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Objectives: Agreement between real-time and static ultrasonography has not been studied in musculoskeletal diseases. We studied this agreement in inflammatory hand OA., Methods: Ultrasonography was performed blinded to clinical information of 30 joints of 75 patients with hand OA, treated with prednisolone in a randomized placebo-controlled double-blind trial. Images were scored real-time at acquisition and stored images were scored static (paired in known chronological order) for inflammatory features and osteophytes (score 0-3). Agreement between methods was studied at joint level with quadratic weighted kappa. At patient level intra-class correlations (ICC) of sum scores and change in sum-scores (delta baseline-week 6) were calculated. Responsiveness of scoring methods was analysed with generalized estimating equations (GEE) with treatment as independent and ultrasonography findings as dependent variable., Results: Agreement at baseline was good to excellent at joint level (kappa 0.72-0.88) and moderate to excellent at patient level (ICC 0.58-0.91). Agreement for change in sum scores was poor to fair for synovial thickening and effusion (ICC 0.18 and 0.34, respectively), while excellent for Doppler signal (ICC 0.80). Real-time ultrasonography discriminated between prednisolone and placebo with a mean between-group difference of synovial thickening of -2.5 (95% CI: -4.7, -0.3). Static ultrasonography did not show a decrease in synovial thickening., Conclusion: While cross-sectional agreement between real-time and static ultrasonography is good, static ultrasonography measurement of synovial thickening did not show responsiveness to prednisone therapy while real-time ultrasonography did. Therefore, when ultrasonography is used in clinical trials, real-time dynamic scoring should remain the standard for now., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To investigate the two-year course of pain and osteoarthritic features on magnetic resonance imaging (MRI) in the thumb base., Methods: Patients in the Hand Osteoarthritis in Secondary Care (HOSTAS) cohort who had received radiographic examination, MRI, and clinical examination of the right thumb base at baseline and who had a 2-year follow-up period were studied. Pain on palpation of the thumb base was assessed on a 0-3 scale. MRIs were analyzed with the Outcome Measures in Rheumatology (OMERACT) thumb base osteoarthritis MRI scoring system for synovitis, bone marrow lesions (BMLs), subchondral bone defects, cartilage space loss, osteophytes, and subluxation. Radiographs were assessed for osteophytes and joint space narrowing. We studied the associations of changes in synovitis and BMLs with changes in pain using a logistic regression model adjusted for radiographic damage, with values expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs)., Results: Of 165 patients, 83% were women and the mean age was 60.7 years. At baseline, 65 patients had thumb base pain. At 2-year follow-up, pain had decreased in 32 patients and increased in 33 patients. MRI features remained stable in most patients. Structural MRI features generally deteriorated, while synovitis and BMLs improved in some individuals and deteriorated in others. Change in radiographic osteophytes rarely occurred (n = 10). Increased synovitis (odds ratio [OR] 3.4 [95% CI 1.3-9.3]) and increased BMLs (OR 5.1 [95% CI 2.1-12.6]) were associated with increased pain. Decreased BMLs appeared to be associated with decreased pain (OR 2.7 [95% CI 0.8-8.9]), and reductions in synovitis occurred too infrequently to calculate associations., Conclusion: Over 2 years, thumb base pain fluctuated, while MRI features changed in a minority of patients with hand osteoarthritis. Changes in synovitis and BMLs were associated with changes in pain on palpation, even after adjustment for radiographic damage., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

An exploratory study to determine the role of effusion, i.e., fluid in the joint, in pain, and radiographic progression in patients with hand osteoarthritis. Distal and proximal interphalangeal joints (87 patients, 82% women, mean age 59 years) were assessed for pain. T2-weighted and Gd-chelate contrast-enhanced T1-weighted magnetic resonance images were scored for enhanced synovial thickening (EST, i.e., synovitis), effusion (EST and T2-high signal intensity [hsi]) and bone marrow lesions (BMLs). Effusion was defined as follows: (1) T2-hsi > 0 and EST = 0; or 2) T2-hsi = EST but in different joint locations. Baseline and 2-year follow-up radiographs were scored following Kellgren-Lawrence, increase ≥ 1 defined progression. Associations between the presence of effusion and pain and radiographic progression, taking into account EST and BML presence, were explored on the joint level. Effusion was present in 17% (120/691) of joints, with (63/120) and without (57/120) EST. Effusion on itself was not associated with pain or progression. The association with pain and progression, taking in account other known risk factors, was stronger in the absence of effusion (OR [95% CI] 1.7 [1.0-2.9] and 3.2 [1.7-5.8]) than in its presence (1.6 [0.8-3.0] and 1.3 [0.5-3.1]). Effusion can be assessed on MR images and seems not to be associated with pain or radiographic progression but attenuates the association between synovitis and progression. Key Points • Effusion is present apart from synovitis in interphalangeal joints in patients with hand OA. • Effusion in finger joints can be assessed as a separate feature on MR images. • Effusion seems to be of importance for its attenuating effect on the association between synovitis and radiographic progression.

