the Clinical Assessment Study of the Foot 
Arthritis Care & Research  2016;68(2):217-227.
To investigate the existence of distinct foot osteoarthritis (OA) phenotypes based on pattern of joint involvement and comparative symptom and risk profiles.
Participants ages ≥50 years reporting foot pain in the previous year were drawn from a population‐based cohort. Radiographs were scored for OA in the first metatarsophalangeal (MTP) joint, first and second cuneometatarsal, navicular first cuneiform, and talonavicular joints according to a published atlas. Chi‐square tests established clustering, and odds ratios (ORs) examined symmetry and pairwise associations of radiographic OA in the feet. Distinct underlying classes of foot OA were investigated by latent class analysis (LCA) and their association with symptoms and risk factors was assessed.
In 533 participants (mean age 64.9 years, 55.9% female) radiographic OA clustered across both feet (P < 0.001) and was highly symmetrical (adjusted OR 3.0, 95% confidence interval 2.1, 4.2). LCA identified 3 distinct classes of foot OA: no or minimal foot OA (64%), isolated first MTP joint OA (22%), and polyarticular foot OA (15%). After adjustment for age and sex, polyarticular foot OA was associated with nodal OA, increased body mass index, and more pain and functional limitation compared to the other classes.
Patterning of radiographic foot OA has provided insight into the existence of 2 forms of foot OA: isolated first MTP joint OA and polyarticular foot OA. The symptom and risk factor profiles in individuals with polyarticular foot OA indicate a possible distinctive phenotype of foot OA, but further research is needed to explore the characteristics of isolated first MTP joint and polyarticular foot OA.
PMCID: PMC4819686  PMID: 26238801
14.  Gout, Urate Lowering Therapy and Uric Acid Levels among US Adults 
Arthritis care & research  2015;67(4):588-592.
Evidence strongly suggests the delivery of gout care is suboptimal. The 2012 American College of Rheumatology (ACR) guidelines emphasize a serum uric acid (SUA) target of <6 mg/dl when utilizing urate lowering therapy (ULT). However, the proportion and characteristics of Americans with gout on ULT, or with a ULT indication, achieving this target is unknown.
We identified US adults with gout on ULT, and those with an indication for ULT, using the National Health and Nutrition Examination Surveys from 2007–2010. A ULT indication, by ACR guidelines, comprised chronic kidney disease stages 2–5 (CKD), a history of nephrolithiasis, or current ULT use. Demographic and clinical factors associated with a SUA ≥6 mg/dl were determined using Poisson regression.
In 2007–2010, an estimated 4.5 million US adults with gout had an indication for ULT; two-thirds had a SUA ≥6 mg/dl. In adjusted analyses among those with gout and CKD or nephrolithiasis, those 70 years and older were less likely (prevalence ratio [PR] 0.77; 95% CI 0.61– 0.97) to have a SUA ≥6 mg/dl. Regarding those taking ULT, hypertension was related to a reduced prevalence (PR=0.51; 95%CI 0.30–0.87) whereas diabetes mellitus (PR=1.42; 95%CI 1.06–1.90) and obesity (PR=1.74; 95%CI 1.19–2.56) were each associated with a higher prevalence of a SUA value ≥6 mg/dl.
Half of all Americans with gout on ULT, and two-thirds with an indication for ULT, have a SUA above target. This study furnishes a meaningful baseline for assessing the effectiveness of the ACR guidelines in future years.
PMCID: PMC4362996  PMID: 25201123
gout; uric acid; NHANES; epidemiology; prevalence; hyperuricemia
15.  Association of Time to Kidney Transplantation with Graft Failure among U.S. Patients with End-Stage Renal Disease Due to Lupus Nephritis 
Arthritis care & research  2015;67(4):571-581.
Providers recommend waiting to transplant patients with end-stage renal disease (ESRD) secondary to lupus nephritis (LN), to allow for quiescence of systemic lupus erythematosus (SLE)-related immune activity. However, these recommendations are not standardized, and we sought to examine whether duration of time to transplant was associated with risk of graft failure in U.S. LN-ESRD patients.
