Predicting Disease Activity in Rheumatoid Arthritis With the Fibromyalgia Survey Questionnaire: Does the Severity of Fibromyalgia Symptoms Matter?

OBJECTIVE: To determine if the degree of baseline fibromyalgia (FM) symptoms in patients with rheumatoid arthritis (RA), as indicated by the Fibromyalgia Survey Questionnaire (FSQ) score, predicts RA disease activity after initiation or change of a disease-modifying antirheumatic drug (DMARD). METHODS: One hundred ninety-two participants with active RA were followed for 12 weeks after initiation or change of DMARD therapy. Participants completed the FSQ at the initial visit. The Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) was measured at baseline and follow-up to assess RA disease activity. We evaluated the association between baseline FSQ score and follow-up DAS28-CRP. As a secondary analysis, we examined the relationship between the 2 components of the FSQ, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), with follow-up DAS28-CRP. Multiple linear regression analyses were performed, adjusting for clinical and demographic variables. RESULTS: In multiple linear regression models, FSQ score was independently associated with elevated DAS28-CRP scores 12 weeks after DMARD initiation (B = 0.04, P = 0.01). In secondary analyses, the WPI was significantly associated with increased follow-up DAS28-CRP scores (B = 0.08, P = 0.001), whereas the SSS was not (B = -0.03, P = 0.43). CONCLUSION: Higher levels of FM symptoms weakly predicted worse disease activity after treatment. The primary factor that informed the FSQ's prediction of disease activity was the spatial extent of pain, as measured by the WPI.

Fibromyalgianess and glucocorticoid persistence among patients with rheumatoid arthritis.

OBJECTIVES: Over one-third of patients with RA exhibit evidence of fibromyalgianess, which is associated with higher rates of disability and inadequate responsiveness to RA treatment. Patients with RA often remain on glucocorticoids long-term, despite the known risk of dose-dependent morbidity. We undertook this study to examine the relationship between fibromyalgianess and glucocorticoid persistence among RA patients. METHODS: We followed participants with active RA on oral prednisone for ∼3 months after initiating a new DMARD. Fibromyalgianess was measured using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key FM features often superimposed upon RA. Severity of fibromyalgianess was stratified as follows: FSQ <8 low, FSQ 8-10 moderate and FSQ >10 high/very high. The association between baseline fibromyalgianess and glucocorticoid persistence, defined as prednisone use at 3-month follow-up visit after DMARD initiation, was assessed using multiple logistic regression adjusted for baseline demographics, RA duration, serostatus and inflammatory activity assessed using swollen joint count and CRP. RESULTS: Of the 97 participants on prednisone at baseline, 65% were still taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent glucocorticoid use, compared with 84% of participants with high or very high fibromyalgianess. After adjustment for non-inflammatory factors and inflammatory activity, participants with high/very high baseline fibromyalgianess were more likely to be taking prednisone at follow-up relative to those with low fibromyalgianess [odds ratio 4.99 (95% CI 1.20, 20.73)]. CONCLUSION: High fibromyalgianess is associated with persistent glucocorticoid use, independent of inflammatory activity.

Daily Walking and the Risk of Knee Replacement Over 5 Years Among Adults With Advanced Knee Osteoarthritis in the United States.

OBJECTIVE: To examine the association of the volume and intensity of daily walking at baseline with the risk of knee replacement (KR) over 5 years in adults with advanced structural knee osteoarthritis. DESIGN: Prospective, longitudinal, and multicenter observational study. SETTING: Osteoarthritis Initiative study with follow-up from 2008-2015. PARTICIPANTS: Community-dwelling adults with or at risk of knee osteoarthritis were recruited from 4 sites in the United States (N=516; mean age, 67.7±8.6y; body mass index, 29.3±4.7 kg/m2; 52% female). We included participants with advanced structural disease, without KR and had valid daily walking data (quantified using Actigraph GT1M), at baseline. INTERVENTIONS: Not applicable. MAIN OUTCOMES: KR. Walking volume was measured as steps/day and intensity as minutes/day spent not walking (0 steps/min) and walking at very light (1-49 steps/min), light (50-100 steps/min), or moderate (>100 steps/min) intensities. To examine the relationship of walking volume and intensity with the risk of KR, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for covariates. RESULTS: Of 516 adults with advanced structural disease, 88 received a KR over 5 years (17%). Walking an additional 1000 steps/d was not associated with the risk of KR (adjusted HR=0.95; 95% CI, 0.84-1.04). Statistically, replacing 10 min/d of very light and light walking with 10 min/d of moderate walking reduced the risk of KR incidence by 35% and 37%, respectively (adjusted HR=0.65, 95% CI, 0.45-0.94, for very light and adjusted HR=0.63; 95% CI, 0.40-1.00, for light). CONCLUSIONS: Daily walking volume and intensity did not increase KR risk over 5 years and may be protective in some cases in adults with advanced structural knee osteoarthritis.

