ORCID Profile
0000-0003-3172-9390
Current Organisation
University of Sydney
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Publisher: Springer Science and Business Media LLC
Date: 03-11-2019
DOI: 10.1186/S12891-019-2900-X
Abstract: To evaluate the effectiveness and safety of technology-assisted rehabilitation following total hip/knee replacement (THR/TKR). Six electronic databases were searched without language or time restrictions for relevant studies: MEDLINE, EMBASE, Cochrane Library, CINAHL, SPORTDiscus, Physiotherapy Evidence Database (PEDro) from inception to November 7th, 2018. Two reviewers independently applied inclusion criteria to select eligible randomised controlled trials (RCTs) that investigated the effectiveness of technology-based interventions, compared with usual care or no intervention for people undergoing THR/TKR. Two reviewers independently extracted trial details (e.g. patients’ profile, intervention, outcomes, attrition and adverse events). Study methodological quality was assessed using the PEDro scale. Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. We identified 21 eligible studies assessing telerehabilitation, game- or web-based therapy. There were 17 studies ( N = 2188) in post-TKR rehabilitation and 4 studies ( N = 783) in post-THR rehabilitation. Compared to usual care, technology-based intervention was more effective in reducing pain (mean difference (MD): − 0.25 95% confidence interval (CI): − 0.48, − 0.02 moderate evidence) and improving function measured with the timed up-and-go test (MD: -7.03 95% CI: − 11.18, − 2.88) in people undergoing TKR. No between-group differences were observed in rates of hospital readmissions or treatment-related adverse events (AEs) in those studies. There is moderate-quality of evidence showed technology-assisted rehabilitation, in particular, telerehabilitation, results in a statistically significant improvement in pain and low-quality of evidence for the improvement in functional mobility in people undergoing TKR. The effects were however too small to be clinically significant. For THR, there is very limited low-quality evidence shows no significant effects.
Publisher: BMJ
Date: 03-11-2015
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.JOCA.2017.02.804
Abstract: To develop a measure of knee joint effusion-synovitis volume and to examine the effect of vitamin D supplementation on effusion-synovitis in people with knee osteoarthritis (OA) and low vitamin D levels over 24 months. Symptomatic knee OA patients with low 25-(OH)D levels (12.5-60 nmol/l) were recruited for a multi-centre, randomised, placebo-controlled and double-blind trial. Participants (age 63 ± 7 years, 208 females) were allocated to either 50,000 IU monthly vitamin D The reproducibilities of effusion-synovitis volume measurement were high with ICCs ranging from 0.93 to 0.99. Over 24 months, effusion-synovitis volume remained stable in the vitamin D group but increased in placebos with a significant between-group difference (-1.94 ml, 95% confidence interval (CI): -3.54, -0.33). This effect was evident in those with baseline effusion-synovitis and with suprapatellar effusion-synovitis. The proportion with an increase in effusion-synovitis volume was lower in the vitamin D group than placebo (risk ratio (RR): 0.87, 95% CI: 0.77, 0.97). This highly reproducible effusion-synovitis volume measurement could be a promising outcome measure in OA trials. Vitamin D supplementation could retard the progression of effusion-synovitis which can potentially benefit people with an inflammatory OA phenotype.
Publisher: The Journal of Rheumatology
Date: 15-11-2015
Abstract: To describe the cross-sectional and longitudinal associations between knee regional effusion synovitis and knee pain in older adults. Data from a population-based random s le (n = 880, mean age 62 yrs, 50% women) were used. Baseline knee joint effusion synovitis was graded (0–3) using T2-weighted magnetic resonance imaging (MRI) in the suprapatellar pouch, central portion, posterior femoral recess, and subpopliteal recess. Effusion synovitis of the whole joint was defined as a score of ≥ 2 in any subregion. Other knee structural (including cartilage, bone marrow, and menisci) lesions were assessed by MRI at baseline. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire at baseline and 2.6 years later. Multivariable analyses were performed after adjustment for age, sex, body mass index, and other structural lesions. The prevalence of effusion synovitis was 67%. Suprapatellar pouch effusion synovitis was significantly and independently associated with increased total and nonweight-bearing knee pain in both cross-sectional and longitudinal analyses (for an increase in total knee pain of ≥ 5, RR 1.26 per grade, 95% CI 1.04–1.52), and increased weight-bearing knee pain in longitudinal analysis only. Effusion synovitis in posterior femoral recess and central portion were independently associated with increases in nonweight-bearing pain (RR 1.63 per grade, 95% CI 1.32–2.01 and RR 1.29 per grade, 95% CI 1.01–1.65, respectively) in longitudinal analyses only. Knee joint effusion synovitis has independent associations with knee pain in older adults. Suprapatellar pouch effusion synovitis is associated with nonweight-bearing and weight-bearing knee pain, while posterior femoral recess and central portion effusion synovitis are only associated with nonweight-bearing pain.
