Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. METHODS: In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40-75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381). FINDINGS: Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was -15·2 mm (SD 24·0) in the methotrexate group and -7·7 mm (25·3) in the placebo group, with a mean between-group difference of -9·9 (95% CI -19·3 to -0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. INTERPRETATION: Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype. FUNDING: National Health and Medical Research Council of Australia.

Association between medial meniscal extrusion and knee structural progression in adults with symptomatic knee osteoarthritis - a prospective cohort study.

OBJECTIVE: To examine the association between medial meniscal extrusion and structural progression in adults with symptomatic knee osteoarthritis (OA). METHODS: This prospective cohort study examined 176 participants with symptomatic knee OA recruited into a randomised controlled trial. The participants underwent magnetic resonance imaging (MRI) of the study knee at baseline and approximately 2 years later. Meniscal extrusion, tibial cartilage volume, and tibiofemoral bone marrow lesions (BMLs) were measured from MRI using validated methods. RESULTS: Participants with medial meniscal extrusion ≥ 3 mm had a higher prevalence of lateral tibiofemoral BMLs at baseline (OR = 2.21, 95% CI 1.06-4.61, p = 0.035), and those with medial meniscal extrusion 2-3 mm had a higher likelihood of lateral BML worsening over 2 years (OR = 3.76, 95% CI 1.35-10.52, p = 0.011), compared with those with medial meniscal extrusion < 2 mm. Participants with stable medial meniscal extrusion had a lower likelihood of lateral BML worsening compared with those with regression of medial meniscal extrusion over 2 years (OR = 0.20, 95% CI 0.07-0.56, p = 0.002). There were no associations between medial meniscal extrusion and tibial cartilage volume or medial tibiofemoral BMLs. CONCLUSIONS: Our study showed associations between medial meniscal extrusion and baseline prevalence and worsening over 2 years of lateral tibiofemoral BMLs in people with symptomatic knee OA. Although the reasons for the lack of associations in the medial compartment are not clear, our results suggest a role of medial meniscal extrusion in predicting structural progression in lateral knee OA and that meniscal extrusion might be a potential target in the management of knee OA.

Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.

Association between popliteal artery wall thickness and structural progression in patients with symptomatic knee osteoarthritis.

OBJECTIVE: There is increasing evidence for the involvement of vascular disease in the pathogenesis of knee OA. Popliteal artery wall thickness can be used as a surrogate marker of atherosclerosis. We examined the association between popliteal artery wall thickness and knee cartilage volume in individuals with symptomatic knee OA. METHODS: This prospective cohort study analysed 176 participants from a randomized placebo-controlled trial examining the effect of atorvastatin on structural progression in knee OA. The participants underwent MRI of the study knee at baseline and 2-year follow-up. Popliteal artery wall thickness and tibial cartilage volume were measured from MRI using validated methods. The top quartile of the rate of tibial cartilage volume loss was defined as rapid progression. RESULTS: At baseline, every 10% increase in popliteal artery wall thickness was associated with 120.8 mm3 (95% CI 5.4, 236.2, P = 0.04) lower of medial tibial cartilage volume and 151.9 mm3 (95% CI 12.1, 291.7, P = 0.03) lower of lateral tibial cartilage volume. Longitudinally, for every 10% increase in popliteal artery wall thickness, the annual rate of medial tibial cartilage volume loss was increased by 1.14% (95% CI 0.09%, 2.20%, P = 0.03), and there was a 2.28-fold (95% CI 1.07, 4.83, P = 0.03) risk of rapid progression of medial tibial cartilage loss, adjusted for age, sex, BMI, tibial bone area, smoking, vigorous physical activity, and intervention group allocation. CONCLUSION: The findings support a role for vascular pathology in the progression of knee OA. Targeting atherosclerosis has the potential to improve outcomes in knee OA.

Negative back beliefs are associated with increased odds of low back pain and disability: a 10-year cohort study in men.

