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Objective: This study investigated the association of perceived neighborhood qualities with likelihood of transit walking, leisure walking, neighborhood walking, and meeting physical activity (PA) recommendations among US adults with arthritis. Methods: This cross‐sectional study used 2020 National Health Interview Survey data. Included participants were adults who reported with clinician‐diagnosed arthritis and who reported the ability to walk. Exposures of interest were perceived neighborhood attributes. Outcomes were transit walking, leisure walking, neighborhood walking, and meeting PA recommendations. Standardized mean difference percentage (SMD%) was used to assess relationships between exposures and outcomes, with an SMD% >10% resulting in inclusion in final adjusted multivariate logistic regression models for odds of outcomes. All analyses were weighted to account for complex survey methodology. Results: The analytic sample included 7,322 adults with arthritis. Fully adjusted logistic regression models showed the presence of roads to walk on was associated with meeting PA recommendations (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.07–1.49]). Three attributes were positively associated with transit walking, whereas safety from crime was negatively associated (OR 2.33, 95% CI 1.75–3.10; OR 1.49, 95% CI 1.17–1.91; OR 1.67, 95% CI 1.34–2.08; and OR 0.70, 95% CI 0.53–0.92, respectively). Roads to walk and places to walk and relax were associated with leisure and neighborhood walking (OR 1.46, 95% CI 1.21–1.76; OR 1.56, 95% CI 1.34–1.82; OR 1.58, 95% CI 1.29–1.93; and OR 1.63, 95% CI 1.40–1.90, respectively). Conclusion: This study identified several neighborhood characteristics associated with higher a likelihood of walking behaviors among adults with arthritis. Factors associated with walking behavior varied by the type of walking. The shared correlates between leisure and neighborhood walking imply they occur in the same setting. Patients with arthritis may benefit from exercise recommendations that are informed by the presence or absence of facilitating infrastructure in their neighborhoods. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to determine whether the clinical response of older adults with knee osteoarthritis and overweight or obesity to 18 months of diet and exercise (D + E) or attention control (C) interventions differed between participants from rural versus urban communities. Methods: Participants were 823 older adults (mean age, 64.6 years; 77% women) with knee osteoarthritis and overweight or obesity who resided in rural (n = 410) and urban (n = 413) counties in North Carolina. All were enrolled in the Weight Loss and Exercise for Communities with Arthritis in North Carolina clinical trial that randomly assigned participants to either 18 months of D + E or C interventions. General linear models were used to examine differences in clinical outcomes between rural and urban groups after adjusting for covariates. Results: The rural group had significant differences (P < 0.05) at baseline in clinical outcomes, education, comorbidities, medication use, and income compared with the urban dwellers. After adjusting for baseline differences, the group (rural or urban) by treatment (D + E or C) interactions for Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) pain (rural: D + E – C = −0.63, 95% confidence interval [CI] −1.31 to 0.06; urban: D + E − C= −0.29, 95% CI −0.99 to 0.41; P = 0.50) and WOMAC function (rural: D + E − C = −4.60, 95% CI −6.89 to −2.31; urban: D + E − C = −1.38, 95% CI −3.73 to 0.94; P = 0.054) indicated that the groups responded similarly to the interventions. Conclusion: Among participants with knee osteoarthritis and overweight or obesity, D + E compared to C led to similar pain outcomes in rural and urban dwellers that favored D + E. The possibility that there may be greater differential efficacy in functional outcomes among rural participants needs further study. [ABSTRACT FROM AUTHOR]

Objective: Obesity exacerbates pain and functional limitation in persons with knee osteoarthritis (OA). In the Weight Loss and Exercise for Communities with Arthritis in North Carolina (WE‐CAN) study, a community‐based diet and exercise (D + E) intervention led to an additional 6 kg weight loss and 20% greater pain relief in persons with knee OA and body mass index (BMI) >27 kg/m2 relative to a group‐based health education (HE) intervention. We sought to determine the incremental cost‐effectiveness of the usual care (UC), UC + HE, and UC + (D + E) programs, comparing each strategy with the "next‐best" strategy ranked by increasing lifetime cost. Methods: We used the Osteoarthritis Policy Model to project long‐term clinical and economic benefits of the WE‐CAN interventions. We considered three strategies: UC, UC + HE, and UC + (D + E). We derived cohort characteristics, weight, and pain reduction from the WE‐CAN trial. Our outcomes included quality‐adjusted life years (QALYs), cost, and incremental cost‐effectiveness ratios (ICERs). Results: In a cohort with mean age 65 years, BMI 37 kg/m2, and Western Ontario and McMaster Universities Osteoarthritis Index pain score 38 (scale 0–100, 100 = worst), UC leads to 9.36 QALYs/person, compared with 9.44 QALYs for UC + HE and 9.49 QALYS for UC + (D + E). The corresponding lifetime costs are $147,102, $148,139, and $151,478. From the societal perspective, UC + HE leads to an ICER of $12,700/QALY; adding D + E to UC leads to an ICER of $61,700/QALY. Conclusion: The community‐based D + E program for persons with knee OA and BMI >27kg/m2 could be cost‐effective for willingness‐to‐pay thresholds greater than $62,000/QALY. These findings suggest that incorporation of community‐based D + E programs into OA care may be beneficial for public health. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine whether clinical, health‐related quality of life (HRQL), and gait characteristics in adults with knee osteoarthritis (OA) differed by obesity category. Methods: This cross‐sectional analysis of 823 older adults (mean age 64.6 years, SD 7.8 years) with knee OA and overweight or obesity compared clinical, HRQL, and gait outcomes among obesity classifications (overweight or class I, body mass index [BMI] 27.0–34.9; class II, BMI 35.0–39.9; class III BMI ≥40.0). Results: Patients with class III obesity had worse Western Ontario McMasters Universities Arthritis Index knee pain (0–20) than the overweight or class I (mean 8.6 vs 7.0; difference 1.5; 95% confidence interval [CI] 1.0–2.1; P < 0.0001) and class II (mean 8.6 vs 7.4; difference 1.1; 95% CI 0.6–1.7; P = 0.0002) obesity groups. The Short Form 36 physical HRQL measure was lower in the class III obesity group compared to the overweight or class I (mean 31.0 vs 37.3; difference −6.2; 95% CI −7.8 to −4.7; P < 0.0001) and class II (mean 31.0 vs 35.0; difference −3.9; 95% CI −5.6 to −2.2; P < 0.0001) obesity groups. The class III obesity group had a base of support (cm) during gait that was wider than that for the overweight or class I (mean 14.0 vs 11.6; difference 3.3; 95% CI 2.6–4.0; P < 0.0001) and class II (mean 14.0 vs 11.6; difference 2.4; 95% CI 1.6–3.2; P < 0.0001) obesity groups. Conclusion: Among adults with knee OA, those with class III obesity had significantly higher pain levels and worse physical HRQL and gait characteristics compared to adults with overweight or class I or class II obesity. [ABSTRACT FROM AUTHOR]

Physical activity (PA) and weight management are critical components of an effective knee and hip osteoarthritis (OA) management plan, yet most people with OA remain insufficiently active and/or overweight. Clinicians and their care teams play an important role in educating patients with OA about PA and weight management, eliciting patient motivation to engage in these strategies, and referring patients to appropriate self-management interventions. The purpose of this review is to educate clinicians about the current public health and clinical OA guidelines for PA and weight management and highlight a variety of evidence-based self-management interventions available in community and clinical settings and online. [ABSTRACT FROM AUTHOR]