Background: Hand osteoarthritis is a prevalent joint condition that has a high burden of disease and an unmet medical need for effective therapeutic options. Since local inflammation is recognised as contributing to osteoarthritic complaints, the Hand Osteoarthritis Prednisolone Efficacy (HOPE) study aimed to investigate the efficacy and safety of short-term prednisolone in patients with painful hand osteoarthritis and synovial inflammation., Methods: The HOPE study is a double-blind, randomised, placebo-controlled trial. We recruited eligible adults from rheumatology outpatient clinics at two sites in the Netherlands. Patients were considered eligible if they had symptomatic hand osteoarthritis and signs of inflammation in their distal and proximal interphalangeal (DIP/PIP) joints. For inclusion, patients were required to have four or more DIP/PIP joints with osteoarthritic nodes; at least one DIP/PIP joint with soft swelling or erythema; at least one DIP/PIP joint with a positive power Doppler signal or synovial thickening of at least grade 2 on ultrasound; and finger pain of at least 30 mm on a 100-mm visual analogue scale (VAS) that flared up during a 48-h non-steroidal anti-inflammatory drug (NSAID) washout (defined as worsening of finger pain by at least 20 mm on the VAS). Eligible patients were randomly assigned (1:1) to receive 10 mg prednisolone or placebo orally once daily for 6 weeks, followed by a 2-week tapering scheme, and a 6-week follow-up without study medication. The patients and study team were masked to treatment assignment. The primary endpoint was finger pain, assessed on a VAS, at 6 weeks in participants who had been randomly assigned to groups and attended the baseline visit. This study is registered with the Netherlands Trial Registry, number NTR5263., Findings: We screened patients for enrolment between Dec 3, 2015, and May 31, 2018. Patients completed baseline visits and started treatment between Dec 14, 2015, and July 2, 2018, and the last study visit of the last patient was Oct 4, 2018. Of 149 patients assessed for eligibility, 57 (38%) patients were excluded (predominantly because they did not meet one or several inclusion criteria, most often because of an absence of synovial inflammation or of flare-ups after NSAID washout) and 92 (62%) patients were eligible for inclusion. We randomly assigned 46 (50%) patients to receive prednisolone and 46 (50%) patients to receive placebo, all of whom were included in the modified intention-to-treat analysis of the primary endpoint. 42 (91%) patients in the prednisolone group and 42 (91%) in the placebo group completed the 14-week study. The mean change between baseline and week 6 on VAS-reported finger pain was -21·5 (SD 21·7) in the prednisolone group and -5·2 (24·3) in the placebo group, with a mean between-group difference (of prednisolone vs placebo) of -16·5 (95% CI -26·1 to -6·9; p=0·0007). The number of non-serious adverse events was similar between the groups. Five serious adverse events were reported during our study: one serious adverse event in the prednisolone group (a myocardial infarction) and four serious adverse events in the placebo group (an infected traumatic leg haematoma that required surgery, bowel surgery, atrial fibrillation that required a pacemaker implantation, and symptomatic uterine myomas that required a hysterectomy). Four (4%) patients discontinued the study because of an adverse event: one (2%) patient receiving prednisolone (for a myocardial infarction) and three (7%) patients receiving placebo (for surgery of the bowel and for an infected leg haematoma and for Lyme disease arthritis of the knee)., Interpretation: Treatment with 10 mg prednisolone for 6 weeks is efficacious and safe for the treatment of patients with painful hand osteoarthritis and signs of inflammation. The results of our study provide clinicians with a new short-term treatment option for patients with hand osteoarthritis who report a flare-up of their disease., Funding: Dutch Arthritis Society., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate determinants of decrease and increase in joint pain in symptomatic finger osteoarthritis (OA) on magnetic resonance (MR) imaging over 2 years., Design: Eighty-five patients (81.2% women, mean age 59.2 years) with primary hand OA (89.4% fulfilling American College of Rheumatology (ACR) classification criteria) from a rheumatology outpatient clinic received contrast-enhanced MR imaging (1.5T) and physical examination of the right interphalangeal finger joints 2-5 at baseline and at follow-up 2 years later. MR images were scored paired in unknown time order, following the Hand OA MRI scoring system (HOAMRIS). Joint pain upon palpation was assessed by research nurses. Odds ratios (ORs; 95% confidence intervals) were estimated on joint level (n = 680), using generalized estimating equations (GEE) to account for the within patient effects. Additional adjustments were made for change in MR-defined osteophytes, synovitis, and bone marrow lesions (BMLs)., Results: Of 116 painful joints at baseline, at follow-up: 76 had less pain, 21 less synovitis, and 13 less BMLs. A decrease in synovitis (OR = 5.9; 