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The objectives of this study are to ascertain the determinants of quality of life (QoL) and hand function among persons with hand osteoarthritis (OA) and to assess the influence of hand function on QoL among persons with OA.Two hundred and four participants in a clinical trial completed the baseline assessment. Demographic, socioeconomic, QoL (AqoL-4D), hand function (Functional Index for Hand Osteoarthritis, FIHOA), pain assessment, radiographic and clinical characteristics of participants were measured using standard methods. Univariate and multivariate analyses were performed to evaluate potential associations.We studied 204 participants (76% female, age 65.63 ± 8.13 years, body mass index 28.7 ± 6.5 kg/mThe results indicate increasing impairment in hand function decreases the QoL of persons with hand OA. Some determinants were significantly associated with hand function and QoL. Determinants related to hand functions may be modifiable. In future, appropriate intervention strategies should be implemented, and further studies should be conducted to identify the effectiveness of those interventions.

Background Thumb osteoarthritis (OA) is a common and disabling condition. Adherence to prescribed conservative interventions may affect outcomes of thumb OA trials. Purpose The aim of the study was to determine whether baseline pain and hand function is associated with treatment adherence over 12 weeks in participants with thumb base OA. Study design Observational cohort study nested within a randomized-controlled trial. Methods Ninety-four participants from the intervention group were included in the analysis. Baseline pain and function were assessed using a 100 mm Visual Analogue Scale and the Functional Index for Hand Osteoarthritis questionnaire (0-30), respectively. Participants received a combination of treatments including education, orthosis, hand exercises, and topical anti–inflammatory gel. Adherence was measured using a daily self-reported diary. Participants were classified as non–adherent, partially adherent or fully adherent if they completed none, 1 and/or 2 or all 3 of the interventions as prescribed. Ordinal logistic regression modelling was performed. Results At 12-week follow-up, half of the participants were fully adherent to the treatments (n = 46, 48.9%), 30.9% of participants were partially adherent (n = 29) and 20.2% were non–adherent (n = 19, 20.2%). High baseline pain was a significantly associated with better adherence in the unadjusted model [OR = 3.15, 95% CI (1.18, 8.42)] and adjusted model [OR = 3.20, 95% CI (1.13, 8.20)]. Baseline function was not associated with adherence [OR = 1.03, 95% CI (0.47, 2.23)]. Conclusion High baseline pain was associated with better adherence in participants with thumb base OA. Higher baseline functional impairment was not associated with better adherence.

To determine the optimal combination of imaging and biochemical biomarkers for use in the prediction of knee osteoarthritis (OA) progression.The present study was a nested case-control trial from the Foundation of the National Institutes of Health OA Biomarkers Consortium that assessed study participants with a Kellgren/Lawrence grade of 1-3 who had complete biomarker data available (n = 539 to 550). Cases were participants' knees that had radiographic and pain progression between 24 and 48 months compared to baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) that had a P value of0.10 in univariate analysis were selected, including quantitative cartilage thickness and volume on magnetic resonance imaging (MRI), semiquantitative MRI markers, bone shape and area, quantitative meniscal volume, radiographic progression (trabecular bone texture [TBT]), and serum and/or urine biochemical markers. Multivariable logistic regression models were built using 3 different stepwise selection methods (complex models versus parsimonious models).Among baseline biomarkers, the number of locations affected by osteophytes (semiquantitative), quantitative central medial femoral and central lateral femoral cartilage thickness, patellar bone shape, and semiquantitative Hoffa-synovitis predicted OA progression in most models (C statistic 0.641-0.671). In most models, 24-month changes in semiquantitative MRI markers (effusion-synovitis, meniscal morphologic changes, and cartilage damage), quantitative central medial femoral cartilage thickness, quantitative medial tibial cartilage volume, quantitative lateral patellofemoral bone area, horizontal TBT (intercept term), and urine N-telopeptide of type I collagen predicted OA progression (C statistic 0.680-0.724). A different combination of imaging and biochemical biomarkers (baseline and 24-month change) predicted radiographic progression only, which had a higher C statistic of 0.716-0.832.The present study highlights the combination of biomarkers with potential prognostic utility in OA disease-modifying trials. Properly qualified, these biomarkers could be used to enrich future trials with participants likely to experience progression of knee OA.

Summary Objective To investigate heterogeneous effects of a combination of conservative therapies compared with an education comparator for thumb base (TB) osteoarthritis (OA) according to clinically relevant characteristics. Methods Pre-planned subgroup analysis of the COMBO trial (n = 204) which compared a combination of education on self-management and ergonomic principles, a prefabricated neoprene splint, hand exercises, and diclofenac sodium gel, with education alone for radiographic and symptomatic TB OA. Primary outcomes were change in pain (visual analogue scale [VAS], 0–100 mm) and hand function (Functional Index for Hand Osteoarthritis questionnaire, 0–30) from baseline to week-6. Other outcomes were grip and tip-pinch strength and patient's global assessment (PGA) (VAS, 0–100 mm). Possible treatment effect modifiers were the presence of interphalangeal joint pain, erosive hand OA, radiographic thumb carpometacarpal joint subluxation (higher vs equal or lower than the sample mean), and baseline radiographic OA severity (Kellgren Lawrence grade). Linear regression models were fitted, adding interaction terms for each subgroup of interest. Results The treatment effects of the combined intervention at 6 weeks were greater in participants with lower joint subluxation compared with those with greater subluxation (pain −11.6 [95%CI −22.2, −9.9] and 2.6 [−5.5, 10.7], respectively, difference between the subluxation groups 14.2 units (95% CI 2.3, 26.1), p-value 0.02; and PGA −14.0 [−22.4, −5.5] and 1.5 [−6.2, 9.3), respectively, difference between the subluxation groups 15.5 units (95% CI 4.2, 26.8), p-value 0.03). There was no statistically significant heterogeneity for the other subgroups. Conclusion A combination of conservative therapies may provide greater benefits over 6 weeks in individuals with lower joint subluxation, although the clinical relevance is uncertain given the wide confidence intervals. Treatment strategies may need to be customized for those with greater joint subluxation. Trial registration number ACTRN 12616000353493.

