Development and validation of risk stratification trees for incident slow gait speed in persons at high risk for knee osteoarthritis.

OBJECTIVES: Disability prevention strategies are more achievable before osteoarthritis disease drives impairment. It is critical to identify high-risk groups, for strategy implementation and trial eligibility. An established measure, gait speed is associated with disability and mortality. We sought to develop and validate risk stratification trees for incident slow gait in persons at high risk for knee osteoarthritis, feasible in community and clinical settings. METHODS: Osteoarthritis Initiative (derivation cohort) and Multicenter Osteoarthritis Study (validation cohort) participants at high risk for knee osteoarthritis were included. Outcome was incident slow gait over up to 10-year follow-up. Derivation cohort classification and regression tree analysis identified predictors from easily assessed variables and developed risk stratification models, then applied to the validation cohort. Logistic regression compared risk group predictive values; area under the receiver operating characteristic curves (AUCs) summarised discrimination ability. RESULTS: 1870 (derivation) and 1279 (validation) persons were included. The most parsimonious tree identified three risk groups, from stratification based on age and WOMAC Function. A 7-risk-group tree also included education, strenuous sport/recreational activity, obesity and depressive symptoms; outcome occurred in 11%, varying 0%-29 % (derivation) and 2%-23 % (validation) depending on risk group. AUCs were comparable in the two cohorts (7-risk-group tree, 0.75, 95% CI 0.72 to 0.78 (derivation); 0.72, 95% CI 0.68 to 0.76 (validation)). CONCLUSIONS: In persons at high risk for knee osteoarthritis, easily acquired data can be used to identify those at high risk of incident functional impairment. Outcome risk varied greatly depending on tree-based risk group membership. These trees can inform individual awareness of risk for impaired function and define eligibility for prevention trials.

Clinical significance of worsening versus stable preradiographic MRI lesions in a cohort study of persons at higher risk for knee osteoarthritis.

BACKGROUND: Whether preradiographic lesions in knees at risk for osteoarthritis are incidental versus disease is unclear. We hypothesised, in persons without but at higher risk for knee osteoarthritis, that: 12-48 month MRI lesion status worsening is associated with 12-48 month incident radiographic osteoarthritis (objective component of clinical definition of knee osteoarthritis) and 48-84 month persistent symptoms. METHODS: In 849 Osteoarthritis Initiative participants Kellgren/Lawrence (KL) 0 in both knees, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci on 12 month (baseline) and 48 month MRIs. Multivariable logistic regression was used to evaluate associations between 12-48 month worsening versus stable status and outcome (12-48 month incident KL ≥1 and KL ≥2, and 48-84 month persistent symptoms defined as frequent symptoms or medication use most days of ≥1 month in past 12 month, at consecutive visits 48-84 months), adjusting for age, gender, body mass index (BMI), injury and surgery. RESULTS: Mean age was 59.6 (8.8), BMI 26.7 (4.2) and 55.9% were women. 12-48 month status worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs was associated with 12-48 month incident radiographic outcomes, and worsening of cartilage damage and BMLs with 48-84 month persistent symptoms. There was a dose-response association for magnitude of worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs and radiographic outcomes, and cartilage damage and BMLs and persistent symptoms. CONCLUSIONS: In persons at higher risk, worsening MRI lesion status was associated with concurrent incident radiographic osteoarthritis and subsequent persistent symptoms. These findings suggest that such lesions represent early osteoarthritis, and add support for a paradigm shift towards investigation of intervention effectiveness at this stage.

Optimal Strategies for Reporting Pain in Clinical Trials and Systematic Reviews: Recommendations from an OMERACT 12 Workshop.