Introduction: Non-professional care partners play an important and often evolving role in the care of persons living with Alzheimer's disease (PLWAD). We investigated two elements of the care partner experience, namely time and strain incurred by care partners providing care to PLWAD across the severity spectrum. Methods: Data gathered from the Alzheimer's Disease Patient and Caregiver Engagement (AD PACE) What Matters Most (WMM) study series were analyzed to determine how much time care partners spent providing care to PLWAD based on where the care recipients lived. Additionally, quantitative assessments of weekly hours providing care and the strain experienced by care partners were conducted using the UsAgainstAlzheimer's A-LIST Insights Series survey, which included the Modified Caregiver Strain Index (MCSI). Finally, a targeted literature review was conducted to contextualize findings and characterize the existing literature landscape. Results: Care partners in the AD PACE WMM studies (n = 139) spent significantly more hours providing care for recipients who lived with someone (mean ± standard deviation [SD], 57.3 ± 44.3 h/week) than for recipients who lived alone (26.0 ± 12.0 h/week) (P = 0.0096) or lived in assisted living/nursing home (23.6 ± 14.4 h/week) (P = 0.0002). In the A-LIST Insights Series survey, care partners provided an overall mean (± SD) 58.1 ± 53.0 h of direct care each week, with caregiving hours increasing with increasing severity of AD/AD-related dementias (AD/ADRD). Additionally, care partners for recipients with mild (n = 14), moderate (n = 111), and severe AD/ADRD (n = 91) had overall mean MCSI scores of 9.0 ± 3.8 (range 2–14), 13.3 ± 4.8 (range 4–23), and 17.5 ± 5.3 (range 4–26), respectively, with higher scores suggesting greater care partner strain. Conclusions: Persons living with AD require increasing levels of care along the spectrum of disease, and even individuals with early disease need care from partners. Early interventions that slow progression of AD and programs that improve family function may have beneficial impact on the experiences of care partners for recipients with mild, moderate, or severe AD. [ABSTRACT FROM AUTHOR]

Objective. We applied a precision medicine-based machine learning approach to discover underlying patient characteristics associated with differential improvement in knee osteoarthritis symptoms following standard physical therapy (PT), internet-based exercise training (IBET), and a usual care/wait list control condition. Methods. Participants (n = 303) were from the Physical Therapy vs Internet-Based Training for Patients with Knee Osteoarthritis trial. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12-month follow-up. Random forest-informed tree-based learning was applied to identify patient characteristics that were critical to improving outcomes, and patients with those features were grouped. Results. Age, BMI, and Brief Fear of Movement (BFOM) score, all at baseline, were identified as characteristics that effectively divided participants, creating 6 subgroups. Assigning treatments according to these models, compared to assigning a single best treatment to all patients, resulted in greater improvements of the average WOMAC at 12 months (P = 0.01). Key patterns were that IBET was the optimal treatment for patients of younger age and low BFOM, whereas PT was the optimal treatment for patients of older age, high BFOM, and BMI (kg/m²) between 26.3 and 37.2. Conclusion. These results suggest that easily assessed patient characteristics including age, fear of movement, and BMI could be used to guide patients toward either home-based exercise or PT, though additional studies are needed to confirm these findings. (ClinicalTrials.gov: NCT02312713) [ABSTRACT FROM AUTHOR]

While there is some research investigating whole foods or diets that are easily understood and accessible to patients with osteoarthritis, specific nutrients or nutraceuticals are more commonly identified. Unfortunately, guidelines and evidence surrounding individual nutrients, extracts, and nutraceuticals are conflicting and are more difficult to interpret and implement for patients with osteoarthritis. The purpose of this umbrella review is to provide a comprehensive understanding of the existing evidence of whole foods and dietary patterns effects on osteoarthritis-related outcomes to inform evidence-based recommendations for healthcare professionals and identify areas where more research is warranted. A literature search identified relevant systematic reviews/meta-analyses using five databases from inception to May 2022. Five systematic reviews/meta-analyses were included in the current umbrella review. Most evidence supported the Mediterranean diet improving osteoarthritis-related outcomes (e.g., pain, stiffness, inflammation, biomarkers of cartilage degeneration). There was little to no evidence supporting the effects of fruits and herbs on osteoarthritis-related outcomes; however, there was some suggestion that specific foods could potentiate symptom improvement through antioxidative mechanisms. The overall lack of homogeneity between the studies limits the conclusions that can be made and highlights the need for quality research that can identify consumer-accessible foods to improve osteoarthritis-related symptoms. [ABSTRACT FROM AUTHOR]

Objective: The COVID‐19 pandemic has impacted the careers of trainees and early career investigators (ECIs). We sought to assess how the American College of Rheumatology (ACR) and the Rheumatology Research Foundation (RRF) can address the needs of those pursuing research careers. Methods: The Committee on Research created a survey to assess the impact of COVID‐19 and identify topics for the ACR and the RRF to address. In fall of 2020, we surveyed postdoctoral trainees and ECIs within 9 years of terminal training. Responses were analyzed using descriptive statistics and qualitative content analysis. Results: Twenty‐one percent of invitees responded to the survey (n = 365); of these, 60% were pursuing careers in academic research. Seventy‐five percent of respondents in academic research career paths placed their primary projects on hold during the pandemic. The number of individuals pursuing a research career from 2020 to 2021 decreased by 5%. Respondents reported funding, caregiving, and lack of preliminary data as significant challenges. Suggested impactful interventions included increased funding, funding process reform, and expanding mentoring and networking resources. Conclusion: Major stressors identified during the pandemic included increased caregiving responsibilities and difficulty obtaining data and funding, for which respondents suggested increases and changes in funding programs as well as more mentoring and networking opportunities. Based on these, the Committee on Research proposes 3 priorities: 1) flexible funding mechanisms for ECIs and additional support for those impacted by caregiving; 2) virtual and in‐person programs for career development and networking; and 3) curated content relevant to building a research career available on demand. [ABSTRACT FROM AUTHOR]

