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Musculoskeletal (MSK) conditions are the leading cause of disability and health costs in Australia and worldwide yet MSK research funding continues to be substantially lower than other chronic health conditions with similar and even lower overall disease burden. The chronic underfunding of musculoskeletal research has left sufferers frustrated by increasing burden, worsening outcomes, and complete overwhelm. People affected by musculoskeletal conditions often lack support, and certainty of care due to fundamental gaps in research and slow or no implementation of new research. Despite chronic underfunding, Australian-led research has delivered practice-changing outcomes to patients, clinicians, and policymakers, but we need to do more. Australia has the research and clinical workforce and skills to be worth investing in. We point to The Global Strategic Framework quoted from Briggs et al 2021, pp e006045 as a way forward.

Abstract 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.

Background Global policy to guide action on musculoskeletal (MSK) health is in a nascent phase. Lagging behind other non-communicable diseases (NCDs) there is currently little global policy to assist governments to develop national approaches to MSK health. Considering the importance of comparison and learning for global policy development, we aimed to perform a comparative analysis of national MSK policies to identify areas of innovation and draw common themes and principles that could guide MSK health policy.Methods Multi-modal search strategy incorporating a systematic online search targeted at the 30 most populated nations; a call to networked experts; a specified question in a related eDelphi questionnaire; and snowballing methods. Extracted data were organised using an a priori framework adapted from the World Health Organization (WHO) Building Blocks and further inductive coding. Subsequently, texts were open coded and thematically analysed to derive specific sub-themes and principles underlying texts within each theme, serving as abstracted, transferable concepts for future global policy.Results The search yielded 165 documents with 41 retained after removal of duplicates and exclusions. Only three documents were comprehensive national strategies addressing MSK health. The most common conditions addressed in the documents were pain (non-cancer), low back pain, occupational health, inflammatory conditions, and osteoarthritis. Across eight categories, we derived 47 sub-themes with transferable principles that could guide global policy for: service delivery; workforce; medicines and technologies; financing; data and information systems; leadership and governance; citizens, consumers and communities; and research and innovation.Conclusion There are few examples of national strategic policy to address MSK health; however, many countries are moving towards this by documenting the burden of disease and developing policies for MSK services. This review found a breadth of principles that can add to this existing work and may be adopted to develop comprehensive system-wide MSK health approaches at national and global levels.

Disorders affecting the neurological and musculoskeletal systems represent international health priorities. A significant impediment to progress in trials of new therapies is the absence of responsive, objective, and valid outcome measures sensitive to early disease changes. A key finding in individuals with neuromuscular and musculoskeletal disorders is the compositional changes to muscles, evinced by the expression of fatty infiltrates. Quantification of skeletal muscle composition by MRI has emerged as a sensitive marker for the severity of these disorders; however, little is known about the composition of healthy muscles across the lifespan. Knowledge of what is ‘typical’ age-related muscle composition is essential to accurately identify and evaluate what is ‘atypical’. This innovative project, known as the MuscleMap, will achieve the first important steps towards establishing a world-first, normative reference MRI dataset of skeletal muscle composition with the potential to provide valuable insights into various diseases and disorders, ultimately improving patient care and advancing research in the field.

Objective: To investigate the prognostic value of illness perception (IP) on knee pain, quality of life (QoL) and functional level in elderly individuals reporting knee pain. Design: A prospective cohort study of 1552 elderly with knee pain comparing two previously established clusters based on the Brief Illness Perception questionnaire. Cluster 1 (“Concerned optimists” [hypothesized unfavorable profile]; n ​= ​642) perceived their knee pain as a greater threat to them than Cluster 2 (“Unconcerned confident” [hypothesized favorable profile]; n ​= ​910). Primary outcome was the change from baseline to year 2 in the KOOS Pain subscale. Secondary outcomes were changes from baseline in quality of life (EuroQol-5 Domain and EQ VAS) and in the KOOS subscales Symptom, Activities of Daily Living, Knee-related QoL and Sports and recreation. Analyses were done on the original Intention-To-Survey (ITS) population, using repeated measures mixed linear models. Results: Among the ITS population, 841 (54%) responded to the 2-year survey. There was a statistically significant but clinically irrelevant cluster difference in the 2-year change from baseline in KOOS pain (mean difference: 6.0 KOOS points [95% CI: 7.3 to −4.7]) explained by a minor improvement in Cluster 1: (6.2 points) and no changes in Cluster 2: (0.2 points). Comparable results were found across the secondary outcomes. Clinically irrelevant cluster changes in IP were seen. Conclusion: In a cohort of people with knee pain, IP phenotype (i.e., Clusters) were of no prognostic value for the 2-year changes in pain, function, and QoL. Targeting IP may not be relevant in this patient population. Trial registration number and date of registration: The Frederiksberg Cohort study was pre-registered at clinicaltrials.gov (NCT03472300) on March 21, 2018.

