To develop a quality standard, termed a Clinical Care Standard (CCS), for the diagnosis and management of rheumatoid arthritis (RA). A Working Group with consumer representation cocreated guiding principles and quality statements for RA care through a series of workshops. The process was informed by consumer recommendations, clinical practice guidelines, and international quality criteria. A national survey of healthcare professionals (HCPs) and consumers was conducted to establish consensus. For each quality statement, respondents were asked to indicate, on a scale of 1-9, (1) if it is a priority area for improvement in RA care, and (2) their agreement with the content of the statement. For (1) and (2), respectively, scores between 1 and 4 indicated it was not a priority and disagreement; 5 and 6 indicated it was important but not critical and moderate agreement; and 7 to 9 indicated it was high priority and agreement. Criteria for inclusion were a mean score ≥ 7 for priority and a mean score ≥ 7 for content. The Working Group formulated 13 quality statements and established 7 guiding principles for RA care. The survey was completed by 605 consumers and 308 HCPs. The predefined criteria for inclusion were met by 12/13 quality statements. The Australian Rheumatology Association has developed the first CCS for RA in Australia. This standard will serve as an important lever for HCPs and services, consumer organizations, and policy makers to improve the quality of care for adults with RA.

The endothelial protein C receptor (EPCR) is gaining recognition for its diverse functions that extend beyond its traditional role in the protein C anticoagulant pathway. This comprehensive review examines how EPCR contributes to the pathophysiology of rheumatoid arthritis (RA), an autoimmune disorder characterized by persistent inflammation and joint destruction. We explore how EPCR influences inflammatory responses and the coagulation cascade, affects endothelial function and vascular integrity, and regulates the characteristics of synovial fibroblasts in the context of RA. Furthermore, the review highlights the mechanisms by which EPCR affects disease progression, its potential use as a biomarker for disease activity, and the therapeutic implications of targeting EPCR in the treatment of RA. By synthesizing current research findings, this review aims to provide a detailed understanding of EPCR’s role in RA, offering insights into innovative diagnostic and therapeutic strategies that could improve patient outcomes.

Regular laboratory testing is recommended for monitoring disease activity and adverse effects in people taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), yet the perspectives and experiences of patients have not been examined and may inform practice. As such, we aimed to determine the experiences and perceptions of laboratory monitoring in Australian adults using csDMARDs for rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Participants in the Australian Rheumatology Association Database who had RA or PsA were sent an online questionnaire capturing their demographics, frequency of advised and actual blood tests, barriers, benefits and whether they felt they had been given an adequate rationale for testing or felt they needed more information. Data were reported using descriptive statistics. The survey was distributed to 904 ARAD participants with RA and/or PsA with 679 responses (75.1

BACKGROUND:People with rheumatoid arthritis (RA) are at increased risk of osteoporosis. The Australian Rheumatology Association RA Clinical Care Standard recommends fracture risk assessment at RA diagnosis and as clinically indicated. AIMS:The aim of this study was to evaluate the use of dual-energy X-ray absorptiometry (DEXA) for osteoporosis screening among Australian patients with early RA enrolled in the Australian Rheumatology Association Database (ARAD). We also aimed to assess the dispensing patterns of anti-osteoporotic medications in this population. METHODS:ARAD participants aged ≥18 years with a RA diagnosis from 2011 onwards and linked 2011-2023 Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data were included (n = 306). Time to first DEXA and anti-osteoporotic medication dispensing was assessed using Kaplan-Meier failure functions and multivariable Cox regression. Covariates included age, sex, BMI, alcohol use, smoking and glucocorticoid use. RESULTS:The median time to first DEXA was 3 years (IQR 0, 10) following RA diagnosis. Predictors for DEXA included female sex (HR 1.6, 95% CI 1.1, 2.4), age ≥50 (HR 2.6, 95% CI 1.8, 3.9) and glucocorticoid use (HR 1.7, 95% CI 1.3, 2.4). DEXA was less likely with BMI ≥25 (HR 0.68, 95% CI 0.48, 0.96). By 8 years after RA diagnosis, 25% of participants received anti-osteoporotic medication, predicted by age ≥50 (HR 6.7, 95% CI 2.1, 21.4) and glucocorticoid use (HR 2.8, 95% CI 1.5, 5.0). CONCLUSION:Our findings reveal delays and variability in osteoporosis screening for individuals with RA, despite higher fracture risk. Screening practices were influenced by age, glucocorticoid use and BMI, with significant gaps, particularly after diagnosis. These gaps highlight the need for standardised screening protocols to ensure timely DEXA scans and treatment, ultimately improving osteoporosis management and reducing fracture burden.