Sleep Disturbance Trajectories in Osteoarthritis.

BACKGROUND/OBJECTIVE: Sleep disturbance is common among adults with osteoarthritis (OA), but little is known about patterns over time. In this cohort study, we identified restless sleep trajectories and associated factors in adults with or at high risk for knee OA. METHODS: Longitudinal (2004-2014) restless sleep (≥3 nights/week) annual reports over 8 years from 4359 Osteoarthritis Initiative participants were analyzed. Group-based trajectory modeling identified heterogeneous temporal patterns. Logistic regression identified baseline health and behavioral predictors of trajectory membership. RESULTS: Four restless sleep trajectory groups were identified: good (69.7%, persistently low restless sleep probabilities), worsening (9.1%), improving (11.7%), and poor (9.5%, persistently high). Among 2 groups initially having low restless sleep prevalence, the worsening trajectory group had an increased likelihood of baseline cardiovascular disease (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.01-2.33), pulmonary disease (OR, 1.48; 95% CI, 1.07-2.05), lower physical activity (OR, 1.29; 95% CI, 1.03-1.61), knee pain (OR, 1.04; 95% CI, 1.00-1.07), depressive symptoms (OR, 1.03; 95% CI, 1.01-1.06), and a decreased likelihood of better mental health (OR, 0.97; 95% CI, 0.95-0.98) at baseline. Among 2 groups initially having high restless sleep prevalence, the poor group had an increased likelihood of baseline depressive symptoms (OR, 1.03; 95% CI, 1.00-1.05). CONCLUSIONS: Four trajectories of restless sleep over 8 years were identified using data collected from over 4000 older adults aged 45 to 79 years with or at higher risk for knee OA. The presence of depressive symptoms, less physical activity, knee pain, poor mental health, cardiovascular disease, or pulmonary disease was each associated with unfavorable trajectories.

Community Health and Employee Work Performance in the American Manufacturing Environment.

Although better community health has long been assumed to be good for local businesses, evidence demonstrating the relationship between community health and employee performance is quite limited. Drawing on human resources data on 6103 employees from four large US manufacturing plants, we found that employees living in counties with poor community health outcomes had considerably higher rates of absenteeism and tardiness (ABT). For example, in one company, employees living in communities with high rates of children on free or reduced lunch had higher rates of ABT compared to other employees [adjusted odds ratio (OR) 2.76, 95% confidence interval (CI) 2.52-3.04], and employees living in communities with high rates of drug overdose deaths had higher rates of ABT (OR 1.51, 95% CI 1.29-1.77). In one plant, the annual value of lost wages due to ABT was over $1.3 million per year. Employees reported that poor community health (e.g., poverty, caregiving burdens, family dysfunction, drug use) resulted in "mental stress" leading to distraction, poor job performance, and more rarely, lapses in safety. These findings bolster the case for greater private sector investment in community health.

Serum adipokine levels and associations with patient-reported fatigue in systemic lupus erythematosus.

