Randomized Controlled Trial of a Home‐Based Walking Program to Reduce Moderate to Severe Aromatase Inhibitor‐Associated Arthralgia in Breast Cancer Survivors

BACKGROUND: In postmenopausal women diagnosed with breast cancer (BC), most BC tumors are hormone receptor positive and guidelines recommend adjuvant endocrine therapy that includes an aromatase inhibitor (AI). This study investigates the impact of a 6-week, home-based, self-directed walking program on the commonly reported side effect of AI-associated arthralgia (AIAA). MATERIALS AND METHODS: In this phase II trial, consented BC patients were randomized to walking Intervention (n = 31) or Wait List Control (WLC; n = 31). Eligibility criteria included: stage 0-III BC, on AI for at least 4 weeks, ≥3 on a 5-point scale inquiring about joint symptom intensity "at its worst," and exercising ≤150 minutes per week. Outcomes were self-reported joint symptoms and psychosocial measures. Analyses comparing Intervention and WLC groups were conducted on an intention-to-treat basis to assess intervention impact at 6 weeks (postintervention) and at 6-months follow-up. Adjusted means were calculated to assess differences in two groups. RESULTS: In our final sample (n = 62), mean age was 64 years, 74% were white, and 63% had a body mass index of 30 or higher. At postintervention, Intervention group participants reported significantly increased walking minutes per week, reduced stiffness, less difficulty with activities of daily living (ADL), and less perceived helplessness in managing joint symptoms. At 6-months follow-up (postwalking period in both Intervention and WLC), walking minutes per week had decreased significantly; however, improvements in stiffness and difficulty with ADLs were maintained. CONCLUSION: This study adds to the growing evidence base suggesting exercise as a safe alternative or adjunct to medications for the management of AIAA. IMPLICATIONS FOR PRACTICE: Breast cancer survivors whose adjuvant endocrine treatment includes an aromatase inhibitor (AI) often experience the side effect of AI-associated arthralgia (AIAA). This study investigates the impact of a 6-week, home-based, self-directed walking program in the management of AIAA. Compared with Wait List Control, women in the Intervention group reported significantly increased walking minutes per week, reduced stiffness, less difficulty with activities of daily living, and less perceived helplessness in managing joint symptoms. This study adds to the growing evidence base suggesting exercise as a safe alternative or adjunct to medications for the management of AIAA

Accelerometer-Based Physical Activity Patterns and Associations with Outcomes among Individuals with Osteoarthritis

Background This study examined patterns of physical activity and associations with pain, function, fatigue, and sleep disturbance among individuals with knee or hip osteoarthritis. Methods Participants (n = 54) were enrolled in a telephone-based physical activity coaching intervention trial; all data were collected at baseline. Self-reported measures of pain and function (WOMAC [Western Ontario and McMaster Universities Osteoarthritis Index] subscales), fatigue (10-point numeric rating scale), and PROMIS (Patient-Reported Outcomes Information System) Sleep Disturbance were collected via telephone. Accelerometers were mailed to participants and were worn for at least 3 days. Proportion of time participants spent in sedentary behavior during the morning (from wake until 12:00 pm), afternoon (12:00 pm until 5:59 pm) and evening (6:00 pm until sleep) each day was averaged across all days of wear. Pearson correlations assessed associations between activity and self-reported measures. Results Participants spent a large proportion of time in sedentary behavior: 65.6% of mornings, 70.0% of afternoons, and 76.6% of evenings. Associations between proportion of time spent in sedentary behavior and reported outcomes were generally strongest in the afternoon, strongest for WOMAC function, and lowest for PROMIS Sleep Disturbance. In the evening hours, sedentary time was most strongly associated with fatigue. Conclusions Overall, findings stress the importance of reducing sedentary behavior among adults with osteoarthritis and suggest behavioral interventions may be strengthened by considering patients' within-day variation in symptoms and activity

Pain coping skills training for African Americans with osteoarthritis: Results of a randomized controlled trial