OBJECTIVE: Pain is a patient-important outcome, but current reporting in randomized controlled trials and systematic reviews is often suboptimal, impeding clinical interpretation and decision making. METHODS: A working group at the 2014 Outcome Measures in Rheumatology (OMERACT 12) was convened to provide guidance for reporting treatment effects regarding pain for individual studies and systematic reviews. RESULTS: For individual trials, authors should report, in addition to mean change, the proportion of patients achieving 1 or more thresholds of improvement from baseline pain (e.g., ≥ 20%, ≥ 30%, ≥ 50%), achievement of a desirable pain state (e.g., no worse than mild pain), and/or a combination of change and state. Effects on pain should be accompanied by other patient-important outcomes to facilitate interpretation. When pooling data for metaanalysis, authors should consider converting all continuous measures for pain to a 100 mm visual analog scale (VAS) for pain and use the established, minimally important difference (MID) of 10 mm, and the conventionally used, appreciably important differences of 20 mm, 30 mm, and 50 mm, to facilitate interpretation. Effects ≤ 0.5 units suggest a small or very small effect. To further increase interpretability, the pooled estimate on the VAS should also be transformed to a binary outcome and expressed as a relative risk and risk difference. This transformation can be achieved by calculating the probability of experiencing a treatment effect greater than the MID and the thresholds for appreciably important differences in pain reduction in the control and intervention groups. CONCLUSION: Presentation of relative effects regarding pain will facilitate interpretation of treatment effects.

Vitamin D deficiency is associated with progression of knee osteoarthritis.

BACKGROUND: Knee osteoarthritis causes functional limitation and disability in the elderly. Vitamin D has biological functions on multiple knee joint structures and can play important roles in the progression of knee osteoarthritis. The metabolism of vitamin D is regulated by parathyroid hormone (PTH). OBJECTIVE: The objective was to investigate whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH, individually and jointly, predict the progression of knee osteoarthritis. METHODS: Serum 25(OH)D and PTH were measured at the 30- or 36-mo visit in 418 participants enrolled in the Osteoarthritis Initiative (OAI) who had ≥1 knee with both symptomatic and radiographic osteoarthritis. Progression of knee osteoarthritis was defined as any increase in the radiographic joint space narrowing (JSN) score between the 24- and 48-mo OAI visits. RESULTS: The mean concentrations of serum 25(OH)D and PTH were 26.2 µg/L and 54.5 pg/mL, respectively. Approximately 16% of the population had serum 25(OH)D < 15 µg/L. Between the baseline and follow-up visits, 14% progressed in JSN score. Participants with low vitamin D [25(OH)D < 15 µg/L] had >2-fold elevated risk of knee osteoarthritis progression compared with those with greater vitamin D concentrations (≥15 µg/L; OR: 2.3; 95% CI: 1.1, 4.5). High serum PTH (≥73 pg/mL) was not associated with a significant increase in JSN score. However, participants with both low vitamin D and high PTH had >3-fold increased risk of progression (OR: 3.2; 95%CI: 1.2, 8.4). CONCLUSION: Our results suggest that individuals deficient in vitamin D have an increased risk of knee osteoarthritis progression.

Relationship of meeting physical activity guidelines with quality-adjusted life-years.

OBJECTIVE: The quality-adjusted life-year (QALY) is a standard outcome measure used in cost-effectiveness analyses. This study investigates whether attainment of federal physical activity guidelines is associated with higher QALY estimates among adults with or at an increased risk for knee osteoarthritis. METHODS: This is a prospective study of 1794 Osteoarthritis Initiative participants. Physical activity was measured using accelerometers at baseline. Participants were classified as (1) Meeting Guidelines [≥150min of moderate-to-vigorous (MV) activity per week acquired in sessions ≥10min], (2) Insufficiently Active (≥1 MV session[s]/week but below the guideline), or (3) Inactive (zero MV sessions/week). A health-related utility score was derived from participant responses to the 12-item Short-Form Health Survey at baseline and 2 years later. The QALY was calculated as the area under utility curve over 2 years. The relationship of physical activity level to median QALY adjusted for socioeconomic and health factors was estimated using quantile regression. RESULTS: Relative to the Inactive group, median QALYs over 2 years were significantly higher for the Meeting Guidelines (0.112, 95% CI: 0.067-0.157) and Insufficiently Active (0.058, 95% CI: 0.028-0.088) groups, controlling for socioeconomic and health factors. CONCLUSION: We found a significant graded relationship between greater physical activity level and higher QALYs. Using the more conservative estimate of 0.058, if an intervention could move someone out of the Inactive group and costs <$2900 over 2 years, it would be considered cost effective. Our analysis supports interventions to promote physical activity even if recommended levels are not fully attained.

Relationship of meeting physical activity guidelines with health-related utility.