OBJECTIVE: Although negative back beliefs are associated with high-intensity low back pain (LBP)/disability, whether they influence incident high-intensity LBP/high-disability over the long-term is unknown. This study aimed to investigate whether negative back beliefs were associated with developing high-intensity LBP and/or high-disability over 10 years in men. METHODS: Men with no or low-intensity LBP and/or disability attending the Geelong Osteoporosis Study between 2006-2010 were included. Data on age, body mass index, mobility, education, back beliefs (Back Beliefs Questionnaire), LBP and disability (Graded Chronic Pain Scale) were collected between 2006-2010. Beliefs, LBP and disability were re-assessed in 2016-2021. Binary logistic regression was used to examine the association between negative back beliefs and incident high-intensity pain and/or high-disability, adjusting for age, body mass index, mobility, and education. RESULTS: At baseline, 705 participants (mean age 53.8 years) had no or low LBP and no or low-disability; 441 (62.6%) participants completed a 10-year follow-up. Of these, 37 (8.4%) developed high-intensity pain and/or high-disability. In multivariate analyses, participants with more negative back beliefs at baseline were more likely to develop high-intensity pain and/or high-disability (Odds ratio 1.05, 95% CI 1.00-1.11). Developing more negative back beliefs was also associated with incident high-intensity pain and/or high-disability (Odds Ratio 1.20, 95% CI 1.12-1.30). CONCLUSION: In a male community-based population, negative beliefs regarding the consequences of LBP were associated with an increased likelihood of developing high-intensity pain and/or high-disability. Addressing negative back beliefs in the community may reduce the incidence of high-intensity pain and/or high-disability over 10 years in men.

Functional outcomes following knee replacement in community-dwelling older adults.

BACKGROUND: Knee replacements are increasingly performed in older adults but uncertainty remains regarding their benefits in the context of age-related decline in physical function and other comorbidities. This study aimed to examine (1) the effect of knee replacement on functional outcomes in the context of age-related decline in physical function and (2) the factors associated with minimal important improvement in physical function after knee replacement in community-dwelling older adults aged ≥ 70 years. METHODS: This cohort study was performed within the ASPREE trial, with 889 participants undergoing knee replacement during the trial and 858 age- and sex-matched controls without knee or hip replacement identified from 16,703 Australian participants aged ≥ 70 years. Health-related quality of life was assessed annually using the SF-12, including its physical and mental component summary (PCS and MCS). Gait speed was measured biennially. Multiple linear regression and analysis of covariance were used to adjust for potential confounders. RESULTS: Participants with knee replacement had significantly lower pre- and post-replacement PCS scores and gait speed compared with age- and sex-matched controls. Participants with knee replacement had significant improvement in PCS score following knee replacement (mean change 3.6, 95% CI 2.9-4.3) while PCS score remaining unchanged in age- and sex-matched controls (-0.02, 95% CI -0.6 to 0.6) during follow-up period. The greatest improvements were observed for bodily pain and physical function. Following knee replacement, 53% of participants experienced minimal important improvement in PCS score (increased by ≥ 2.7), while 24% experienced worsened PCS score (reduced by > 2.7). Participants experiencing improved PCS score postoperatively had significantly lower PCS and higher MCS scores pre-surgery. CONCLUSIONS: Although community-based older adults experienced a significant improvement in PCS scores after knee replacement, their postoperative physical functional status remained significantly lower than age- and sex-matched controls. The degree of preoperative physical function impairment was a strong predictor of functional improvement, suggesting that this could be an important consideration when identifying older people most likely to benefit from knee replacement surgery.

Association between arthritis and cardiovascular risk factors in community-based adults: an opportunity to target cardiovascular risk.