Introduction Due to the complex shape of the carpometacarpal (CMC) joint, a fixed joint collapse deformity of the thumb CMC (CMC1) and metacarpophalangeal (MCP1) joint can present in advanced stages of CMC1 osteoarthritis (OA), resulting in adduction of the first metacarpal (MC1) and hyperextension of the MCP1. Purpose of the Study To determine whether joint collapse deformity is associated with worse pain and/or functional impairment. Study Design Cross-sectional. Methods This study used the baseline data from 140 patients enrolled in a longitudinal study of treatment for CMC1 OA. (efficacy of combined conservative therapies on clinical outcomes in patients with CMC1 OA). Joint collapse was determined at baseline using a pinch gauge. Pain was assessed on a visual analog scale (0-100) and function was assessed using the Functional Index for Hand Osteoarthritis questionnaire (0-30). Pain and function and the presence of joint collapse were entered in a univariate logistic regression. The final adjusted model for pain and joint collapse included age and sex. The final adjusted model for function and joint collapse included Kellgren Lawrence grade and grip strength. Results About 20% of participants demonstrated joint collapse on the tip-pinch test. The presence of joint collapse was associated with increased pain in the unadjusted [P = .047, OR = 2.45, 95% CI (1.01, 5.910)] and adjusted model [P = .049, OR = 2.45, 95% CI (1.00, 5.98)]. Conclusion CMC1 patients with joint collapse reported increased pain compared with those without joint collapse. Future studies should determine the relationship between thumb hypermobility and joint collapse and how to manage these conditions effectively.

Objective To test the effectiveness of a 32-week, stepped-care intervention on disease remission rates in overweight and obese patients with medial tibiofemoral osteoarthritis (OA) compared to controls. Methods In this randomized controlled trial, eligible participants were ≥50 years of age with a body mass index of ≥28 kg/m2 and radiographic evidence of medial tibiofemoral OA. Participants were randomized to stepped-care (n = 87) or control group (n = 84). The stepped-care group received a 2-step intervention. The first step consisted of an 18-week diet and exercise program. The second step consisted of 4 treatment subgroups: 1) diet and exercise maintenance; 2) cognitive-behavioral therapy; 3) unloader knee brace; and 4) muscle strengthening exercises. Allocation into subgroups was based on disease remission state and clinical characteristics. The primary end point was the disease remission rate (yes/no) at 32 weeks, which was reached when participants achieved the Patient Acceptable Symptom State cutoff value for pain and for the patient global assessment of disease activity and/or functional impairment. Results Disease remission at 32 weeks was achieved by 18 of 68 (26%) in the control group and 32 of 82 (39%) in the stepped-care group (difference 12.6% [95% confidence interval -2.3, 27.4], P = 0.10). The stepped-care group showed an improvement in pain and function between baseline and 20 weeks. While functional improvement was maintained at 32 weeks, pain levels tended to get worse between weeks 20 and 32. Conclusion The proposed intervention did not promote a significant difference in the rate of disease remission in comparison to the control group for overweight or obese patients with medial tibiofemoral OA.

ObjectivesTo evaluate the association between psychological factors and pain exacerbations in people with hip OA.MethodsEligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10 days over a 90-day follow-up period. In addition, they were required to complete the questionnaire whenever they perceived they were experiencing a hip pain exacerbation. Hip pain exacerbation was defined as an increase of 2 points in pain intensity compared with baseline on an 11-point numeric rating scale (0–10). The Depression, Anxiety and Stress Scale–21 Items, Positive and Negative Affect Schedule, Pain Catastrophizing Scale and Pain Self-Efficacy Questionnaire were used to evaluate psychological factors. The associations of these with risk of hip pain exacerbation were examined by conditional logistic regression.ResultsOf 252 participants recruited, 131 (52.0%) contributed both case and control period data and were included in the analysis. A significant association was found between Pain Catastrophizing Scale overall score (1 point increase) with hip pain exacerbations (odds ratio: 1.07, 95% CI: 1.04, 1.11). An increase of a minimal important change (5.5 points) of Pain Self-Efficacy Questionnaire score was associated with a lower odds of pain exacerbations (odds ratio: 0.74, 95% CI: 0.65, 0.85). No significant associations were found between Depression, Anxiety and Stress Scale–21 Items or Positive and Negative Affect Schedule scores with hip pain exacerbations.ConclusionBoth pain catastrophizing and pain self-efficacy beliefs were associated with pain exacerbations in people with hip OA, but other psychological factors including depression, anxiety and stress or positive and negative affects, were not associated with pain exacerbations.