Physical activity ameliorates fatigue in systemic lupus erythematosus (SLE) patients by an unknown mechanism. Adipokines, which are influenced by adiposity and physical activity, may be associated with patient-reported fatigue. We describe cross-sectional associations between adipokines and fatigue, physical activity, and SLE disease activity. We measured adipokines, self-reported fatigue, and objective physical activity in 129 SLE patients. Fatigue was assessed with the Fatigue Severity Scale (FSS) and Patient Reported Outcomes Measurement Information System® (PROMIS®) Fatigue score. Disease activity was measured with the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI). Participants wore an accelerometer for 7 days to measure physical activity. Leptin, adiponectin, and resistin were measured in stored serum with a Luminex bead-based assay. Multivariable regression models assessed relationships between fatigue and adipokines, and Spearman correlation coefficients summarized associations between adipokines, physical activity, and SELENA-SLEDAI. Median adipokine levels were: leptin 30.5 ng/ml (Interquartile Range 14.0, 56.6), adiponectin 11.6 µg/ml (7.2, 16.8) and resistin 1.4 ng/ml (1.0, 2.2). Associations between adipokines and FSS or PROMIS fatigue were not significant. Body mass index (BMI) ≥ 30 kg/m2 was associated with FSS and PROMIS fatigue in regression analyses (p < 0.05). Weak correlations between leptin, adiponectin, leptin/adiponectin (L/A) ratio, and physical activity and between adiponectin and SELENA-SLEDAI score were not significant after adjusting for BMI. Adipokines were not associated with fatigue in SLE. Adipokines were correlated with physical activity (leptin, adiponectin, L/A ratio) and SLE disease activity (adiponectin), but most of these associations were explained by BMI.

Corporate Philanthropy Toward Community Health Improvement in Manufacturing Communities.

Virtually all large employers engage in corporate philanthropy, but little is known about the extent to which it is directed toward improving community health. We conducted in-depth interviews with leaders of corporate philanthropy from 13 of the largest manufacturing companies in the US to understand how giving decisions were made, the extent to which funding was directed towards improving community health, and whether companies coordinate with local public health agencies. We found that corporate giving was sizable and directed towards communities in which the manufacturers have a large presence. Giving was aligned with the social determinants of health (i.e., aimed at improving economic stability, the neighborhood and physical environment, education, food security and nutrition, the community and social context, and the health care system). However, improving public health was not often cited as a goal of corporate giving, and coordination with public health agencies was limited. Our results suggest that there may be opportunities for public health agencies to help guide corporate philanthropy, particularly by sharing community-level data and offering their measurement and evaluation expertise.

Association Between Sedentary Time and Quality of Life From the Osteoarthritis Initiative: Who Might Benefit Most From Treatment?

OBJECTIVE: To investigate the relationship between sedentary behavior and quality-adjusted life years (QALYs) among participants in the Osteoarthritis Initiative. DESIGN: Longitudinal, observational design. SETTING: Osteoarthritis Initiative cohort. PARTICIPANTS: Individuals (N=1794) from a prospective, multicenter longitudinal cohort were classified into quantile groups based on average daily sedentary time (most sedentary, quartile 1 [Q1] ≥11.6h; 10.7h≤ Q2 <11.6h; 9.7h≤ Q3 <10.7h; least sedentary, Q4 <9.7h). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Individual QALYs were estimated over 2 years from the area under the curve of health-related utility scores derived from the Medical Outcomes Study 12-Item Short-Form Health Survey versus time. The relationship between baseline sedentary behavior and median 2-year QALYs was estimated using quantile regression adjusted for socioeconomic factors and body mass index. RESULTS: Lower QALYs over 2 years were more frequently found among the most sedentary (Q1, median 1.59), and QALYs increased as time spent in baseline sedentary behavior decreased (median QALYs for Q2, 1.64; Q3, 1.65; Q4, 1.65). The relationship of sedentary time and median QALY change was only significant for the most sedentary Q1 group, where an additional hour of sedentary behavior significantly reduced QALYs by -.072 (95% confidence interval, -.121 to -.020). CONCLUSIONS: Our findings suggest that individuals with the most extreme sedentary profiles may be vulnerable to additional losses of quality of life if they become more sedentary. Targeting these individuals to decrease sedentary behavior has the potential to be cost-effective.

Patients Less Likely to Lose Weight Following a Knee Replacement: Results From the Osteoarthritis Initiative.