Introduction: In this phase of the ongoing What Matters Most study series, designed to evaluate concepts that are meaningful to people affected by Alzheimer's disease (AD), we quantified the importance of symptoms, impacts, and outcomes of AD to people at risk for or with AD and care partners of people with AD. Methods: We administered a web-based survey to individuals at risk for or with AD (Group 1: unimpaired cognition with evidence of AD pathology; Group 2: AD risk factors and subjective cognitive complaints/mild cognitive impairment; Group 3: mild AD) and to care partners of individuals with moderate AD (Group 4) or severe AD (Group 5). Respondents rated the importance of 42 symptoms, impacts, and outcomes on a scale ranging from 1 ("not at all important") to 5 ("extremely important"). Results: Among the 274 respondents (70.4% female; 63.1% white), over half of patient respondents rated all 42 items as "very important" or "extremely important," while care partners rated fewer items as "very important" or "extremely important." Among the three patient groups, the minimum (maximum) mean importance rating for any item was 3.4 (4.6), indicating that all items were at least moderately to very important. Among care partners of people with moderate or severe AD, the minimum (maximum) mean importance rating was 2.1 (4.4), indicating that most items were rated as at least moderately important. Overall, taking medications correctly, not feeling down or depressed, and staying safe had the highest importance ratings among both patients and care partners, regardless of AD phase. Conclusion: Concepts of importance to individuals affected by AD go beyond the common understanding of "cognition" or "function" alone, reflecting a desire to maintain independence, overall physical and mental health, emotional well-being, and safety. Preservation of these attributes may be key to understanding whether interventions deliver clinically meaningful outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Insight into the relationship between concepts that matter to the people affected by Alzheimer's disease (AD) and the clinical outcome assessments (COAs) commonly used in AD clinical studies is limited. Phases 1 and 2 of the What Matters Most (WMM) study series identified and quantitatively confirmed 42 treatment-related outcomes that are important to people affected by AD. Methods: We compared WMM concepts rated as "very important" or higher to items included in COAs used commonly in AD studies. Results: Twenty COAs designed to assess signs, symptoms, and impacts across the spectrum of AD were selected for review. Among these 20 COAs, only 5 reflected 12 or more WMM concepts [Integrated Alzheimer's Disease Rating Scale (iADRS), Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory (ADCS-ADL), Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory–Mild Cognitive Impairment (ADCS-ADL-MCI), Alzheimer's Disease Composite Scores (ADCOMS), and Clinical Dementia Rating; Clinical Dementia Rating-Sum of Boxes (CDR/CDR-SB)]. Multiple symptoms and impacts of AD identified as important and meaningful in the WMM studies map only indirectly at best to 7 of the 20 most widely used COAs. Conclusion: While many frequently used COAs in AD capture some concepts identified as important to AD populations and their care partners, overlap between any single measure and the concepts that matter to people affected by AD is limited. The highest singly matched COA reflects fewer than half (45%) of WMM concepts. Use of multiple COAs expands coverage of meaningful concepts. Future research should explore the content validity of AD COAs planned for AD trials based on further confirmation of the ecological validity of the WMM items. This research should inform development and use of core outcome sets that capture WMM items and selection or development of new companion tools to fully demonstrate clinically meaningful outcomes spanning WMM. [ABSTRACT FROM AUTHOR]

The Osteoarthritis Action Alliance formed a secondary prevention task group to develop a consensus on secondary prevention recommendations to reduce the risk of osteoarthritis after a knee injury. Our goal was to provide clinicians with secondary prevention recommendations that are intended to reduce the risk of osteoarthritis after a person has sustained an anterior cruciate ligament injury. Specifically, this manuscript describes our methods, literature reviews, and dissenting opinions to elaborate on the rationale for our recommendations and to identify critical gaps. Consensus process. Virtual video conference calls and online voting. The Secondary Prevention Task Group consisted of 29 members from various clinical backgrounds. The group initially convened online in August 2020 to discuss the target population, goals, and key topics. After a second call, the task group divided into 9 subgroups to draft the recommendations and supportive text for crucial content areas. Twenty-one members completed 2 rounds of voting and revising the recommendations and supportive text between February and April 2021. A virtual meeting was held to review the wording of the recommendations and obtain final votes. We defined consensus as >80% of voting members supporting a proposed recommendation. The group achieved consensus on 15 of 16 recommendations. The recommendations address patient education, exercise and rehabilitation, psychological skills training, graded-exposure therapy, cognitive-behavioral counseling (lacked consensus), outcomes to monitor, secondary injury prevention, system-level social support, leveraging technology, and coordinated care models. This consensus statement reflects information synthesized from an interdisciplinary group of experts based on the best available evidence from the literature or personal experience. We hope this document raises awareness among clinicians and researchers to take steps to mitigate the risk of osteoarthritis after an anterior cruciate ligament injury. [ABSTRACT FROM AUTHOR]

After an anterior cruciate ligament (ACL) injury, people need secondary prevention strategies to identify osteoarthritis at its earliest stages so that interventions can be implemented to halt or slow the progression toward its long-term burden. The Osteoarthritis Action Alliance formed an interdisciplinary Secondary Prevention Task Group to develop a consensus on recommendations to provide clinicians with secondary prevention strategies that are intended to reduce the risk of osteoarthritis after a person has an ACL injury. The group achieved consensus on 15 out of 16 recommendations that address patient education, exercise and rehabilitation, psychological skills training, graded-exposure therapy, cognitive-behavioral counseling (lacked consensus), outcomes to monitor, secondary injury prevention, system-level social support, leveraging technology, and coordinated care models. We hope this statement raises awareness among clinicians and researchers on the importance of taking steps to mitigate the risk of osteoarthritis after an ACL injury. [ABSTRACT FROM AUTHOR]

Objective: In prior cross‐sectional analyses of African American patients with rheumatoid arthritis (RA), measures of socioeconomic status (SES) were associated with clinical joint damage and poorer patient‐reported outcome scores. The purpose of this study was to determine whether SES measures are associated with disease progression in a cohort of African American patients with early RA (<2 years duration). Methods: We analyzed baseline SES and change in 60‐month clinical radiographs and patient‐reported outcomes data (n = 101 and 177, respectively) in individuals with early RA. SES measures were educational attainment, occupation, homeownership, household income, and block group poverty. Outcomes were based on radiographs (total erosion and joint space narrowing [JSN] scores on hands and feet) and patient‐reported outcomes (pain, fatigue, disability, and learned helplessness). We used logistic regression with mixed effects accounting for study site to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Both low education and occupation status were associated with worsening pain (adjusted OR 5.86 [95% CI 3.05–11.3] and adjusted OR 2.55 [95% CI 1.54–4.21], respectively). Patients without a high‐school diploma were more likely to have worsened reports of learned helplessness (OR 1.92 [95% CI 1.37–2.67]). Community measures of SES were also significantly associated with patient‐reported outcomes score changes. Patients living in areas of block group poverty ≥20% were twice as likely to experience increased disability scores over 60 months of disease duration (OR 1.95 [95% CI 1.17–3.25]). We found no association between SES measures and erosion or JSN score progression. Conclusion: Low educational attainment and nonprofessional occupation status were associated with increased worsening of patient‐reported outcomes. However, there were no corresponding increases in radiographically assessed erosion or JSN score progression. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does a weight loss and exercise program in community settings lead to improvement in knee pain in patients with osteoarthritis and overweight or obesity? Findings: This randomized clinical trial included 823 patients with knee osteoarthritis and overweight or obesity treated with diet and exercise vs an attention control. After 18 months, the adjusted mean difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (range, 0-20) was −0.6, a difference that met statistical significance. Meaning: In patients with knee osteoarthritis and overweight or obesity, an 18-month program of weight loss and exercise based in community settings, compared with an attention control group, led to a small difference in knee pain of uncertain clinical importance. Importance: Some weight loss and exercise programs that have been successful in academic center–based trials have not been evaluated in community settings. Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Interventions: Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. Main Outcomes and Measures: The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Results: Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, −0.6; 95% CI, −1.0 to −0.1; P =.02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was −7.7 kg (8%) in the diet and exercise group (n = 289) and −1.7 kg (2%) in the attention control group (n = 273) (mean difference, −6.0 kg; 95% CI, −7.3 kg to −4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Conclusions and Relevance: Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02577549 This randomized clinical trial assesses the effect of a diet and exercise intervention vs an attention control condition on knee pain at 18-month follow-up among individuals aged 50 years or older with knee osteoarthritis and overweight or obesity. [ABSTRACT FROM AUTHOR]