Summary Objective To investigate whether baseline cartilage thickness and its longitudinal change are associated with incident widespread full-thickness cartilage loss (wsFTCL) in knee osteoarthritis, and whether there are optimal cut-off values for predicting wsFTCL. Methods Central medial tibial (cMT) and femoral (cMF) cartilage were assessed using quantitative magnetic resonance imaging data from the Osteoarthritis Initiative cohort (N = 600 knees). Cartilage thickness was measured at baseline and 12 months. wsFTCL was defined semi-quantitatively (scores 2 and 3 from the MRI Osteoarthritis Knee Score) and its incidence at 24 months recorded. Logistic regression was used to determine the odds of developing wsFTCL for baseline and for each 0.1 mm decrease in cartilage thickness. Cut-off values were investigated using the minimal-p method and area under the Receiver Operating Characteristic curves (AUC). Results Incident wsFTCL was observed in 66 (12%) and 73 (14%) knees in cMT and cMF, respectively. Lower baseline cMT and cMF cartilage thickness values were associated with wsFTCL (OR = 1.20; 95% CI: 1.11, 1.28 and OR = 1.15; 95% CI: 1.06 to 1.24, respectively). Optimal cut-off AUCs for the tibia and femur were 0.64 (0.57–0.70) and 0.63 (0.57–0.69), respectively. Longitudinal decrease in femoral, but not tibial, cartilage thickness was associated with incident wsFTCL (OR = 1.77; 95% CI: 1.30 to 2.40); optimal cut-off AUC 0.65 (95% CI: 0.58–0.72). Conclusion Lower baseline cMT and baseline/change (decrease) over 12 months in cMF cartilage thickness were associated with incident, location-specific, wsFTCL at 24 months. Optimal cut-off values were relatively low and of uncertain utility for predicting incident wsFTCL.

Objective Hand osteoarthritis (OA) trials often target exclusively the thumb base joint, although concomitant widespread interphalangeal (IP) joint involvement is frequent. We aimed to compare hand strength and function between individuals with isolated thumb base OA and those with coexistent IP joint pain and erosive OA. Methods Baseline data from a thumb base OA trial were analyzed (n = 204). Participants were age ≥40 years with symptomatic and radiographic thumb base OA. Only the index hand was included. Self-reported IP joint pain (in any proximal, distal, or thumb IP joint), hand function score (Functional Index for Hand Osteoarthritis questionnaire [range 0-30]), and hand grip and tip-pinch strength test results were obtained at baseline. Radiographs were scored for OA severity at each joint (Kellgren/Lawrence grade) and for the presence of erosive OA at the thumb base or IP joints. Multiple linear regression was used adjusting for age, sex, body mass index, and radiographic thumb base OA severity. Results Compared to individuals with isolated thumb base OA (62%), those with concomitant IP joint pain (17%) and erosive OA (21%) had significantly worse hand function (β = 1.82 [95% confidence interval (95% CI) 0.36, 3.28] and β = 1.47 [95% CI 0.74, 2.88], respectively). In addition, coexistence of erosive OA was independently associated with lower grip and tip-pinch strength (β = -5.14 [95% CI -7.58, -2.70] and β = -0.61 [95% CI -1.05, -0.17], respectively). Conclusion Concomitant IP joint pain and erosive OA are associated with worse hand function in individuals with thumb base OA. Patient stratification based on these characteristics may improve the design of future thumb base OA trials.

This article is part of the Osteoarthritis issue for the Clinics in Geriatric Medicine journal. It covers the main aspects related to research and clinical practice of osteoarthritis phenotyping, including the concepts, the rationale for studies of OA phenotypes and their history, the approaches to OA phenotyping, recent advances in this area, and future directions.

IntroductionKnee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months.Methods and analysisThe Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat.Ethics and disseminationThis protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications.Trial registration numbersAustralian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897.

Aim To investigate the associations of ultrasound and radiographic features of thumb-base osteoarthritis (OA) with thumb-base pain and hand function at baseline and 12 weeks. Method Data from a randomized controlled trial conducted in participants with symptomatic radiographic thumb-base OA were analyzed. Participants who finished follow up were included in this secondary analysis. Pain and hand function were assessed using self-reported measures. All participants underwent ultrasound examinations for synovitis, power Doppler signal (PDS), and osteophytes, and underwent radiography for osteophytes, joint space narrowing (JSN), and subchondral bone sclerosis at baseline. Hand pain and function were reassessed after the 12-week follow up. The associations of ultrasound and radiographic findings with clinical features were further evaluated, using linear regression analyses, after adjustment for relevant confounding factors. Results A total of 166 participants (average age 66.2 years; 76.5% female) were included. At baseline, radiographic JSN and subchondral bone sclerosis were associated with hand function. There was a significant association between ultrasound-detected PDS and patient's global assessment (PGA) at baseline. Baseline radiographic JSN was significantly associated with the changes in stiffness and PGA from baseline to 12 weeks. There was no association between ultrasound features and changes in the clinical outcomes over 12 weeks. Conclusion This study indicates that radiographic features significantly correlate with hand function, and ultrasound PDS is closely related to the PGA at baseline in thumb-base OA. Radiographic JSN may be a predictor for stiffness and PGA in thumb-base OA.

AIMS: To determine: 1) inter-rater reliability of quantitative measurements of ultrasound-detected synovitis, meniscal extrusion, and osteophytes; and 2) construct (convergent) validity via correlations and absolute agreements between ultrasound- and gold-standard magnetic resonance imaging (MRI)-outcomes in knee osteoarthritis. METHODS: Dynamic ultrasound images for supra-patellar synovitis, meniscal extrusion, and osteophytes were acquired and quantified by a physician operator, musculoskeletal ultrasonographer, and medical student independently. On the same day, 3T MRI images were acquired. Effusion-synovitis, meniscal extrusion, and osteophytes were quantified on sagittal or coronal proton-density-weighted fat-suppressed noncontrast TSE sequences, respectively. Intra-class correlation coefficients (ICCs), Pearson's correlations (r), and Bland-Altman plots were used to analyze inter-rater reliability, and correlations, and agreements between the two imaging modalities. RESULTS: Eighty-nine participants [48 females (53.9%)] with mean (standard deviation) age of 61.5 ± 6.9 years were included. The inter-rater reliability was excellent for osteophytes (ICC range = 0.90-0.96), meniscal extrusion (ICC range = 0.90-0.93), and synovitis (ICC range = 0.86-0.88). The correlations between ultrasound pathologies and their MRI counterparts were very strong (ICC range = 0.85-0.98) except for lateral meniscal extrusion [0.66 (95% CI, 0.52-0.76)]. Bland-Altman plots showed 0.01, 0.05, 0.10, 0.53, and 0.60 mm larger size in ultrasound medial tibial and medial femoral osteophytes, medial meniscal extrusions, synovitis, and lateral meniscal extrusions with 95% limits of agreements [±0.39, ±0.44, ±0.85, ±0.70, and ±0.90 (SDs)] than MRI measures, respectively. The lines of equality were within 95% CI of the mean differences (bias) only for medial osteophytes and medial meniscal extrusion. CONCLUSION: The quantitative assessment of synovitis, meniscal extrusion, and osteophytes generally showed excellent inter-rater reliability and strong correlations with MRI-based measurements. Absolute agreement was strong for medial tibiofemoral pathologies.