1.12─31.0), but not in BMLs (OR = 0.39; 0.10─1.50), was associated with less pain. Of 678 joints without maximum baseline pain, at follow-up: 115 had increased pain, 132 increased synovitis, 96 increased BMLs, and 44 increased osteophytes. Increased synovitis (OR = 1.81; 1.11─2.94), osteophytes (OR = 2.75; 1.59─4.8), but not BMLs (OR = 1.14; 0.81─1.60), was associated with increased pain. Through stratification it became apparent that BMLs were mainly acting as effect modifier of the synovitis-pain association., Conclusion: Decrease in MR-defined synovitis is associated with reduced joint pain, identifying synovitis as a possible target for treatment of finger OA., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the construct validity of the new thumb base OA magnetic resonance imaging (MRI) scoring system (TOMS) by comparing TOMS scores with radiographic scores in patients with primary hand OA., Design: In 200 patients (83.5% women, mean (SD) age 61.0 (8.4) years), postero-anterior radiographs and MR scans (1.5 T) of the right first carpometacarpal (CMC-1) and scaphotrapeziotrapezoid (STT) joints, were scored using the OARSI atlas and TOMS, respectively. The distributions of the TOMS scores (specified in results section) were stratified for the OARSI scores of corresponding radiographic features and investigated using boxplots and non-parametric tests. Furthermore, Spearman's rank or Phi correlation coefficients (ρ/φ) were calculated., Results: For all features, especially for erosions and osteophytes, the prevalence found with MRI was higher than with radiography. TOMS osteophyte and cartilage loss scores differed statistically significant between corresponding OARSI scores in CMC-1 (0 vs 1; 1 vs 2). TOMS scores were positively correlated with radiographic scores in CMC-1 for osteophytes (coefficient [95% confidence interval], ρ = 0.75 [0.69; 0.81]), cartilage loss/joint space narrowing (ρ = 0.70 [0.62; 0.76]), subchondral bone defects (SBDs)/erosion-cyst (ρ = 0.41 [0.29; 0.52]), bone marrow lesions (BMLs)/subchondral sclerosis (ρ = 0.65 [0.56; 0.73]) and subluxation (φ = 0.65 [0.57; 0.73]); and in STT for osteophytes (ρ = 0.30 [0.17; 0.42]) and cartilage loss/joint space narrowing (ρ = 0.53 [0.42; 0.62])., Conclusions: In patients with hand OA, TOMS scores positively correlated with radiographic scores, indicating good construct validity. However, the prevalence of features on MR images was higher compared to radiographs, suggesting that TOMS might be more sensitive than radiography. The clinical meaning of these extra MR detected cases is currently still unknown., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Osteoarthritis in thumb base joints (first carpometacarpal (CMC-1), scaphotrapeziotrapezoid (STT)) is prevalent and disabling, yet focussed studies are scarce. Our aim was to investigate associations between ultrasonographic and magnetic resonance imaging (MRI) inflammatory features, radiographic osteophytes, and thumb base pain in hand osteoarthritis patients., Design: Cross-sectional analyses were performed in cohorts with MRI (n = 202) and ultrasound measurements (n = 87). Pain upon thumb base palpation was assessed. Radiographs were scored for CMC-1/STT osteophytes. Synovial thickening, effusion and power Doppler signal in CMC-1 joints were assessed with ultrasound. MRIs were scored for synovitis and bone marrow lesions (BMLs) in CMC-1 and STT joints using OMERACT-TOMS. Associations between ultrasound/MRI features, osteophytes, and thumb base pain were assessed. Interaction between MRI features and osteophytes was explored., Results: In 289 patients (mean age 60.2, 83% women) 139/376 thumb bases were painful. Osteophyte presence was associated with pain (MRI cohort: odds ratio (OR) 5.1 (2.7-9.8)). Ultrasound features were present in 25-33% of CMC-1 joints, though no associations were seen with pain. MRI-synovitis and BMLs grade ≥2 were scored in 25% and 43% of thumb bases, and positively associated with pain (OR 3.6 (95% CI 1.7-7.6) and 3.0 (1.6-5.5)). Associations attenuated after adjustment for osteophyte presence. Combined presence of osteophytes and MRI-synovitis had an additive effect., Conclusions: Ultrasonographic and MRI inflammatory features were often present in the thumb base. Osteophytes were more strongly associated with thumb base pain than inflammatory features, in contrast to findings in finger OA studies, supporting thumb base osteoarthritis as a distinct phenotype., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Because the association and its clinical relevance between comorbidities and primary hand osteoarthritis (OA) disease burden is unclear, we studied this in patients with hand OA from our Hand OSTeoArthritis in Secondary care (HOSTAS) cohort., Methods: Cross-sectional data from the HOSTAS study were used, including consecutive patients with primary hand OA. Nineteen comorbidities were assessed: 18 self-reported (modified Charlson index and osteoporosis) and obesity (body mass index ≥ 30 kg/m 2 ). Mean differences were estimated between patients with versus without comorbidities, adjusted for age and sex: for general disease burden [health-related quality of life (HRQOL), Medical