OBJECTIVE: Health-related utility measures overall health status and quality of life and is commonly incorporated into cost-effectiveness analyses. This study investigates whether attainment of federal physical activity guidelines translates into better health-related utility in adults with or at risk for knee osteoarthritis (OA). METHODS: Cross-sectional data from 1,908 adults with or at risk for knee OA participating in the accelerometer ancillary study of the Osteoarthritis Initiative were assessed. Physical activity was measured using 7 days of accelerometer monitoring and was classified as 1) meeting guidelines (≥150 bouted moderate-to-vigorous [MV] minutes per week); 2) insufficiently active (≥1 MV bout[s] per week but below guidelines); or 3) inactive (zero MV bouts per week). A Short Form 6D health-related utility score was derived from patient-reported health status. Relationship of physical activity levels to median health-related utility adjusted for socioeconomic and health factors was tested using quantile regression. RESULTS: Only 13% of participants met physical activity guidelines, and 45% were inactive. Relative to the inactive group, median health-related utility scores were significantly greater for the meeting guidelines group (0.063; 95% confidence interval [95% CI] 0.055, 0.071) and the insufficiently active group (0.059; 95% CI 0.054, 0.064). These differences showed a statistically significant linear trend and strong cross-sectional relationship with physical activity level even after adjusting for socioeconomic and health factors. CONCLUSION: We found a significant positive relationship between physical activity level and health-related utility. Interventions that encourage adults, including persons with knee OA, to increase physical activity even if recommended levels are not attained may improve their quality of life.

Racial disparities in the monitoring of patients on chronic opioid therapy.

Despite well-documented racial disparities in prescribing opioid medications for pain, little is known about whether there are disparities in the monitoring and follow-up treatment of patients who are prescribed opioid medications. We conducted a retrospective cohort study to examine whether there are racial differences in the use of recommended opioid monitoring and follow-up treatment practices. Our sample included 1646 white and 253 black patients who filled opioid prescriptions for noncancer pain for ≥ 90 consecutive days at the Veterans Affairs Pittsburgh Healthcare System pharmacy in fiscal years 2007 and 2008. Several opioid monitoring and follow-up treatment practices were extracted from electronic health records for a 12-month follow-up period. Findings indicated that 26.3% of patients had opioid agreements on file, pain was documented in 71.7% of primary care follow-up visits, urine drug tests were administered to 49.3% of patients, and 21.2% and 4.2% of patients were referred to pain and substance abuse specialists, respectively. Racial differences were observed in several of these practices. In adjusted comparisons, pain was documented less frequently for black patients than for white patients. Among those who had at least 1 urine drug test, black patients were subjected to more tests, especially if they were on higher doses of opioids. Compared with white patients, black patients were less likely to be referred to a pain specialist and more likely to be referred for substance abuse assessment. Addressing disparities in opioid monitoring and follow-up treatment practices may be a previously neglected route to reducing racial disparities in pain management.

Assistive walking device use and knee osteoarthritis: results from the Health, Aging and Body Composition Study (Health ABC Study).

OBJECTIVES: To identify factors that predicted incident use of assistive walking devices (AWDs) and to explore whether AWD use was associated with changes in osteoarthritis of the knee. DESIGN: Prospective cohort study. SETTING: Community. PARTICIPANTS: Older adults (N=2639) in the Health, Aging and Body Composition (Health ABC) Study including a subset of 874 patients with prevalent knee pain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Incident use of AWDs, mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores, and the frequency of joint space narrowing on knee radiographs over a 3-year time period. RESULTS: AWD use was initiated by 9% of the entire Health ABC cohort and 12% of the knee pain subset. Factors that predicted use in both groups were age ≥73 (entire cohort: odds ratio [OR]=2.07; 95% confidence interval [CI], 1.43-3.01; knee pain subset: OR=1.87; 95% CI, 1.16-3.03), black race (entire cohort: OR=2.95; 95% CI, 2.09-4.16; knee pain subset: OR=3.21; 95% CI, 2.01-5.11), and lower balance ratios (entire cohort: OR=3.18; 95% CI, 2.21-4.59; knee pain subset: OR=3.77; 95% CI, 2.34-6.07). Mean WOMAC pain scores decreased slightly over time in both AWD and non-AWD users. Twenty percent of non-AWD users and 28% of AWD users had radiographic progression in joint space narrowing of the tibiofemoral joint in at least 1 knee. Fourteen percent of non-AWD users and 12% of AWD users had radiographic progression in joint space narrowing in the patellofemoral joint in at least 1 knee. CONCLUSIONS: AWDs are frequently used by older adults. Knee pain and balance problems are significant reasons why older adults initiate use of an AWD. In an exploratory analysis, there was no consistent relation between the use or nonuse of an AWD and WOMAC pain scores or knee joint space narrowing progression. Further studies of the relation of use of AWDs to changes in knee osteoarthritis are needed.