OBJECTIVE To evaluate the association between hip injury/giving way and hip pain exacerbations in patients with symptomatic hip osteoarthritis (OA). METHODS We conducted an internet-based case-crossover study to assess hip injury and giving way for hip pain exacerbation. Eligible participants with symptomatic hip OA were followed up for 90 days and asked to complete online questionnaires at baseline and 10-day intervals (control periods). They also logged on to the study web site to complete questionnaires for an episode of a hip pain exacerbation (case periods) defined as an increase of 2 points in pain intensity compared with the baseline rating on a numeric rating scale (range 0-10). The relationship of hip injury and giving way to the risk of pain exacerbation was examined using conditional logistic regression. RESULTS Of 252 patients recruited into the study, we included 133 patients (53%) who provided data from both case and control periods. Hip injury during the last 7 days increased the risk of hip pain exacerbation (odds ratio [OR] 2.74 [95% confidence interval (95% CI) 1.62-4.62]). The hip giving way during the last 2 days was associated with an increased risk of hip pain exacerbation (OR 2.10 [95% CI 1.30-3.39]) and showed a significant relationship between the number of hip giving way events and the risk of hip pain exacerbations (P < 0.001). CONCLUSION Hip injury and episodes of the hip giving way were significantly related to pain exacerbation in patients with symptomatic hip OA. Methods to prevent exposure to injury may help to reduce the burden of pain in patients with hip OA.

Objective.To evaluate the association of sleep quality, sleep duration, and fatigue with hip pain exacerbations in persons with symptomatic hip osteoarthritis (OA).Methods.Participants (n = 252) were followed for 90 days and asked to complete online questionnaires at 10-day intervals (control periods). A hip pain exacerbation (case periods) was defined as an increase of 2 points in pain intensity compared with baseline on a numeric rating scale (0–10). Subjective sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index, and fatigue was measured by Multidimensional Assessment of Fatigue in both periods. Univariable and multivariable conditional logistic regressions were used to assess the association.Results.Of the 252 participants, 130 (52%) were included in the final analysis. Univariate association analysis showed that both poor sleep quality and greater fatigue were associated with increased odds of pain exacerbations (OR 1.72, 95% CI 1.04–2.86; OR 1.92, 95% CI 1.21–3.05, respectively). Short sleep duration was not associated with pain exacerbations. Poor sleep quality and greater fatigue remained associated with pain exacerbations after adjustment for physical activity and night pain levels in multivariable analysis. There was no significant interaction between sleep quality and fatigue (p = 0.21).Conclusion.Poor sleep quality and greater fatigue were related to pain exacerbation in persons with symptomatic hip OA. Sleep disorders and fatigue should be considered when dealing with pain exacerbations.

Background Platelet-rich plasma (PRP) has a still conflicting efficacy for knee osteoarthritis (KOA) and might be a minimally invasive and safe treatment alternative. The potential benefit of only plasma (non-enriched) has never been investigated. Our aim was to evaluate the efficacy of intra-articular platelet-rich plasma (PRP) and plasma to improve pain and function in participants with KOA over 24 weeks. Methods Randomized, double-blind, placebo-controlled trial with 3 groups (n = 62): PRP (n = 20), plasma (n = 21) and saline (n = 21). Two ultrasound-guided knee injections were performed with a 2-week interval. The primary outcome was visual analog scale 0-10 cm (VAS) for overall pain at week 24, with intermediate assessments at weeks 6 and 12. Main secondary outcomes were: KOOS, OMERACT-OARSI criteria and TUGT. Results At baseline, 92% of participants were female, with a mean age of 65 years, mean BMI of 28.0 Kg/m2and mean VAS pain of 6.2 cm. Change in pain from baseline at week 24 were -2.9 (SD 2.5), -2.4 (SD 2.5) and -3.5 cm (SD 3.3) for PRP, plasma and saline, respectively (p intergroup = 0.499). There were no differences between the three groups at weeks 6 and 12. Similarly, there were no differences between groups regarding secondary outcomes. The PRP group showed higher frequency of adverse events (65% versus 24% and 33% for plasma and saline, respectively, p = 0.02), mostly mild transitory increase in pain. Conclusions PRP and plasma were not superior to placebo for pain and function improvement in KOA over 24 weeks. The PRP group had a higher frequency of mild transitory increase in pain. Trial registration ClinicalTrials.gov, NCT03138317, 03/05/2017.