BACKGROUND: Undertreated risk factors are major contributors to the burden of cardiovascular disease (CVD). Those with arthritis have an increased prevalence of CVD risk factors. CVD risk factors are often asymptomatic, which may be a barrier their treatment. Arthritis causes pain and immobility, and is a common reason for individuals to seek healthcare. Our aims were to (1) examine the relationship between arthritis and CVD risk factors in Australian adults, and (2) calculate the proportion of CVD risk factors that could be reduced if individuals with arthritis were targeted. METHODS: This cross-sectional study uses data from the 2017-18 Australian National Health Survey which included 13,776 participants, categorised into young (18-39 years), middle aged (40-64 years) and older (≥ 65 years) adults. Hypertension, height and weight were measured. Arthritis, dyslipidemia and diabetes were self-reported. The associations between arthritis and CVD risk factors were examined using logistic regression, and the population attributable fraction (PAF) of arthritis for each CVD risk factor was calculated. RESULTS: Arthritis was reported by 4.0% of young adults, 28.8% of middle-aged adults and 54.5% of older adults. Those with arthritis were at increased odds of obesity (2.07 fold in young, 1.75 fold in middle-aged and 1.89 fold in older adults), increased odds of diabetes (5.70 fold in young, 1.64 fold in middle-aged and 1.37 fold in older adults), increased odds of hypertension (2.72 fold in young, 1.78 fold in middle-aged and 1.48 fold in older adults) and an increased odds of dyslipidaemia (4.64 fold in young, 2.14 fold in middle-aged and 1.22 fold in older adults) compared to those without arthritis. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. The PAF of the presence of arthritis for having at least one CVD risk factor was 30.7% in middle-aged adults and 70.4% in older adults. CONCLUSION: Australian adults of all ages with arthritis are at increased odds of having CVD risk factors. For young and middle-aged adults, this increased odds remains significant even when adjusted for obesity. Presentation to healthcare practitioners with arthritis is an opportunity to screen for asymptomatic CVD risk factors with the potential of improving outcomes for both diseases. By adopting an approach of managing arthritis and CVD risk factors in parallel, rather than in silos, we could reduce the burden of CVD risk factors by 20-30%.

Antidepressants for hip and knee osteoarthritis.

BACKGROUND: Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has resulted in the investigation of medications affecting pain processing with central effects. Antidepressants contribute to pain management in other conditions where pain sensitisation is present. OBJECTIVES: To assess the benefits and harms of antidepressants for the treatment of symptomatic knee and hip osteoarthritis in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was January 2021. SELECTION CRITERIA: We included randomised controlled trials of adults with osteoarthritis that compared use of antidepressants to placebo or alternative comparator. We included trials that focused on efficacy (pain and function), treatment-related adverse effects and had documentation regarding discontinuation of participants. We excluded trials of less than six weeks of duration or had participants with concurrent mental health disorders. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Major outcomes were pain; responder rate; physical function; quality of life; and proportion of participants who withdrew due to adverse events, experienced any adverse events or had serious adverse events. Minor outcomes were proportion meeting the OARSI (Osteoarthritis Research Society International) Response Criteria, radiographic joint structure changes and proportion of participants who dropped out of the study for any reason. We used GRADE to assess certainty of evidence. MAIN RESULTS: Nine trials (2122 participants) met the inclusion criteria. Seven trials examined only knee osteoarthritis. Two also included participants with hip osteoarthritis. All trials compared antidepressants to placebo, with or without non-steroidal anti-inflammatory drugs. Trial sizes were 36 to 388 participants. Most participants were female, with mean ages of 54.5 to 65.9 years. Trial durations were 8 to 16 weeks. Six trials examined duloxetine. We combined data from nine trials in meta-analyses for knee and hip osteoarthritis. One trial was at low risk of bias in all domains. Five trials were at risk of attrition and reporting bias. High-certainty evidence found that antidepressants resulted in a clinically unimportant improvement in pain compared to placebo. Mean reduction in pain (0 to 10 scale, 0 = no pain) was 1.7 points with placebo and 2.3 points with antidepressants (mean difference (MD) -0.59, 95% confidence interval (CI) -0.88 to -0.31; 9 trials, 2122 participants). Clinical response was defined as achieving a 50% or greater reduction in 24-hour mean pain. High-certainty evidence demonstrated that 45% of participants receiving antidepressants had a clinical response compared to 28.6% receiving placebo (RR 1.55, 95% CI 1.32 to 1.82; 6 RCTs, 1904 participants). This corresponded to an absolute improvement in pain of 16% more responders with antidepressants (8.9% more to 26% more) and a number needed to treat for an additional beneficial effect (NNTB) of 6 (95% CI 4 to 11). High-certainty evidence showed that the mean improvement in function (on 0 to 100 Western Ontario and McMaster Universities Arthritis Index, 0 = best function) was 10.51 points with placebo and 16.16 points with antidepressants (MD -5.65 points, 95% CI -7.08 to -4.23; 6 RCTs, 1909 participants). This demonstrates a small, clinically unimportant response. Moderate-certainty evidence (downgraded for imprecision) showed that quality of life measured using the EuroQol 5-Dimension scale (-0.11 to 1.0, 1.0 = perfect health) improved by 0.07 points with placebo and 0.11 points with antidepressants (MD 0.04, 95% CI 0.01 to 0.07; 3 RCTs, 815 participants). This is clinically unimportant. High-certainty evidence showed that total adverse events increased in the antidepressant group (64%) compared to the placebo group (49%) (RR 1.27, 95% CI 1.15 to 1.41; 9 RCTs, 2102 participants). The number needed to treat for an additional harmful outcome (NNTH) was 7 (95% CI 5 to 11). Low-certainty evidence (downgraded twice for imprecision for very low numbers of events) found no evidence of a difference in serious adverse events between groups (RR 0.94, 95% CI 0.46 to 1.94; 9 RCTs, 2101 participants). The NNTH was 1000.  Moderate-certainty evidence (downgraded for imprecision) showed that 11% of participants receiving antidepressants withdrew from trials due to an adverse event compared to 5% receiving placebo (RR 2.15, 95% CI 1.56 to 2.97; 6 RCTs, 1977 participants). The NNTH was 17 (95% CI 10 to 35). AUTHORS' CONCLUSIONS: There is high-certainty evidence that use of antidepressants for knee osteoarthritis leads to a non-clinically important improvement in mean pain and function. However, a small number of people will have a 50% or greater important improvement in pain and function. This finding was consistent across all trials. Pain in osteoarthritis may be due to a variety of causes that differ between individuals. It may be that the cause of pain that responds to this therapy is only present in a small number of people. There is moderate-certainty evidence that antidepressants have a small positive effect on quality of life with heterogeneity between trials. High-certainty evidence indicates antidepressants result in more adverse events and moderate-certainty evidence indicates more withdrawal due to adverse events. There was little to no difference in serious adverse events (low-certainty evidence due to low numbers of events). This suggests that if antidepressants were being considered, there needs to be careful patient selection to optimise clinical benefit given the known propensity for adverse events with antidepressant use. Future trials should include alternative antidepressant agents or phenotyping of pain in people with osteoarthritis, or both.