Objective: Electronic health record (EHR) databases are a powerful resource to investigate clinical trajectories of osteoarthritis (OA). There are no existing EHR tools to evaluate risk for knee arthroplasty (KA). We developed an OA severity index (OASI) using EHR data and demonstrate the index's association with time to KA. Methods: This retrospective cohort study used 2010‐2018 nationally distributed Optum EHR data. Eligible patients were 45 to 80 years old with a new diagnosis of knee OA in 2011‐2012 and no prior KA. The OASI was a sum of first instance of x‐ray imaging, advanced imaging, intra‐articular injection, nonsteroidal anti‐inflammatory drugs, and opioids. Principal components analysis index (PCI) score was also explored. Extended Cox proportional hazard models assessed time‐dependent OASI and time to KA. Results: Among 16,675 eligible patients, 12.7% underwent KA. Median follow‐up time was 72 months. Adjusted OASI models showed each additional event almost doubled the risk for KA (adjusted hazard ratio = 1.80, 95% confidence interval: 1.75‐1.86). Similar results were observed for PCI. Conclusion: The sum OASI performs well identifying patients who would undergo KA and offers simplicity versus the PCI. Although replication in other cohorts is recommended, the OASI appears to be a novel and valid means to measure clinical OA severity in research studies using large EHR‐based cohorts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The Arthritis Foundation's Walk With Ease (WWE) program has been shown to reduce arthritis symptoms and increase physical performance for up to 1 year. However, research on community-based WWE implementation is limited. The purpose of this study was to examine early implementation at community organizations that received 1-year WWE implementation grants from the Osteoarthritis Action Alliance. Method: Program managers at five Osteoarthritis Action Alliance grantee organizations participated in 45-minute telephone interviews. Interviewees represented organizations with the highest WWE enrollment at 6 months (n = 3, >30% of goal enrollment) and no enrollment at 6 months (n = 2). The Planning for Sustainability framework guided qualitative analysis of factors affecting early implementation. Results: All grantees were confident in WWE's evidence base, thought it a beneficial supplement to other programming, stressed the importance of senior leadership support for WWE, and engaged community partners for marketing support and as walking sites. Implementation experiences unique to low enrollment grantees were (1) recent major structural changes within their organization, (2) difficulties in communicating logistics internally, and (3) difficulties in balancing WWE with other responsibilities. All organizations experienced barriers that required altering their original implementation plans; however, practical solutions like adapting the program to improve flexibility, training organizational staff as leaders, and utilizing community partnerships served to address multiple barriers simultaneously. Discussion: Building organizational capacity by overcoming early barriers is a key element of early implementation. Our findings offer concrete solutions to early WWE implementation barriers and suggest the need for further research on adaptations to improve WWE's flexibility in community organizations. [ABSTRACT FROM AUTHOR]

Background: Physical activity reduces osteoarthritis symptoms, yet many individuals with the disease are insufficiently active.Purpose: We identified physical activity trajectories over 12 months of individuals with osteoarthritis and examined how their cohabiting spouses'/partners' baseline physical activity and relationship factors affected trajectory membership.Methods: In this longitudinal observational study, we collected data from 168 adults with knee/hip osteoarthritis. We used latent class growth curve analysis to identify physical activity trajectories and logistic regression to predict trajectory membership using partners' physical activity, relationship satisfaction, and communal coping (belief that both partners are responsible for osteoarthritis management). Measures, including objectively assessed physical activity, were collected at baseline from the couple, who then received an educational class on physical activity and social support. Objectively assessed physical activity was also collected from individuals with osteoarthritis at 1 week, 3 months, 6 months, and 12 months post-baseline.Results: Three trajectories were identified: stable active, increaser, and stable sedentary (24%, 40%, 37% of participants, respectively). Individuals with osteoarthritis with partners who were more active and who believed they alone were responsible for their osteoarthritis were more likely to follow the stable active (versus stable sedentary) trajectory. Those with partners who were less active and had higher relationship satisfaction were more likely to follow the increaser (vs. stable active) trajectory.Conclusions: Findings demonstrate the importance of considering partner and relationship factors in physical activity interventions for couples. [ABSTRACT FROM AUTHOR]

Background For persons with osteoarthritis (OA), nutrition education may facilitate weight and OA symptom management. Objectives The primary aim of this study was to determine preferred OA-related nutritional and weight management topics and their preferred delivery modality. The secondary aim was to determine whether there is a disconnect between what patients want to know about nutrition and OA management and what information health-care professionals (HCPs) are providing to patients. Methods The Osteoarthritis Action Alliance surveyed individuals with OA to identify their preferences, categorized in 4 domains: 1) strategies for weight management and a healthy lifestyle; 2) vitamins, minerals, and other supplements; 3) foods or nutrients that may reduce inflammation; and 4) diets for weight loss. HCPs were provided these domains and asked which topics they discussed with patients with OA. Both groups were asked to select currently utilized or preferred formats of nutritional resources. Results Survey responses from 338 individuals with OA and 104 HCPs were included. The highest preference rankings in each domain were: 1) foods that make OA symptoms worse (65%), foods and nutrients to reduce inflammation (57%), and healthy weight loss (42%); 2) glucosamine (53%), vitamin D (49%), and omega-3 fatty acids (45%); 3) spices and herbs (65%), fruits and vegetables (58%), and nuts (40%); and 4) Mediterranean diet (21%), low-carbohydrate diet (18%), and fasting or intermittent fasting (15%). There was greater than 20% discrepancy between interests reported by individuals with OA and discussions reported by HCPs on: weight loss strategies, general information on vitamins and minerals, special dietary considerations for other conditions, mindful eating, controlling caloric intake or portion sizes, and what foods worsen OA symptoms. Most respondents preferred to receive nutrition information in a passive format and did not want information from social media messaging. Conclusions There is disparity between the nutrition education content preferred by individuals with OA (which often lacks empirical support) and evidence-based topics being discussed by HCPs. HCPs must communicate evidence-based management of joint health and OA symptoms in patient-preferred formats. This study explored the information gap between what individuals with OA want to know and what HCPs believe they need to know. [ABSTRACT FROM AUTHOR]

Objective: To apply biclustering, a methodology originally developed for analysis of gene expression data, to simultaneously cluster observations and clinical features to explore candidate phenotypes of knee osteoarthritis (KOA) for the first time. Methods: Data from the baseline Osteoarthritis Initiative (OAI) visit were cleaned, transformed, and standardized as indicated (leaving 6461 knees with 86 features). Biclustering produced submatrices of the overall data matrix, representing similar observations across a subset of variables. Statistical validation was determined using the novel SigClust procedure. After identifying biclusters, relationships with key outcome measures were assessed, including progression of radiographic KOA, total knee arthroplasty, loss of joint space width, and worsening Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, over 96 months of follow-up. Results: The final analytic set included 6461 knees from 3330 individuals (mean age 61 years, mean body mass index 28 kg/m2, 57% women and 86% White). We identified 6 mutually exclusive biclusters characterized by different feature profiles at baseline, particularly related to symptoms and function. Biclusters represented overall better (#1), similar (#2, 3, 6), and poorer (#4, 5) prognosis compared to the overall cohort of knees, respectively. In general, knees in biclusters #4 and 5 had more structural progression (based on Kellgren-Lawrence grade, total knee arthroplasty, and loss of joint space width) but tended to have an improvement in WOMAC pain scores over time. In contrast, knees in bicluster #1 had less incident and progressive KOA, fewer total knee arthroplasties, less loss of joint space width, and stable pain scores compared with the overall cohort. Significance: We identified six biclusters within the baseline OAI dataset which have varying relationships with key outcomes in KOA. Such biclusters represent potential phenotypes within the larger cohort and may suggest subgroups at greater or lesser risk of progression over time. [ABSTRACT FROM AUTHOR]