Publisher: Springer Science and Business Media LLC
Date: 12-10-2016
Publisher: Wiley
Date: 28-03-2016
DOI: 10.1002/ART.39526
Abstract: To describe the natural history of quantitatively measured knee effusion-synovitis and the longitudinal associations between effusion-synovitis and knee structural factors, including cartilage defects, cartilage volume, subchondral bone marrow lesions, and meniscal pathology, in older adults. A total of 406 subjects (with a mean age of 63 years, 50% women) were randomly selected at baseline and followed up 2.7 years later. T2- or T1-weighted fat saturation magnetic resonance imaging was used to assess knee effusion-synovitis maximal area, cartilage defects, cartilage volume, bone marrow lesions, and meniscal pathology at baseline and follow-up. Multivariable generalized linear regression was performed to analyze the associations between the maximal area of effusion-synovitis and other joint structural factors after adjustment for age, sex, body mass index, tibial bone area, and/or radiographic osteoarthritis (OA). Over 2.7 years of follow-up, the size of effusion-synovitis increased in 29%, remained stable in 50%, and decreased in 22% of the participants. Baseline effusion-synovitis maximal area was significantly associated with changes in knee cartilage defects (β = 0.18 [95% confidence interval (95% CI)] 0.07, 0.29), bone marrow lesions (β = 0.17 [95% CI 0.05, 0.30]), and cartilage volume (β = -0.40 [95% CI -0.71, -0.09]) but not with change in meniscal pathology. In contrast, baseline structural measures were not associated with change or increase in effusion-synovitis maximal area. Our findings indicate that knee effusion-synovitis is not static in older adults. It is predictive of, but not predicted by, other structural abnormalities, suggesting a potential role in early knee OA changes.
Publisher: Oxford University Press (OUP)
Date: 27-01-2021
DOI: 10.1093/RHEUMATOLOGY/KEAB059
Abstract: Use of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA. We used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren–Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW. Of 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s.d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics sychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = −0.042, 95% CI −0.08, −0.0004). No other associations were observed. In current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.
Publisher: Springer Science and Business Media LLC
Date: 2014
DOI: 10.1186/AR4496
Publisher: The Journal of Rheumatology
Date: 09-2017
Abstract: To describe the associations between effusion-synovitis and joint structural abnormalities in patients with knee osteoarthritis (OA) over 24 months. A posthoc analysis using data from a randomized controlled trial in 413 patients with symptomatic OA (aged 63 ± 7 yrs, 208 women). Knee effusion-synovitis volume and score, cartilage defects, cartilage volume, and bone marrow lesions (BML) were assessed using magnetic resonance imaging. Joint space narrowing (JSN) and osteophytes were assessed using radiograph. Least significant change criterion was used to define change in effusion-synovitis volume. Knee symptoms were assessed by Western Ontario and McMaster University OA Index. Multivariable linear/logistic regression and multilevel generalized mixed-effects models were used in longitudinal analyses. Total effusion-synovitis volume increased modestly from baseline (8.0 ± 8.5 ml) to followup (9.0 ± 10.5 ml). Baseline BML, cartilage defect, JSN, and osteophyte scores were positively associated with change in effusion-synovitis volume (p 0.05). Baseline cartilage defects and JSN were also associated with change in effusion-synovitis score (p 0.05). However, neither baseline effusion-synovitis score nor volume consistently predicted change in the above structures except cartilage volume. In the mixed-effects models, knee effusion-synovitis was positively associated with BML (volume: β = 1.19 ml/grade score: OR = 1.75/grade) and cartilage defects (volume: β = 1.87 ml/grade score: OR = 2.22/grade), while negatively associated with cartilage volume loss. Change in effusion-synovitis volume was positively correlated with changes in knee pain and stiffness scores (p 0.05). Knee cartilage and subchondral bone abnormalities predicted change in effusion-synovitis, but effusion-synovitis did not predict knee structural changes. These findings suggest that synovial inflammation is likely the result of joint structural abnormalities in established OA. ClinicalTrials.gov identifier: NCT01176344 . Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.