BACKGROUND: Knee replacement typically results in reduced pain and improved function, but it is unclear if these improvements lead to weight loss. OBJECTIVE: The purpose of this study was to examine weight change patterns preoperatively and postoperatively among overweight/obese knee replacement patients. METHODS: The study evaluated 210 overweight/obese patients from the Osteoarthritis Initiative who underwent a knee replacement during an 8-year longitudinal study. Average annual weight changes during 1- to 2-year intervals prior to, including, and subsequent to knee replacement were categorized as loss (≥-2.5%), maintain (>-2.5% to <2.5%), and gain (≥2.5%). Weight changes across time intervals were compared using logistic regression with generalized estimating equations, adjusting for demographic, health, and knee factors. RESULTS: On average, patients lost -0.6 kg/y during the interval when the surgery was performed, but weight gain (0.9 kg/y) in the initial postoperative interval represented an overall net weight gain (0.3 kg/y) compared with presurgery. Continued weight gain (0.3 kg/y) was also seen among patients with additional follow-ups. Patients were significantly less likely to have a meaningful weight loss in the time interval immediately following the surgery compared with the interval in which the surgery took place (odds ratio, 0.37; 95% confidence interval, 0.18-0.79). CONCLUSIONS: Overweight and obese patients initially lost weight during the interval including knee replacement; however, they were less likely to lose more than 2.5% of their weight in the 1 to 2 years immediately after the surgery. Knee replacement patients may benefit from weight management interventions both preoperatively and postoperatively.

Do Inactive Older Adults Who Increase Physical Activity Experience Less Disability: Evidence From the Osteoarthritis Initiative.

BACKGROUND: Physical inactivity is a leading risk factor for developing disability. Although randomized clinical trials have demonstrated improving physical activity can reduce this risk in older adults with arthritis, these studies did not specifically evaluate inactive adults. OBJECTIVES: The aim of this study was to evaluate the relationship of changes in physical activity with disability changes among initially inactive adults with or at high risk of knee osteoarthritis from Osteoarthritis Initiative. METHODS: Inactive persons were identified at baseline based on the US Department of Health and Human Services classification (no [zero] 10-minute session of moderate-to-vigorous [MV] activity over 1 week) from objective accelerometer monitoring. Two years later, physical activity change status was classified as follows: (1) met Federal physical activity guidelines (≥150 MV minutes/week acquired in bouts ≥10 minutes), (2) insufficiently increased activity (some but <150 MV bout minutes/week), or (3) remained inactive. Disability at baseline and 2 years was assessed by Late Life Disability Instrument limitation and frequency scores. Multiple regression evaluated the relationship of physical activity change status with baseline-to-2-year changes in disability scores adjusting for socioeconomics, health factors, and baseline disability score. RESULTS: Increased physical activity showed a graded relationship with improved disability scores in Late Life Disability Instrument limitation (P < 0.001) and frequency scores (P = 0.027). While increasing MV activity to guideline levels showed the greatest reduction, even insufficiently increased physical activity was related to reduced disability. CONCLUSIONS: Findings support advice to increase MV physical activity to reduce disability among inactive adults with or at high risk of knee osteoarthritis, even when guidelines are not met.

Sedentary Behavior as a Risk Factor for Physical Frailty Independent of Moderate Activity: Results From the Osteoarthritis Initiative.

OBJECTIVES: This prospective longitudinal study investigated the association between baseline objectively measured sedentary time and 2-year onset of physical frailty. METHODS: We studied 1333 Osteoarthritis Initiative participants 55 to 83 years of age who were at risk for physical frailty, as assessed via low gait speed (< 0.6 m per second) or inability to perform a single chair stand. Baseline sedentary time was assessed through accelerometer monitoring. Hazard ratios (HRs) for physical frailty onset were estimated with discrete survival methods that controlled for moderate physical activity, sociodemographic characteristics, baseline gait and chair stand functioning, and health factors. RESULTS: The incidence of physical frailty in this high-risk group was 20.7 per 1000 person-years. Greater baseline sedentary time (adjusted HR = 1.36 per sedentary hour; 95% confidence interval [CI] = 1.02, 1.79) was significantly related to incident physical frailty after control for time spent in moderate-intensity activities and other covariates. CONCLUSIONS: Our prospective data demonstrated a strong relationship between daily sedentary time and development of physical frailty distinct from insufficient moderate activity. Interventions that promote reductions in sedentary behaviors in addition to increases in physical activity may help decrease physical frailty onset.