Summary Objective The RADIANT study aimed to investigate the efficacy and safety of a complementary medicine supplement combination in people with hand osteoarthritis (HOA). Method This was an internet-based, double-blind, randomised, placebo-controlled trial. Participants aged over 40 years with symptomatic HOA with radiographic confirmation (Kellgren Lawrence grade ≥ 2) throughout Australia were recruited and randomly assigned (1:1) to receive either a supplement combination composed of Boswellia serrata extract 250 mg/day, pine bark extract 100 mg/day, methylsulfonylmethane 1,500 mg/day and curcumin 168 mg/day or placebo for 12 weeks. The primary outcome was change in hand pain assessed using a visual analogue scale (VAS 0–100) from baseline to week 12. A range of secondary outcomes and additional measures were recorded. Adverse events were monitored weekly. Results One hundred and six participants were included with mean age 65.6 years and 81% were women. 45% of the participants were graded as KLG 4, 40% KLG three and 39 (37%) had erosive OA. There was no significant difference in pain VAS reduction between groups. The adjusted between group difference in means (95%CI) was 5.34 (−2.39 to 13.07). Five participants (10%) in the supplement combination group discontinued study treatment due to AE vs four participants (7%) in the placebo group. Conclusion There were no significant differences in symptomatic relief between the two groups over 12 weeks. These findings do not support the use of the supplement combination for treating hand pain in people with HOA. Registration Prospectively registered (Australian New Zealand Clinical Trials Registry ACTRN12619000835145, 31/05/2019).

Objectives: Our objective was to evaluate the association of weather factors with the risk of pain exacerbations in people with symptomatic hip osteoarthritis (OA). Method: Eligible participants with symptomatic hip OA were instructed to log on to the study website and complete questionnaires every 10 days and additionally whenever they considered they were experiencing a pain exacerbation (case period) during the 90 day follow-up. Pain exacerbation was defined as an increase of two points in pain intensity on an 11-point numeric rating scale (0-10) during the follow-up compared with baseline. Each case period was anchored to four control periods within a 35 day interval using a time-stratified approach. Weather data were obtained for both periods from the publicly available meteorological database of the Australian Bureau of Meteorology. We examined the association of weather factors across 72 h before the index date with the risk of pain exacerbation, using conditional logistic regression. Results: Among 252 participants recruited, 129 participants had at least one episode of pain exacerbation and were included in the analysis. A significant dose-response relationship was found between average daily temperature variation in the prior 72 h and risk of pain exacerbations (p = 0.04 for linear trend). There was no significant association between maximum daily temperature, minimum daily temperature, relative humidity, precipitation, or barometric pressure and hip pain exacerbations. Conclusion: The overall results suggest that only daily temperature variation among different weather factors was associated with hip pain exacerbations in people with symptomatic hip OA.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of telerehabilitation for patients with OA of the knee or hip.

The etiology of osteoarthritis (OA) pain exacerbations is not well understood. The purpose of this study is to evaluate the association of heel height and duration of wearing shoes with higher heels with pain exacerbations in people with hip OA. Eligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10 days over a 90-day follow-up period. They were required to complete the questionnaire whenever they were experiencing hip pain exacerbation. Of 252 participants recruited, 137 (54.4%) contributed both case and control period data, and were included in the analysis. Wearing shoes with a heel height &ge, 2.5 cm during the past 24 h was associated with lower odds of pain exacerbations (OR: 0.54, 95% CI: 0.30 to 0.99). A longer duration (&gt, 6 h) of wearing shoes with heel height &ge, 2.5 cm was also associated with a lower risk of hip pain exacerbations (p for linear trend = 0.003). Wearing shoes with heel height &ge, 2.5 cm and longer duration in the past 24 h may be protective against hip pain exacerbations in people with symptomatic hip OA. Given the observational study nature, it would be prudent for this to be replicated in an independent data set.

Osteoarthritis (OA) is a complex musculoskeletal disease and a leading cause of pain and disability worldwide. Hip and knee OA alone are major contributors to global disability, having notable effects on individual well-being, increasing the reliance of individuals on health-care services and contributing to a rise in the socioeconomic burden. Consistent, coordinated and tailored approaches are important for providing appropriate care to all people with OA, but despite the scale of the challenge many individuals are still not offered the safe, best-evidence treatments recommended for OA care. This Review discusses the core priority treatments for OA, including exercise and physical activity, weight-loss, education and support for self-management. Additional physical or psychological evidence-based adjunctive therapies and combined therapies that can be used to tailor individual programmes are also discussed. These options include cognitive behavioural therapy, heat therapy, walking aids and splints, manual therapies and transcutaneous electrical nerve stimulation. International examples of OA treatment options, models of care and resources available are also given. Many challenges still need to be addressed to advance the uptake of these conditions, including further discussion around the risks and costs involved with all treatments. Various core and adjunctive therapies are available for osteoarthritis (OA) that can have beneficial effects on the well-being of the individual; however, challenges remain in implementing best-evidence, high-value care.

Background The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. Methods A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. Results Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. Conclusions This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients.