Publisher: BMJ
Date: 11-2021
DOI: 10.1136/BMJOPEN-2021-056382
Abstract: Knee 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. The 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. This 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. Australian New Zealand Clinical Trials Registry (ACTRN12620000870954) U1111-1234-4897.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.JOCA.2014.05.018
Abstract: To describe cross-sectional associations between mass effect or signal intensity alteration of the suprapatellar fat pad (SPFP) with knee symptoms and structure in older adults. A cross-sectional s le of 904 randomly selected subjects (mean 62.4 years, 49.9% female) was studied. T1- or T2-weighted fat suppressed magnetic resonance imaging (MRI) was used to assess mass effect or signal intensity alteration of SPFP, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. The Osteoarthritis Research Society International (OARSI) atlas was used to assess knee osteophyte, joint space narrowing (JSN) and radiographic osteoarthritis (ROA). Univariable and multivariable linear or logistic regression analyses were used to examine the associations. After adjustment for confounders including age, sex, body mass index (BMI), disease status, tibial bone area and/or ROA, the presence of SPFP mass effect was significantly associated with any knee pain (OR: 2.39 95% confidence interval (CI): 1.54, 3.70) and ROA (OR: 2.10 95% CI: 1.33, 3.31) but not with cartilage volume, cartilage defects or BMLs. The presence of SPFP signal intensity alteration was significantly associated with any knee pain (OR: 1.90 95% CI: 1.43, 2.53), ROA (OR: 1.83 95% CI: 1.37, 2.45), any BMLs (OR: 1.55 95% CI: 1.17, 2.06) but not with cartilage volume and cartilage defects. Significant associations with knee pain and BMLs were more evident in subjects with ROA. Presence of SPFP mass effect and/or signal intensity alteration combined was associated with any tibial cartilage defects (OR: 1.45 95% CI: 1.04, 2.04). SPFP mass effect and/or signal intensity alterations are deleteriously associated with knee pain, radiographic OA and BMLs in this cross-sectional study, suggesting that SPFP abnormalities may contribute to pain and structural abnormalities in the knee.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JOCA.2017.01.015
Abstract: To investigate the longitudinal association between endogenous sex hormones and knee osteoarthritis (OA) structures and pain. We examined 200 participants (mean age 63.0 ± 7.3 years) from a clinical trial of vitamin D supplement for symptomatic knee OA. Serum levels of estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) were analyzed at baseline and 24 months later. Magnetic resonance imaging (MRI) scans of selected knee were obtained at both baseline and follow-up for the measurement of cartilage volume, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis volume. Knee pain was assessed using a 100 mm visual analogue scale (VAS). Longitudinal data were analyzed using linear mixed-effects model. One hundred and seven males and 93 females were included in this study. For females, after adjustment for age, body mass index (BMI), and vitamin D level, progesterone was positively associated with cartilage volume (β = 0.12 mm In women but not men, low serum levels of endogenous estradiol, progesterone and testosterone are associated with increased knee effusion-synovitis and possibly other OA-related structural changes. This may contribute to observed sex differences in knee OA.