OBJECTIVES:To examine associations between osteoarthritis (OA)-related biochemical markers and knee symptoms in middle-aged adults over 10-13 year follow-up. METHODS:Blood samples were collected during the Childhood Determinants of Adult Health (CDAH)-1 study (2004-06) and follow-up at CDAH-3. Serum samples from baseline (n=156) and follow-up (n=167) were analyzed for cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3, and hyaluronan (HA) using enzyme-linked immunosorbent assays. Knee symptoms were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale at follow-up. Zero-inflated Poisson regression models adjusted for age, sex, and body mass index were used for analysis. RESULTS:Significant associations were observed between COMP, MMP-3, and HA with knee pain and WOMAC-total score at follow-up. Baseline MMP-3 [ratio of means (RoM): 1.013; 95% CI: 1.006, 1.020], cumulative COMP (baseline + follow-up) [RoM: 1.022; 95% CI: 1.011, 1.033], and increased HA levels over time [RoM: 1.014; 95% CI: 1.007, 1.020] were positively associated with knee pain after 10-13 years. CONCLUSION:Cumulative COMP, baseline MMP-3, and changes in HA were associated with knee pain over a a 10-13 year follow-up. These markers may help predict future knee symptoms in middle-aged adults.

OBJECTIVE:To assess agreement between prescription claims data and self-reported medication use via longitudinal questionnaires in the Australian Rheumatology Association Database inflammatory arthritis cohort and to identify predictors of discordant self-reports. METHODS:Agreement was determined between longitudinal questionnaire self-reports (2012-2023) of disease-modifying antirheumatic drug (DMARD), glucocorticoid, anti-inflammatory, and analgesic use and Australian reference standard prescription medication dispensing data (Pharmaceutical Benefits Scheme) using Cohen's kappa, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). Analyses were repeated using four look-back windows of dispensing data (1, 3, 6, and 12 months) before each questionnaire to characterize variations in agreement metrics at the individual medication level. Predictors of discordant self-reports were explored using multivariable logistic regression. RESULTS:In our study population (N = 3,407, 67% female, 93.7% White, 64.4% with rheumatoid arthritis, 18.5% with psoriatic arthritis, 14.6% with ankylosing spondylitis, 2.6% with juvenile idiopathic arthritis), agreement with prescription claims data was substantial to high for DMARDs (κ 0.67-0.95, sensitivity 0.69-0.96, PPV 0.64-0.96, NPV 0.9-1), substantial for prescription-only nonopioid analgesics and oral prednisolone/prednisone (κ 0.66-0.80, sensitivity 0.65-0.88, PPV 0.68-0.77, NPV 0.93-1), and moderate to substantial for prescription-only opioid analgesics (κ 0.48-0.7, sensitivity 0.57-0.74, PPV 0.36-0.69, NPV 0.94-1). A 3-month look-back window optimized agreement for most medications, whereas 6- and 12-month windows further improved agreement for specific drugs. No consistent predictors of discordant self-reports were identified, though greater self-rated disability severity and poorer overall health showed the most consistent associations with discordance. CONCLUSION:Agreement between self-reported and pharmaceutical claims data was moderate to high. Poorer overall health and disability may impact accuracy of medication self-report.