Association between socioeconomic status and joint replacement of the hip and knee: a population-based cohort study of older adults in Tasmania.

BACKGROUND: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. AIM: To describe the association between SES and time to THR and TKR. METHODS: One thousand and seventy-two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area-level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group; and (ii) the cohort dichotomised at the quartile 1 cut-point. RESULTS: The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2-13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR; hazard ratio (HR): 0.56; 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90; 95% CI 0.53, 1.54). However, the former became non-significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. CONCLUSIONS: The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES.

Does aerobic exercise effect pain sensitisation in individuals with musculoskeletal pain? A systematic review.

BACKGROUND: Pain sensitisation plays a major role in musculoskeletal pain. However, effective treatments are limited, and although there is growing evidence that exercise may improve pain sensitisation, the amount and type of exercise remains unclear. This systematic review examines the evidence for an effect of aerobic exercise on pain sensitisation in musculoskeletal conditions. METHODS: Systematic searches of six electronic databases were conducted. Studies were included if they examined the relationship between aerobic physical activity and pain sensitisation in individuals with chronic musculoskeletal pain, but excluding specific patient subgroups such as fibromyalgia. Risk of bias was assessed using Cochrane methods and a qualitative analysis was conducted. RESULTS: Eleven studies (seven repeated measures studies and four clinical trials) of 590 participants were included. Eight studies had low to moderate risk of bias. All 11 studies found that aerobic exercise increased pressure pain thresholds or decreased pain ratings in those with musculoskeletal pain [median (minimum, maximum) improvement in pain sensitisation: 10.6% (2.2%, 24.1%)]. In these studies, the aerobic exercise involved walking or cycling, performed at a submaximal intensity but with incremental increases, for a 4-60 min duration. Improvement in pain sensitisation occurred after one session in the observational studies and after 2-12 weeks in the clinical trials. CONCLUSIONS: These findings provide evidence that aerobic exercise reduces pain sensitisation in individuals with musculoskeletal pain. Further work is needed to determine whether this translates to improved patient outcomes, including reduced disability and greater quality of life.