Publisher: Cambridge University Press (CUP)
Date: 25-06-2018
DOI: 10.1017/S0007114518001174
Abstract: The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D 3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group mean age 63·1 ( sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1093/AJCN/NQY017
Publisher: Springer Science and Business Media LLC
Date: 06-02-2020
DOI: 10.1186/S12891-020-3074-2
Abstract: To evaluate the effects of the updated version of an evidence-based osteoarthritis (OA) resource and consumer hub, ‘My Joint Pain’ website, on health education and quality of care over 12 months. Using a classic quasi-experimental design, participants with symptomatic hip or knee OA were recruited across Australia to evaluate the ‘My Joint Pain’ website, compared to a control group of non-users from 12 to 24 months. Outcome measures included the Health Education Impact Questionnaire (HEIQ) and the OA Quality Indicator (OAQI) questionnaire. The changes from 12 to 24 months in the HEIQ were evaluated using a generalised linear model. The differences between users and non-users in the OAQI were evaluated using a chi-square test. A total of 277 eligible participants with symptomatic hip or knee OA were recruited at baseline, and 122 participants completed the 24-month surveys (users: n = 35, non-users: n = 87). There was no significant difference between users and non-users for the HEIQ scores at 24 months after adjustments for age, sex and body mass index (BMI). Users had higher emotional distress scores than non-users in univariable analysis. When compared with non-users in the OAQI, users showed favourable changes in receiving information about “self-management” and “acetaminophen” and “non-steroidal anti-inflammatory drugs (NSAIDs)” from 12 to 24 months. The evaluation of the updated ‘My Joint Pain’ website didn’t find significant improvements in terms of health education, but it may help delivering useful information about self-management and appropriate use of pharmacological treatments. More strategies are needed to facilitate the uptake of evidence-based self-management and education online resources for OA consumers.
Publisher: BMJ
Date: 15-05-2014
DOI: 10.1136/ANNRHEUMDIS-2013-205108
Abstract: The infrapatellar fat pad (IPFP) is of uncertain significance for knee osteoarthritis. The aim of this study was to describe the longitudinal associations between baseline IPFP maximal area and changes in knee pain, knee cartilage volume and cartilage defects in older adults. 356 community-dwelling male and female adults aged 50-80 years were measured at baseline and approximately 2.6 years later. T1-weighted or T2-weighted fat-suppressed MRI was used to assess maximal IPFP area, cartilage volume and cartilage defects at baseline and/or follow-up. Knee pain was assessed by the self-administered Western Ontario McMaster Osteoarthritis Index questionnaire. After adjustment for confounders, IPFP maximal area in women was significantly and negatively associated with changes in knee pain (β: -0.18 to -0.86 for total knee pain, pain at night while in bed, pain when sitting/lying and pain when standing upright, all p<0.05) but not with other knee pain subscales. IPFP maximal area in women was beneficially associated with change in tibial cartilage volume per annum (β: +1.56% per cm(2) at medial site +0.86% per cm(2) at lateral site, both p<0.05), but not with change in patellar cartilage volume. Further, it was significantly associated with reduced risks of increases in medial cartilage defects (relative risk: 0·46 at tibial site, relative risk: 0.59 at femoral site both p<0.05) but not with increases at other sites in women. No significant associations were found in men. While the associations are not fully consistent, IPFP maximal area appears to have a protective role for knee symptoms and cartilage damage in older female adults.
Publisher: The Journal of Rheumatology
Date: 15-05-2021
Abstract: To investigate the associations of Outcome Measures in Rheumatology (OMERACT) ultrasound scores for knee osteoarthritis (OA) with pain severity, other symptoms, and OA severity on radiographs and magnetic resonance imaging (MRI). Participants with symptomatic and mild to moderate radiographic knee OA underwent baseline dynamic ultrasound (US) assessment according to standardized OMERACT scanning protocol. Using the published US image atlas, a physician operator obtained semiquantitative or binary scores for US pathologies. Clinical severity was measured on numerical rating scale (NRS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) symptoms and pain subscores. OA severity was assessed using the Kellgren-Lawrence (KL) grade on radiographs and MRI Osteoarthritis Knee Score (MOAKS) on noncontrast-enhanced MRI. Separate linear regression models were used to determine associations of US OA pathologies with pain and KOOS subscores, and Spearman correlations were used for US scores with KL grade and MOAKS. Eighty-nine