Accelerometer-monitored sedentary behavior and observed physical function loss.

OBJECTIVES: We examined whether objectively measured sedentary behavior is related to subsequent functional loss among community-dwelling adults with or at high risk for knee osteoarthritis. METHODS: We analyzed longitudinal data (2008-2012) from 1659 Osteoarthritis Initiative participants aged 49 to 83 years in 4 cities. Baseline sedentary time was assessed by accelerometer monitoring. Functional loss (gait speed and chair stand testing) was regressed on baseline sedentary time and covariates (baseline function; socioeconomics [age, gender, race/ethnicity, income, education], health factors [obesity, depression, comorbidities, knee symptoms, knee osteoarthritis severity, prior knee injury, other lower extremity pain, smoking], and moderate-to-vigorous activity). RESULTS: This cohort spent almost two thirds of their waking hours (average=9.8 h) in sedentary behaviors. Sedentary time was significantly positively associated with subsequent functional loss in both gait speed (-1.66 ft/min decrease per 10% increment sedentary percentage waking hours) and chair stand rate (-0.75 repetitions/min decrease), controlling for covariates. CONCLUSIONS: Being less sedentary was related to less future decline in function, independent of time spent in moderate-to-vigorous activity. Both limiting sedentary activities and promoting physical activity in adults with knee osteoarthritis may be important in maintaining function.

Characterization of sleep disturbance in established rheumatoid arthritis patients: exploring the relationship with central nervous system pain regulation.

BACKGROUND: To characterize sleep disturbance in patients with established rheumatoid arthritis (RA) and explore the relationship between sleep and mechanisms of central nervous system pain regulation. METHODS: Forty-eight RA participants completed wrist-worn actigraphy monitoring and daily sleep diaries for 14 days to assess sleep-wake parameters. Participants underwent quantitative sensory testing to assess pressure pain thresholds, temporal summation, and conditioned pain modulation. Data were analyzed using descriptive statistics, Spearman's correlation, and multivariable median regression analyses. RESULTS: Median actigraphy and sleep diary derived sleep duration was 7.6 h (interquartile range (IQR) 7.0, 8.2) and 7.1 h (IQR 6.7, 7.6), respectively. Actigraphy based sleep fragmentation (rho = 0.34), wake after sleep onset (rho = 0.36), and sleep efficiency (rho = -0.32) were each related to higher temporal summation values in unadjusted analyses, but these relationships did not persist after controlling for age, body mass index, disease duration, and swollen joint count. No significant relationships were observed between sleep with pressure pain thresholds and conditioned pain modulation. CONCLUSION: Actigraphy and sleep diary monitoring are well tolerated in established RA patients. Future investigations should include both subjective and objective assessments, as they may provide information relating to different components and mechanisms.

Knee confidence as it relates to physical function outcome in persons with or at high risk of knee osteoarthritis in the osteoarthritis initiative.