Objectives: This study compared the frequencies of circulating CD4+ T helper (Th) cell subsets in rheumatoid arthritis (RA) patients and healthy controls (HCs) and investigated their relationship with RA disease activity. Methods: Peripheral blood samples and demographic/clinical data were collected from 75 RA patients and 28 HCs from the A3BC Biobank. Flow cytometry was utilized to identify cell subsets. Data were analyzed using FlowJo and GraphPad Prism. Results: RA patients displayed altered Th cell subset frequencies compared with HCs, including a higher overall proportion of Th cells (p = 0.02) but lower proportions of memory Th (p = 0.03), Th1 (p < 0.0001), and Th17.1 (p = 0.004) cells. In DMARD-naïve RA patients (n = 16), lower proportions of Th1 (p = 0.0005), Th9 (p = 0.04), and Th17.1 (p = 0.003) cells, alongside a higher Th17 cell proportion (p = 0.017), were observed compared with those in HCs. Further analysis of matched treatment-naïve, new-onset RA patients and HCs confirmed these findings. Within the RA cohort, lower proportions of Th1 (p = 0.002) and Th17.1 (p = 0.025) cells and a higher proportion of Th2 cells (p = 0.015) were correlated with increased disease activity. Inverse correlations were also found between the proportions of Th1 (p = 0.002), Th9 (p = 0.024), and Th17.1 (p = 0.00017) cells and CRP levels in RA patients. Conclusions: This study demonstrates an imbalance in circulating Th cell subset frequencies in RA patients compared with those in HCs, with notably lower Th1 and Th17.1 cell proportions in RA patients. Decreased frequencies of these cell subsets were linked to increased disease activity, indicating that restoring the balance of Th cell subsets could be a potential therapeutic strategy for RA.

Objective: Rheumatoid arthritis (RA) is a common musculoskeletal condition with an estimated prevalence of 0.27% in Australia and New Zealand. Recently, interest in the role of the human microbiome regarding RA pathogenesis has increased. This study is aimed at determining the composition of the stool and oral microbiome of RA patients taking common disease‐modifying antirheumatic drugs (DMARDs). Methods: For this cross‐sectional study, RA patients ( n = 28) with established disease (> 12 months since diagnosis) and healthy individuals ( n = 10) were recruited by the Australian Arthritis and Autoimmune Biobank Collaborative (A3BC). Stool samples and oral swabs were collected, processed, and sequenced to obtain 16s rRNA amplicon sequencing data. Data was processed using a QIIME2/DADA2 pipeline. Diversity and taxonomic analyses were performed using QIIME2 core metrics functions and RStudio packages. Results: Diversity analyses identified differences in the RA stool microbiome, in comparison to healthy controls and between RA patients taking different DMARDs. This includes differences in microbial richness, diversity, and structure. For example, the microbiome of patients taking JAK inhibitors (JAKis) significantly differed to the microbiome of patients on combination therapy (TNF inhibitors [TNFi] +/− methotrexate [MTX]) or taking MTX only. Furthermore, patients taking MTX had a more similar microbiome to healthy individuals. In contrast, limited differences in the oral microbiome were observed for all diversity metrics, although a number of taxa previously linked to oral disease were identified as differentially abundant to healthy individuals. Conclusion: Differences in the diversity and taxa of the stool and oral microbiome of patients with established RA were identified. Overall, there was some concordance with previous research. This work highlights the importance of further investigation into the impact of JAKi, TNFi, and MTX on the RA microbiome.

OBJECTIVE:The increasing burden associated with low back pain (LBP) is a critical issue. This is a novel analysis of trends in risk factors for LBP aiming to identify risk factors that require further attention or consideration in global policies to reduce the burden of LBP. METHODS:The Global Burden of Disease study metadata were used to describe the trends in three modifiable categories of risk factors that contribute to the burden associated with LBP. The trends in occupational/ergonomic, behavioral (smoking), and metabolic (high body mass index [BMI]) risk factors for LBP between 1990 and 2021 have been described with attention to global areas, high sociodemographic index (SDI) areas, and low SDI areas. RESULTS:The number of years lived with disability (YLDs) caused by LBP increased globally, in high and low SDI areas between 1990 and 2021. The impact of smoking and occupational/ergonomic risk factors have decreased; however, the impact of high BMI has increased markedly in the same time frame, with a particularly concerning impact in high SDI areas and on women. CONCLUSION:The burden of LBP is increasing globally, with a significant proportion of the YLDs caused by LBP attributed to three modifiable lifestyle factors: occupation/ergonomics, smoking, and high BMI. Of significant concern is the rapidly increasing impact of high BMI on YLDs caused by LBP, with the greatest impact seen among women in low and high SDI areas. The role of additional risk factors (eg, physical inactivity) still needs to be determined in the context of the global burden of LBP.