Actions towards the health-related Sustainable Development Goal 3.4 typically focus on non-communicable diseases (NCDs) associated with premature mortality, with less emphasis on NCDs associated with disability, such as musculoskeletal conditions—the leading contributor to the global burden of disability. Can systems strengthening priorities for an underprioritised NCD be codesigned, disseminated and evaluated? A ‘roadmap’ for strengthening global health systems for improved musculoskeletal health was launched in 2021. In this practice paper, we outline dissemination efforts for this Roadmap and insights on evaluating its reach, user experience and early adoption. A global network of 22 dissemination partners was established to drive dissemination efforts, focussing on Africa, Asia and Latin America, each supported with a suite of dissemination assets. Within a 6-month evaluation window, 52 Twitter posts were distributed, 2195 visitors from 109 countries accessed the online multilingual Roadmap and 138 downloads of the Roadmap per month were recorded. Among 254 end users who answered a user-experience survey, respondents ‘agreed’ or ‘strongly agreed’ the Roadmap was valuable (88.3%), credible (91.2%), useful (90.1%) and usable (85.4%). Most (77.8%) agreed or strongly agreed they would adopt the Roadmap in some way. Collection of real-world adoption case studies allowed unique insights into adoption practices in different contexts, settings and health system levels. Diversity in adoption examples suggests that the Roadmap has value and adoption potential at multiple touchpoints within health systems globally. With resourcing, harnessing an engaged global community and establishing a global network of partners, a systems strengthening tool can be cocreated, disseminated and formatively evaluated.

Objective To determine vaccination rates, perceptions, and information sources in people with inflammatory arthritis. Methods Participants enrolled in the Australian Rheumatology Association Database were invited to participate in an online questionnaire, conducted in January 2020, prior to the COVID‐19 pandemic. Included questions were about vaccination history, modified World Health Organization Vaccination Hesitancy Scale, views of the information sources consulted, the Beliefs About Medicines Questionnaire, education, and the Single‐Item Health Literacy Screener. Results Response rate was 994 of 1498 (66%). The median age of participants was 62 years, with 67% female. Self‐reported adherence was 83% for the influenza vaccine. Participants generally expressed positive vaccination views, particularly regarding safety, efficacy, and access. However, only 43% knew which vaccines were recommended for them. Vaccine hesitancy was primarily attributable to uncertainty and a perceived lack of information about which vaccines were recommended. Participants consulted multiple vaccination information sources (median 3, interquartile range 2‐7). General practitioners (89%) and rheumatologists (76%) were the most frequently used information sources and were most likely to yield positive views. Negative views of vaccination were most often from internet chatrooms, social media, and mainstream media. Factors of younger age, male gender, and having more concerns about the harms and overuse of medicines in general were associated with lower adherence and greater uncertainty about vaccinations, whereas education and self‐reported literacy were not. Conclusion Participants with inflammatory arthritis generally held positive views about vaccination, although there was considerable uncertainty as to which vaccinations were recommended for them. This study highlights the need for improved consumer information about vaccination recommendations for people with inflammatory arthritis.

Objective To determine distinct trajectories of self-reported pain-related health status in rheumatoid arthritis (RA), their relationship with sociodemographic factors and medication use.Methods 988 Australian Rheumatology Association Database participants with RA (71% female, mean age 54 years, mean disease duration 2.3 years) were included. Distinct multi-trajectories over 15-year follow-up for five different self-reported pain-related health outcome measures (Health Assessment Questionnaire Disability Index, visual analogue scores for pain, arthritis, global health and the Assessment of Quality of Life utility index) were identified using latent variable discrete mixture modelling. Random effects models were used to determine associations with medication use and biologic therapy modification during follow-up.Results Four, approximately equally sized, pain/health status groups were identified, ranging from ‘better’ to ‘poorer’, within which changes over time were relatively small. Important determinants of those with poorer pain/health status included female gender, obesity, smoking, socioeconomic indicators and comorbidities. While biologic therapy use was similar between groups during follow-up, biologic therapy modifications (plinear