OBJECTIVE: To evaluate whether low knee confidence at baseline is associated with poor baseline-to-3-year physical function outcome in the Osteoarthritis Initiative. METHODS: Knee confidence was assessed using an item from the Knee Injury and Osteoarthritis Outcome Score instrument. Physical function was assessed using self-report measures (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] function score and Short Form 12 physical component scale) and performance-based measures (20-meter walk and chair stand test). Poor function outcome was defined as moving into a worse function group or remaining in the 2 worst function groups between baseline and 3 years. Logistic regression was used to evaluate the relationship between baseline knee confidence level and poor baseline-to-3-year function outcome, adjusting for potential confounders. RESULTS: The sample included 3,975 men and women with or at high risk of developing osteoarthritis of the knee, of whom 37-53% had poor baseline-to-3-year function outcome. For both self-report measures, increasingly worse knee confidence was associated with a greater risk of poor function outcome, and trend tests supported a graded response (e.g., the adjusted odds ratios [95% confidence intervals] for the WOMAC function score for worsening confidence categories were 1.26 [1.07-1.49], 1.43 [1.16-1.77], and 2.05 [1.49-2.82], P for trend <0.0001). Similar associations between confidence and performance-based function outcome were observed, but statistical significance did not persist in adjusted analyses. Factors independently associated with poor function outcome for all 4 outcome measures were depressive symptoms, comorbidity, body mass index, and joint space narrowing. CONCLUSION: These findings indicate that worse knee confidence at baseline is independently associated with greater risk of poor function outcome by self-report measures, with evidence of a graded response; the relationship with performance measures is not significant in fully adjusted models.

Modifiable physical and behavioural factors associated with widespread pain in older adults with radiographic evidence of knee osteoarthritis.

OBJECTIVE: To identify modifiable physical and behavioural factors associated with widespread pain (WSP) in older adults with radiographic evidence of knee osteoarthritis (OA). METHODS: Cross-sectional initial visit data of participants with radiographic knee OA (Kellgren-Lawrence grade of ≥2) from the Osteoarthritis Initiative Study were analysed. WSP was defined as pain on both sides of the body, above and below the waist, and in the axial skeleton. Time (hrs/d) spent participating in sitting and moderate-strenuous physical activities were calculated from the Physical Activity Scale for the Elderly questionnaire. Physical function was quantified using gait speed and the chair stand test. Restless sleep was assessed using an item on the CES-D Scale. Logistic regression models were constructed to examine the strength of the associations between primary exposures and WSP in unadjusted and adjusted analyses. RESULTS: Among the 2637 participants (mean age 62.6 years, 58.6% female), 16.8% met the criteria for WSP. All primary measures of interest were related to WSP in unadjusted analyses. In adjusted multivariable analysis, slow gait speed (adjusted odds ratio [aOR] 1.43; 95% CI 1.01, 2.02), lower chair stand rate (aOR 0.98; 95% CI 0.97-0.99), and restless sleep (aOR 1.61; 95% CI 1.25-2.08) maintained significant associations with WSP. CONCLUSION: Poor sleep behaviours and low physical function capacity are associated with WSP in adults with radiographic knee OA. These findings highlight the importance of assessing sleep, physical function, and pain distribution in this population. Interventions to improve physical function and sleep behaviours should be investigated as potential strategies to mitigate WSP.

Sex Differences in Pain and Quantitative Sensory Testing in Patients With Rheumatoid Arthritis.

OBJECTIVE: Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference, and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA. METHODS: This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis cohort. Pain intensity was assessed using a 0-10 numeric rating scale. Pain interference was measured using a Patient-Reported Outcomes Measurement Information System computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count, and C-reactive protein. RESULTS: Mean ± SD pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83 [95% confidence interval (95% CI) 0.14, 1.53]). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference -1.22 [95% CI -1.73, -0.72]), wrist (adjusted difference -0.57 [95% CI -1.07, -0.06]), and knee (adjusted difference -1.10 [95% CI -2.00, -0.21]). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed. CONCLUSION: Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women.

Pain Sensitization as a Potential Mediator of the Relationship Between Sleep Disturbance and Subsequent Pain in Rheumatoid Arthritis.