participants were included. Greater synovial hypertrophy, power Doppler (PD), and meniscal extrusion scores were associated with worse NRS pain [β 0.92 (95% CI 0.25–1.58), β 0.73 (95% CI 0.11–1.35), and β 1.01 (95% CI 0.22–1.80), respectively]. All greater US scores, except for cartilage grade, demonstrated significant associations with worse KOOS symptoms, whereas only PD and meniscal extrusion were associated with worse KOOS pain. All US scores, except for PD, were significantly correlated with KL grade. US pathologies, except for cartilage, revealed moderate to good correlation with their MOAKS counterparts, with US synovitis having the greatest correlation (0.69, 95% CI 0.60–0.78). OMERACT US scores revealed significant associations with pain severity, KL grade, and MOAKS.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JOCA.2015.02.018
Abstract: To examine the cross-sectional and longitudinal associations of patellar bone marrow lesion (BMLs) with knee pain, cartilage defects and cartilage volume in older adults. A total of 904 randomly selected subjects (mean 62.4 years, 49.9% female) were studied. Fat suppressed T1-weighted spoiled gradient recall and T2-weighted fast spin echo magnetic resonance imaging (MRI) sequences were used to assess cartilage volume, cartilage defects and/or BMLs at baseline (n = 904) and 2.6 (range: 1.4-4.8) years' follow-up (n = 414). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire at baseline (n = 904) and follow-up (n = 790). The prevalence of any patellar BMLs was 19% and was higher in those with tibiofemoral BMLs. In multivariable analyses, patellar BMLs were positively associated with any knee pain at baseline and an increase in knee pain when going up/down stairs (odds ratio (OR): 1.67, 95% confidence interval (CI): 1.08, 2.59) but not with other knee pain subscales. Patella BMLs were also associated with patellar cartilage defects both at baseline and change over time (OR: 1.76, 95% CI: 1.00, 3.70) but not tibiofemoral defects. Patellar BMLs were negatively associated with baseline and change in patella cartilage volume (β: -2.10%, 95% CI: -3.39%, -0.80%). These associations remained significant after further adjustment for tibiofemoral BMLs. Patellar BMLs were consistently associated with increased knee pain especially going up/down stairs, increased patellar cartilage defects, and decreased patellar cartilage volume cross-sectionally and longitudinally, suggesting a predominantly compartment specific role for patellar BMLs.
Publisher: BMJ
Date: 30-12-2014
DOI: 10.1136/ANNRHEUMDIS-2014-206676
Abstract: To describe the cross-sectional and longitudinal associations between knee regional effusion-synovitis and structural changes in older adults. A total of 977 subjects were randomly selected from the local community (mean 62 years, 50% female) at baseline and 404 were followed up 2.6 years later. T2-weighted MRI was used to assess knee effusion-synovitis in four subregions: suprapatellar pouch, central portion, posterior femoral recess and subpopliteal recess. Knee cartilage defects, cartilage volume and bone marrow lesions (BMLs) were measured using MRI at baseline and follow-up. Cross-sectionally, effusion-synovitis in most subregions was significantly associated with a higher risk of cartilage defects, BMLs and reduced cartilage volume. Longitudinally, suprapatellar pouch effusion-synovitis at baseline predicted an increase in cartilage defects (p .01), loss of cartilage volume (p=0.04) and an increase in BMLs (p=0.02) in multivariable analyses. The significant associations of effusion-synovitis with cartilage volume and BMLs disappeared after adjustment for cartilage defects. Effusion-synovitis in whole knee joint (p .01) and subpopliteal recess (p .05) was consistently associated with longitudinal changes in cartilage defects but not in cartilage volume and BMLs. There are independent associations between knee joint effusion-synovitis and knee cartilage defects in both cross-sectional and longitudinal analyses, suggesting a potential causal relationship. The associations of effusion-synovitis with BMLs and cartilage volume were largely dependent on cartilage defects, suggesting potential causal pathways.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.JOCA.2017.11.015
Abstract: Synovial abnormalities have been observed at multiple stages of osteoarthritis (OA). Increasing evidence suggests that it may play an important role in the OA pathological process. Many assessment systems using magnetic resonance imaging (MRI) and ultrasound have been established to detect synovial inflammation in OA. These have been used to inform the current investigation of OA disease phenotypes and progression and can be utilised in the future for clinical trials developing potential treatments. This narrative review aims to illustrate the importance of synovial tissue in OA and provide an overview of imaging assessments and possible therapies targeting synovial abnormalities.