Outcomes Study Short Form-36 physical component scale (0-100)] and disease-specific burden [self-reported hand function (0-36), pain (0-20; Australian/Canadian Hand OA Index), and tender joint count (TJC, 0-30)]. Differences above a minimal clinically important improvement/difference were considered clinically relevant., Results: The study included 538 patients (mean age 61 yrs, 86% women, 88% fulfilled American College of Rheumatology classification criteria). Mean (SD) HRQOL, function, pain, and TJC were 44.7 (8), 15.6 (9), 9.3 (4), and 4.8 (5), respectively. Any comorbidity was present in 54% (287/531) of patients and this was unfavorable [adjusted mean difference presence/absence any comorbidity (95% CI): HRQOL -4.4 (-5.8 to -3.0), function 1.9 (0.4-3.3), pain 1.4 (0.6-2.1), TJC 1.3 (0.4-2.2)]. Number of comorbidities and both musculoskeletal (e.g., connective tissue disease) and nonmusculoskeletal comorbidities (e.g., pulmonary and cardiovascular disease) were associated with disease burden. Associations with HRQOL and function were clinically relevant., Conclusion: Comorbidities showed clinically relevant associations with disease burden. Therefore, the role of comorbidities in hand OA should be considered when interpreting disease outcomes and in patient management.

Objective: To determine the association between bone marrow lesions (BMLs) and (teno)synovitis as assessed on magnetic resonance (MR) imaging in patients with pain in hand osteoarthritis (OA)., Methods: In 105 consecutive primary hand OA patients (83% women, mean age 59 years), who were diagnosed by rheumatologists and included in the HOSTAS (Hand OSTeoArthritis in Secondary care) cohort, contrast enhanced MR imaging of right distal and proximal interphalangeal joints were obtained. In 92 patients joint site specific pain upon palpation was assessed within 3 weeks of magnetic resonance imaging (MRI) examination. MR features were scored (0-3) following the Oslo hand OA score: BMLs, synovitis, cysts, flexor tenosynovitis (FTS). Additionally, extensor tendon inflammation (ETI) (0-3) was scored. Odds ratios (OR, 95% confidence interval (CI)) were calculated using generalized estimating equations for MR features with joint pain, adjusted for putative confounders. Stratified analyses were performed to investigate interaction., Results: BMLs, synovitis, cysts, FTS and ETI were demonstrated in 56%, 90%, 22%, 16% and 30% of patients, respectively. BMLs (grade 2/3 vs 0: 3.5 (1.6-7.7)) and synovitis (3 vs 0: OR 3.6 (95% CI 1.9-6.6)) were severity-dependent associated with joint pain, but FTS and ETI were not. Stratified analyses showed that BMLs did not associate with pain in the absence of synovitis, whereas synovitis was associated with pain in the absence of BMLs. Interaction was seen between BMLs and synovitis grade 2 or 3., Conclusion: In hand OA patients severe synovitis is associated with joint pain, which is worsened when BMLs co-occur, suggesting synovitis as primary target of treatment., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the association of magnetic resonance (MR) features with radiographic progression of hand osteoarthritis over 2 years., Methods: Of 87 primary patients with hand osteoarthritis (82% women, mean age 59 years), baseline distal and proximal interphalangeal joint contrast-enhanced MR images were scored 0-3 for bone marrow lesions (BMLs) and synovitis following the Oslo score. Baseline and 2-year follow-up radiographs were scored following Kellgren-Lawrence (KL) (0-4) and OsteoArthritis Research Society International (OARSI) scoring methods (0-3 osteophytes, joint space narrowing (JSN)). Increase ≥1 defined progression. Associations between MR features and radiographic progression were explored on joint and on patient level, adjusting for age, sex, body mass index, synovitis and BML. Joints in end-stage were excluded., Results: Of 696 analysed joints, 324 had baseline KL=0, 28 KL=4 and after 2 years 78 joints progressed. BML grade 2/3 was associated with KL progression (2/3 vs 0: adjusted risk ratio (RR) (95% CI) 3.3 (2.1 to 5.3)) and with osteophyte or JSN progression, as was synovitis. Summated scores were associated with radiographic progression on patient level (RR crude BML 1.08 (1.01 to 1.2), synovitis 1.09 (1.04 to 1.1), adjusted synovitis 1.08 (1.03 to 1.1))., Conclusions: BMLs, next to synovitis, show, already after 2 years, graded associations with radiographic progression, suggesting that both joint tissues could be important targets for therapy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To investigate the association between features of ultrasound-detected inflammation and development of erosive disease in patients with hand osteoarthritis (OA) over 2.3 years of followup., Methods: The study group comprised 56 consecutive patients with hand OA (mean age 61 years, 86% female) fulfilling the American College of Rheumatology criteria. Effusion, synovial thickening, and power Doppler signal in all interphalangeal (IP) joints were assessed with ultrasonography, using standardized methods, at baseline and followup. Radiographs were scored at both time points for osteophytes/joint space narrowing using