Abstract Background To report the national prevalence, years lived with disability (YLDs) and attributable risk factors for all musculoskeletal conditions and separately for low back pain (LBP), as well as compare the disability burden related to musculoskeletal with other health conditions in Australia in 2019. Methods Global Burden of Disease (GBD) 2019 study meta-data on all musculoskeletal conditions and LBP specifically were accessed and aggregated. Counts and age-standardised rates, for both sexes and across all ages, for prevalence, YLDs and attributable risk factors are reported. Results In 2019, musculoskeletal conditions were estimated to be the leading cause of YLDs in Australia (20.1%). There were 7,219,894.5 (95% UI: 6,847,113–7,616,567) prevalent cases of musculoskeletal conditions and 685,363 (95% UI: 487,722–921,471) YLDs due to musculoskeletal conditions. There were 2,676,192 (95% UI: 2,339,327–3,061,066) prevalent cases of LBP and 298,624 (95% UI: 209,364–402,395) YLDs due to LBP. LBP was attributed to 44% of YLDs due to musculoskeletal conditions. In 2019, 22.3% and 39.8% of YLDs due to musculoskeletal conditions and LBP, respectively, were attributed to modifiable GBD risk factors. Conclusions The ongoing high burden due to musculoskeletal conditions impacts Australians across the life course, and in particular females and older Australians. Strategies for integrative and organisational interventions in the Australian healthcare system should support high-value care and address key modifiable risk factors for disability such as smoking, occupational ergonomic factors and obesity.

BackgroundMultimorbidity is common among fracture patients. However, its association with osteoporosis investigation and treatment to prevent future fractures is unclear. This limited knowledge impedes optimal patient care. This study investigated the association between multimorbidity and osteoporosis investigation and treatment in persons at high risk following an osteoporotic fracture.Methods and findingsThe Sax Institute's 45 and Up Study is a prospective population-based cohort of 267,153 people in New South Wales, Australia, recruited between 2005 and 2009. This analysis followed up participants until 2017 for a median of 6 years (IQR: 4 to 8). Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection (APDC)), emergency presentations (Emergency Department Data Collection (EDDC)), Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS). Data were linked by the Centre for Health Record Linkage and stored in a secured computing environment. Fractures were identified from APDC and EDDC, Charlson Comorbidity Index (CCI) from APDC, Dual-energy X-ray absorptiometry (DXA) investigation from MBS, and osteoporosis treatment from PBS. Out of 25,280 persons with index fracture, 10,540 were classified as high-risk based on 10-year Garvan Fracture Risk (age, sex, weight, prior fracture and falls) threshold ≥20%. The association of CCI with likelihood of investigation and treatment initiation was determined by logistic regression adjusted for education, socioeconomic and lifestyle factors). The high-risk females and males averaged 77 ± 10 and 86 ± 5 years, respectively; >40% had a CCI ≥2. Only 17% of females and 7% of males received a DXA referral, and 22% of females and 14% males received osteoporosis medication following fracture. A higher CCI was associated with a lower probability of being investigated [adjusted OR, females: 0.73 (95% CI, 0.61 to 0.87) and 0.43 (95% CI, 0.30 to 0.62); males: 0.47 (95% CI, 0.33 to 0.68) and 0.52 (0.31 to 0.85) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] and of receiving osteoporosis medication [adjusted OR, females: 0.85 (95% CI, 0.74 to 0.98) and 0.78 (95% CI, 0.61 to 0.99); males: 0.75 (95% CI, 0.59 to 0.94) and 0.37 (95% CI, 0.23 to 0.53) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively]. The cohort is relatively healthy; therefore, the impact of multimorbidity on osteoporosis management may have been underestimated.ConclusionsMultimorbidity contributed significantly to osteoporosis treatment gap. This suggests that fracture risk is either underestimated or underprioritized in the context of multimorbidity and highlights the need for extra vigilance and improved fracture care in this setting.

Abstract Background Research on adherence interventions in rheumatology is limited by methodological issues, particularly heterogeneous outcomes. We aimed to describe researchers’ experiences with conducting interventional studies targeting medication adherence in rheumatology and their perspectives on establishing core outcomes. Methods Semi-structured interviews using audio conference were conducted with researchers who had conducted an adherence study of any design in the past 10 years. Data collection and thematic analysis were performed iteratively, until saturation. Results We interviewed 13 researchers, most of whom worked in academia and specialized in epidemiology and/or health services research. We identified three themes: 1) improving measurement of adherence (considering all phases of adherence, using appropriate and relevant measures, and establishing clinically meaningful thresholds); 2) challenges in designing and appraising adherence intervention studies (considering the confusion over a plethora of outcomes, difficulties with powering studies to demonstrate meaningful changes, and suboptimal descriptions of adherence interventions in published studies); and 3) advancing outcome assessment in adherence intervention studies (capturing rationale for developing a core domain set as well as recommendations and anticipated challenges by participants). Conclusions Uniquely gathering perspectives from international adherence researchers, our findings led to researcher-informed recommendations for improving adherence research including specifying the targeted adherence phase in designing interventions and studies and providing a glossary of terms to promote consistency in reporting. We also identified recommendations for developing a core domain set for interventional studies targeting medication adherence including involvement of patients, clinicians, and other stakeholders and methodological and practical considerations to establish rigor and support uptake.