Publisher: Oxford University Press (OUP)
Date: 16-01-2018
DOI: 10.1093/RHEUMATOLOGY/KEX501
Abstract: While OA is predominantly diagnosed on the basis of clinical criteria, imaging may aid with differential diagnosis in clinically suspected cases. While plain radiographs are traditionally the first choice of imaging modality, MRI and US also have a valuable role in assessing multiple pathologic features of OA, although each has particular advantages and disadvantages. Although modern imaging modalities provide the capability to detect a wide range of osseous and soft tissue (cartilage, menisci, ligaments, synovitis, effusion) OA-related structural damage, this extra information has not yet favourably influenced the clinical decision-making and management process. Imaging is recommended if there are unexpected rapid changes in clinical outcomes to determine whether it relates to disease severity or an additional diagnosis. On developing specific treatments, imaging serves as a sensitive tool to measure treatment response. This narrative review aims to describe the role of imaging modalities to aid in OA diagnosis, disease progression and management. It also provides insight into the use of these modalities in finding targeted treatment strategies in clinical research.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.SEMARTHRIT.2015.10.006
Abstract: The aim of this study was to describe the longitudinal relationship between adiposity and change in knee pain. A total of 1099 participants aged 50-79 were randomly selected from the local community in Southern Tasmania, of which 767 were followed up on average 5.1 years later. Knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at each time point. Consistent knee pain was defined as knee pain at all three time-points. The five pain subscales were grouped into weight-bearing pain and non-weight-bearing pain according to the nature of pain. Body fat and lean mass were assessed using dual energy x-ray absorptiometry (DXA). Baseline body mass index (BMI) and body fat mass were deleteriously associated with consistent knee pain over follow-up. BMI was consistently associated with increases in weight-bearing and non-weight-bearing pain. Fat mass was associated with an increase in non-weight-bearing pain. In mixed-model analyses, WOMAC total pain score was associated with BMI (β = 1.27) and body fat mass (β = 1.17). The association of lean mass was not significant after adjustment for fat mass. BMI is the most consistent correlate of knee pain in older adults. Fat mass is associated with non-weight-bearing knee pain suggesting systemic mechanisms are involved.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JOCA.2017.01.007
Abstract: To describe cross-sectional and longitudinal associations between magnetic resonance imaging (MRI)-detected osteophytes (OPs) and knee structural abnormalities and knee pain in older adults. A prospective population-based cohort study of 895 participants aged 50-80 years (mean age 62 years, 50% female) was performed. T1-or T2-weighted fat suppressed MRI was used to assess knee OPs, cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and after 2.6 years. Radiographically-detected OPs were scored according to the Osteoarthritis Research Society International (OARSI) atlas. Knee pain was assessed using a self-administered questionnaire at baseline, 2.6 and 5 years later. 85% of participants had MRI-detected OPs at baseline, while 10% of participants had radiographically-detected OPs. Cross-sectionally, higher gardes of MRI-detected OPs in all compartments were significantly, independently and site-specifically associated with higher prevalences of cartilage defects and BMLs, lower cartilage volume and higher prevalence of knee pain. Longitudinally, higher gardes of baseline MRI-detected OPs site-specifically predicted greater risks of any increase in cartilage defects or BMLs, and loss of cartilage volume in medial and lateral tibiofemoral (LTF) and total compartments over 2.6 years in multivariable analyses. These significant associations were similar in those without radiographically-detected OPs. MTF and total OP scores were significantly associated with change in total knee pain over 2.6 and 5 years but these became non-significant after adjustment for cartilage defects and BMLs. MRI-detected knee OPs are common and appear to be clinically relevant to knee structural changes in older adults.
Publisher: BMJ
Date: 26-11-2015
DOI: 10.1136/ANNRHEUMDIS-2015-208360
Abstract: To describe the associations between infrapatellar fat pad (IPFP) signal intensity alteration at baseline and knee symptoms and structural changes in older adults. A total of 874 subjects (mean 62.1 years, 50.1% female) selected randomly from local community were studied at baseline and 770 were followed up (only 357 had MRI at follow-up) over 2.6 years. T1-weighted or T2-weighted fat suppressed MRI was used to assess IPFP signal intensity alteration (0-3), cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and 2.6 years later. Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index questionnaire. Radiographic osteoarthritis (OA) was assessed. In cross-sectional analyses, IPFP signal intensity alteration was significantly and positively associated with total knee pain as well as knee cartilage defects, BMLs and knee radiographic OA and negatively associated with patellar cartilage volume after adjustment for age, sex, body mass index and/or radiographic OA. Longitudinally, baseline signal intensity alteration within IPFP was significantly and positively associated with increases in knee pain when going upstairs/downstairs as well as increases in tibiofemoral cartilage defects and BMLs, and negatively associated with change in lateral tibial cartilage volume in multivariable analyses. IPFP signal intensity alteration at baseline was associated with knee structural abnormalities and clinical symptoms cross-sectionally and longitudinally in older adults, suggesting that it may serve as an important imaging biomarker in knee OA.
