OBJECTIVE:Many individuals use complementary medicine therapies for osteoarthritis, despite limited scientific supporting evidence. These therapies have demonstrated anti-inflammatory, antioxidative, and chondroprotective effects via different molecular pathways, suggesting potential therapeutic benefits. This trial aimed to evaluate the efficacy and safety of a novel oral complementary medicine combination in adults with symptomatic knee osteoarthritis at 12 weeks. DESIGN:The 12-week, double-blind, randomized, placebo-controlled ATLAS trial was conducted in Australia from July 2024 to April 2025 (ACTRN12623000380695). Eligible participants were aged ≥40 years with symptomatic knee osteoarthritis and radiographic Kellgren-Lawrence grade ≥2. Participants were randomized 1:1 to receive the complementary medicine combination, comprising a total daily dose of Boswellia serrata extract 250 mg, pine bark extract 100 mg, methylsulfonylmethane 1500 mg, curcumin 500 mg, and piperine 5 mg, or placebo. The primary outcome was the 12-week change in knee pain (0-100 mm visual analogue scale (VAS)). A 95% confidence interval excluding differences >18 mm between groups was interpreted as the absence of a clinically meaningful difference. Harms were monitored weekly. RESULTS:Eighty-four participants were recruited (mean [SD], age 63.7 [8.0] years, BMI 29.0 [5.5] kg/m2), and 57% were female. At 12-weeks, both groups (intention-to-treat population: complementary medicine, n=42; placebo, n=41) showed a decrease in VAS pain (least squares means: complementary medicine 20.1 mm vs placebo 20.3 mm), however with no difference between groups: 0.16 mm (95% CI -6.81 to 7.12). The safety profile of experiencing any AE was similar between groups (risk difference, -3.4% [95% CI -24.8-17.9%]); and most adverse events were mild or moderate. Four participants experienced serious adverse events, unrelated to the treatment. CONCLUSIONS:The complementary medicine combination was not superior to placebo for improving pain over 12 weeks, and the evidence does not support the use of this combination to treat people with symptomatic knee osteoarthritis.

Objective: To investigate the efficacy and safety of an oral complementary medicine combination formulation relative to placebo, on changes in pain intensity from baseline to week 12, in people with knee osteoarthritis (OA). Design: A placebo-controlled, double-blind, two-arm, superiority, phase II, Randomized Controlled Trial (RCT) (ACTRN12623000380695). We will recruit 82 participants (similar to 41 per arm), aged >= 40 years, with a clinical diagnosis of symptomatic knee OA and radiographic change on x-ray (Kellgren-Lawrence Grade >= 2). Participants will be randomly allocated to receive either a complementary medicine formulation containing a daily dose of Boswellia serrata extract (Boswellin (R) Super, 250 mg/day), pine bark extract (Fenoprolic (TM) 70 Organic 100 mg/day), curcumin (500 mg/day), piperine (5 mg/day), and methylsulfonylmethane (MSM, 1500 mg/day), or placebo, for 12-weeks. The primary endpoint will be change from baseline in average knee pain intensity at 12-weeks (visual analogue scale). Secondary endpoints will include change in knee pain from baseline to 12-weeks in the Knee Injury and Osteoarthritis Outcome Score (KOOS), global assessment of disease activity, global rating of change, and health-related quality of life (AQoL-8D). Ethics and dissemination: This protocol has been approved by the University of Sydney Human Research Ethics Committee (#2021/877). Dissemination will occur through lay summaries, infographics, conference abstracts, oral presentations, theses, and scientific publications. Conclusion: This RCT will provide credible evidence about the efficacy and safety of this complementary medicine combination and inform updates to international clinical practice standards on the use of complementary medicines in the management of symptomatic knee OA.