Summary Objective The aims of this study were to systematically review clinimetrics of commonly assessed ultrasound pathologies in knee, hip and hand osteoarthritis (OA), and to conduct a meta-analysis for each clinimetric. Methods Medline, Embase, and Cochrane Library databases were searched from their inceptions to September 2016. According to the Outcome Measures in Rheumatology (OMERACT) Instrument Selection Algorithm, data extraction focused on ultrasound technical features and performance metrics. Methodological quality was assessed with modified 19-item Downs and Black score and 11-item Quality Appraisal of Diagnostic Reliability (QAREL) score. Separate meta-analyses were performed for clinimetrics: (1) inter-rater/intra-rater reliability; (2) construct validity; (3) criteria validity; and (4) internal/external responsiveness. Statistical Package for the Social Sciences (SPSS), Excel and Comprehensive Meta-analysis were used. Result Our search identified 1126 records; of these, 100 were eligible, including a total of 8542 patients and 32,373 joints. The average Downs and Black score was 13.01, and average QAREL was 5.93. The stratified meta-analysis was performed only for knee OA, which demonstrated moderate to substantial reliability [minimum kappa > 0.44(0.15,0.74), minimum intraclass correlation coefficient (ICC) > 0.82(0.73–0.89)], weak construct validity against pain ( r = 0.12 to 0.27), function ( r = 0.15 to 0.23), and blood biomarkers ( r = 0.01 to 0.21), but weak to strong correlation with plain radiography ( r = 0.13 to 0.60), strong association with Magnetic Resonance Imaging (MRI) [minimum r = 0.60(0.52,0.67)] and strong discrimination against symptomatic patients (OR = 3.08 to 7.46). There was strong criterion validity against cartilage histology [ r = 0.66(−0.05,0.93)], and small to moderate internal [standardized mean difference(SMD) = 0.20 to 0.58] and external ( r = 0.35 to 0.43) responsiveness to interventions. Conclusion Ultrasound demonstrated strong criterion validity with cartilage histology, poor to strong correlation with patient findings and MRI, moderate reliability, and low responsiveness to interventions. PROSPERO registration no. CRD42016039954

PURPOSE: To investigate change in knee cartilage composition over 96 months in overweight and obese participants with constant weight compared to those with weight loss, and to assess how different weight loss regimens are associated with these changes. METHODS: We studied right knees of 760 participants (age 62.6±9.0y; 465 females) with a baseline BMI>25kg/m2 from the Osteoarthritis Initiative with mild to moderate or with risk factors for knee osteoarthritis. Participants losing weight (>5% of baseline BMI over 72 months; N=380) were compared to controls with stable weight (SW, N=380). Participants losing weight were categorized based on weight loss method (diet and exercise, diet only, exercise only) and compared to those with stable weight. MRI at 3T was performed at baseline, 48- and 96-months. The association of weight loss and weight loss method with change in cartilage composition, measured with T2 mapping, was analyzed using mixed random effects models. RESULTS: Compared to SW, weight loss was associated with a significantly slower increase in global (averaged over all compartments) cartilage T2 ((adjusted mean difference of change in T2 ms/year [95%CI] between the groups: 0.24 [0.20, 0.41] ms/year; P

OA is a multifaceted and heterogeneous syndrome that may be amenable to tailored treatment. There has been an increasing focus within the OA research community on the identification of meaningful OA phenotypes with potential implications for prognosis and treatment. Experimental and clinical data combined with sophisticated statistical approaches have been used to characterize and define phenotypes from the symptomatic and structural perspectives. An improved understanding of the existing phenotypes based on underlying disease mechanisms may shed light on the distinct entities that make up the disease. This narrative review provides an updated summary of the most recent advances in this field as well as limitations from previous approaches that can be addressed in future studies.

ObjectivesTo determine the relationship between synovitis detected on non-contrast-enhanced (non-CE) magnetic resonance imaging (MRI), biochemical markers of inflammation, and clinical assessment of effusion in people with knee osteoarthritis (OA).MethodWe examined data from the OA Biomarkers Consortium within the Osteoarthritis Initiative (n=600). Non-CE MRIs were semi-quantitatively scored (grades 0-3) for severity of Hoffa synovitis and effusion synovitis. Serum (s) matrix metalloproteinase-3 (sMMP-3), hyaluronic acid (sHA), and nitrated epitope of the α-helical region of type II collagen (sColl2-1NO2) were quantified. The bulge and patellar tap clinical tests were performed at baseline and performance characteristics were assessed for the detection of effusion synovitis on MRI. Multinomial logistic regression adjusted for covariates was used to assess the association between biochemical and imaging markers at baseline and over 12 and 24months.ResultsAt baseline, sHA and sMMP-3 were associated with moderate to large (score ≥2, n=117) effusion synovitis, with odds ratio=1.35 and 1.30 per 1 standard deviation in biochemical markers (95% confidence intervals 1.07, 1.71 and 1.00, 1.69), c-statistics 0.640 and 0.626, respectively. The c-statistics for the presence of Hoffa synovitis (score ≥2) were 0.693, 0.694, and 0.694 for sHA, sMMP-3, and sColl2-1NO2, respectively. There was no significant association between biochemical markers (baseline and 12 and 24month time-integrated concentrations) and changes in MRI markers. The bulge and patellar tap signs were 22.0% and 4.3% sensitive and 88.8% and 94.8% specific, respectively, for detecting effusion synovitis (score ≥1) on MRI.ConclusionssHA and sMMP-3 were modestly associated with effusion synovitis at baseline. Clinical signs of effusion are insensitive but highly specific for the presence of any effusion synovitis on non-CE MRI.

Aim To compare the musculoskeletal (MSK) physical examination skills, knowledge acquisition and performance of first-year medical students trained by MSK specialist tutors to students trained by non-MSK specialist tutors, after a 6-week MSK physical examination tutorial program. Methods Twenty-first year medical students took part in the study. They were recruited into two groups, according to their exposure to either an MSK specialist or a non-MSK specialist tutor during their 6-week MSK training block. Knowledge acquisition was measured via a pre- and post-training objective structured clinical examination (OSCE). We assessed students’ self-belief and confidence levels regarding their newly acquired skills via a questionnaire. Independent t tests were used to examine mean group differences of OSCE scores and perceived level of confidence. Results Both groups demonstrated a significant improvement (3.9 and 3.8 points, respectively, on an eight-point scale for shoulder assessment, P < 0.01, 3.3 and 3.5, respectively, on a five-point scale for spine assessment, P < 0.01) in OSCE scores compared to baseline after completing the 6-week MSK physical examination tutorial program. There was no between-group difference in the OSCE scores from pre- to post-training (P = 0.92 for shoulder, P = 0.66 for spine) or for perceived level of confidence in performing a basic MSK examination after training (P = 0.91). Conclusion Students exposed to MSK specialist tutors did not demonstrate increased skill levels or knowledge in the area of MSK physical examination compared to those receiving the same training under the supervision of non-MSK specialist tutors. Both student groups demonstrated improvement.