Publisher: American Medical Association (AMA)
Date: 08-03-2016
Abstract: Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory. To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels. A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013. Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU n = 209) or an identical placebo (n = 204) for 2 years. Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI). Of 413 enrolled participants (mean age, 63.2 years 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text]. Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis. clinicaltrials.gov Identifier: NCT01176344 anzctr.org.au Identifier: ACTRN12610000495022.
Publisher: Wiley
Date: 24-11-2021
Abstract: 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. 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. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 02-02-2015
DOI: 10.1038/SREP08133
Abstract: Inflammation can cause endoplasmic reticulum (ER) stress and therefore activates the unfolded protein response (UPR). ER stress and the consequent UPR have the potential to activate NF-κB. However, the factors mediating the crosstalk between ER stress and the NF-κB pathway remain unclear. Here, we determined that ER stress inducible protein Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) was up-regulated in autoimmune diseases and inflammatory disease models. Inflammation caused MANF to relocalize to the nuclei. MANF interacted with the DNA binding domain of p65 through its C-terminal SAP-like domain in the nuclei under the condition of inflammation or ER stress. MANF consequently inhibited p65-mediated transcriptional activation by interfering with the binding of p65 to its target genes promoters. Consistently, MANF suppressed the expressions of NF-κB-dependent target genes and the proliferation of inflammatory synoviocytes. These findings suggest that MANF may be a negative regulator of inflammation and mediate the crosstalk between the NF-κB pathway and ER stress.
Publisher: Springer Science and Business Media LLC
Date: 2014
DOI: 10.1186/AR4607
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JOCA.2014.10.002
Abstract: Osteoarthritis (OA) is a common chronic joint disorder with a multifactorial etiology including genetic and environmental factors. Metabolic triggered inflammation, induced by nutrient overload and metabolic surplus, consists of components such as obesity, pro-inflammatory cytokines and adipokines, abnormal metabolites, acute phase proteins, vitamin D deficiency, and deregulated microRNAs that may play a role in OA pathophysiology. Obesity-related metabolic factors, especially adipokines, contribute to OA development by inducing pro-inflammatory cytokines and degradative enzymes, leading to cartilage matrix impairment and subchondral bone remodeling. Ectopic metabolite deposition and low-grade systemic inflammation can contribute to a toxic internal environment that exacerbates OA. Complement components highly expressed in osteoarthritic joints have also been proposed as causative factors. Vitamin D deficiency has been associated with obesity and is implicated to be associated with cartilage loss in OA. Metabolic microRNAs may explain the inflammatory link between obesity and OA. Therapies targeting metabolic-triggered inflammation and its components are anticipated to have potential for the treatment of OA.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.ULTRASMEDBIO.2019.11.017
Abstract: We compared the assessment of active synovitis in knee osteoarthritis (OA) by utilising superb microvascular imaging (SMI) and conventional power Doppler (cPD) techniques, and then correlated each technique with paients' symptoms, radiographic features and magnetic resonance imaging (MRI)-detected synovitis. A subgroup of participants with symptomatic knee OA underwent dynamic ultrasound assessment for semi-quantitative scores for SMI and cPD in the suprapatellar, medial and lateral parapatellar knee recesses. Knee pain and other symptoms were evaluated with the knee injury and osteoarthritis outcome score (KOOS). OA severity was assessed using the Kellgren and Lawrence grade (KLG) on radiograph and effusion-synovitis and Hoffa's synovitis score of MRI osteoarthritis knee score on non-contrast-enhanced MRI sequences. The χ
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.HUMIMM.2015.09.043
Abstract: Mesencephalic astrocyte-derived neurotrophic factor (MANF also known as arginine-rich, mutated in early tumors ARMET), is an ER stress-inducible protein, and widely expressed in mammalian tissues. In this study, we are interested in the profile of MANF expression in human splenocytes. Three patients with spleen trauma were enrolled in this study. Immunohistochemistry and immunofluorescence were used to detect MANF expression in the four types of cells, including T cells, B cells, plasma cells, and macrophages in spleens by using the specific antibodies of anti-CD3, anti-CD20, anti-CD138, and anti-CD68, respectively. We found that MANF-positive cells extensively distributed in the red pulp and marginal-zone of spleen, and MANF was almost localized in the cytoplasm of splenocytes. Double immunofluorescent staining results showed that MANF localized mainly in the plasma cells and macrophages, but not in T and B cells. Meanwhile, we found that some MANF-positive cells expressed ER stress-related proteins, including ATF6, XBP1s, BiP, and CHOP. These results suggest that the selective expression of MANF in splenocytes may be involved in plasma cell differentiation and immune regulation.