Abstract Background Musculoskeletal (MSK) conditions, MSK pain and MSK injury/trauma are the largest contributors to the global burden of disability, yet global guidance to arrest the rising disability burden is lacking. We aimed to explore contemporary context, challenges and opportunities at a global level and relevant to health systems strengthening for MSK health, as identified by international key informants (KIs) to inform a global MSK health strategic response. Methods An in-depth qualitative study was undertaken with international KIs, purposively sampled across high-income and low and middle-income countries (LMICs). KIs identified as representatives of peak global and international organisations (clinical/professional, advocacy, national government and the World Health Organization), thought leaders, and people with lived experience in advocacy roles. Verbatim transcripts of individual semi-structured interviews were analysed inductively using a grounded theory method. Data were organised into categories describing 1) contemporary context; 2) goals; 3) guiding principles; 4) accelerators for action; and 5) strategic priority areas (pillars), to build a data-driven logic model. Here, we report on categories 1–4 of the logic model. Results Thirty-one KIs from 20 countries (40% LMICs) affiliated with 25 organisations participated. Six themes described contemporary context (category 1): 1) MSK health is afforded relatively lower priority status compared with other health conditions and is poorly legitimised; 2) improving MSK health is more than just healthcare; 3) global guidance for country-level system strengthening is needed; 4) impact of COVID-19 on MSK health; 5) multiple inequities associated with MSK health; and 6) complexity in health service delivery for MSK health. Five guiding principles (category 3) focussed on adaptability; inclusiveness through co-design; prevention and reducing disability; a lifecourse approach; and equity and value-based care. Goals (category 2) and seven accelerators for action (category 4) were also derived. Conclusion KIs strongly supported the creation of an adaptable global strategy to catalyse and steward country-level health systems strengthening responses for MSK health. The data-driven logic model provides a blueprint for global agencies and countries to initiate appropriate whole-of-health system reforms to improve population-level prevention and management of MSK health. Contextual considerations about MSK health and accelerators for action should be considered in reform activities.

Abstract Background The aim of this study was to identify modifiable clinical factors associated with radiographic osteoarthritis progression over 1 to 2 years in people with painful medial knee osteoarthritis. Methods A longitudinal study was conducted within a randomised controlled trial, the “Long-term Evaluation of Glucosamine Sulfate” (LEGS study). Recruitment occurred in 2007–2009, with 1- and 2-year follow-up assessments by blinded assessors. Community-dwelling people with chronic knee pain (≥4/10) and medial tibiofemoral narrowing (but retaining >2mm medial joint space width) on radiographs were recruited. From 605 participants, follow-up data were available for 498 (82%, mean [sd] age 60 [8] years). Risk factors evaluated at baseline were pain, physical function, use of non-steroidal anti-inflammatory drugs (NSAIDs), statin use, not meeting physical activity guidelines, presence of Heberden’s nodes, history of knee surgery/trauma, and manual occupation. Multivariable logistic regression analysis was conducted adjusting for age, sex, obesity, high blood pressure, allocation to glucosamine and chondroitin treatment, and baseline structural disease severity (Kellgren and Lawrence grade, joint space width, and varus alignment). Radiographic osteoarthritis progression was defined as joint space narrowing ≥0.5mm over 1 to 2 years (latest follow-up used where available). Results Radiographic osteoarthritis progression occurred in 58 participants (12%). Clinical factors independently associated with radiographic progression were the use of NSAIDs, adjusted odds ratios (OR) and 95% confidence intervals (CI) 2.05 (95% CI 1.1 to 3.8), and not meeting physical activity guidelines, OR 2.07 (95% CI 0.9 to 4.7). Conclusions Among people with mild radiographic knee osteoarthritis, people who use NSAIDs and/or do not meet physical activity guidelines have a greater risk of radiographic osteoarthritis progression. Trial registration ClinicalTrials.gov , NCT00513422 . This original study trial was registered a priori, on August 8, 2007. The current study hypothesis arose before inspection of the data.