In the most recent years, an extraordinary research effort has emerged to disentangle osteoarthritis heterogeneity, opening new avenues for progressing with therapeutic development and unravelling the pathogenesis of this complex condition. Several phenotypes and endotypes have been proposed albeit none has been sufficiently validated for clinical or research use as yet. This review discusses the latest advances in OA phenotyping including how new modern statistical strategies based on machine learning and big data can help advance this field of research.

Background Ultrasound can visualize both structural and inflammatory changes of osteoarthritis (OA) with greater accessibility. Therefore, the Outcome Measures in Rheumatology (OMERACT) Ultrasound Task Force recently proposed a semi-quantitative knee ultrasound scoring system1 which requires further validation. Objectives To investigate inter-rater reliability (IRR) of ultrasound pathologies between three raters with varying experiences and examine construct validity of these features against magnetic resonance imaging (MRI) using OMERACT semi-quantitative ultrasound image atlas and quantitative ultrasound measures. Methods According to standardized OMERACT scanning protocol, 20 participants with symptomatic and radiographic knee OA were scanned dynamically with a multi-frequency linear transducer (6-18MHz) of Aplio Platinum 500 machine, Toshiba, Japan. Following an initial calibration of ultrasound scores using the image atlas, three raters with varying experience (a physician operator certified with RhMSUS, a musculoskeletal ultrasonographer and a medical student) independently obtained semi-quantitative scores (0-3) for synovitis and power Doppler activity in suprapatellar recess, medial osteophytes and medial meniscal extrusion, as well as quantitative measurements (mm) of synovitis, effusion, synovial hypertrophy, medial osteophyte and meniscal extrusion (maximal measures). Semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) scores of effusion-synovitis, osteophyte and meniscal extrusion were independently calculated by an experienced researcher. 3-T Sagittal proton-density (PD) weighted fat-suppressed turbo spin-echo (TSE) non-contrast MRI sequences were used for quantitative effusion-synovitis, and coronal plane for osteophyte and meniscal extrusion. Weighted kappa coefficient (Kw) or intra-class correlation coefficient (ICC) were calculated for IRR, Spearman’s rank (rs) and Pearson (rp) correlation coefficients for construct validity and Bland-Altman plots for extent of agreement between ultrasound and MRI. Results Demographics were 60.2±8.3 years of age, 65% female, BMI of 28.6±4.5 of kg/m2; 60% with Kellgren and Lawrence (KL) grade 2 and 40% with a KL grade 3. Semi-quantitative OMERACT ultrasound scores (Table.1) revealed good to excellent IRR (Kw=0.73 -0.88) for osteophyte, and moderate to good IRR (Kw=0.42-0.66) for synovitis. Conversely, quantitative measures of ultrasound pathologies had excellent IRR (ICC= 0.84-0.95) except for synovial hypertrophy (ICC=0.67-0.72). A significant association was found between semi-quantitative ultrasound synovitis and MRI effusion-synovitis (rs= 0.48, p=0.03). All three quantitative ultrasound measurements were significantly associated with quantitative scores of MRI (Table. 2). In Bland–Altman plots for quantitative measurements, there were systemic offsets of 0.6 mm, 1.9 mm and 9.8 mm for osteophyte and meniscal extrusion and synovitis respectively (Fig. 1). Conclusion These is moderate to good IRR between operators with varying experience using the OMERACT knee scoring image atlas for osteophyte and synovitis. While quantitative ultrasound measurements showed excellent IRR and significant association with MRI quantitative outcomes, the absolute feature-specific agreement is called into question. References [1] Bruyn, G.A.W., et al., An OMERACT reliability exercise of inflammatory and structural abnormalities in patients with knee osteoarthritis using ultrasound assessment. Annals of the Rheumatic Diseases, 2016. 75(5): p. 842-846. Disclosure of Interests None declared

Background Thumb-base osteoarthritis (OA) is a common cause of pain and disability This study aimed to investigate the associations of musculoskeletal ultrasound OA pathologies with the extent of pain, function, radiographic scores, and muscle strength in symptomatic thumb-base osteoarthritis. Methods This is a cross-sectional study of an ongoing clinical trial with eligibility criteria including thumb-base pain on Visual Analogue Scale (VAS) ≥40 (0 to 100 mm), Functional Index for Hand OA (FIHOA) ≥ 6 (0 to 30) and Kellgren Lawrence (KL) grade ≥ 2. The most symptomatic side was scanned to measure synovitis and osteophyte severity using a 0–3 semi-quantitative score, power Doppler and erosion in binary score. A linear regression model was used for associations of ultrasound findings with VAS pain, FIHOA and hand grip and pinch strength tests after adjusting for age, gender, body mass index, disease duration and KL grade as appropriate. For correlation of ultrasound features with KL grade, OARSI ((Osteoarthritis Research Society International) osteophyte and JSN scores, Eaton grades, Spearman coefficients were calculated, and a significant test defined as a p-value less than 0.05. Results The study included 93 participants (mean age of 67.04 years, 78.5% females). Presence of power Doppler has a significant association with VAS pain [adjusted β coefficient = 11.29, P = 0.02] while other ultrasound pathologies revealed no significant associations with all clinical outcomes. In comparison to radiograph, ultrasonographic osteophyte score was significantly associated with KL grade [rs = 0.44 (P