Using national ESRD surveillance data (United States Renal Data System), we identified 4743 U.S. patients with LN-ESRD who received a first transplant on or after 1/1/00 (follow-up through 9/30/11). The association of wait time (time from ESRD start to transplant) with graft failure was assessed with Cox proportional hazards models, with splines of the exposure to allow for non-linearity of the association and with adjustment for potential confounding demographic, clinical, and transplant factors.
White LN-ESRD patients who were transplanted later (vs. <3 months on dialysis) were at increased risk of graft failure [adjusted HR (95% confidence interval): 3–12 months, 1.23 (0.93–1.63); 12–24 months, 1.37 (0.92–2.06); 24–36 months, 1.34 (0.92–1.97); and >36 months, 1.98 (1.31–2.99)]. However, no such association was seen among black recipients [3–12 months, 1.07 (0.79–1.45); 12–24 months, 1.01 (0.64–1.60); 24–36 months, 0.78 (0.51–1.18); and >36 months, 0.74 (0.48–1.13)].
While future studies are needed to examine the potential confounding effect of clinically recognized SLE activity on the observed associations, these results suggest that longer wait times to transplant may be associated with equivalent or worse, not better, graft outcomes among LN-ESRD patients.
PMCID: PMC4370810  PMID: 25251922
Arthritis care & research  2015;67(4):509-518.
To determine the relationship between thigh muscle strength and clinically relevant differences in self-assessed lower limb function.
Isometric knee extensor and flexor strength of 4553 Osteoarthritis Initiative participants (2651 women/1902 men) was related to Western Ontario McMasters Universities (WOMAC) physical function scores by linear regression. Further, groups of Male and female participant strata with minimal clinically important differences (MCIDs) in WOMAC function scores (6/68) were compared across the full range of observed values, and to participants without functional deficits (WOMAC=0). The effect of WOMAC knee pain and body mass index on the above relationships was explored using stepwise regression.
Per regression equations, a 3.7% reduction in extensor and a 4.0% reduction in flexor strength were associated with an MCID in WOMAC function in women, and a 3.6%/4.8% reduction in men. For strength divided by body weight, reductions were 5.2%/6.7% in women and 5.8%/6.7% in men. Comparing MCID strata across the full observed range of WOMAC function confirmed the above estimates and did not suggest non-linear relationships across the spectrum of observed values. WOMAC pain correlated strongly with WOMAC function, but extensor (and flexor) muscle strength contributed significant independent information.
Reductions of approximately 4% in isometric muscle strength and of 6% in strength/weight were related to a clinically relevant difference in WOMAC functional disability. Longitudinal studies will need to confirm these relationships within persons. Muscle extensor (and flexor) strength (per body weight) provided significant independent information in addition to pain in explaining variability in lower limb function.
PMCID: PMC4376605  PMID: 25303012
Muscle Strength; Function; WOMAC; Minimal Clinically Important Difference; Knee Osteoarthritis
17.  Reliability of the Adult Myopathy Assessment Tool in Individuals with Myositis 
Arthritis care & research  2015;67(4):563-570.
The Adult Myopathy Assessment Tool (AMAT) is a 13-item performance-based battery developed to assess functional status and muscle endurance. The purpose of this study was to determine the intrarater and interrater reliability of the AMAT in adults with myosits.
Nineteen raters (13 physical therapists and 6 physicians) scored videotaped recordings of patients with myositis performing the AMAT for a total of 114 tests and 1,482 item observations per session. Raters rescored the AMAT test and item observations during a follow up session (19 ±6 days between scoring sessions). All raters completed a single, self-directed, electronic training module prior to the initial scoring session.
Intrarater and interrater reliability correlation coefficients were .94 or greater for the AMAT Functional Subscale, Endurance Subscale, and Total score (all p < 0.02 for Ho:ρ ≤ 0.75). All AMAT items had satisfactory intrarater agreement (Kappa statistics with Fleiss-Cohen weights, Kw = .57-1.00). Interrater agreement was acceptable for each AMAT item (K = .56-.89) except the sit up (K = .16). The standard error of measurement and 95% confidence interval range for the AMAT Total scores did not exceed 2 points across all observations (AMAT Total score range = 0-45).