Objective: The effect of physical activity on the risk of developing knee osteoarthritis (OA) is unclear. We undertook this study to examine the relationship between recreational physical activity and incident knee OA outcomes using comparable physical activity and OA definitions. Methods: Data were acquired from 6 global, community‐based cohorts of participants with and those without knee OA. Eligible participants had no evidence of knee OA or rheumatoid arthritis at baseline. Participants were followed up for 5–12 years for incident outcomes including the following: 1) radiographic knee OA (Kellgren‐Lawrence [K/L] grade ≥2), 2) painful radiographic knee OA (radiographic OA with knee pain), and 3) OA‐related knee pain. Self‐reported recreational physical activity included sports and walking/cycling activities and was quantified at baseline as metabolic equivalents of task (METs) in days per week. Risk ratios (RRs) were calculated and pooled using individual participant data meta‐analysis. Secondary analysis assessed the association between physical activity, defined as time (hours per week) spent in recreational physical activity and incident knee OA outcomes. Results: Based on a total of 5,065 participants, pooled RR estimates for the association of MET days per week with painful radiographic OA (RR 1.02 [95% confidence interval (95% CI) 0.93–1.12]), radiographic OA (RR 1.00 [95% CI 0.94–1.07]), and OA‐related knee pain (RR 1.00 [95% CI 0.96–1.04]) were not significant. Similarly, the analysis of hours per week spent in physical activity also showed no significant associations with all outcomes. Conclusion: Our findings suggest that whole‐body, physiologic energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes. [ABSTRACT FROM AUTHOR]

Objective: Research indicates that social support may promote physical activity; however, most Latina individuals with osteoarthritis (OA) are not sufficiently active. The purpose of this qualitative dyadic study was to explore how Latina patients with OA and a self‐selected physical activity "supporter" motivate each other to be more active. Furthermore, perceptions of how OA symptoms impact support and physical activity were examined. Methods: Semistructured dyadic interviews were conducted with Latina patients with OA and a member of their social network age ≥16 years who supports their physical activity (n = 14 dyads). We used framework analysis to reduce qualitative data to themes and subthemes. Results: Daughters (n = 5), spouses (n = 4), sons (n = 2), a granddaughter (n = 1), a nephew (n = 1), and a friend (n = 1) provided support for the target behavior. In many cases, members of dyads said the motivation to engage in physical activity was reciprocated rather than focused solely on Latina patients with OA. Support was often reciprocated by engaging in physical activity together, using pressure, talking about being active, modeling physical activity, and helping with household responsibilities. Although participants agreed that physical activity was beneficial and Latina patients desired additional support when experiencing OA symptoms, there was concern about the safety of activity in the presence of symptoms. Several adult daughters indicated that their mothers' OA symptoms motivated their own physical activity. Conclusion: Dyadic strategies for promoting physical activity among Latina patients with OA and how support may be reciprocated were identified. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of disease activity and disability with rehabilitation utilization in African American adults with rheumatoid arthritis (RA).Methods: We analyzed cross-sectional baseline data from the Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR) I and CLEAR II registry. Disease activity was quantified with the Disease Activity Score in 28 joints using the C-reactive protein level. Disability was measured with the Health Assessment Questionnaire. Rehabilitation utilization was determined by self-reported recall of physical therapy or occupational therapy visits in the prior 6 months or ever. We examined the association of disease activity and disability with rehabilitation utilization using separate binary logistic regression models to estimate odds ratios and 95% confidence intervals and adjusted for potential confounders. We repeated the analyses with the sample stratified by disease duration (early RA and established RA).Results: Of 1,067 participants, 14% reported utilizing rehabilitation in the prior 6 months, and 41% reported ever utilizing rehabilitation. Rehabilitation utilization in the prior 6 months was similar among those with early and established RA (12% versus 16%). A greater proportion of those with established RA reported any past rehabilitation utilization (28% versus 50%). Among those with established RA but not early RA, worse disability was associated with rehabilitation utilization in the prior 6 months. Disease activity was not associated with either outcome.Conclusion: Among African American adults with RA, rehabilitation utilization in the 6 months prior to assessment was low and associated with disability but not disease activity. Factors driving rehabilitation utilization are unclear. [ABSTRACT FROM AUTHOR]

Physical activity (PA) is important for managing osteoarthritis (OA), but many patients are inactive. Research is needed on strategies to leverage clinical encounters to engage patients in PA. Guided by the socioecological model of health behavior, this study aimed to engage stakeholders in the process of refining an Osteoarthritis Physical Activity Care Pathway (OA-PCP). Six focus groups and seven individual interviews were conducted with key stakeholders. Focus groups were specific to stakeholder roles and included patients with OA, support partners, and clinic personnel (n = 6 focus groups). Interview participants were local and national PA program representatives (n = 7 interviews). Data were analyzed by thematic analysis. Themes identified in the data included ways the OA-PCP can help patients with OA address challenges to PA engagement, strategies for connecting patients with PA resources, methods for implementing OA-PCP into clinical settings and potential use of PA trackers in the OA-PCP program. Stakeholders' comments were summarized into key recommendations for OA-PCP. Some recommendations reinforced and led to refinements in planned aspects of OA-PCP, including tailoring to individual patients, involvement of a support partner, and addressing pain with PA. Other recommendations resulted in larger changes for OA-PCP, including the addition of three email- or mail-based contacts and not requiring use of a PA tracker. The refined OA-PCP program is being evaluated in an exploratory trial, with the ultimate goal of establishing a PA program for OA that can be successfully implemented in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Physical activity can improve osteoarthritis-related symptoms; however, many people with osteoarthritis (PWOA) are insufficiently active. Social support for physical activity from an intimate partner can help PWOA increase activity, but managing multiple, chronic physical or mental health conditions (i.e., multimorbidity) may influence provision and receipt of that support. Method: Data from a 1-year longitudinal observational study was used to examine associations between multimorbidity and three dimensions of partner support for physical activity—companionship partner support (doing activity together), enacted partner support, and social support effectiveness—in 169 insufficiently active PWOA and their partners. Results: Multivariable-adjusted multi-level models indicated baseline differences in support by multimorbidity status: when partners had multimorbidity, PWOA reported receiving less companionship support and less effective support from partners; when PWOA had multimorbidity, partners reported providing less enacted support and both partners and PWOA reported less effective partner support. Broad trends (p <.05) indicate initial increases and subsequent decreases in companionship and enacted partner support when PWOA had multimorbidity, and among partners with and without multimorbidity. When PWOA had multimorbidity, an initial increase in support effectiveness was followed by no significant change; a similar trend was seen among partners with and without multimorbidity. Conclusion: Multimorbidity may generally contribute to less partner support for physical activity or less effective support, although influences on support over time are less clear. Physical activity interventions for couples experiencing multimorbidity would likely benefit from attention to the impact of multiple chronic health conditions on physical activity and physical activity–related partner support. [ABSTRACT FROM AUTHOR]

Objective: Evaluate effectiveness of the Arthritis Foundation Tai Chi Program for community participants with arthritis. Methods: 343 individuals were randomized to either the intervention or wait-list control group. Performance and self-reported outcome (SRO) measures were assessed at baseline and eight weeks. At one year, SROs only were assessed. Adjusted means were determined using regression models adjusting for covariates, and effect sizes (ES) were calculated. Results: Average participant age was 66 years, 87% were female, and 87% were Caucasian. Among 284 (83%) participants who returned at eight weeks, balance by reach (ES = 0.30) and helplessness, sleep, and role participation satisfaction (ES = 0.24–0.54) improved significantly; pain, fatigue, and stiffness improvement (ES = 0.15–0.23) approached significance. No change was noted in mobility, lower extremity strength, or single-leg stance balance. At one year, improvements in pain, fatigue, stiffness, helplessness, and role participation satisfaction at eight weeks were maintained; 30% continued tai chi practice. Conclusion: Moderate effectiveness of the Arthritis Foundation Tai Chi Program was confirmed. [ABSTRACT FROM AUTHOR]