Publisher: Elsevier BV
Date: 12-2014
Publisher: BMJ
Date: 2021
DOI: 10.1136/BMJOPEN-2020-041328
Abstract: Postsurgical rehabilitation is critical for optimal recovery in people undergoing orthopaedic surgery. Currently, knee and lumbar spine postsurgical care is not standardised, economically sustainable, nor based on quality evidence, contributing to substantial clinical variation, poor outcomes and increasing healthcare costs. This protocol describes the design of a randomised controlled trial aiming to evaluate the effectiveness and cost-effectiveness of a postsurgical clinical pathway augmented by disruptive technology and compared with standardised rehabilitation alone, in decreasing pain and improving function after total knee replacement (TKR) or lumbar laminectomy (with or without fusion). An assessor-blinded, parallel group, randomised controlled trial will be conducted to recruit 204 consenting participants (102 per arm) of whom 50% are undergoing TKR and 50% lumbar surgery. The intervention group will receive a 6-month technology-enabled rehabilitation package in addition to usual postsurgical care. The package includes (1) an exercise program delivered via the Physitrack app on the iPad, (2) a health-coaching program delivered via video calls and motivational messages, (3) use of physical activity tracker with goal setting and motivational reminders (Fitbit). For those undergoing TKR, the intervention will also include knee joint range of motion self-monitoring via the Goniometer app. The control group will receive usual postsurgical care. Participants will be followed up at 3, 6 and 12 months from the enrolment date. The primary outcome is pain measured with the Numerical Rating Scale at 3 months. Secondary outcomes include pain-related disability, quality of life, computer self-efficacy, physical activity participation and sedentary behaviour. Data analysis will be blinded and by intention-to-treat. A trial-based cost-effectiveness analysis will determine the potential incremental cost per quality-adjusted life-year gained. This protocol is approved by the human research ethics committee of the University of Sydney. Dissemination will occur through lay summary, infographics, conferences and journal publications. ACTRN12618001448235.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.JOCA.2016.10.024
Abstract: To describe cross-sectional and longitudinal associations between serum levels of interleukin (IL) - 6, IL-17A, IL-17F, IL-23 and knee bone marrow lesions (BMLs) in patients with knee osteoarthritis (OA). Patients (n = 192) with symptomatic knee OA (mean 63 years, range 50-79, female 53%) were assessed at baseline and after 24 months. At each time point, serum IL-6, IL-17A, IL-17F and IL-23 were measured using Bio-Plex Baseline IL-6 (quarters) were significantly associated with total knee BMLs (P < 0.01 for the trend) as well as associated with an increase in BML score (P = 0.05 for the trend), after adjustment for confounders. Baseline IL-17F and IL-23 (highest quarters vs others) was associated with an increase in BML score in females (P = 0.04 for IL-17F P = 0.01 for IL-23), but not in males, in multivariable analyses. In contrast, IL-17A was not significantly associated with BMLs in either females or males. IL-6 is associated with increased knee BMLs in both females and males with OA. Serum IL-17F and IL-23 predicted increased knee BML scores in females only, suggesting that inflammation is involved in BML pathogenesis in knee OA, especially in women. ClinicalTrials.gov identifier: NCT01176344 Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.
Publisher: Wiley
Date: 31-08-2020
DOI: 10.1002/ACR.24333
No related grants have been discovered for Xia Wang.