Background Osteoarthritis (OA) is a leading cause of pain and disability in middle-aged or older adults worldwide. The prevalence of symptomatic knee OA has been increasing over the past several decades, indicating the need for the deployment of innovative prevention and treatment strategies for knee OA. The aim of this study is to investigate the efficacy and safety of an oral complementary medicine formulation in people with symptomatic knee OA. Methods This is a randomised, placebo-controlled, double-blinded (participants and investigators), two-arm, superiority, parallel, phase II trial. The study will recruit 82 ([Formula: see text]41 per arm) community-based participants with knee OA living in Australia. Participants aged [Formula: see text] 40 years with a clinical diagnosis of symptomatic knee OA and radiographic change on X-ray (Kellgren-Lawrence Grade [Formula: see text] 2) will be recruited. Participants will be randomly allocated to receive either a complementary medicine formulation containing a daily dose of Boswellia serrata extract (Boswellin[Formula: see text]Super, 250 mg/day), pine bark extract (Fenoprolic™70 Organic 100mg/day), curcumin (500mg/day), piperine (5mg/day), and methylsulfonylmethane (MSM, 1500mg/day), or placebo, for 12 weeks. The primary endpoint is change from baseline in average index knee pain at 12 weeks (visual analogue scale). Secondary endpoints include change in knee pain at other timepoints, the Knee Injury and Osteoarthritis Outcome Score (KOOS), global assessment of disease activity, global rating of change, health-related quality of life (AQoL-8D), and adverse events. Ethics, trial registration and dissemination: The study protocol has been approved by the University of Sydney Human Research Ethics Committee (#2021/877). The trial has been prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12623000380695, 14/04/2023). Dissemination will occur through lay summaries, scientific publications, conference abstracts, poster or oral presentations, infographics, and theses. Conclusion The outcomes of this study will provide high-quality evidence guiding the clinical use of the complementary medicine combination and will inform updates on international OA clinical practice standards on the use of complementary medicines.

ObjectiveThe aim of this study was to compare the magnitude and the predictors of the placebo response in an internet versus onsite randomised controlled trials (RCTs) in people with hand osteoarthritis (HOA).MethodThis study is a post-hoc analysis based on one internet RCT (RADIANT) and previously published onsite RCTs for HOA identified through a rigorous searching and selection strategy. The magnitude of the placebo response in the two different types of RCTs were compared using heterogeneity statistics and forest plots visualisation. Classic placebo predictors as well as a combined model, defined with data from onsite RCTs, were tested to predict the placebo response.ResultsWe analysed the dataset from RADIANT and fourteen previously published onsite RCTs. None of the analyses showed a significant difference between the placebo response for the internet versus onsite RCTs. The “classic” placebo predictors combined in a multivariate predictive model correlated significantly with the placebo response measured in RADIANT study.ConclusionDespite the absence of face-to-face interactions with the study personnel, there is no evidence that either the magnitude or the predictors of the placebo response of this internet RCT differ from those of onsite RCTs. This analysis is considered as a first step towards evaluating the difference between these designs and strengthens the argument that internet RCTs remain an acceptable alternative way to assess the efficacy of an active treatment in comparison to a placebo.

Background Nowadays, technological advances enable instant data collection in a secure and confidential manner. Integrating electronic data capture technologies into the online clinical trial design, has been rarely investigated. The aim of this study was to test the feasibility and logistics of the online clinical trial model in osteoarthritis. Methods We used Research Electronic Data Capture (REDCap), a versatile and secure database, as the data management platform. Without face-to-face interactions, the majority of the communications among investigators and between investigators and participants were through the REDCap platform. The embedded randomisation procedure was also completed on the same platform. Results We developed the online trial model in a 12-week, phase II, placebo-controlled, randomised clinical trial (RCT) investigating the efficacy and safety of a supplement combination in people with hand osteoarthritis (RADIANT study). We replicated the same platform and questionnaire model to a larger hybrid RCT, a phase III, two-year placebo-controlled trial investigating the use of stem cells in the treatment of knee osteoarthritis (SCUlpTOR study). In the RADIANT study, we screened 301 participants within five months’ timeframe between October 2019 and March 2020 during the pandemic of COVID. 106 eligible participants were randomised, and the adherence rate was 100%. By leveraging advanced REDCap features, including custom record status dashboards, automated alerts and notifications, text messaging integration via Twilio, and comprehensive project dashboards, we significantly enhanced the efficiency of the recruitment process and participant management. These improvements also effectively reduced the survey burden on participants, contributing to the overall success and robustness of our data collection methodology. In the SCUlpTOR study, we successfully completed the recruitment between May 2021 to Nov 2023 in two sites with screening of 10,110 participants and eventually 321 participants were randomised. The visualisation of the process provides an efficient system to adjust the recruitment strategy in a cost-effective and efficient manner (Figure 1). Conclusion This online trial implementation and data management system successfully work for RCT recruitment and conduction. The two well-performed trials prove the feasibility of online clinic trial model. This is particularly important in the post-COVID era when face-to-face interactions may be limited. However, the incorporation of technology and secure data management system in the implementation of RCT is still underexplored. Further validation is needed to generalize this method to a broader trial design in other medical disorders.