OBJECTIVE:To identify and quantify risk factors for incident knee osteoarthritis (KOA) across the lifespan. METHODS:This systematic review and meta-analysis identified eligible studies from seven electronic databases and three registries. Longitudinal cohort studies or randomised controlled trials evaluating participants who developed incident symptomatic and/or radiographic KOA were included. Two independent reviewers completed data screening and extraction. Estimates were pooled using a random effects model and reported as odds ratio (OR), hazard ratio, or risk ratio and corresponding 95% confidence intervals (95% CI). Grading of Recommendations, Assessment, Development and Evaluation was used to determine the certainty of evidence. Population attributable fractions were calculated, including risk factors significantly associated with radiographic KOA based on the pooled meta-analysis and where we could determine communality scores using existing clinical datasets. RESULTS:We identified 131 studies evaluating > 150 risk factors. Previous knee injury, older age and high bone mineral density were associated with an increased risk of incident radiographic KOA based on the pooled analysis [OR (95% CI): 2.67 (1.41, 5.05), 1.15 (1.00, 1.33) and 1.82 (1.12, 2.94), respectively], with moderate-to-high certainty. Two risk factors (overweight/obesity and previous knee injury) accounted for 14% of incident radiographic KOA. Other modifiable risk factors, including occupational physical activity, also contribute to radiographic or symptomatic KOA. CONCLUSION:Novel strategies addressing known modifiable risk factors including overweight/obesity, knee injuries and occupational physical activity are needed to reduce overall burden of KOA. SYSTEMATIC REVIEW REGISTRATION:PROSPERO ID: CRD42023391187.

The increasing burden associated with low back pain (LBP) is a critical issue. This is a novel analysis of trends in risk factors for LBP aiming to identify risk factors that require further attention or consideration in global policies, to reduce the burden of LBP. The Global Burden of Disease (GBD) study meta-data were used to describe the trends in three modifiable categories of risk factors that contribute to the burden associated with LBP. The trends in occupational/ergonomic, behavioural (smoking), and metabolic (high body mass index (BMI)) risk factors for LBP between 1990 and 2021 have been described with attention to global, high sociodemographic index (SDI) areas, and low SDI areas. The number of YLDs due to LBP increased globally, in high and low SDI areas between 1990 and 2021. The impact of smoking and occupational/ergonomic risk factors have decreased however, the impact of high BMI has increased markedly in the same time frame, with a particularly concerning impact in high SDI areas and on females. The burden of LBP is increasing globally, with a significant proportion of the YLDs due to LBP attributed to three modifiable lifestyle factors - occupational/ergonomic, smoking, and high BMI. Of significant concern is the rapidly increasing impact of high BMI on YLDs due to LBP with the greatest impact seen among females in low and high SDI areas. The role of additional risk factors, e.g. physical inactivity, still needs to be determined in the context of the global burden of LBP.