Efficacy of corticosteroids for hand osteoarthritis - a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is some evidence that corticosteroids may have a beneficial effect in hand osteoarthritis. We examined the efficacy of corticosteroids on symptoms and structural outcomes in hand osteoarthritis. METHODS: Ovid MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched from inception to October 2021 for randomized controlled trials investigating the efficacy of corticosteroids in hand osteoarthritis. Two authors independently screened records, extracted data, and assessed risk of bias using the RoB 2 tool. Standardized mean difference (SMD) or mean difference (MD) was calculated, and random-effects meta-analyses were performed. RESULTS: Of 13 included trials, 3 examined oral corticosteroids and clinical outcomes in any hand joints, 9 examined intra-articular injection of corticosteroids and clinical outcomes at the first carpometacarpal joint and one in the interphalangeal joints. In meta-analysis, oral corticosteroids reduced pain (SMD -0.53, 95% CI -0.79 to -0.28) and improved stiffness (MD -5.03, 95% CI -9.91 to -0.15; Australian Canadian Osteoarthritis Hand Index stiffness subscale) and function (SMD -0.37, 95% CI -0.63 to -0.12) at 4-6 weeks. However, there was no significant persistent effect on pain and function at 3 months which was 6-8 weeks after study medication was stopped. There was no significant effect of intra-articular corticosteroids on pain or function at 4-6 weeks or over 3-12 months in first carpometacarpal osteoarthritis. Two trials evaluated joint structure at 4-6 weeks: one study showed oral corticosteroids reduced synovial thickening, neither showed an effect on synovitis. CONCLUSIONS: There was low-certainty evidence for a medium effect of oral corticosteroids on pain relief and stiffness improvement and small-to-medium effect on functional improvement at 4-6 weeks, with no significant effect for intra-articular corticosteroids. Corticosteroids had no significant effect on any outcomes over longer term (3-12 months) off treatment. No trials examined the effect of corticosteroids on disease progression. The role of corticosteroids in hand osteoarthritis is limited.

Smartphone-Based Ecological Momentary Assessment for Collecting Pain and Function Data for Those with Low Back Pain.

Smartphone-based ecological momentary assessment (EMA) methods are widely used for data collection and monitoring in healthcare but their uptake clinically has been limited. Low back pain, a condition with limited effective treatments, has the potential to benefit from EMA. This study aimed to (i) determine the feasibility of collecting pain and function data using smartphone-based EMA, (ii) examine pain data collected using EMA compared to traditional methods, (iii) characterize individuals' progress in relation to pain and function, and (iv) investigate the appropriation of the method. Our results showed that an individual's 'pain intensity index' provided a measure of the burden of their low back pain, which differed from but complemented traditional 'change in pain intensity' measures. We found significant variations in the pain and function over the course of an individual's back pain that was not captured by the cohort's mean scores, the approach currently used as the gold standard in clinical trials. The EMA method was highly acceptable to the participants, and the Model of Technology Appropriation provided information on technology adoption. This study highlights the potential of the smartphone-based EMA method for enhancing the collection of outcome data and providing a personalized approach to the management of low back pain.

METHODS - A randomised controlled trial of METhotrexate to treat Hand Osteoarthritis with Synovitis: study protocol for a randomised controlled trial.

BACKGROUND: Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis. METHODS: Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. DISCUSSION: This study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124.

Person-centred care in osteoarthritis and inflammatory arthritis: a scoping review of people's needs outside of healthcare.

BACKGROUND: Arthritis, regardless of cause, has significant physical, social and psychological impacts on patients. We aimed to identify the non-healthcare needs perceived by patients with inflammatory arthritis (IA) and osteoarthritis (OA), and to determine if these differ. METHODS: We electronically searched MEDLINE, PsycINFO, EMBASE and CINAHL (1990-2020) systematically to identify non-healthcare-related needs of people with IA or OA. All citations were screened and quality appraised by two reviewers. Data was extracted by a single reviewer. RESULTS: The search identified 7853 citations, with 31 studies included (12 for OA, 20 for IA). Six areas of need emerged and these were similar in both group These were: 1) Assistance with activities of daily living especially related to a lack of independence; 2) Social connectedness: need for social participation; 3) Financial security: worry about financial security and increased costs of health-seeking behaviours; 4) Occupational needs: desire to continue work for financial and social reasons, facilitated by flexibility of workplace conditions/environment; 5) Exercise and leisure: including limitation due to pain; 6) Transportation: limitations in ability to drive and take public transport due to mobility concerns. Many areas of need were linked; e.g. loss of employment and requiring support from family was associated with a sense of "failure" and loss of identity, as social isolation. CONCLUSIONS: This review highlights the pervasive impact of arthritis on peoples' lives, regardless of aetiology, albeit with a limited evidence base. Improved identification and targeting of non-healthcare needs of people with arthritis is likely to improve person-centred care.