Purpose: To evaluate the association between physical activity and primary knee replacement (KR) following knee osteoarthritis (OA).

OBJECTIVE:To investigate whether baseline joint space narrowing (JSN) predicted disease remission, knee pain, and physical function changes in persons with knee osteoarthritis (OA).METHODS:This study is a secondary analysis of a two-armed randomized controlled trial. Participants were aged ≥50 years (n = 171) with a body mass index ≥28 kg/m2 and radiographic medial tibiofemoral OA. Participants in the intervention group received diet and exercise programs and special treatment (cognitive behavioral therapy, knee brace, and muscle strengthening exercises) according to the disease remission. Remission of pain and remission of patient global assessment of disease activity and/or functional impairment were used to define the disease remission. The control group were provided with an education pamphlet. The primary outcome was disease remission at 32 weeks, and the secondary outcomes were the changes in knee pain and physical function at 20 and 32 weeks. Baseline JSN was scored from 0 to 3, and the association between baseline JSN and outcomes was assessed using multiple regression.RESULTS:There was no association of baseline JSN with disease remission at 32 weeks when the disease remission has been achieved. The baseline JSN grade 3 was associated with changes in knee pain at 20 weeks (p < .05). There was no association between baseline JSN and physical function.CONCLUSION:Baseline JSN severity predicted changes in knee pain but not the disease remission or changes in physical functions. Identification of baseline radiographic severity may be helpful in identifying differences in response to diet and exercise programs in knee OA.

AIM:Despite high-interest rates in sex in people with hip osteoarthritis (OA), clinicians tend not to address sexual issues, especially in older adults. The objective of this study is to evaluate sexual activity and factors associated with sexual activity satisfaction in people with symptomatic hip OA.METHODS:A cross-sectional study was conducted among 252 participants with symptomatic hip OA in Australia. Quality of sex life was assessed using the online composite of sexual activities and positions questionnaires. A Poisson model with robust variance was used to calculate the prevalence ratio (PR). Factors that showed a univariate association with sexual satisfaction were then included in a multivariable model. PR with corresponding 95% confidence intervals (CI) are reported.RESULTS:Among the 282 participants registered on the study website, 252 met the inclusion criteria, and 60.3% (152/252) completed the sexual activity questionnaires. Hip OA interfered with sexual activity in 70.0% of the participants. High confidence in completing sexual activity (PR: 0.53, 95% CI: 0.36 to 0.77) was associated with an increased prevalence ratio of sexual satisfaction. High anxiety, depression or stress during sexual activity (PR: 1.33, 95% CI: 1.10 to 1.60) was associated with an increased prevalence ratio of sexual dissatisfaction after adjusting for hip pain level and perceived partner's orgasm.CONCLUSION:Although a large proportion of people with hip OA remain sexually active, a substantial proportion of persons are dissatisfied with their sexual activity. Hip OA interfered with sexual activity in most participants. Psychological factors were found to be associated with sexual activity satisfaction.

Importance:Digital technology represents an opportunity to improve outcomes following total knee replacement (TKR). Digitally delivered interventions have been shown to be similar to face-to-face interventions and to increase participation levels in people with osteoarthritis. Objective:To assess the effect of a digital technology package in reducing pain compared with usual care following TKR. Design, Setting, and Participants:This randomized clinical trial recruited 102 adults after they received TKR in 3 rehabilitation hospitals in Sydney, Australia, between June 2020 and July 2021. Interventions:All participants underwent usual care. In addition to usual care, 51 participants received a digital technology package consisting of an exercise app, fitness tracker, and online health coaching. In the usual care group, 51 participants received a fitness tracker but with all notifications turned off and goals for step count, sleep, and active hours removed. Participants were followed up for 12 months (June 2021 to July 2022). Main Outcome and Measures:The primary outcome was mean knee pain during the past week assessed using a numerical rating scale (range, 0-10, with 10 indicating worst possible pain) at 3 months. In unadjusted analyses, considered primary and based on multiple imputations, independent t tests were used to compare means between groups. Secondary outcomes, including measures of function, activity participation, and quality of life, were analyzed using a generalized estimating equation model that accounted for repeated measurements. Results:Of 102 participants (mean [SD] age, 67.9 [7.2] years; 68 [67%] female; and 92 [90%] White) randomly assigned to intervention or usual care groups, 47 (92%) in each group completed the 3-month follow up. At 3 months, participants in the intervention group demonstrated small but not clinically meaningful improvements in pain compared with the usual care group in the unadjusted intention-to-treat analysis (mean difference, -0.84; 95% CI, -1.59 to -0.10; P = .03). Secondary outcomes indicated a statistically significant reduction in pain intensity, (mean difference, -0.94; 95% CI, -1.82 to -0.06), pain disability (mean difference, -5.42; 95% CI, -10.00 to -0.83), and sedentary behavior (mean difference, -9.76; 95% CI, -19.17 to -0.34) favoring the intervention from baseline to 3, 6, and 12 months. Conclusions and Relevance:In this randomized clinical trial, a combined digital technology program provided small but not clinically meaningful improvements in pain at 3 months and other longer-term favorable outcomes following TKR compared with usual care. Future studies should tailor digital interventions based on participants' abilities and preferences to ensure that the intervention is appropriate and fosters long-term self-management. Trial Registration:Anzctr.org.au Identifier: ACTRN12618001448235.