OBJECTIVE:The OMERACT Composite Working Group hosted a workshop at OMERACT 2023 to explore the complexities of weighting components in the development of composite outcomes. This study presents the methodology and findings of this workshop, exploring the complexities of weighting the individual components of composite outcome measures. METHODS:The workshop featured a multifaceted program, beginning with a plenary session that introduced the concept of composite outcomes, shared a patient's journey with rheumatic disease through a narrative, illustrated a composite outcome for Osteoarthritis Flares, and outlined the five domains selected for this composite outcome. A breakout exercise engaged participants in ranking and assigning weights to these domains, followed by group discussions to reach a consensus on weights. The workshop concluded with another plenary session that discussed various weighting approaches, including discrete choice and conjoint analysis from the ANCA-Associated Vasculitis working group, and outlined future directions for research on composite outcome methods. RESULTS:The breakout exercise revealed the challenges in assigning relative importance to different domains, highlighting the variability in participant perspectives. Consensus discussions highlighted the diversity in approaches to weighting, the need for appropriate methods to determine domain weights and the impact of such weights on the interpretation of composite scores. CONCLUSION:The OMERACT 2023 workshop underscored the significance of a systematic approach to weighting components in composite outcome development. It highlighted the complexity of achieving consensus on the importance of domains and the role of incorporating the perspectives of patient research partners in this process. Future research directions include refining weighting methodologies, moving composites through the OMERACT Filter and enhancing understanding of their implications for clinical trials. The findings contribute to the ongoing discourse on optimizing composite outcome measures in rheumatology and beyond, advocating for a balanced integration of scientific rigour and patient-centeredness in their development.

ObjectiveDyadic coping, the process of coping that transpires between couples challenged by one partner’s illness, is an important predictor of disease adjustment and patient well-being. However, the extent of dyadic coping in rheumatoid arthritis (RA) remains unclear. This study examines the effect of dyadic coping on psychological distress and relationship quality from the perspectives of both participants with RA and their spouses.MethodsParticipants and their spouses were invited to participate in an online survey study if they were aged ≥ 18 years and had lived together for more than a year. The survey included the Chronic Pain Grade Scale, Dyadic Coping Inventory, Depression Anxiety Stress Scale, and Dyadic Adjustment Scale. Participants and spouses completed the survey independently. The actor-partner interdependence model was used to analyze the dyadic data.ResultsOne hundred sixty-three couples participated. Our findings showed that participants who reported higher supportive dyadic coping reported lower depression, anxiety, and stress, and higher relationship quality, whereas participants who reported higher negative dyadic coping reported higher depression, anxiety, and stress, and lower relationship quality. Spouses who reported higher supportive dyadic coping reported higher relationship quality, but no effect on depression, anxiety, and stress was observed. In contrast, spouses who reported higher negative dyadic coping reported higher levels of depression, anxiety, and stress, and lower relationship quality.ConclusionParticipants’ and spouses’ perceptions of supportive and negative dyadic coping closely influenced their psychological distress and relationship quality. Further, having a partner with RA also seemed to affect the spouse, especially when there was a negative dyadic coping pattern.

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Endothelial protein C receptor (EPCR) is a receptor for the natural anti-coagulant activated protein C (aPC). It mediates the anti-inflammatory and barrier-protective functions of aPC through the cleavage of protease-activated receptor (PAR)1/2. Allergic contact dermatitis is a common skin disease characterized by inflammation and defective skin barrier. This study investigated the effect of EPCR and 3K3A-aPC on allergic contact dermatitis using a contact hypersensitivity (CHS) model. CHS was induced using 1-Fluoro-2,4-dinitrobenzene in EPCR-deficient (KO) and matched wild-type mice and mice treated with 3K3A-aPC, a mutant form of aPC with diminished anti-coagulant activity. Changes in clinical and histological features, cytokines, and immune cells were examined. EPCRKO mice displayed more severe CHS, with increased immune cell infiltration in the skin and higher levels of inflammatory cytokines and IgE than wild-type mice. EPCR, aPC, and PAR1/2 were expressed by the skin epidermis, with EPCR presenting almost exclusively in the basal layer. EPCRKO increased the epidermal expression of aPC and PAR1, whereas in CHS, their expression was reduced compared to wild-type mice. 3K3A-aPC reduced CHS severity in wild-type and EPCRKO mice by suppressing immune cell infiltration/activation and inflammatory cytokines. In summary, EPCRKO exacerbated CHS, whereas 3K3A-aPC could reduce the severity of CHS in both EPCRKO and wild-type mice.