Introduction Despite the profound burden of disease, a strategic global response to optimise musculoskeletal (MSK) health and guide national-level health systems strengthening priorities remains absent. Auspiced by the Global Alliance for Musculoskeletal Health (G-MUSC), we aimed to empirically derive requisite priorities and components of a strategic response to guide global and national-level action on MSK health.Methods Design: mixed-methods, three-phase design.Phase 1: qualitative study with international key informants (KIs), including patient representatives and people with lived experience. KIs characterised the contemporary landscape for MSK health and priorities for a global strategic response.Phase 2: scoping review of national health policies to identify contemporary MSK policy trends and foci.Phase 3: informed by phases 1–2, was a global eDelphi where multisectoral panellists rated and iterated a framework of priorities and detailed components/actions.Results Phase 1: 31 KIs representing 25 organisations were sampled from 20 countries (40% low and middle income (LMIC)). Inductively derived themes were used to construct a logic model to underpin latter phases, consisting of five guiding principles, eight strategic priority areas and seven accelerators for action.Phase 2: of the 165 documents identified, 41 (24.8%) from 22 countries (88% high-income countries) and 2 regions met the inclusion criteria. Eight overarching policy themes, supported by 47 subthemes, were derived, aligning closely with the logic model.Phase 3: 674 panellists from 72 countries (46% LMICs) participated in round 1 and 439 (65%) in round 2 of the eDelphi. Fifty-nine components were retained with 10 (17%) identified as essential for health systems. 97.6% and 94.8% agreed or strongly agreed the framework was valuable and credible, respectively, for health systems strengthening.Conclusion An empirically derived framework, co-designed and strongly supported by multisectoral stakeholders, can now be used as a blueprint for global and country-level responses to improve MSK health and prioritise system strengthening initiatives.

Abstract Background Tumour necrosis factor inhibitor (TNFi) therapy has been available for rheumatoid arthritis (RA) patients for several decades but data on the long-term risk of malignancy associated with its use is limited. Our aims were to assess malignancy risk in a cohort of Australian RA patients relative to the Australian population and to compare cancer risk for patients exposed to TNFi therapy versus a biologic-naïve group. Methods Demographic data for RA participants enrolled in the Australian Rheumatology Association Database (ARAD) before 31 Dec 2012 were matched to national cancer records in May 2016 (linkage complete to 2012). Standardised incidence ratios (SIRs) were used to compare malignancy incidence in TNFi-exposed and biologic-naïve ARAD participants with the Australian general population using site-, age- and sex-specific rates by calendar year. Malignancy incidence in TNFi-exposed participants and biologic-naïve RA patients, were compared using rate ratios (RRs), adjusted for age, sex, smoking, methotrexate use and prior malignancy. Results There were 107 malignancies reported after 10,120 person-years in the TNFi-exposed group (N = 2451) and 49 malignancies after 2232 person-years in the biologic-naïve group (N = 574). Compared with the general population, biologic-naïve RA patients showed an increased risk for overall malignancy (SIR 1.52 (95% confidence interval (CI) 1.16, 2.02) prostate cancer (SIR 2.10, 95% CI 1.18, 4.12). The risk of lung cancer was increased for both biologic naïve and TNFi-exposed patients compared with the general population (SIR 2.69 (95% CI 1.43 to 5.68) and SIR 1.69 (95% CI 1.05 to 2.90) respectively). For the TNFi-exposed patients there was an increased risk of lymphoid cancers (SIR 1.82, 95% CI 1.12, 3.18). There were no differences between the exposure groups in the risk of cancer for any of the specific sites examined. Conclusions Overall malignancy incidence was elevated for biologic-naïve RA patients but not for those exposed to TNFi. TNFi exposure did not increase malignancy risk beyond that experienced by biologic-naïve patients. Lung cancer risk was increased for both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status or RA treatments other than TNFi may be responsible in some way.

Abstract Background Chronic inflammatory arthritis is associated with increased cardiovascular (CV) morbidity and mortality. Pharmacological management and healthy lifestyle modification is recommended to manage these risks, but it is not known how often these are utilised and whether there is any difference in their use between patients with different types of arthritis. The aim of this study was to determine and compare the proportion of participants with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) receiving pharmacological or lifestyle management strategies for CV risk factors. The secondary objective was to identify factors associated with use of management strategies. Methods A survey was sent to online participants in the Australian Rheumatology Association Database, a voluntary national registry for inflammatory arthritis. Participants were asked whether they took medications for hypertension, hyperlipidaemia and diabetes, and to report their height, weight, level of physical activity, and dietary changes made. The use of management strategies was compared between participants with RA and PsA. Logistic regression analyses were performed to identify factors associated with physical activity and dietary changes. Results There were 858 respondents with RA and 161 with PsA (response rate 64.5%). Pharmacological treatment was reported by 93% of participants with hypertension and 70% with hyperlipidaemia. All participants with diabetes reported being managed with dietary modification, pharmacological treatment, or a combination of both. Adequate physical activity was reported by 50.8%. Only 27% of overweight or obese participants reported making any dietary change for their health in the past year. There was no difference between RA and PsA in reported utilisation of management strategies. Hyperlipidaemia and being overweight were associated with making dietary change. Obesity and arthritis disease activity were negatively associated with physical activity. Conclusions Most participants with RA and PsA reported using pharmacological treatment for CV risk factors. Relatively few reported using lifestyle modifications. Targeted lifestyle interventions should be implemented for RA and PsA patients.