Purpose: The purpose of the through behavioural engagement and disruptive digital technology for postoperative rehabilitation (PATHway) trial was to assess the effect of a standard rehabilitation pathway augmented by a disruptive digital technology package compared to usual care in decreasing pain after total knee replacement (TKR).

OBJECTIVE: To determine if participants demonstrate distinct trajectories of step count following total knee replacement, and whether their baseline characteristics differ. DESIGN: Longitudinal repeated measures study within a randomized-controlled trial. METHODS: Participants were recruited from 3 hospitals in Sydney, Australia. Only participant data from the intervention group were used for this study (n = 51). Baseline data including demographics, pain (0-10 numerical rating scale), 13-item Patient Activation Measure scale, and modified Computer Self-efficacy Scale were collected. Participants received an activity tracker to monitor daily step counts. Latent class analyses were used to identify distinct trajectories of step count from baseline to 3-month follow-up. Baseline characteristics were compared using multinomial logistic regression. RESULTS: 43 participants were included in the analysis. Participants were predominantly female (n = 30, 70%) with an average age (SD) of 67.7 (7.5) years and body mass index (SD) of 30.3 (6.0). Three distinct step count trajectories were identified: a “high and rapidly increasing” group (n = 6, 14%), who began at 6251 ± 3508 steps and achieved 12794 ± 3173 steps by weeks 9 to 11; a “low and gradually increasing” (n = 24, 56%), (baseline: 2843 ± 1058 steps, 12 weeks: 6441 ± 1677 steps) ; and “high and gradually increasing” (n = 13, 30%), (baseline: 6299 ± 1777 steps, 12 weeks: 9614 ± 1436 steps). At baseline, body mass index and pain significantly differed between groups. CONCLUSION: Three distinct step count trajectories were found in people with total knee replacement. Findings highlight the variability between patient groups and the need for support for those who may not be reaching prescribed step goals. JOSPT Open 2023;1(1):78-85. Epub 11 August 2023. doi:10.2519/josptopen.2023.0011

Objectives To investigate the laser effect associated with stretching exercise on pain and functionality in patients with knee osteoarthritis. Design A randomised controlled trial Setting Special Rehabilitation Services. Subjects We enrolled 215 knee osteoarthritis patients (430 knees were treated). Intervention Group Laser + Stretch (n = 43), Placebo + Stretch (n = 43), Stretch (n = 43), Laser (n = 43) and Control (n = 43) were treated with active laser and stretching exercises; placebo laser and stretching exercises; stretching exercises; active laser, and control, respectively. Interventions were conducted 3 times a week for 8 or 11 weeks. Main outcome measures The primary outcome was the change in knee pain and disability. Secondary outcomes included severity of osteoarthritis, mobility, knee range of motion, flexibility, activity, severity of osteoarthritis and medication intake for pain relief. Results The patients' average age was 63.52 (6.8) years. Pain scores at baseline and post treatment (p < 0.001) were 7.43 (2.10) and 2.79 (1.92) for group Laser + Stretch, 7.39 (1.98) and 4.47 (2.82) for group Placebo + Stretch, 6.83 (1.42) and 4.24 (2.43) for group Stretch, 6.61 (1.68) and 2.94 (2.65) for group Laser, 6.74 (1.75) and 6.47 (2.29) for group Control, respectively. Disability score at baseline and post treatment (p = 0.000237) were 12.36 (5.02) and 8.08 (4.64) for group Laser + Stretch, 12.71 (5.12) and 9.90 (4.95) for group Placebo + Stretch, 11.83 (2.77) and 7.20 (5.28) for group Stretch, 11.58 (5.59) and 8.21 (6.18) for group Laser, 11.23 (4.68) and 11.45 (4.83) for group Control, respectively. Conclusion Laser therapy combined with stretching exercises improves pain during rest, activities of daily living, stiffness, muscle shortening and range of motion in patients with knee osteoarthritis.