Background: Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients.Methods: Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as the trans-diaphragmatic pressure generated by supramaximal magnetic phrenic nerve stimulation (PdiTw). Quadriceps strength was assessed as leg force generated by supramaximal magnetic femoral nerve stimulation (QuadTw). Diaphragm and quadriceps thickness were assessed by ultrasound. Baseline measurements of muscle strength and size were performed, and patients were then randomized to one of four treatment groups (placebo, HMB 3 gm/day, EPA 2 gm/day and HMB plus EPA). Strength and size measurements were repeated 11 days after study entry. ANCOVA statistical testing was used to compare variables across the four experimental groups.Results: Treatments failed to increase the strength and thickness of either the diaphragm or quadriceps when compared to placebo. In addition, treatments also failed to decrease the duration of mechanical ventilation after study entry.Conclusions: These results indicate that a 10-day course of HMB and/or EPA does not improve skeletal muscle strength in critically ill mechanically ventilated patients. These findings also confirm previous reports that diaphragm and leg strength in these patients are profoundly low. Additional studies will be needed to examine the effects of other anabolic agents and innovative forms of physical therapy.Trial Registration: ClinicalTrials.gov, NCT01270516. Registered 5 January 2011, https://clinicaltrials.gov/ct2/show/NCT01270516?term=Supinski&draw=2&rank=4 . [ABSTRACT FROM AUTHOR]

Objective: To examine relationships between knee osteoarthritis (KOA) and obesity, diabetes mellitus (DM), and cardiovascular disease (CVD). Methods: Associations of time‐dependent obesity, DM, and CVD with KOA transition states over approximately 18 years were examined among 4093 participants from a community‐based cohort. Transition states were 1) no knee symptoms and no radiographic KOA (rKOA; Kellgren‐Lawrence grade ≥2 in at least one knee), 2) asymptomatic rKOA, 3) knee symptoms only, 4) symptomatic rKOA (sxKOA; rKOA and symptoms in same knee). Markov multistate models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for associations between comorbid conditions and transitions across states, adjusting for baseline age, sex, race, education, enrollment cohort, birth year, and time‐dependent knee injury history. Results: At baseline, 40% of participants had obesity, 13% had DM, and 22% had CVD (mean age = 61 years; 34% Black; 37% male). Compared with those without obesity, those with obesity had a higher hazard of worsening from no rKOA/no symptoms to asymptomatic rKOA (aHR = 1.7; 95% CI = 1.3‐2.2) and from knee symptoms to sxKOA (aHR = 1.7; 95% CI = 1.3‐2.3), as well as a lower hazard of symptom resolution from sxKOA to asymptomatic rKOA (aHR = 0.5 [95% = CI 0.4‐0.7]). Compared with those without CVD, those with CVD had a higher hazard of worsening from no rKOA/symptoms to knee symptoms (aHR = 1.5; 95% CI = 1.1‐2.1). DM was not associated with transitions of rKOA. Conclusion: Prevention of obesity and CVD may limit the development or worsening of rKOA and symptoms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. There are no pharmacological treatments for this syndrome, but studies suggest that diaphragm weakness is linked to mitochondrial free radical generation. We hypothesized that administration of mitoquinone mesylate (MitoQ), a mitochondrially targeted free radical scavenger, would prevent sepsis-induced diaphragm dysfunction. We compared diaphragm function in 4 groups of male mice: 1) sham-operated controls treated with saline (0.3 mL ip), 2) sham-operated treated with MitoQ (3.5 mg/kg/day given intraperitoneally in saline), 3) cecal ligation puncture (CLP) mice treated with saline, and 4) CLP mice treated with MitoQ. Forty-eight hours after surgery, we assessed diaphragm force generation, myosin heavy chain content, state 3 mitochondrial oxygen consumption (OCR), and aconitase activity. We also determined effects of MitoQ in female mice with CLP sepsis and in mice with endotoxininduced sepsis. CLP decreased diaphragm specific force generation and MitoQ prevented these decrements (e.g. maximal force averaged 30.2 ± 1.3, 28.0 ± 1.3, 12.8 ± 1.9, and 30.0 ± 1.0 N/cm2 for sham, sham þ MitoQ, CLP, and CLP þ MitoQ groups, respectively, P < 0.001). CLP also reduced diaphragm mitochondrial OCR and aconitase activity; MitoQ blocked both effects. Similar responses were observed in female mice and in endotoxin-induced sepsis. Moreover, delayed MitoQ treatment (by 6 h) was as effective as immediate treatment. These data indicate that MitoQ prevents sepsis-induced diaphragm dysfunction, preserving force generation. MitoQ may be a useful therapeutic agent to preserve diaphragm function in critically ill patients with sepsis. [ABSTRACT FROM AUTHOR]

Calpain activation has been postulated as a potential contributor to the loss of muscle mass and function associated with both aging and disease, but limitations of previous experimental approaches have failed to completely examine this issue. We hypothesized that mice overexpressing calpastatin (CalpOX), an endogenous inhibitor of calpain, solely in skeletal muscle would show an amelioration of the aging muscle phenotype. We assessed four groups of mice (age in months): 1) young wild type (WT; 5.71 ± 0.43), 2) young CalpOX (5.6 ± 0.5), 3) old WT (25.81 ± 0.56), and 4) old CalpOX (25.91 ± 0.60) for diaphragm and limb muscle (extensor digitorum longus, EDL) force frequency relations. Aging significantly reduced diaphragm and EDL peak force in old WT mice, and decreased the force-time integral during a fatiguing protocol by 48% and 23% in aged WT diaphragm and EDL, respectively. In contrast, we found that CalpOX mice had significantly increased diaphragm and EDL peak force in old mice, similar to that observed in young mice. The impact of aging on the force-time integral during a fatiguing protocol was abolished in the diaphragm and EDL of old CalpOX animals. Surprisingly, we found that CalpOX had a significant impact on longevity, increasing median survival from 20.55mo in WT mice to 24mo in CalpOX mice (P = 0.0006). [ABSTRACT FROM AUTHOR]

Background: Physical and psychological symptoms limit physical activity for people with arthritis. This study examined if self-efficacy mediated a relationship between symptom and physical activity (PA) frequency change. Methods: This was a secondary analysis of older adults with arthritis and joint pain in a trial of a lifestyle PA program (n = 339). Measures were depressive symptoms, pain, fatigue, arthritis self-efficacy, PA self-efficacy, and PA frequency. A panel model was used to analyze relationships at baseline and changes at 20 weeks. Results: The mean age was 68.8 years. At baseline, depression and fatigue were associated with arthritis self-efficacy (ß = -.34 and -.24) and, in turn, PA self-efficacy (ß = .63); PA self-efficacy was associated with PA (ß = .15). Pain and depression changes were associated with arthritis self-efficacy change (ß = -.20 and -.21) and, in turn, PA self-efficacy (ß = .32) change; PA self-efficacy change was associated with PA change (ß = .36). Conclusion: Change in symptom severity affected change in PA frequency. These relationships appeared to operate through self-efficacy. Over time, pain appeared to have a stronger relationship than fatigue with self-efficacy and PA. These findings support strategies to help people with arthritis strengthen their confidence for symptom coping and PA participation. [ABSTRACT FROM AUTHOR]