Abstract Background Inflammatory arthritides including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are associated with increased risk of cardiovascular disease. This process may be driven by systemic inflammation, and the use of tumour necrosis factor (TNF) inhibitors could therefore potentially reduce cardiovascular risk by reducing this inflammatory burden. The aims of this study were to evaluate whether the risk of cardiovascular events (CVEs) in patients with inflammatory arthritis is associated with treatment with anti-TNF therapy, compared with other biologics or non-biologic therapy, and to compare the CVE risk between participants with RA, PsA and AS. Methods Data from consecutive participants in the Australian Rheumatology Association Database with RA, PsA and AS from September 2001 to January 2015 were included in the study. The Cox proportional hazards model using the counting process with time-varying covariates tested for risk of having CVEs, defined as angina, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, other heart disease, stroke/transient ischaemic attack or death from cardiovascular causes. The model was adjusted for age, sex, diagnosis, methotrexate use, prednisone use, non-steroidal anti-inflammatory use, smoking, alcohol consumption, hypertension, hyperlipidaemia, diabetes and functional status (Health Assessment Questionnaire Disability Score). Results There were 4140 patients included in the analysis, totalling 19,627 patient-years. After multivariate adjustment, the CVE risk was reduced with anti-TNF use (HR 0.85, 95% CI 0.76–0.95) or other biologic therapies (HR 0.81, 95% CI 0.70–0.95), but not in those who had ceased biologic therapy (HR 0.96, 95% CI 0.83–1.11). After adjustment, no significant difference in CVE risk was observed between participants with RA and PsA (HR 0.92, 95% CI 0.77–1.10) or AS (HR 1.14, 95% CI 0.96–1.36). Conclusions Current biologic use was associated with a reduction in major CVEs. No reduction in CVE risk was seen in those who had ceased biologic therapy. After adjustment, the CVE risk was not significantly different between RA, AS or PsA.

Abstract Background Bisphosphonates are a class of drugs that slow bone loss and are a promising candidate to treat knee osteoarthritis (OA) patients. In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with significant knee pain and BMLs. A longer, larger study is required to assess whether decreases in BML size will translate to reductions in cartilage loss over time. We are currently conducting a multicentre, randomised, double-blind, placebo-controlled trial over 24 months that aims to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change (assessed using magnetic resonance imaging (MRI)) and knee pain in knee OA patients. Methods Two hundred sixty-four patients with clinical knee OA, significant knee pain and subchondral BMLs present on MRI will be recruited in Hobart, Melbourne, Sydney and Adelaide. They will be randomly allocated to the two arms of the study, receiving an annual identical intravenous infusion of either 100 mL of fluid containing zoledronic acid (5 mg/100 mL) or placebo (0.9% NaCl 100 mL), at baseline and 1 year later. MRI of the study knee will be performed at screening, month 6 and 24. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is absolute change in tibiofemoral cartilage volume (mm3) over 24 months. Secondary outcomes include improvement in knee pain over 3, 6, 12, 18, and 24 months and reductions in BML size over 6 and 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses will be performed as the secondary analyses. Discussion This study will provide high-quality evidence to assess whether zoledronic acid has a novel disease modifying effect in OA by slowing cartilage loss and reducing pain. If zoledronic acid proves effective, it suggests great potential for cost savings through a delay or reduced need for joint replacement surgery, and potential for great improvements in quality of life for OA suffers. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12613000039785, registered on 14 January 2013.

Abstract Background Over the last 20 years, there have been marked improvements in the availability of effective medications for rheumatic conditions such as gout, osteoporosis and rheumatoid arthritis (RA), which have led to a reduction in disease flares and the risk of re-fracture in osteoporosis, and the slowing of disease progression in RA. However, medication adherence remains suboptimal, as treatment regimens can be complex and difficult to continue long term. Many trials have been conducted to improve adherence to medication. Core domains, which are the outcomes of most relevance to patients and clinicians, are a pivotal component of any trial. These core domains should be measured consistently, so that all relevant trials can be combined in systematic reviews and meta-analyses to reach conclusions that are more valid. Failure to do this severely limits the potential for trial-based evidence to inform decisions on how to support medication adherence. The Outcome Measures in Rheumatology (OMERACT) – Interventions for Medication Adherence study by the OMERACT-Adherence Group aims to develop a core domain set for interventions that aim to support medication adherence in rheumatology. Methods/design This OMERACT-Adherence study has five phases: (1) a systematic review to identify outcome domains that have been reported in interventions focused on supporting medication adherence in rheumatology; (2) semi-structured stakeholder interviews with patients and caregivers to determine their views on the core domains; (3) focus groups using the nominal group technique with patients and caregivers to identify and rank domains that are relevant to them, including the reasons for their choices; (4) an international three-round modified Delphi survey involving patients with diverse rheumatic conditions, caregivers, health professionals, researchers and other stakeholders to develop a preliminary core domain set; and (5) a stakeholder workshop with OMERACT members to review, vote on and reach a consensus on the core domain set for interventions to support medication adherence in rheumatology. Discussion Establishing a core domain set to be reported in all intervention studies undertaken to support patients with medication adherence will enhance the relevance and the impact of these results and improve the lives of people with rheumatic conditions.