Topical corticosteroid for treatment of hand osteoarthritis: study protocol for a randomised controlled trial.

BACKGROUND: Hand osteoarthritis is a common and disabling chronic joint disease with a lack of effective therapies. Emerging evidence suggests the role of local inflammation in causing pain in hand osteoarthritis. Corticosteroids are potent anti-inflammatory drugs used in many rheumatic diseases. The aim of this randomised, double-blind, placebo-controlled trial is to determine whether topical corticosteroid reduces pain over 6 weeks in patients with hand osteoarthritis. METHODS: One hundred participants with hand osteoarthritis will be recruited from the community in Melbourne, Australia, and randomly allocated in a 1:1 ratio to receive either topical Diprosone OV or placebo ointment administered 3 times daily on the painful hand joints for 6 weeks. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 weeks. The secondary outcomes include changes in pain and function assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Michigan Hand Outcomes Questionnaire, and tender and swollen joint count at 6 weeks. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. DISCUSSION: This study will provide high-quality evidence to determine whether topical corticosteroid reduces pain over 6 weeks in patients with hand osteoarthritis, with major clinical and public health importance by informing clinical practice guidelines for the management of hand osteoarthritis and reducing the burden of the disabling disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12620000599976 . Registered 22 May 2020.

Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double blind, placebo-controlled trial.

BACKGROUND: Knee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo. METHODS/DESIGN: One hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done. DISCUSSION: This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry prior to recruitment commencing ( ACTRN12615000301561 , March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.

Association between circulating 25-hydroxyvitamin D concentrations and hip replacement for osteoarthritis: a prospective cohort study.

BACKGROUND: To examine the association between circulating 25(OH)D concentrations and incidence of total hip replacement for osteoarthritis in a prospective cohort study. METHODS: This study examined a random sample of 2651 participants in the Melbourne Collaborative Cohort Study who had 25(OH)D concentrations measured from dried blood spots collected in 1990-1994. Participants who underwent total hip replacement for osteoarthritis between January 2001 and December 2018 were identified by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total hip replacement for osteoarthritis in relation to 25(OH)D concentrations, adjusted for confounders. RESULTS: Eighty-six men and eighty-seven women had a total hip replacement for osteoarthritis. Compared with men in the lowest (1st) quartile of 25(OH)D concentration, the HR for total hip replacement was 2.32 (95% CI 1.05, 5.13) for those in the 2nd quartile, 2.77 (95% CI 1.28, 6.00) for those in the 3rd quartile, and 1.73 (95% CI 0.75, 4.02) for those in the highest quartile of 25(OH)D concentrations (p for trend 0.02). There was little evidence of an association in women. CONCLUSIONS: Higher circulating 25(OH)D concentrations were associated with an increased risk of total hip replacement for osteoarthritis in men but not in women. Although the underlying mechanism warrants further investigation, our findings highlight the need to determine the optimal levels of circulating 25(OH)D to reduce the risk of hip osteoarthritis.

Association between clusters of back and joint pain with opioid use in middle-aged community-based women: a prospective cohort study.

BACKGROUND: To determine the relationship between clusters of back pain and joint pain and prescription opioid dispensing. METHODS: Of 11,221 middle-aged participants from the Australian Longitudinal Study of Women's Health, clusters of back pain and joint pain from 2001 to 2013 were identified using group-based trajectory modelling. Prescription opioid dispensing from 2003 to 2015 was identified by linking the cohort to Pharmaceutical Benefit Scheme dispensing data. Multinomial logistic regression was used to examine the association between back pain and joint pain clusters and dispensing of prescription opioids. The proportion of opioids dispensed in the population attributable to back and join pain was calculated. RESULTS: Over 12 years, 68.5 and 72.0% women reported frequent or persistent back pain and joint pain, respectively. There were three clusters ('none or infrequent', 'frequent' and 'persistent') for both back pain and joint pain. Those in the persistent back pain cluster had a 6.33 (95%CI 4.38-9.16) times increased risk of having > 50 opioid prescriptions and those in persistent joint pain cluster had a 6.19 (95%CI 4.18-9.16) times increased risk of having > 50 opioid prescriptions. Frequent and persistent back and joint pain clusters together explained 41.7% (95%CI 34.9-47.8%) of prescription opioid dispensing. Women in the frequent and persistent back pain and joint pain clusters were less educated and reported more depression and physical inactivity. CONCLUSION: Back pain and joint pain are major contributors to opioid prescription dispensing in community-based middle-aged women. Additional approaches to reduce opioid use, targeted at those with frequent and persistent back pain and joint pain, will be important in order to reduce the use of opioids and their consequent harm in this population.