Objective To provide a summary of the translational gaps in musculoskeletal research as identified in the Mine the Gap workshop and propose possible solutions. Methods The Mine the Gap online workshop was hosted on October 14th and 15th, 2020. Five international panels, each comprised of a clinician, clinical researcher and basic scientist, presented gaps and proposed solutions for the themes of biomechanics, pain, biological measurements, phenotypes and imaging. This was followed by an interactive panel discussion with consumer insights. Results A number of translational gaps and proposed solutions across each of the five themes were identified. A consumer panel provided constructive feedback highlighting the need for improved resources, communication and shared decision making, and treatment individualisation. Conclusion This brief report provides a greater understanding of the diverse work and gaps relevant to fundamental/discovery scientists, clinical researchers and clinicians working across the musculoskeletal field. The numerous translational gaps highlight the need to improve communication and collaboration across the musculoskeletal field.

IntroductionOsteoarthritis (OA) is a highly prevalent and disabling condition with limited safe and effective treatment options. Intra-articular therapies are increasingly being used, however whether the effect of these agents is due to active treatment or placebo remains unclear. As the placebo response can be attributed to multiple factors, assessment of the placebo response using individual patient data (IPD) meta-analysis will give insight into the different modifiers of response to placebo. The aim of this IPD meta-analysis is to investigate the predictors of placebo response in intra-articular injection trials in OA. IPD meta-analysis is considered to be superior to conventional meta-analysis, as it combines multiple trial data, facilitates the standardisation of analyses across different studies and allows measuring derivation of the desired information.Method and analysisA systematic literature search will be conducted for randomised clinical trials comparing corticosteroid and viscosupplementation/hyaluronic acid intra-articular injections with placebo for knee and hip OA. Pubmed (Medline), EMBASE, Web of Science, Cochrane Central and SCOPUS will be searched from inception to September 2018. Corresponding authors of the original trials will be contacted to obtain IPD. Risk of bias will be assessed using the Cochrane Collaboration’s tool. The primary outcome will be change in pain from baseline. Secondary outcomes will be change in function and patient’s global assessment. Potential predictors of placebo response assessed will include patient’s characteristics, pain mechanism characteristics, radiographic severity, pain severity, intervention characteristics and trial design characteristics. A multilevel logistic regression analyses will be applied. Results will be reported using the Preferred Reporting Items for Systematic review and Meta-Analysis -IPD guidelines.Ethics and disseminationThis study does not include identifiable data and ethical approval was obtained by the original investigators. Results of the IPD meta-analysis will be disseminated for publication in peer-reviewed journals and conference presentations.PROSPERO registration numberCRD42018095188

IntroductionHand osteoarthritis (HOA) is a highly prevalent disabling joint disease. The current management regimens are limited. Potentially as a consequence, many people turn to complementary and alternative medicines for symptomatic relief. A combination of two or more supplements is common in clinical practice; however, evidence for the efficacy of this approach is lacking. The aim of this study is to investigate the efficacy of a supplement combination for treating symptomatic HOA in comparison to placebo.Methods and analysisThe RADIANT study is an internet-based, parallel, superiority, double-blind, placebo-controlled, randomised, two-arm clinical trial. A participatory design is used to facilitate the study procedures. One hundred and six participants aged over 40 years with painful HOA and structural change on X-ray (Kellgren and Lawrence grade (KLG) ≥2) will be recruited from the community and randomly allocated to receive either a supplement combination composed of: (1) combined supplement containingBoswellia serrataextract, pine bark extract and methylsulfonylmethane and (2) curcumin or placebo for 12 weeks. The primary outcome will be 12-week change in hand pain on a visual analogue scale (VAS). Main secondary outcomes include adverse events, change in hand function, patient global assessment of disease activity and quality of life. A range of additional measures will be recorded, and an individual patient placebo response will be performed. The primary analysis will be conducted using an intention-to-treat approach. Adverse events will be monitored weekly throughout the study.Ethics and disseminationThis protocol has been approved by the University of Sydney Human Research Ethics Committee (HREC No. 2018/766). Dissemination will occur through conferences, social media, scientific publications and PhD thesis.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12619000835145); Pre-results

Objective Greater joint laxity and radial subluxation of the thumb metacarpal base have been shown to be risk factors for the development of trapeziometacarpal osteoarthritis in an asymptomatic and radiographically normal joint. Despite this, it is unknown whether joint laxity changes with disease progression from mild to severe osteoarthritis. This study aimed to investigate the relationship between joint laxity and osteoarthritis severity, using the trapeziometacarpal subluxation ratio as an indicator of joint laxity. Method Baseline data were used from the first 100 participants included in the COMBO (Efficacy of combined conservative therapies on clinical outcomes in base of thumb OA) trial. All participants had bilateral posteroanterior (PA) and Eaton stress view hand radiographs, as well as grip and tip-pinch strength measurements. The PA view was used to assess Kellgren-Lawrence and Eaton grades, and the Eaton stress view was used to assess the trapeziometacarpal joint subluxation ratios. Generalised estimating equations were utilized to account for the fact that hand data are paired, and within-person measurements are therefore not independent. Results Lower radial subluxation ratios were associated with higher Kellgren-Lawrence grades (B-coefficient -0.302; p-value 0.027), and lower grip strength scores (B-coefficient 2.06; p-value 0.006). Conclusions Radial subluxation ratios decreased with increasing disease severity, contrary to the progression from a normal joint to one with mild osteoarthritis, wherein higher joint laxity is a risk factor for disease. This may be explained by the mechanical stabilization provided by osteophytes and capsular changes in worsening osteoarthritis, as has been shown to be the case in the knee. Trial registration number ACTRN 12616000353493. Level of evidence III.