Background: Residual/reconverted red bone marrow (RBM) in adult knees is occasionally observed on routine knee magnetic resonance imaging (MRI). We aimed to identify its prevalence, distribution, and associations with lifestyle factors, knee structural abnormalities, and knee symptoms in young adults. Methods: Participants (n = 327; aged = 31–41 years) were selected from the Childhood Determinants of Adult Health (CDAH) knee study. They underwent T1-weighted and proton-density-weighted fat-suppressed MRI scans of knees. Residual/reconverted RBM in distal femur and proximal tibia were graded semi-quantitatively (grades: 0–3) based on the percentage area occupied. Knee structural abnormalities were graded semi-quantitatively using previously published MRI scoring systems. Knee symptoms (pain, stiffness, and dysfunction) were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale during CDAH knee study (year: 2008–2010) and at 6–9-year follow-up during the CDAH-3 study (year: 2014–2019). Associations between definite RBM (grade ≥ 2) and lifestyle factors, knee symptoms, and structural abnormalities were described using log-binomial regressions. Results: Definite RBM was seen in females only, in 29 out of 154 cases (18.8%), with femoral involvement preceding tibial involvement. Definite RBM was associated with increased BMI (PR = 1.09/kg/m2; 95% CI: 1.03, 1.16), overweight status (PR = 2.19; 95% CI: 1.07, 4.51), and WOMAC knee pain (PR = 1.75; 95% CI: 1.11, 2.74) in cross-section analysis. However, there was no association between RBM and knee-pain after seven years (PR = 1.15; 95% CI: 0.66, 2.00). There were no associations between RBM and knee structural abnormalities. Conclusion: Presence of definite RBM in young adult knees was observed in females only. Definite RBM was associated with overweight measures, and the modest association with knee pain may not be causally related.

Abstract Background Glucocorticoids (GCs) are used in ~ 60% of patients with rheumatoid arthritis (RA). Although disease-modifying, they also have significant adverse effects. Understanding factors associated with GC use may help minimise exposure. The aims of the present study were to describe oral GC use in RA; determine any change in use over time; and determine factors associated with oral GC use, commencement or cessation. Methods Adult patients with RA were identified in the Australian Rheumatology Association Database (ARAD), a national Australian registry that collects long-term outcome data from patients with inflammatory arthritis. Patients were categorised by their ARAD date of entry (DOE), with population-averaged logistic regression and transition state analysis used to determine any change in GC use over time. Fixed-effects panel regression was used to examine whether GC current use was associated with pain/arthritis activity/Health Assessment Questionnaire (HAQ) scores or medication use. Transition state analysis was used to assess whether these factors influenced the commencement or cessation of GCs. Results A total of 3699 patients with RA completed a baseline ARAD questionnaire (73% female, mean age 57 years). The probability of GC use decreased over time according to ARAD DOE: September 2001 to March 2005, 55% (95% CI 52–58%); March 2005 to September 2008, 47% (45–49%); September 2008 to March 2012, 42% (39–45%); and March 2012 to October 2015, 39% (34–43%) (p

Background: The aim of this study was to compare the efficacy and safety of zoledronic acid (ZA) plus intravenous methylprednisolone (VOLT01) to ZA, and placebo for knee osteoarthritis. Methods: A single-center, double-blind, randomized controlled trial (RCT) was carried out. Adults (aged ⩾50 years) with knee osteoarthritis, significant knee pain [⩾40 mm on a 100 mm visual analog scale (VAS)], and magnetic resonance imaging-detected bone marrow lesion (BML) were randomized to receive a one-off administration of VOLT01, ZA, or placebo. The primary hypothesis was that VOLT01 was superior to ZA in having a lower incidence of acute phase responses (APRs) over 3 days. Secondary hypotheses were that VOLT01 was noninferior to ZA, and both treatments were superior to placebo in decreasing BML size over 6 months and in improving knee pain [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and VAS] and function (WOMAC) over 3 and 6 months. Results: A total of 117 patients (62.2 ± 8.1 years, 63 women) were enrolled. The incidence of APRs was similar in the VOLT01 (90%) and ZA (87%) groups ( p = 0.74). VOLT01 was superior to ZA in improving knee pain and function after 6 months and noninferior to ZA in reducing BML size. However, BML size change was small in all groups and there were no between-group differences. Compared with placebo, VOLT01 but not ZA improved knee function and showed a trend toward improving knee pain after 6 months. Conclusions: Administering intravenous methylprednisolone with ZA did not reduce APRs or change knee BML size over 6 months, but in contrast to ZA or placebo, it may have a beneficial effect on symptoms in knee osteoarthritis. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000039785.