OBJECTIVE: Many patients with rheumatoid arthritis (RA) experience sleep disturbances, commonly attributed to joint pain. Sleep disturbances could also influence pain. One mechanism may be through dysregulated pain processing, manifested by enhanced pain sensitivity. The present study was undertaken to examine the role of pain sensitization, measured by quantitative sensory testing (QST), as a mediator in the pathway of sleep disturbance leading to subsequent pain. METHODS: We used longitudinal data from 221 patients with active RA who were followed for 12 weeks after initiating a disease-modifying antirheumatic drug. Baseline QST included pressure pain thresholds at articular (wrists, knees) and nonarticular (trapezius, thumbnails) sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). Baseline sleep disturbance and subsequent pain intensity were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS). We evaluated correlations between sleep disturbance, QSTs, and subsequent pain intensity. Mediation analyses separately assessed each QST as a mediator, adjusting for baseline confounding factors. RESULTS: Sleep disturbance was correlated with all QST measures except wrist TS and CPM. Sleep disturbance significantly predicted subsequent pain (coefficient for a meaningful increase of 5 units in sleep disturbance = 0.32 (95% confidence interval 0.11, 0.50) in multiple regression. QST mediated 10-19% of this effect. CONCLUSION: Pain sensitization may be one mechanism through which sleep disturbance contributes to pain. The small magnitude of association indicates that unmeasured pathways may contribute to this relationship. Intervention studies are needed to establish causality and determine whether improving sleep can improve pain in patients with RA.

Pain Mechanisms Associated With Disease Activity in Patients With Rheumatoid Arthritis Treated With Disease-Modifying Antirheumatic Drugs: A Regression Tree Analysis.

OBJECTIVE: Although pain affects the assessment of disease activity in patients with rheumatoid arthritis (RA), pain is not always directly related to peripheral joint inflammation. Peripheral and central nervous system regulatory mechanisms also affect pain perception. We used regression tree methodology to identify mechanisms most predictive of disease activity after disease-modifying antirheumatic drug (DMARD) treatment. METHODS: Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28) in 176 patients with RA, before and after starting a DMARD. Quantitative sensory testing (QST), including pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation (CPM), were used to assess pain mechanisms. Regression tree methodology was used to determine the QST modalities most predictive of DAS28 after DMARD treatment. RESULTS: This analysis identified 4 groups defined by baseline DAS28 category and either knee PPT (a combined measure of peripheral and central nervous system dysregulation) or CPM (a measure of descending pain inhibition). Among patients starting with low/moderate disease activity, lower knee PPT (PPT ≤ 4.65 kgf) most strongly predicted higher posttreatment disease activity (group 1 mean DAS28 2.8 [SD 1.0] vs group 2 mean DAS28 3.5 [SD 1.0]). Among patients starting with high baseline disease activity, less efficient descending pain modulation (CPM ≤ 1.55) most strongly predicted higher posttreatment disease activity (group 3 mean DAS28 3.4 [SD 1.4] vs group 4 mean DAS28 4.6 [SD 1.1]). CONCLUSION: These results highlight the importance of identifying and treating aberrant peripheral and central pain regulation in patients with RA starting or switching DMARD therapy.

Incorporating Expected Outcomes Into Clinical Decision-Making for Total Knee Arthroplasty.

OBJECTIVE: Expected outcomes (e.g., expected survivorship after a cancer treatment) have improved decision-making around treatment options in many clinical fields. Our objective was to evaluate the effect of expected values of 3 widely available total knee arthroplasty (TKA) outcomes (risk of serious complications, time to revision, and improvement in pain and function at 2 years after surgery) on clinical recommendation of TKA. METHODS: The RAND/University of California Los Angeles appropriateness criteria method was used to evaluate the role of the 3 expected outcomes in clinical recommendation of TKA. The expected outcomes were added to 5 established preoperative factors from the modified Escobar appropriateness criteria. The 8 indication factors were used to develop 279 clinical scenarios, and a panel of 9 clinicians rated the appropriateness of TKA for each scenario as inappropriate, inconclusive, and appropriate. Classification tree analysis was applied to these ratings to identify the most influential of the 8 factors in discriminating TKA appropriateness classifications. RESULTS: Ratings for the 279 appropriateness scenarios deemed 34.4% of the scenarios as appropriate, 40.1% as inconclusive, and 25.5% as inappropriate. Classification tree analyses showed that expected improvement in pain and function and expected time to revision were the most influential factors that discriminated among the TKA appropriateness classification categories. CONCLUSION: Our results showed that clinicians would use expected postoperative outcome factors in determining appropriateness for TKA. These results call for further work in this area to incorporate estimates of expected pain/function and revision outcomes into clinical practice to improve decision-making for TKA.