Background Most estimates of rheumatoid arthritis (RA) prevalence, including all official figures in Australia and many other countries, are based on self-report. Self-report has been shown to overestimate RA, but the ‘gold standard’ of reviewing individual medical records is costly, time-consuming and impractical for large-scale research and population monitoring. This study provides an algorithm to estimate RA cases using administrative data that can be adjusted for use in multiple contexts to provide the first approximate RA cohort in Australia that does not rely on self-report. Methods Survey data on self-reported RA and medications from 25 467 respondents of the Australian Longitudinal Study on Women’s Health (ALSWH) were linked with data from the national medication reimbursement database, hospital and emergency department (ED) episodes, and Medicare Benefits codes. RA prevalence was calculated for self-reported RA, self-reported RA medications, dispensed RA medications, and hospital/ED RA presentations. Linked data were used to exclude individuals with confounding autoimmune conditions. Results Of 25 467 survey respondents, 1367 (5·4%) women self-reported disease. Of the 26 840 women with hospital or ED presentations, 292 (1·1%) received ICD-10 codes for RA. There were 1038 (2·8%) cases by the medication database definition, and 294 cases (1·5%) by the self-reported medication definition. After excluding individuals with other rheumatic conditions, prevalence was 3·9% for self-reported RA, 1·9% based on the medication database definition and 0·5% by self-reported medication definition. This confirms the overestimation of RA based on self-reporting. Conclusions We provide an algorithm for identifying individuals with RA, which could be used for population studies and monitoring RA in Australia and, with adjustments, internationally. Its balance of accuracy and practicality will be useful for health service planning using relatively easily accessible input data.

Accelerated sub-lesional bone loss is common in the first 2–3 years after traumatic spinal cord injury (TSCI), particularly in the distal femur and proximal tibia. Few studies have explored efficacy of antiresorptives for acute bone loss prevention post-TSCI, with limited data for knee bone mineral density (BMD) or beyond two years follow-up. An open-label non-randomized study was performed at Royal North Shore Hospital and Royal Rehab Centre, Sydney between 2018 and 2023. An ‘acute interventional cohort’ (n = 11) with TSCI (duration ≤ 12-weeks) received a single infusion of 4 mg zoledronic acid (ZOL) at baseline. A ‘chronic non-interventional cohort’ (n = 9) with TSCI (duration 1–5-years) did not receive ZOL. All participants underwent baseline and 6-monthly blood tests (including CTx and P1NP) and 12-monthly DXA BMD scans (including distal femur and proximal tibia). Participants were predominantly Caucasian and male (mean age 38.4 years). At baseline, the ‘acute’ cohort had higher serum CTx, P1NP and sclerostin concentrations, while the ‘chronic’ cohort had lower left hip and knee BMD. Majority with acute TSCI experienced an acute phase reaction after ZOL (9/11; 82

Endothelial Protein C Receptor (EPCR) is a key regulator of the activated protein C anti-coagulation pathway due to its role in the binding and activation of this protein. EPCR also binds to other ligands such as Factor VII and X, γδ T-cells, plasmodium falciparum erythrocyte membrane protein 1, and Secretory group V Phospholipases A2, facilitating ligand-specific functions. The functions of EPCR can also be regulated by soluble (s)EPCR that competes for the binding sites of membrane-bound (m)EPCR. sEPCR is created when mEPCR is shed from the cell surface. The propensity of shedding alters depending on the genetic haplotype of the EPCR gene that an individual may possess. EPCR plays an active role in normal homeostasis, anti-coagulation pathways, inflammation, and cell stemness. Due to these properties, EPCR is considered a potential effector/mediator of inflammatory diseases. Rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are autoimmune/inflammatory conditions that are associated with elevated EPCR levels and disease activity, potentially driven by EPCR. This review highlights the functions of EPCR and its contribution to rheumatic diseases.