The AMAT is a reliable, domain-specific assessment of functional status and muscle endurance for adult subjects with myositis. Results of this study suggest that physicians and physical therapists may reliably score the AMAT following a single training session. The AMAT Functional Subscale, Endurance Subscale, and Total score exhibit interrater and intrarater reliability suitable for clinical and research use.
PMCID: PMC4450351  PMID: 25201624
18.  Disease modifying anti-rheumatic drug use and the risk of incident hyperlipidemia in patients with early rheumatoid arthritis: A retrospective cohort study 
Arthritis care & research  2015;67(4):457-466.
To compare the risk of incident hyperlipidemia in early rheumatoid arthritis (ERA) patients after initiation of various disease modifying anti-rheumatic drugs (DMARDs).
We conducted a cohort study using insurance claims data (2001–2012) in ERA patients. ERA was defined by the absence of any RA diagnosis or DMARD prescriptions for 12 months. Four mutually exclusive groups were defined based on DMARD initiation, TNF-α inhibitors ± non-biologic (nb) DMARDs, methotrexate ± non-hydroxycholorquine nbDMARDs, hydroxychloroquine ± non-methotrexate nbDMARDs, and other nbDMARDs only. The primary outcome was incident hyperlipidemia, defined by a diagnosis and a prescription for a lipid-lowering agent. For the subgroup of patients with laboratory results available, change in lipid levels was assessed. Multivariable Cox proportional hazard models and propensity score (PS) decile stratification with asymmetric trimming were used to control for confounding.
Of the 17,145 ERA patients included in the study, 364 developed incident hyperlipidemia. The adjusted hazard ratios (95% CI) for hyperlipidemia were 1.41 (0.99–2.00) for TNF-α inhibitors, 0.81 (0.63–1.04) for hydroxychloroquine, and 1.33 (0.95–1.84) for other nbDMARDs compared with methotrexate in the full cohort, while 1.18 (0.80–1.73), 0.75 (0.58–0.98) and 1.41 (1.01–1.98), respectively in the PS trimmed cohort. In the subgroup analysis, hydroxychloroquine use showed significant reduction in low density lipoprotein (−8.9 mg/dl, 95% CI −15.8, −2.0), total cholesterol (−12.3 mg/dl, 95% CI −19.8, −4.8) and triglyceride (−19.5 mg/dl, 95% CI −38.7, −0.3) levels from baseline compared with methotrexate.
Use of hydroxychloroquine may be associated with a lower risk of hyperlipidemia among ERA patients.
PMCID: PMC4751079  PMID: 25302481
19.  Within-Day Variability of Fatigue and Pain Among African Americans and Non-Hispanic Whites With Osteoarthritis of the Knee 
Arthritis care & research  2016;68(1):115-122.
Fatigue is common among persons with osteoarthritis (OA), but little is known about racial/ethnic differences in the prevalence, correlates, or dynamics of fatigue in OA. This research therefore used experience sampling methodology (ESM) to examine fatigue and pain at global and momentary levels among African Americans and non-Hispanic whites with OA.
Thirty-nine African Americans and 81 non-Hispanic whites with physician-diagnosed knee OA completed a baseline interview and an ESM protocol assessing fatigue, pain, and mood 4 times daily for 7 days. In addition to analyzing basic group differences, multilevel modeling examined within- versus between-subject patterns and correlates of variability in momentary fatigue, controlling for demographics and other potential confounders.
Both racial groups experienced moderate levels of fatigue; however, there were clear individual differences in both mean fatigue level and variability across momentary assessments. Mean fatigue levels were associated with global pain and depression. Increase in fatigue over the course of the day was much stronger among non-Hispanic whites than African Americans. Momentary fatigue and pain were closely correlated. Mean fatigue predicted variability in mood; at the momentary level, both fatigue and pain were independently associated with mood.
Fatigue is a significant factor for both African Americans and non-Hispanic whites with OA, and is negatively related to quality of life. Pain symptoms, at both the momentary level and across individuals, were robust predictors of fatigue. Although overall levels of reported symptoms were similar across these 2 groups, the pattern of fatigue symptoms across the day differed.