Objective: To apply a precision medicine approach to determine the optimal treatment regime for participants in an exercise (E), dietary weight loss (D), and D + E trial for knee osteoarthritis that would maximize their expected outcomes.Methods: Using data from 343 participants of the Intensive Diet and Exercise for Arthritis (IDEA) trial, we applied 24 machine-learning models to develop individualized treatment rules on 7 outcomes: Short Form 36 physical component score, weight loss, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/function/stiffness scores, compressive force, and interleukin-6 level. The optimal model was selected based on jackknife value function estimates that indicate improvement in the outcomes if future participants follow the estimated decision rule compared to the optimal single, fixed treatment model.Results: Multiple outcome random forest was the optimal model for the WOMAC outcomes. For the other outcomes, list-based models were optimal. For example, the estimated optimal decision rule for weight loss indicated assigning the D + E intervention to participants with baseline weight not exceeding 109.35 kg and waist circumference above 90.25 cm, and assigning D to all other participants except those with a history of a heart attack. If applied to future participants, the optimal rule for weight loss is estimated to increase average weight loss to 11.2 kg at 18 months, contrasted with 9.8 kg if all participants received D + E (P = 0.01).Conclusion: The precision medicine models supported the overall findings from IDEA that the D + E intervention was optimal for most participants, but there was evidence that a subgroup of participants would likely benefit more from diet alone for 2 outcomes. [ABSTRACT FROM AUTHOR]

Objective: To examine how neighborhood characteristics are associated with health outcomes among older adults with osteoarthritis. Methods: In multilevel, cross‐sectional, and longitudinal analyses we examined whether 4 neighborhood characteristics were associated with depressive symptoms and reported knee impact scores, and whether the neighborhood characteristics interacted with race/ethnicity among older adults with radiographic knee osteoarthritis (n = 656 for cross‐sectional analyses and n = 434 for longitudinal analyses). The data came from the Johnston County Osteoarthritis Project, a prospective cohort study in North Carolina designed to examine risk factors for osteoarthritis. Results: Although few longitudinal associations were found, cross‐sectional results suggested that greater perceived neighborhood social cohesion (B = –0.04, P < 0.001) and perceived neighborhood resources for physical activity and walking (B = –0.03, P < 0.001) were associated with fewer depressive symptoms, and that greater perceived neighborhood resources for physical activity and walking were associated with higher (better) knee impact scores (B = 0.48, P = 0.008). We also observed 2 significant interactions among neighborhood characteristics and race/ethnicity related to depressive symptoms (P < 0.01); for African American adults, greater perceived neighborhood resources for physical activity and walking were associated with fewer depressive symptoms (B = –0.03, P < 0.001), but for White adults, greater perceived neighborhood safety was associated with fewer depressive symptoms (B = –0.04, P = 0.003). Conclusion: In a sample of older adults with radiographic knee osteoarthritis, neighborhood context mattered, but in nuanced ways. Interventions aiming to improve mental and physical functioning of older adults with knee osteoarthritis can look to this study as evidence for the importance of neighborhood characteristics. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. Methods: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung–Knapp modification for random-effects meta-analysis. Findings: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. Discussion: Participants with POA or PROA had a 35–37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. Funding: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International. [ABSTRACT FROM AUTHOR]

Background: Adults with arthritis can benefit from participation in physical activity and may be assisted by organized programs. The purpose of this study was to evaluate the effectiveness of a 20-week behavioral life-style intervention, Active Living Every Day (ALED), for improvements in primary outcomes (physical activity levels, aerobic endurance, function, symptoms). Methods: A 20-week randomized controlled community trial was conducted in 354 adults. Outcomes were assessed at baseline and 20 weeks in the intervention and wait-list control groups. The intervention group was also assessed at 6 and 12 months. Mean outcomes were determined by multilevel regression models in the intervention and control groups at follow-up points. Results: At 20 weeks, the intervention group significantly increased participation in physical activity, and improved aerobic endurance, and select measures of function while pain, fatigue and stiffness remained status quo. In the intervention group, significant improvements in physical activity at 20 weeks were maintained at 6 and 12 months, and stiffness decreased. Conclusions: ALED appears to improve participation in physical activity, aerobic endurance, and function without exacerbating disease symptoms in adults with arthritis. [ABSTRACT FROM AUTHOR]

Objective: The authors explored whether demographic and psychosocial variables predicted differences in physical activity for participants with arthritis in a trial of Active Living Every Day (ALED). Method: Participants (N = 280) from 17 community sites were randomized into ALED or usual care. The authors assessed participant demographic characteristics, self-efficacy, outcome expectations, pain, fatigue, and depressive symptoms at baseline and physical activity frequency at 20-wk follow-up. They conducted linear regression with interaction terms (Baseline Characteristic à Randomization Group). Results: Being female (p ≤ .05), less depressed (p ≤ .05), or younger (p ≤ .10) was associated with more frequent posttest physical activity for ALED participants than for those with usual care. Higher education was associated with more physical activity for both ALED and usual-care groups. Discussion: ALED was particularly effective for female, younger, and less depressed participants. Further research should determine whether modifications could produce better outcomes in other subgroups. [ABSTRACT FROM AUTHOR]

Objective: The authors explored whether demographic and psychosocial variables predicted differences in physical activity for participants with arthritis in a trial of Active Living Every Day (ALED). Method: Participants (N = 280) from 17 community sites were randomized into ALED or usual care. The authors assessed participant demographic characteristics, self-efficacy, outcome expectations, pain, fatigue, and depressive symptoms at baseline and physical activity frequency at 20-wk follow-up. They conducted linear regression with interaction terms (Baseline Characteristic × Randomization Group). Results: Being female (p ≤ .05), less depressed (p ≤ .05), or younger (p ≤ .10) was associated with more frequent posttest physical activity for ALED participants than for those with usual care. Higher education was associated with more physical activity for both ALED and usual-care groups. Discussion: ALED was particularly effective for female, younger, and less depressed participants. Further research should determine whether modifications could produce better outcomes in other subgroups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Clinical studies indicate that sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. Currently there is no drug to treat this form of diaphragm weakness. Sepsis-induced muscle dysfunction is thought to be triggered by excessive mitochondrial free radical generation; we therefore hypothesized that therapies that target mitochondrial free radical production may prevent sepsis-induced diaphragm weakness. The present study determined whether MitoTEMPOL, a mitochondrially targeted free radical scavenger, could reduce sepsis-induced diaphragm dysfunction. Using an animal model of sepsis, we compared four groups of mice: 1) sham-operated controls, 2) animals with sepsis induced by cecal ligation puncture (CLP), 3) sham controls given MitoTEMPOL (10 mg·kg1·day1 ip), and 4) CLP animals given MitoTEMPOL. At 48 h after surgery, we measured diaphragm force generation, mitochondrial function, proteolytic enzyme activities, and myosin heavy chain (MHC) content. We also examined the effects of delayed administration of MitoTEMPOL (by 6 h) on CLP-induced diaphragm weakness. The effects of MitoTEMPOL on cytokine-mediated alterations on muscle cell superoxide generation and cell size in vitro were also assessed. Sepsis markedly reduced diaphragm force generation. Both immediate and delayed MitoTEMPOL administration prevented sepsis-induced diaphragm weakness. MitoTEMPOL reversed sepsismediated reductions in mitochondrial function, activation of proteolytic pathways, and decreases in MHC content. Cytokines increased muscle cell superoxide generation and decreased cell size, effects that were ablated by MitoTEMPOL. MitoTEMPOL and other compounds that target mitochondrial free radical generation may be useful therapies for sepsis-induced diaphragm weakness. [ABSTRACT FROM AUTHOR]