Objectives To investigate whether circulating endothelial protein C receptor (EPCR) is associated with disease activity and inflammatory markers in rheumatoid arthritis.Methods Thirty-eight RA patients and 21 healthy controls (HC) were recruited via the A3BC biobank. Peripheral blood mononuclear cells and plasma were isolated from the blood of these participants. Plasma soluble (s)EPCR, IL-6, IL-17 and sCD14 were measured by enzyme-linked immunosorbent assay, cell membrane-associated (m)EPCR by flow cytometry; EPCR gene H3 single nucleotide polymorphism (SNP), which contributes to high plasma sEPCR levels, by PCR and DNA sequencing. Data were analysed using FlowJo10 and GraphPad Prism 10.Results RA patients had higher levels of mEPCR on T cells and plasma sEPCR compared with HC. No difference in the EPCR gene H3 SNP G genotype frequency was found between RA and HC. This SNP was significantly correlated with higher sEPCR levels in HC but not in RA patients. In RA, plasma sEPCR levels were positively correlated with IL-6, IL-17, sCD14, anti-CCP and rheumatoid factor. In contrast, mEPCR levels on T cells and natural killer cells (NK) were inversely associated with disease activity measures including 28/66 swollen joint count, 28/68 tender joint count and/or DAS28-CRP/ESR scores, and positively correlated with EPCR gene H3 SNP, which was also correlated with lower disease activity measures in RA.Conclusion Our findings suggest that EPCR may play an important role in RA, with plasma sEPCR being potentially associated with inflammatory markers and mEPCR and the EPCR gene H3 SNP possibly related to disease activity measures. What does this mean for patients?In this study, we investigated the role of an anticoagulant receptor in rheumatoid arthritis. Our findings revealed that people with rheumatoid arthritis had higher levels of this receptor in their circulating T cells and plasma when compared with healthy individuals. In rheumatoid arthritis, the plasma levels of this receptor were positively associated with several inflammatory markers. Conversely, the abundant presence of the receptor on the T cell surface and a specific gene mutation of this receptor were negatively correlated with disease activity measures. These findings suggest that this receptor may significantly contribute to rheumatoid arthritis.

Importance The relationship between self-reported walking limitation, a proxy of muscle function, and fracture risk has not been investigated. Objective To examine the association between a self-reported walking limitation of 1000 m or less and 5-year risk of fracture. Design, Setting, and Participants This prospective cohort study compared individuals with various degrees of walking ability limitation at 1000 m (a little limitation and a lot of limitation) and those without limitation (no limitation) accounting for age, falls, prior fractures, and weight. Participants from the ongoing population-based Sax Institute 45 and Up Study were followed from recruitment (2005-2008) for 5 years (2010-2013). Data analysis was conducted from July 2020 to September 2023. Exposure Self-reported walking limitation. Main Outcomes and Measures Incident fracture and site-specific fractures (hip, vertebral, and nonhip nonvertebral [NHNV] fractures). Results Among the 266 912 participants enrolled in the 45 and Up Study, 238 969 were included, with 126 015 (53%) women (mean [SD] age, 63 [11] years) and 112 954 (47%) men (mean [SD] age, 61 [11] years). Approximately 20% reported a degree of limitation in walking 1000 m or less at baseline (39 324 women [24%]; 23 191 men [21%]). During a mean (SD) follow-up of 4.1 (0.8) years, 7190 women and 4267 men experienced an incident fracture. Compared with participants who reported no walking limitations, a little limitation and a lot of limitation were associated with higher risk of fracture (a little limitation among women: hazard ratio [HR], 1.32; 95% CI, 1.23-1.41; a little limitation among men: HR, 1.46; 95% CI, 1.34-1.60; a lot of limitation among women: HR, 1.60; 95% CI, 1.49-1.71; a lot of limitation among men: HR, 2.03; 95% CI, 1.86-2.22). Approximately 60% of fractures were attributable to walking limitation. The association was significant for hip, vertebral, and NHNV fracture and ranged between a 21% increase to a greater than 219% increase. Conclusions and Relevance In this cohort study of 238 969 participants, self-reported walking limitations were associated with increased risk of fracture. These findings suggest that walking ability should be sought by clinicians to identify high-risk candidates for further assessment.