PMCID: PMC4780570  PMID: 26315851
20.  Cardiovascular Risk and Acute Coronary Syndrome in Giant Cell Arteritis: A Population Based Retrospective Cohort Study 
Arthritis care & research  2015;67(3):396-402.
We assessed the occurrence of acute coronary syndrome (ACS) in patients with giant cell arteritis (GCA) compared to subjects without GCA.
We retrospectively reviewed a population-based incidence cohort of Olmsted County, Minnesota residents with GCA diagnosed in 1950-2009. We compared this cohort with a cohort of patients without GCA of similar age, sex and calendar year from the same population.
The study included 245 patients with GCA and 245 non-GCA subjects. Mean Framingham cardiovascular risk score was 30% (SD 19%) in GCA and 34% (SD 23%) in non-GCA (p=0.096) at incidence/index date. Diabetes mellitus was significantly less common in GCA than non-GCA at index date. Mean high-density lipoprotein was higher and triglycerides were lower and fewer patients were using lipid-lowering medications in the GCA cohort compared to the non-GCA at index date. During follow-up, no difference between the two cohorts was noted in overall rate of ACS events [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.44, 1.26]. Overall thrombosis in myocardial infarction (TIMI) scores were similar in both cohorts. Revascularization procedures were done less frequently in GCA than non-GCA subjects (19% vs. 50%; p=0.015). Post ACS hospital length of stays and complications were similar in both cohorts.
Multiple cardiovascular risk factors are more favorable at incidence of GCA. There is no overall increased risk of acute coronary syndromes in patients with GCA.
PMCID: PMC4310813  PMID: 25074472
Acute Coronary Syndrome; Giant Cell Arteritis
21.  Interactions between Patients, Providers, and Health Systems and Technical Quality of Care 
Arthritis care & research  2015;67(3):417-424.
Prior studies have established disparities by race/ethnicity and socioeconomic status (SES) in the kind, quantity, and technical quality of SLE care and outcomes. In this study we evaluate whether disparities exist in assessments of interactions with health care providers and health plans and whether such interactions affect the technical quality of SLE care.
Data derive from the Lupus Outcomes Study (LOS). Principal data collection is an annual structured phone interview including items from the Consumer Assessment of Health Plans and Interpersonal Processes of Care Scale measuring dimensions of health care interactions. We use general estimating equations to assess whether disparities exist by race/ethnicity and SES in being in the lowest quartile of ratings of such interactions and whether ratings in the lowest quartile of interactions are associated with technical quality of care after adjustment for sociodemographic and disease characteristics.
In the 2012 LOS interview, there were 793 respondents, of whom 640 had ≥1 visits to their principal SLE provider. Non-white race/ethnicity and education were not associated with low ratings on any dimension of provider or system interaction; poverty was associated only with low ratings of health plan interactions. After adjustment for demographics, SLE status, and health care variables, ratings in the lowest quartile on all dimensions were associated with significantly lower technical quality of care.
Ratings in the lowest quartile on all dimensions of interactions with providers and the health care system were associated with lower technical quality of care, potentially resulting in poorer SLE outcomes.
PMCID: PMC4320034  PMID: 25132660
22.  Using Surgical Appropriateness Criteria to Examine Outcomes of Total Knee Arthroplasty in a United States Sample 
Arthritis care & research  2015;67(3):349-357.
We determined outcomes for patients classified as appropriate, inconclusive or inappropriate for total knee arthroplasty (TKA) using a modified version of a validated appropriateness algorithm. Outcome measurement was conceptualized as short-term postoperative change attributable primarily to surgery and rehabilitation (two-months) and as longer term post-operative change and recovery (one- and two-year).
Pre-operative and yearly post-operative WOMAC Function, KOOS Symptoms and KOOS Pain scores were examined for persons undergoing primary TKA in the Osteoarthritis Initiative. Multi-group two-piece latent growth curve modeling was used to determine differences in outcome variable changes for each group from pre- to two-months post-surgery as well as over a two-year post-operative period.