the Osteoarthritis Research Society International method and for erosive disease (E phase [erosive] and R phase [remodeling]) using the method described by Verbruggen and Veys. Erosion development was defined as progression from N phase (normal) to E phase or R phase. Joints that were in E phase or R phase at baseline were excluded. Associations were analyzed using generalized estimating equations with adjustment for age, sex, body mass index, and baseline structural abnormalities., Results: At baseline, 51 IP joints (in 18 patients) and at followup 89 IP joints (in 26 patients) had erosions; thus, erosions developed in 38 IP joints. Moderate/severe synovial thickening and a power Doppler signal at baseline were associated with erosion development (adjusted odds ratio [OR] 8.8, 95% confidence interval [95% CI] 2.4-32.3 and OR 7.1, 95% CI 1.9-26.9, respectively). Persistent inflammation was particularly associated with the development of erosions., Conclusion: Ultrasound-detected features of inflammation are associated with the development of erosions in patients with hand OA, suggesting that inflammation plays a role in the pathogenesis of hand OA and could be a therapeutic target., (© 2016, American College of Rheumatology.)

Objective: To study the development of inflammatory features and it's relation to structural damage over a 2.3-year period in patients with hand osteoarthritis (HOA)., Methods: Synovial thickening, effusion and power Doppler signal (PDS) in distal interphalangeal (DIP), proximal interphalangeal (PIP), 1st carpometacarpal (CMC) metacarpal phalangeal (MCP) and 1st interphalangeal (IP) joints were assessed using ultrasonography in 56 consecutive HOA patients (mean age 61.2 years, 85.7% female) fulfilling American College of Rheumatology (ACR) classification criteria, at baseline and follow-up. Radiographic progression of osteophytes and joint space narrowing (JSN) was scored using the OARSI atlas. With generalised estimating equations (GEE), OR with 95% CIs were calculated for the associations between inflammatory ultrasound features and radiographic progression taking in account patient effect, age, gender, Body Mass Index, baseline osteophytes and JSN scores, and other inflammatory ultrasound features., Results: Of 1680 joints, 8.4%, 8.7%, and 19.8% had synovial thickening, PDS or effusion at baseline, respectively. 7.1% and 5.7% of joints had progression of osteophytes and JSN, respectively. Independent associations were found between synovial thickening, effusion and PDS (grade 2-3 vs 0), and progression of osteophytes (OR (95% CI): 2.6 (1.02 to 6.5), 3.5 (1.7 to 7.4) and 5.7 (1.5 to 21.1)) and of JSN (OR (95% CI): 3.4 (1.3 to 8.4), 3.3 (1.5 to 7.6) and 3.1 (1.01 to 9.2)). Persistent inflammatory features at baseline and follow-up showed stronger associations with radiographic progression than fluctuating inflammatory features in comparison with no inflammatory features., Conclusions: Inflammatory features, especially when persistently present, are independently associated with radiological progression in HOA after 2.3 years, indicating a role of inflammation in the aetiology of structural damage in HOA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To investigate criterion validity and intraobserver reliability of magnetic resonance imaging (MRI) in hand osteoarthritis (HOA)., Methods: In 16 patients with HOA (median age 57 yrs, 62% women, 13 with erosive OA), 3 Tesla MRI scans with gadolinium-chelate administration of right second to fifth distal interphalangeal/proximal interphalangeal joints were scored according to the Oslo HOA scoring method for synovial thickening, bone marrow lesions (BML), osteophytes, joint space narrowing (JSN), and erosions (grade 0-3). Ultrasound (US) was scored for synovial thickening and osteophytes, radiographs for osteophytes and JSN (Osteoarthritis Research Society International score), and anatomical phases (Verbruggen-Veys score). Pain was assessed during physical examination. Correlations of MRI with US and radiographic features were assessed with generalizability theory. With generalized estimating equations analyses, MRI features were associated with pain, adjusting for confounding., Results: Forty-three percent, 27%, 77%, and 61% of joints had synovial thickening (moderate/severe), BML, osteophytes, and erosions on MRI, respectively. Intraobserver reliability, assessed in 6 patients, was good (ICC 0.77-1.00). Correlations between osteophytes, JSN, and erosions on radiographs and MRI were moderate, substantial, and fair (ICC 0.53, 0.68, and 0.32, respectively); MRI showed more lesions than radiography. Correlation between synovial thickening and osteophytes on MRI and US was moderate (ICC 0.43 and 0.49, respectively). MRI was more sensitive for synovial thickening, US for osteophytes. Pain was associated with moderate/severe synovial thickening (adjusted OR 2.4, 95% CI 1.06-5.5), collateral ligaments (4.2, 2.2-8.3), BML (3.5, 1.6-7.7), erosions (4.5, 1.7-12.2), and osteophytes (2.4, 1.1-5.2)., Conclusion: MRI is a reliable and valid method to assess inflammatory and structural features in HOA. It gives additional information over radiographs and US.