Introduction The Global Burden of Disease 2010 study ranked osteoarthritis (OA) as a leading cause of years lived with disability. With an ageing population, increasing body weight and sedentary lifestyle, a substantial increase especially in knee OA (KOA) is expected. Management strategies for KOA include non-pharmacological, pharmacological and surgical interventions. Meanwhile, over-the-counter pain medications have been discredited as they are associated with several risks with long-term usage. By consequence, the use of exercise and all sorts of complementary and alternative medicine (CAM) for joint pain has increased. The available self-management strategies are plenty, but there is no overview of their use at a population level and whether they are used along with doctors’ prescriptions or replace these. The aim of this study is to estimate the population incidence of developing knee symptoms and analyse the association between (and impact of) the use of self-reported preventive measures and knee symptoms.Methods and analysis This prospective cohort study pragmatically recruits individuals from the municipality of Frederiksberg, Denmark. All citizens aged 60–69 years old will be contacted annually for 10 years and asked to participate in a web-based survey. The major outcomes are self-reported knee symptoms and their association with use of various management strategies, including use of non-pharmacological treatments and CAM. Secondary outcomes include the influence of treatments on use of healthcare system and surgical procedures. Descriptive and analytic statistics (eg, logistic regression) will be used to provide summaries about the sample and observations made and the associations between self-management and development of knee symptoms.Ethics and dissemination This study can be implemented without permission from the Health Research Ethics Committee. Permission has been obtained from the Danish Data Protection Agency. Study findings will be disseminated in peer-reviewed journals and presented at relevant conferences.Trial registration number NCT03472300.

Abstract Objective: To explore impact of incident osteoarthritis (OA) on health services use by Australian women born 1946–51. Methods: Secondary analysis of Australian Longitudinal Study on Women's Health survey data linked to Medicare Australia databases (2002 to 2011). Medicare services use was compared for two groups: OA group (n=761) – reported incident OA in 2007; Never group (n=4346) – did not report arthritis in time frame. Interrupted time series regression compared health services use over time. Results: The OA group had higher health services use than the Never group. Rate of services use increased over time for both groups. Rate of increase in quarterly doctor attendances was significantly lower for the OA group after onset of OA, with no corresponding change for the Never group. Conclusions: A pre‐existing higher use of health services is associated with reporting incident OA, compared to those who never report arthritis. After onset of OA, rate of doctor use reduced and allied health use increased, consistent with recommended Australian treatment guidelines. Implications: This study provides a rare insight into change in healthcare use for people reporting incident OA, against an appropriate comparison group, highlighting the importance of early diagnosis of OA to optimise effective use of health services.

Abstract Synovial fibroblast proliferation Is a hallmark of the Invasive pannus in the rheumatoid joint. Activated protein C (APC) is a natural anticoagulant that exerts antiinflammatory and cyto-protective effects in various diseases via endothelial protein C receptor (EPCR) and proteinase-activated receptor (PAR)-mediated pathways. In this study, we investigated the effect and the underlying cellular signaling mechanisms of APC on proliferation of human rheumatoid synovial fibroblasts (RSFs). We found that APC stimulated proliferation of mouse dermal fibroblasts (MDFs) and normal human dermal fibroblasts (HDFs) by up to 60%, but robustly downregulated proliferation of RSFs. APC induced the phosphorylation of extracellular signal-regulated protein kinase (ERK) and enhanced expression of p21 and p27 in a dose-dependent manner in RSFs. The latter effect was inhibited by pretreatment with the ERK inhibitors PD98059 and U0126 but not by p38 inhibitor SB203580. In addition, APC significantly downregulated tumor necrosis factor (TNF)α-stimulated cell proliferation and activation of p38, c-Jun NH2-terminal kinase (JNK) and Akt in RSFs. These results provide the first evidence that APC selectively inhibits proliferation and the inflammatory signaling pathways of RSFs. Thus, APC may reduce synovial hyperplasia and pannus invasion in rheumatoid arthritis.

OBJECTIVE:To examine when, where and how fractures occur in postmenopausal women. METHODS:We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. RESULTS:Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. CONCLUSION:In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.