Data from 167 persons with primary TKA were examined. Prevalence rates of appropriate, inconclusive and inappropriate judgments were 47.9%, 20.8%, and 31.3%, respectively. The inappropriate group showed no change at two months following surgery while appropriate and inconclusive groups had substantial improvement in all outcomes. One-year and two-year post-operative recovery outcomes were not significantly different among the three groups.
The inappropriate group was unchanged two months after surgery and, on average, improved by 2.3 WOMAC Function points from pre-surgery to one year following surgery based on our models. Appropriate and inconclusive groups improved by an average of 19.8 WOMAC Function points at one year post-surgery. These data provide a compelling case for consensus building efforts to define eligibility criteria for TKA with the goals of reducing variation in patient selection and optimizing both change over time and final outcomes.
PMCID: PMC4320045  PMID: 25132662
Knee; arthroplasty; prognosis; pain; function
23.  Sedentary behavior and physical function: Objective Evidence from the Osteoarthritis Initiative 
Arthritis care & research  2015;67(3):366-373.
Investigate the relationship between sedentary behavior and physical function in adults with knee osteoarthritis (OA), controlling for moderate-vigorous physical activity () levels.
Sedentary behavior was objectively measured by accelerometer on 1,168 participants in the Osteoarthritis Initiative aged 49–83 years with radiographic knee OA at the 48 month clinic visit. Physical function was assessed using 20-meter walk and chair stand testing. Sedentary behavior was identified by accelerometer activity counts/minute <100. The cross-sectional association between sedentary quartiles and physical function was examined by multiple linear regression adjusting for demographic factors (age, sex, race/ethnicity, education level), health factors (comorbidity, body mass index, knee pain, knee OA severity, presence of knee symptoms) and average daily MVPA minutes.
Adults with knee OA spent 2/3 their daily time in sedentary behavior. The average gait speed among the most sedentary quartile was 3.88 feet/second, which was significantly slower than the speed of the less sedentary groups (4.23, 4.33, 4.33 feet/second, respectively). The average chair stand rate among the most sedentary group was significantly lower (25.9 stands/minute) than the rates of the less sedentary behavior groups (28.9, 29.1, 31.1 stands/minute, respectively). These trends remained significant in multivariable analyses adjusted for demographic factors, health factors and average daily MVPA minutes.
Being less sedentary was related to better physical function in adults with knee OA independent of MVPA time. These findings support guidelines to encourage adults with knee OA to decrease time spent in sedentary behavior in order to improve physical function.
PMCID: PMC4336845  PMID: 25155652
24.  Sleep Disturbance in Osteoarthritis: Linkages with Pain, Disability and Depressive Symptoms 
Arthritis care & research  2015;67(3):358-365.
It is known that osteoarthritis (OA) increases risk of sleep disturbance, and that both pain and sleep problems may trigger functional disability and depression. However, studies examining all four variables simultaneously are rare. This research therefore examined cross-sectional and longitudinal associations of self-reported sleep disturbance with OA-related pain and disability, and depressive symptoms.
At baseline, 367 persons with physician-diagnosed knee OA reported sleep disturbances, pain, functional limitations, and depressive symptoms. All measures were repeated a year later (N = 288). Baseline analyses examined the independent and interactive associations of sleep disturbance with pain, disability and depression, net of demographics and general health. Longitudinal analyses used baseline sleep disturbance to predict one-year change in pain, disability and depression.
At baseline, sleep was independently associated with pain and depression, but not disability. The sleep-pain relationship was mediated by depressive symptoms; sleep interacted with pain to exacerbate depression among persons with high levels of pain. Baseline sleep disturbance predicted increased depression and disability, but not pain, at follow-up.
These data confirm known cross-sectional relationships of sleep disturbance with pain and depression, and provide new insights on longitudinal associations among those variables. Depression appears to play a strong role in the sleep-pain linkage, particularly where pain is severe. The unique predictive role of sleep in progression of disability requires further study, but may be an important point of intervention to prevent OA-related functional decline among persons whose sleep is disrupted by OA pain.
PMCID: PMC4342277  PMID: 25283955

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