Relationship of 3D meniscal morphology and position with knee pain in subjects with knee osteoarthritis: a pilot study.

OBJECTIVES: To explore whether quantitative, three-dimensional measurements of meniscal position and size are associated with knee pain using a within-person, between-knee study design. METHODS: We studied 53 subjects (19 men, 34 women) from the Osteoarthritis Initiative, with identical radiographic OA grades in both knees, but frequent pain in one and no pain in the other knee. The tibial plateau and menisci were analyzed using coronally reconstructed double echo steady-state sequence with water excitation (DESSwe) MRI. RESULTS: The medial meniscus covered a smaller proportion of the tibial plateau (-5%) and displayed greater extrusion of the body (+15%) in painful than in painless knees (paired t-test; p < 0.05). The external margin of the lateral meniscus showed greater extrusion of the body in painful knees (+22%; p = 0.03), but no significant difference in the position of its internal margin or tibial coverage. Medial or lateral extrusion ≥3 mm was more frequent in painful (n = 23) than in painless knees (n = 12; McNemar's test; p = 0.02). No significant association was observed between meniscal size and knee pain. CONCLUSIONS: These data suggest a relationship between extrusion of the meniscal body, as measured with quantitative MRI, and knee pain in subjects with knee OA. Further studies need to confirm these findings and their clinical relevance.

Defining optimal self-management in osteoarthritis: racial differences in a population-based sample.

The aim of this study was to examine optimal self-management in osteoarthritis and its association with patient-reported outcomes. We recruited a population-based sample of Medicare beneficiaries (n = 551) residing in Allegheny County, PA, USA and elicited an expanded set of self-management behaviors using open-ended inquiry. We defined optimal self-management according to clinical recommendations, including use of hot compresses on affected joints, alteration of activity, and exercise. Only 20% practiced optimal self-management as defined by two or more of these criteria. Optimal and suboptimal self-managers did not differ in sociodemographic features. Both white and African-Americans who practiced optimal self-management reported significantly less pain, but the benefit was greatest in severe disease for whites and for mild-moderate disease among African-Americans. This backdrop of naturally occurring self-management behaviors may be important to recognize in planning programs that seek to bolster self-management skills.

Longitudinal performance evaluation and validation of fixed-flexion radiography of the knee for detection of joint space loss.

OBJECTIVE: The ability of nonfluoroscopically guided radiography of the knee to assess joint space loss is an important issue in studies of progression and treatment of knee osteoarthritis (OA), given the practical limitations of protocols involving fluoroscopically guided radiography of the knee. We evaluated the ability of the nonfluoroscopically guided fixed-flexion radiography protocol to detect knee joint space loss over 3 years. METHODS: We assessed the same-day test-retest precision for measuring minimum joint space width (JSW), the sensitivity for detection of joint space loss using serial films obtained a median of 37 months (range 23-47 months) apart, and the relationship of joint space loss to radiographic and magnetic resonance imaging (MRI) measures of knee OA. Participants were men and women (ages 70-79 years) with knee pain who were participating in the Health, Aging, and Body Composition Study. We assessed baseline radiographic OA and measured JSW using a computerized algorithm. Serial knee MRIs obtained over the same interval were evaluated for cartilage lesions. RESULTS: A total of 153 knees were studied, 35% of which had radiographic OA at baseline. The mean +/- SD joint space loss for all knees over 3 years was 0.24 +/- 0.59 mm (P < 0.001 for change). In knees with OA at baseline, the mean +/- SD joint space loss over 3 years was 0.43 +/- 0.66 mm (P < 0.001), and in knees with joint space narrowing at baseline, joint space loss was 0.50 +/- 0.67 mm (P < 0.001). Joint space loss and its standardized response mean increased with the severity of baseline joint space narrowing and with the presence of cartilage lesions at baseline and worsening during followup. CONCLUSION: Radiography of the knee in the fixed-flexion view provides a sensitive and valid measure of joint space loss in multiyear longitudinal studies of knee OA, without the use of fluoroscopy to aid knee positioning.