Patellar cartilage increase following ACL reconstruction with and without meniscal pathology: a two-year prospective MRI morphological study.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) together with concomitant meniscal injury are risk factors for the development of tibiofemoral (TF) osteoarthritis (OA), but the potential effect on the patellofemoral (PF) joint is unclear. The aim of this study was to: (i) investigate change in patellar cartilage morphology in individuals 2.5 to 4.5 years after ACLR with or without concomitant meniscal pathology and in healthy controls, and (ii) examine the association between baseline patellar cartilage defects and patellar cartilage volume change. METHODS: Thirty two isolated ACLR participants, 25 ACLR participants with combined meniscal pathology and nine healthy controls underwent knee magnetic resonance imaging (MRI) with 2-year intervals (baseline = 2.5 years post-ACLR). Patellar cartilage volume and cartilage defects were assessed from MRI using validated methods. RESULTS: Both ACLR groups showed patellar cartilage volume increased over 2 years (p < 0.05), and isolated ACLR group had greater annual percentage cartilage volume increase compared with controls (mean difference 3.6, 95% confidence interval (CI) 1.0, 6.3%, p = 0.008) and combined ACLR group (mean difference 2.2, 95% CI 0.2, 4.2%, p = 0.028). Patellar cartilage defects regressed in the isolated ACLR group over 2 years (p = 0.02; Z = - 2.33; r = 0.3). Baseline patellar cartilage defect score was positively associated with annual percentage cartilage volume increase (Regression coefficient B = 0.014; 95% CI 0.001, 0.027; p = 0.03) in the pooled ACLR participants. CONCLUSIONS: Hypertrophic response was evident in the patellar cartilage of ACLR participants with and without meniscal pathology. Surprisingly, the increase in patellar cartilage volume was more pronounced in those with isolated ACLR. Although cartilage defects stabilised in the majority of ACLR participants, the severity of patellar cartilage defects at baseline influenced the magnitude of the cartilage hypertrophic response over the subsequent ~ 2 years.

Evaluation of the Pain Impact Index for Community-Dwelling Older Adults Through the Application of Rasch Modelling.

OBJECTIVE: Evaluate the Pain Impact Index, a simple, brief, easy-to-use, and novel tool to assess the impact of chronic pain in community-dwelling older adults. METHODS: A Rasch modelling analysis was undertaken in Stata using a partial credit model suited to the Likert-type items that comprised the Index. The Index was evaluated for ordering of category thresholds, unidimensionality, overall fit to the Rasch model, measurement bias (Differential Item Functioning, DIF), targeting, and construct validity. RESULTS: The four-item Pain Impact Index was self-completed by 6454 community-dwelling Australians who were aged at least 70 years and experienced pain on most days. Two items showed evidence of threshold disordering, and this was resolved by collapsing response categories (from 5 to 3) for all items. The rescored Index conformed to the unidimensionality assumption and had satisfactory fit with the Rasch model (analyses conducted on a reduced sample size to mitigate the potential for overpowering: n = 377, P > 0.0125, power > 77%). When considering uniform DIF, the most frequent sources of measurement bias were age, knee pain, and upper back pain. When considering nonuniform DIF, the most frequent source of measurement bias was knee pain. The Index had good ability to differentiate between respondents with different levels of pain impact and had highest measurement precision for respondents located around the average level of pain impact in the study sample. Both convergent and discriminant validity of the Index were supported. CONCLUSION: The Pain Impact Index showed evidence of unidimensionality, was able to successfully differentiate between levels of pain impact, and had good evidence of construct validity.