Objective: To study inflammatory ultrasound (US) features and pain over a 3-month period in hand osteoarthritis (HOA)., Design: In 25 consecutive HOA patients (mean age 60 years, 76% female), fulfilling the American College of Rheumatology (ACR) criteria, visual analogue scale (VAS) pain scores were collected at baseline and 3 months. In 750 [all first carpometacarpal (CMC), metacarpalphalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP) and first interphalangeal (IP)] joints, pain was assessed upon palpation and synovial thickening, effusion and power Doppler signal (PDS) were scored with standardized methods by US. Associations between inflammatory features and painful joints were analysed using generalized estimated equations to account for patient effects, adjusting for confounders, and presented as odds ratios (ORs) with 95% confidence intervals (95%CI)., Results: Inflammatory US features were seen in (nearly) all patients. The median number (range) of inflammatory joints per patient did not change over time: 9 (0-16) to 9 (2-18). In 18.7% of joints inflammatory features were present at both time points; in 20.5% inflammatory features occurred only at baseline or follow-up. Pain decreased over time: median VAS pain 49-39 mm; median number of painful joints 8-3. Synovial thickening, effusion and PDS were associated with pain upon palpation both at baseline and follow-up: OR 2.9 (1.4, 5.7), 2.7 (1.7, 4.3), 3.6 (2.1, 6.3) and 7.3 (3.2, 16.5), 3.3 (2.3, 4.7), 4.1 (2.1, 7.9). respectively., Conclusions: In HOA inflammatory US features are stable over time at patient level, but vary on joint level. Pain diminished after 3 months, while associations between painful joints and inflammation seem to increase, emphasizing the multifactorial aetiology of pain., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare inflammation as assessed by ultrasound between patients with the subset erosive hand osteoarthritis (EOA) versus non-EOA., Methods: Consecutive hand osteoarthritis (HOA) patients (fulfilling ACR criteria) were included. Eighteen interphalangeal joints were scored on radiographs using the Verbruggen-Veys anatomical phase score; E and R phases were defined as erosive. Patients were assigned to EOA when at least one joint was erosive. Effusion, synovial thickening and power Doppler signal (PDS) were scored with ultrasound on a 4-point scale. Generalised estimated equation analyses were used to compare ultrasound features between EOA and HOA, and to associate ultrasound features with.anatomical phases; OR with 95% CI were calculated with adjustments for patient effects and confounders., Results: Of 55 HOA patients (mean age 61 years, 86% women) 51% had EOA. In 94 erosive joints, synovial thickening, effusion and PDS were found in 13%, 50% and 15%, respectively; in 896 non-erosive joints in 10%, 26% and 8%, respectively. In summated scores of PDS, effusion was higher in EOA than in non-EOA. Effusion and synovial thickening were more frequent in S, J, E and R phases compared to N phase. PDS was only associated with E phase (OR 5.3, 95% CI 1.3 to 20.5) not with other phases. Non-erosive joints in EOA demonstrated more PDS (OR 3.2, 95% CI 1.6 to 6.4) and effusion (OR 2.2, 95% CI 1.2 to 3.8) in comparison to joints in non-EOA., Conclusions: Inflammatory signs are more frequent in EOA than in non-EOA, not only in erosive joints but also in non-erosive joints, suggesting an underlying systemic cause for erosive evolution.