Background: The What Matters Most (WMM) study was initiated to evaluate symptoms, AD-related impacts, treatment-related needs, preferences, and priorities among individuals with or at risk for Alzheimer's disease (AD) and their care partners. The objective of this qualitative study phase was to identify a comprehensive set of concepts of interest that are meaningful to individuals across the AD continuum. Methods: Interviews were conducted with 60 clinically referred individuals and care partners across 5 AD stages (n = 12 each): group 1 (non-clinically impaired individuals with AD pathology), group 2 (individuals with mild cognitive impairment and AD pathology), group 3 (individuals with mild AD), group 4 (individuals with moderate AD and their care partners), and group 5 (care partners of individuals with severe AD). Interviews were conducted by experienced interviewers, audio-recorded, and transcribed. Dominant trends were identified in each interview and compared across subsequent interviews to generate themes or patterns in descriptions of AD symptoms, impacts, and desired treatment outcomes. Results: All participants endorsed current issues related to memory; nearly all participants (n = 55; 92%) across the five groups endorsed symptoms related to communication and language. Groups 1–3 reported an impact on mood/emotions (n = 23; 64%) and a decrease in social activities or outgoingness (n = 17; 47%). Current and future concerns reported by the overall sample included memory (n = 48; 80%), dependence (n = 40; 67%), and "other" concerns (n = 33; 55.0%) (e.g., uncertainty about the future, burdening others). The most desired AD treatment outcomes were improvement or restoration of memory (n = 40; 67%) and stopping AD progression (n = 35; 58.3%). Group-level differences were observed in the symptoms, impacts, and desired treatment outcomes among patients and care partners across the AD continuum. Conclusions: Cognitive functioning issues—particularly in memory and communication—are present even in preclinical and early-stage AD, including among those without a formal AD diagnosis. While the impacts of AD vary across the disease-severity spectrum, improved memory and disease modification were treatment outcomes considered most important to participants across all 5 AD stages. Neuropsychological assessments traditionally used in AD clinical trials may not evaluate the often-subtle concepts that are important to patients and care partners. Results from this study will inform the second phase of the WMM project—a quantitative study to elicit the relative importance of these concepts of interest to people at risk for and living with AD and their care partners. [ABSTRACT FROM AUTHOR]

Partner-based social support can motivate engagement in physical activity (PA); however, couples approach exchanging support in different ways. This study aimed to elucidate the role of relationship dynamics in couple-based support for PA, with the goal of informing intervention strategies that will effectively leverage couple characteristics to increase support for PA. We conducted a qualitative study of couples who completed a longitudinal study of social support for PA. Participants were people with osteoarthritis who were not meeting PA recommendations and their cohabitating partners (n = 19 couples). We conducted in-depth, semistructured interviews and analyzed transcripts using narrative analysis. Participants were 76% non-Hispanic White and, on average, 62 years old. Themes in the data included (a) attitudes about working together to be more active (ranging from positive to negative) and (b) couples' narrative concordance (high to low shared reality). We developed a couple typology with four categories: "Working together works" (positive attitudes/high shared reality; n = 4 couples), "Doing our own thing" (range of attitudes with practical/preferential barriers to working together/high shared reality; n = 5 couples), "Conscious conflict" (discrepant attitudes/high shared reality; n = 5 couples), and "Different realities" (discrepant attitudes/low shared reality; n = 5 couples). We describe examples of each type. In a sample of 19 couples, there were observable differences in participants' attitudes about working together to be more active and in couples' shared reality around those attitudes. Future research should investigate implications for the efficacy of interventions and, if warranted, develop methods to identify couple types and offer appropriate intervention strategies. [ABSTRACT FROM AUTHOR]

Background: To obtain information on feasibility and acceptability, as well as preliminary data on efficacy, of an Osteoarthritis Physical activity Care Pathway (OA-PCP).Methods: This was a single group pilot study involving 60 participants with symptomatic, physician diagnosed knee or hip OA, recruited from primary care clinics. Participants self-reported completing less than 150 min per week of moderate-to-vigorous physical activity (MVPA) at baseline. The 3-month OA-PCP intervention involved 3 physical activity (PA) coaching calls (focused on goal setting), three check-in emails and linkage with community-based or online resources to support PA. Efficacy outcomes were collected at baseline and 4-month follow-up. The primary efficacy outcome was minutes of MVPA, assessed via accelerometer. Secondary outcomes included minutes of light intensity activity, sedentary minutes, step counts, and Western Ontario and McMaster Universities (WOMAC) pain and function subscales. Participants were also asked to rate the helpfulness of the OA-PCP intervention on a scale of 0-10. Differences in efficacy outcomes between baseline and 4-month follow-up were assessed using paired t-tests.Results: Among participants beginning the study, 88% completed follow-up assessments and ≥ 90% completed each of the intervention calls. Average daily minutes of MVPA was 8.0 at baseline (standard deviation (SD) = 9.9) and 8.9 at follow-up (SD = 12.1, p = 0.515). There were no statistically significant changes in light intensity activity, sedentary time or step counts. The mean WOMAC pain score improved from 8.1 (SD = 3.6) at baseline to 6.2 (SD = 3.8) at follow-up (p < 0.001); the mean WOMAC function score improved from 26.2 (SD = 13.2) to 20.2 (SD = 12.5; p < 0.001). The mean rating of helpfulness was 7.6 (SD = 2.5).Conclusions: Results supported the feasibility and acceptability of the study, and participants reported clinically relevant improvements in pain and function. PA metrics did not improve substantially. Based on these results and participant feedback, modifications including enhanced self-monitoring are being made to increase the impact of the OA-PCP intervention on PA behavior.Trial Registration: NCT03780400, December 19, 2018. [ABSTRACT FROM AUTHOR]

Objective: The goal of this paper is to describe approaches for the joint analysis of repeatedly measured data with time-to-event end points, first separately and then in the framework of a single comprehensive model, emphasizing the efficiency of the latter approach. Data from the Johnston County Osteoarthritis (JoCo OA) Project will be used as an example to investigate the relationship between the change in repeatedly measured body mass index (BMI) and the time-to-event end point of incident worsening of radiographic knee OA that was defined as an increased Kellgren/Lawrence grade in at least 1 knee over time.Methods: First, we provide an overview of the methods for analyzing repeated measurements and time-to-event end points separately. Then, we describe traditional (Cox proportional hazards model [CoxPH]) and emerging (joint model [JM]) approaches, both of which allow combined analysis of repeated measures with a time-to-event end point in the framework of a single statistical model. Finally, we apply the models to JoCo OA data and interpret and compare the results from the different approaches.Results: Applications of the JM (but not the CoxPH) showed that the risk of worsening radiographic OA is higher when BMI is higher or increasing, thus illustrating the advantages of the JM for analyzing such dynamic measures in a longitudinal study.Conclusion: Joint models are preferable for simultaneous analyses of repeated measurement and time-to-event outcomes, particularly in the context of chronic disease, where dependency between the time-to-event end point and the longitudinal trajectory of repeated measurements is inherent. [ABSTRACT FROM AUTHOR]