OBJECTIVE:To determine how physically active individuals are following total knee replacement (TKR) and how accurately they self-report their step count adherence compared to objective measure following TKR.METHODS:Observational cohort study, nested within the PATHway randomised-clinical trial. Participants (n = 102) who had recently undergone TKR were recruited for the main trial. Only participant data from the intervention group were used for this study (n = 51). Participants in the intervention group received an activity tracker to monitor their physical activity and fortnightly health-coaching sessions for 3 months. Adherence was objectively measured as percentage of steps completed divided by the amount prescribed by the health coach. Participants were asked to self-report their adherence on a 1-10 numerical rating scale during health coaching sessions.RESULTS:Data from 44 participants were available, resulting in a total of 224 paired measurements. Participant step count increased over the first 8 weeks of follow-up, and plateaued from 8 weeks onwards at approximately 7500 steps/day. About two-thirds (65.8%) of participants accurately self-reported their step count adherence up until 12 weeks, the remaining one-third (34.2%) underestimated their adherence. Paired t-tests demonstrated statistically significant differences between the paired measurements from weeks 2 to 10.DISCUSSION:Participants were generally active and completed the step goal most occasions. Two-thirds accurately self-reported their step goal adherence. Self-reported measures should be combined with an objective measure of adherence for greater accuracy. A further understanding of how people engage with activity trackers can be used to promote behaviour change in physiotherapy-led interventions.

OBJECTIVE:To explore the person-level predictors of adherence to a step count intervention following total knee replacement (TKR).DESIGN:Prospective cohort study, nested within the PATHway trial.METHODS:Participants who had recently undergone TKR were recruited from 3 rehabilitation hospitals in Sydney, Australia, for the main trial. Only data from participants who were randomized to the TKR intervention group were analyzed. Participants in the intervention group (n = 51) received a wearable tracker to monitor the number of steps taken per day. Step count adherence was objectively measured at 3 months as the number of steps completed divided by the number prescribed and multiplied by 100 to express adherence as a percentage. Participants were classified into 4 groups: withdrawal, low adherence (0%-79%), adherent (80%-100%), and >100% adherent. Ordinal logistic regression was used to identify which factors predicted adherence to the prescribed step count.RESULTS:Of the 51 participants enrolled, nine (18% of 51) withdrew from the study before 3 months. Half of participants were classified as >100% adherent (n = 24%, 47%). Ten were classified as low adherence (20%), and 8 participants were classified as adherent (16%). In the univariable model, lower age (OR 0.90; 95% CI 0.83-0.97), higher patient activation (OR 1.03; 95% CI 1.00-1.06), and higher technology self-efficacy (OR 1.03; 95% CI 1.00-1.06) were associated with higher adherence. After adjusting for age in the multivariable model, patient activation and technology self-efficacy were not significant.CONCLUSION:Younger age, higher patient activation, and higher technology self-efficacy were associated with higher adherence to a step count intervention following TKR in the univariable model. Patient activation and technology self-efficacy were not associated with higher adherence following adjustment for age. J Orthop Sports Phys Ther 2022;52(9):620-629. Epub: 9 July 2022. doi:10.2519/jospt.2022.11133.

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.(c) 2021 Elsevier Inc. All rights reserved.

OBJECTIVE: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.METHODOLOGY: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.RESULTS:We studied 204 participants (76% female, age 65.63 ± 8.13 years, body mass index 28.7 ± 6.5 kg/m2 ) with hand OA. The mean pain score of the participants on a visual analog scale was 57.8 (SD ±13.6). There was a significant, negative moderate correlation between hand function and QoL scores except for the sense domain score. Global assessment, household income and serious illness were associated with QoL (P < .001) and explained 18% of the variance of the QoL. Pain scale, Patient Global Assessment, Mental Health Score, grip strength and cyst index were associated with hand function score and explained 26% of the variance of hand function.CONCLUSION:The 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.