African Americans bear a disproportionate burden of osteoarthritis (OA), but they have been underrepresented in trials of behavioral interventions for pain. This trial examined a culturally tailored pain coping skills training (CST) program, compared to a wait list control group, among 248 African Americans with knee or hip OA. The pain CST program involved 11 telephone-based sessions over 3 months. Outcomes were assessed at baseline, 3 months (primary), and 9 months, and included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (primary outcome), WOMAC total score and function subscale, PROMIS Pain Interference, Short-Form 12 Mental and Physical Composite Subscales, Coping Strategies Questionnaire - Total Coping Attempts, Pain Catastrophizing Scale, Patient Health Questionnaire-8, Arthritis Self-Efficacy Scale, and Patient Global Impression of Arthritis Symptom Change. Linear mixed models were fit for all outcomes. There were no significant between-group differences in WOMAC pain score at 3 months (-0.63 [95% confidence interval -1.45, 0.18]; P = 0.128) or 9 months (-0.84 [95% confidence interval -1.73, 0.06]; P = 0.068). Among secondary outcomes, at 3 months, there were significant differences, in favor of the CST group, for Coping Strategies Questionnaire Total Coping Attempts, Pain Catastrophizing Scale, Arthritis Self-Efficacy, and Patient Global Impression of Arthritis Symptom Change (P < 0.01). Coping Strategies Questionnaire Total Coping Attempts, Arthritis Self-Efficacy, and Patient Global Assessment Change were also significantly improved at 9 months in the CST group, compared with wait list (P < 0.01). The culturally tailored pain CST program did not significantly reduce pain severity but did improve key measures of pain coping and perceived ability to manage pain among African Americans with OA

Application of Heterogeneity of Treatment-Effects Methods: Exploratory Analyses of a Trial of Exercise-Based Interventions for Knee Osteoarthritis

Objective: To evaluate heterogeneity of treatment effects in a trial of exercise-based interventions for knee osteoarthritis (OA). Methods: Participants (n = 350) were randomized to standard physical therapy (PT; n = 140), internet-based exercise training (IBET; n = 142), or wait list (WL; n = 68) control. We applied qualitative interaction trees (QUINT), a sequential partitioning method, and generalized unbiased interaction detection and estimation (GUIDE), a regression tree approach, to identify subgroups with greater improvements in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score over 4 months. Predictors included 24 demographic, clinical, and psychosocial characteristics. We conducted internal validation to estimate optimism (bias) in the range of mean outcome differences among arms. Results: Both QUINT and GUIDE indicated that for participants with lower body mass index (BMI), IBET was better than PT (improvements of WOMAC ranged from 6.3 to 9.1 points lower), and for those with higher BMI and a longer duration of knee OA, PT was better than IBET (WOMAC improvement was 6.3 points). In GUIDE analyses comparing PT or IBET to WL, participants not employed had improvements in WOMAC ranging from 1.8 to 6.8 points lower with PT or IBT versus WL. From internal validation, there were large corrections to the mean outcome differences among arms; however, after correction, some differences remained in the clinically meaningful range. Conclusion: Results suggest there may be subgroups who experience greater improvement in symptoms from PT or IBET, and this finding could guide referrals and future trials. However, uncertainty persists for specific treatment-effects size estimates and how they apply beyond this study sample

Associations Between Baseline and Longitudinal Semiautomated Quantitative Joint Space Width at the Hip and Incident Hip Osteoarthritis: Data From a Community-Based Cohort

Objective: To evaluate quantitative joint space width (JSW) at 10-, 30-, and 50-degree locations in relation to incident radiographic and symptomatic hip osteoarthritis (HOA) in a community-based cohort. Methods: Data were from Johnston County OA Project participants with supine hip radiographs at each of 4 time points; all had Kellgren/Lawrence (K/L) grades and quantitative JSW. We assessed covariates (age, race, height, weight, body mass index [BMI]) associated with quantitative JSW and hip-level associations between quantitative JSW and HOA over time using sex-stratified and multivariable-adjusted linear mixed models. A cluster analysis with logistic regression estimated associations between quantitative JSW trajectory groups and incident radiographic HOA and symptomatic HOA. Results: At baseline, 397 participants (784 hips, 41% men, 24% Black, mean age 57 years) had a mean BMI of 29 kg/m2. Over a mean of 18 years, 20% and 12% developed incident K/L grade–defined radiographic HOA or symptomatic HOA, respectively. Quantitative JSW was more sensitive to changes over time at 50 degrees. Values were stable among men but declined over time in women. Heavier women lost more quantitative JSW; changes in quantitative JSW were not significantly associated with race, education, or injury in women or men. In women only, loss of quantitative JSW over time was associated with 2–3 times higher odds of radiographic HOA and symptomatic HOA; among women and men, narrower baseline quantitative JSW was associated with these outcomes. Conclusion: Hip quantitative JSW demonstrates marked differences in respect to sex, with significant loss over time only in women. Loss of quantitative JSW over time in women and narrower baseline quantitative JSW in men and women were associated with incident radiographic HOA and symptomatic HOA