Objective: Although a few consistent osteoarthritis (OA) susceptibility genes have been identified, little is known on OA progression. Since OA progression is clinically the most relevant phenotype, we investigate the association between asporin (ASPN), bone morphogenetic protein 5 (BMP5) and growth differentiation factor 5 (GDF5) polymorphisms and progression of hand OA., Methods: Single-nucleotide polymorphisms (SNPs) ASPN rs13301537, BMP5 rs373444 and GDF5 rs143383 were genotyped in 251 hand OA patients from the Genetics osteoARthritis and Progression (GARP) study and 725 controls. In a case-control comparison we assessed the association between these SNPs and radiographic progression of hand OA over 6 years, which was based on change in osteophytes or joint space narrowing (JSN), above the smallest detectable change. SNPs with suggestive evidence for association were further analysed for their effect on progression over 2 years, and for the mean change in osteophytes and JSN., Results: The minor allele of ASPN SNP rs13301537 was associated with hand OA progression over 6 years (odds ratio (OR) (95% CI) 1.49 (1.06-2.07); P = 0.020). The mean change in osteophytes and JSN was higher in carriers of the minor allele compared to homozygous carriers of the common allele with mean difference of 0.73 (95% CI - 0.07-1.56; P = 0.073) and 0.82 (95% CI 0.12-1.52; P = 0.022), respectively. An association with similar effect size was found between ASPN SNP rs13301537 and 2-year progression, and the mean change in osteophytes and JSN was significantly higher in homozygotes., Conclusion: ASPN is associated with hand OA progression. This gives insight in the pathogenesis of hand OA progression and identified a potential target for therapeutic approaches., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the associations between structural abnormalities on ultrasound (US) or conventional x-rays (CR) and pain in hand osteoarthritis (HOA)., Methods: In 55 consecutive patients with HOA (mean age 61 years, 86% women) fulfilling the American College of Rheumatology criteria, pain in 30 separate hand joints was assessed upon palpation; osteophytes were assessed by US and CR and joint space narrowing (JSN) by CR. Associations between structural abnormalities and pain per joint were analysed using generalised estimated equations to account for patient effects and adjusted for age, sex, body mass index, US inflammatory features and other remaining structural abnormalities., Results: In 1649 joints, 69% and 46% had osteophytes on US and CR, respectively and 47% had JSN. Osteophytes and JSN showed independent associations with pain per joint adjusted: OR for osteophytes: 4.8 (95% CI 3.1 to 7.5) for US and 4.1 (95% CI 2.4 to 7.1) for CR; for JSN: 4.2 (95% CI 2.0 to 9.0)., Conclusions: Osteophytes and JSN are independently associated with pain in individual HOA joints, taking into account patient effects.

Objectives: To investigate the association of ultrasound (US) features-grey scale (GS) synovitis, synovial thickening, effusion and power Doppler signal (PDS)-with symptoms in hand osteoarthritis (HOA)., Methods: Fifty-five consecutive patients (mean age 62 years, 87% women) with HOA, fulfilling the American College of Rheumatology criteria, were assessed for pain upon palpation and filled in Australian/Canadian Osteoarthritis Index (AUSCAN) scores, visual analogue scale pain and Short Form-36 (SF-36). US was performed in all metacarpophalangeal, proximal interphalangeal, distal interphalangeal, first interphalangeal and first carpometacarpal joints, and features were semiquantitatively scored (0-3). Generalised estimating equations were used to calculate OR (95% CI) for the association between US features and pain per joint adjusted for relevant confounders. The association between US features summated scores and self-reported outcomes was studied by linear regression analysis., Results: GS synovitis, effusion, synovial thickening and PDS were shown in 96%, 91%, 73% and 86% of patients, respectively. US features were dose-dependently associated with pain upon palpation (OR 4.5 (95% CI 2.2 to 9.0), 4.4 (2.0 to 9.4), 4.9 (2.2 to 11.0) and 4.1 (2.2 to 7.9)). GS synovitis was associated with AUSCAN pain, stiffness and SF-36, and effusion with AUSCAN pain., Conclusions: GS synovitis, effusion, synovial thickening and PDS are associated with pain in HOA, suggesting a role for inflammation. Further follow-up studies are warranted.