Acceptability of telephone-based pain coping skills training among African Americans with osteoarthritis enrolled in a randomized controlled trial: A mixed methods analysis

Background: Osteoarthritis (OA) disproportionately impacts African Americans compared to Caucasians, including greater pain severity. The Pain Coping Skills Training for African Americans with Osteoarthritis (STAART) study examined a culturally enhanced Pain Coping Skills Training (CST) program among African Americans with OA. This mixed methods study evaluated the acceptability of the Pain CST program among STAART participants. Methods: STAART was a randomized controlled trial evaluating the effectiveness of an 11-session, telephone-based pain CST program, compared to a usual care control group. Participants were from the University of North Carolina and Durham Veterans Affairs Healthcare Systems. The present analyses included 93 participants in the CST group who completed a questionnaire about experiences with the program. Descriptive statistics of the questionnaire responses were calculated using SAS software. Thematic analysis was applied to open-response data using Dedoose software. Results: Participants' mean rating of overall helpfulness of the pain CST program for managing arthritis symptoms was 8.0 (SD = 2.2) on a scale of 0-10. A majority of participants reported the program made a positive difference in their experience with arthritis (83.1%). Mean ratings of helpfulness of the specific skills ranged from 7.7 to 8.8 (all scales 0-10). Qualitative analysis of the open-response data identified four prominent themes: Improved Pain Coping, Mood and Emotional Benefits, Improved Physical Functioning, and experiences related to Intervention Delivery. Conclusions: The high ratings of helpfulness demonstrate acceptability of this culturally enhanced pain CST program by African Americans with OA. Increasing access to cognitive-behavioral therapy-based programs may be a promising strategy to address racial disparities in OA-related pain and associated outcomes. Trial registration: NCT02560922, registered September 25, 2015

Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians

Background: Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus. Methods: A total of 5925 individuals of European Ancestry were categorized into two groups: 'hallux valgus present' (n = 2314) or 'no deformity' (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex-specific and sex-combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed-effects inverse-variance meta-analyses. Functional Mapping and Annotation web-based platform (FUMA) was used for positional mapping, gene and gene-set analyses. Results: We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E-09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family. Conclusion: In this report of the largest GWAS of hallux valgus to date, we identified a novel genome-wide significant locus for hallux valgus. Additional replication and functional follow-up will be needed to determine the functional role of this locus in hallux valgus biology

The Prevalence of Knee Symptoms, Radiographic, and Symptomatic Osteoarthritis at Four Time Points: The Johnston County Osteoarthritis Project, 1999-2018

Objective: To describe point prevalence of knee symptoms, radiographic knee osteoarthritis (rKOA), severe rKOA, and symptomatic rKOA at four time points in the longitudinal, population-based Johnston County Osteoarthritis Project (JoCo OA). Methods: Data were from 2573 JoCo OA participants with up to 18 years of follow-up (1999-2018) and standardized fixed-flexion knee radiographs read by a single, reliable expert musculoskeletal radiologist. The four outcomes were 1) self-reported knee symptoms, defined by “On most days, do you have pain, aching, or stiffness in your right/left knee?”; 2) rKOA, defined as a Kellgren-Lawrence grade (KLG) of 2 to 4); 3) severe rKOA, defined as a KLG of 3 or 4; and 4) symptomatic rKOA, defined as both symptoms and rKOA in the same joint. Weighted prevalence estimates and 95% confidence intervals (CIs) were generated overall and by age group, sex, race, and body mass index (BMI). Results: Most recently (2017-2018, T4), the overall prevalence (percentage) of knee symptoms, rKOA, severe rKOA, and symptomatic rKOA was 41% (95% CI: 35-47%), 61% (95% CI: 56-67%), 35% (95% CI: 30-40%), and 30% (95% CI: 24-35%), respectively. From time point T1 to T4, prevalence increased for rKOA, severe rKOA, and symptomatic rKOA but not for knee symptoms. The prevalence of both severe rKOA (17-39%) and symptomatic rKOA (23-30%) was consistently higher among women. The prevalence of all outcomes was higher among those with higher BMI and among Black participants at all time points, particularly rKOA (35-69%) and severe rKOA (22-46%). Conclusion: These updated estimates demonstrate a large and increasing burden of knee OA, particularly among women and Black individuals

Racial Differences in Performance-Based Function and Potential Explanatory Factors Among Individuals With Knee Osteoarthritis

Objective: In individuals with knee osteoarthritis (OA), self-reported physical function is poorer in African Americans than in whites, but whether this difference holds true for objective assessments is unclear. The purpose of this study was to examine racial differences in performance-based physical function as well as potential underlying factors contributing to these racial differences. Methods: Participants with knee OA from a randomized controlled trial completed the 2-minute step test (2MST), timed-up-and-go (TUG), and 30-second chair stand (30s-CST) at baseline. Race differences in performance-based function were assessed by logistic regression. Separate models were adjusted for sets of demographic, socioeconomic, psychological health, and physical health variables. Results: In individuals with knee OA (n = 322; 72% women, 22% African American, mean ± SD age 66 ± 11 years, mean ± SD body mass index 31 ± 8 kg/m2), African Americans (versus whites) had greater unadjusted odds of poorer function (30s-CST odds ratio [OR] 2.79 [95% confidence interval (95% CI) 1.65–4.72], 2MST OR 2.37 [95% CI 1.40–4.03], and TUG OR 3.71 [95% CI 2.16–6.36]). Relationships were maintained when adjusted for demographic and psychological health covariates, but they were either partially attenuated or nonsignificant when adjusted for physical health and socioeconomic covariates. Conclusion: African American adults with knee OA had poorer unadjusted performance-based function than whites. Physical health and socioeconomic characteristics diminished these differences, emphasizing the fact that these factors may be important to consider in mitigating racial disparities in function

Pain coping skills training for African Americans with osteoarthritis study: Baseline participant characteristics and comparison to prior studies 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1117 Public Health and Health Services

Background: The Pain Coping Skills Training for African Americans with OsteoaRTthritis (STAART) trial is examining the effectiveness of a culturally enhanced pain coping skills training (CST) program for African Americans with osteoarthritis (OA). This disparities-focused trial aimed to reach a population with greater symptom severity and risk factors for poor pain-related outcomes than previous studies. This paper compares characteristics of STAART participants with prior studies of CST or cognitive behavioral therapy (CBT)-informed training in pain coping strategies for OA. Methods: A literature search identified 10 prior trials of pain CST or CBT-informed pain coping training among individuals with OA. We descriptively compared characteristics of STAART participants with other studies, in 3 domains of the National Institutes of Minority Health and Health Disparities' Research Framework: Sociocultural Environment (e.g., age, education, marital status), Biological Vulnerability and Mechanisms (e.g, pain and function, body mass index), and Health Behaviors and Coping (e.g., pain catastrophizing). Means and standard deviations (SDs) or proportions were calculated for STAART participants and extracted from published manuscripts for comparator studies. Results: The mean age of STAART participants, 59 years (SD = 10.3), was lower than 9 of 10 comparator studies; the proportion of individuals with some education beyond high school, 75%, was comparable to comparator studies (61-86%); and the proportion of individuals who are married or living with a partner, 42%, was lower than comparator studies (62-66%). Comparator studies had less than about 1/3 African American participants. Mean scores on the Western Ontario and McMaster Universities Osteoarthritis Index pain and function scales were higher (worse) for STAART participants than for other studies, and mean body mass index of STAART participants, 35.2 kg/m2 (SD = 8.2), was higher than all other studies (30-34 kg/m2). STAART participants' mean score on the Pain Catastrophizing scale, 19.8 (SD = 12.3), was higher (worse) than other studies reporting this measure (7-17). Conclusions: Compared with prior studies with predominantly white samples, STAART participants have worse pain and function and more risk factors for negative pain-related outcomes across several domains. Given STAART participants' high mean pain catastrophizing scores, this sample may particularly benefit from the CST intervention approach. Trial registration: NCT02560922