Objective: Inflammatory hand arthritis (IHA) results in impaired function. Local gene therapy with ART-I02, a recombinant adeno-associated virus (AAV) serotype 5 vector expressing interferon (IFN)-β, under the transcriptional control of nuclear factor κ-B responsive promoter, was preclinically shown to have favorable effects. This study aimed to investigate the safety and tolerability of local gene therapy with ART-I02 in patients with IHA.Methods: In this first-in-human, dose-escalating, cohort study, 12 IHA patients were to receive a single intra-articular (IA) injection of ART-I02 ranging 0.3 × 1012-1.2 × 1013 genome copies in an affected hand joint. Adverse events (AEs), routine safety laboratory and the clinical course of disease were periodically evaluated. Baseline- and follow-up contrast enhanced magnetic resonance images (MRIs), shedding of viral vectors in bodily fluids, and AAV5 and IFN-β immune responses were evaluated. A data review committee provided safety recommendations.Results: Four patients were enrolled. Long-lasting local AEs were observed in 3 patients upon IA injection of ART-I02. The AEs were moderate in severity and could be treated conservative. Given the duration of the AEs and their possible or probable relation to ART-I02, no additional patients were enrolled. No systemic treatment emergent AEs were observed. The MRIs reflected the AEs by (peri)arthritis. No T-cell response against AAV5 or IFN-β, nor IFN-β antibodies could be detected. Neutralizing antibody titers against AAV5 raised post-dose.Conclusion: Single IA doses of 0.6 × 1012 or 1.2 × 1012 ART-I02 vector genomes were administered without systemic side effects or serious AEs. However, local tolerability was insufficient for continuation.Trial Registration: NCT02727764. [ABSTRACT FROM AUTHOR]

Objective: To investigate if knee osteoarthritis (OA) is associated with lower physical activity in the general middle-aged Dutch population, and if physical activity is associated with patient-reported outcomes in knee OA.Design: Clinical knee OA was defined in the Netherlands Epidemiology of Obesity population using the ACR criteria, and structural knee OA on MRI. We assessed knee pain and function with the Knee Injury and Osteoarthritis Score (KOOS), health-related quality of life (HRQoL) with the Short Form-36, and physical activity (in Metabolic Equivalent of Task (MET) hours) with the Short Questionnaire to Assess Health-enhancing physical activity. We analysed the associations of knee OA with physical activity, and of physical activity with knee pain, function, and HRQoL in knee OA with linear regression adjusted for potential confounders.Results: Clinical knee OA was present in 14% of 6,212 participants, (mean age 56 years, mean BMI 27 kg/m2, 55% women, 24% having any comorbidity) and structural knee OA in 12%. Clinical knee OA was associated with 9.60 (95% CI 3.70; 15.50) MET hours per week more physical activity, vs no clinical knee OA. Structural knee OA was associated with 3.97 (-7.82; 15.76) MET hours per week more physical activity, vs no structural knee OA. In clinical knee OA, physical activity was not associated with knee pain, function or HRQoL.Conclusions: Knee OA was not associated with lower physical activity, and in knee OA physical activity was not associated with patient-reported outcomes. Future research should indicate the optimal treatment advice regarding physical activity for individual knee OA patients. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the effectiveness of exercise therapy in patients with meniscal lesions.Design: Systematic review and meta-analysis.Methods: Nine databases were searched up to July 2015, including EMBASE and Medline OvidSP. Randomized and controlled clinical trials in adults with traumatic or degenerative meniscal lesions were considered for inclusion. Interventions had to consist of exercise therapy in non-surgical patients or after meniscectomy, and had to be compared with meniscectomy, no exercise therapy, or to a different type of exercise therapy. Primary outcomes were pain and function on short term (≤3 months) and long term (>3 months). Two researchers independently selected the studies, assessed the risk of bias, and extracted data.Results: Of the 1415 identified articles 14 articles describing 12 studies were included; all had some concerns about the risk of bias. There was no significant difference between exercise therapy and meniscectomy for pain (MD 0.27 [-4.30,4.83]) and function (SMD -0.32 [-0.68,0.03]). After meniscectomy, there was conflicting evidence for the effectiveness of exercise therapy when compared to no exercise therapy for pain and function. There was no significant difference between various types of exercise therapy for pain (MD 19.30 [-6.60,45.20]) and function (SMD 0.01 [-0.27,0.28]).Conclusions: Exercise therapy and meniscectomy yielded comparable results on pain and function. Exercise therapy compared to no exercise therapy after meniscectomy showed conflicting evidence at short term, but was more effective on function at long term. The preferable type/frequency/intensity of exercise therapy remains unclear. The strength of the evidence was low to very low. [ABSTRACT FROM AUTHOR]

Several genes involved in the familial appearance of thoracic aortic aneurysms and dissections ( FTAAD) have been characterized recently, one of which is SMAD3. Mutations of SMAD3 cause a new syndromic form of aortic aneurysms and dissections associated with skeletal abnormalities. We discovered a small interstitial deletion of chromosome 15, leading to disruption of SMAD3, in a boy with mild mental retardation, behavioral problems and revealed features of the aneurysms-osteoarthritis syndrome ( AOS). Several family members carried the same deletion and showed features including aortic aneurysms and a dissection. This finding demonstrates that haploinsufficiency of SMAD3 leads to development of both thoracic aortic aneurysms and dissections, and the skeletal abnormalities that form part of the aneurysms-osteoarthritis syndrome. Interestingly, the identification of this familial deletion is an example of an unanticipated result of a genomic microarray and led to the discovery of important but unrelated serious aortic disease in the proband and family members. [ABSTRACT FROM AUTHOR]