Synovitis and bone marrow lesions associate with symptoms and radiographic progression in hand osteoarthritis: a systematic review and meta-analysis of observational studies.

AIMS: To systematically review observational studies for the association between features detected on ultrasound (US) and magnetic resonance imaging (MRI) and, symptoms, signs and radiographic progression of hand osteoarthritis (OA). METHODS: Medline, Web of Science, EMBASE, CINAHL and AMED were searched from inception to 14th January 2020 to identify relevant studies. Quality of studies was assessed using the Newcastle-Ottawa scales and data were extracted. Odds ratios (OR) and linear regression coefficients and 95% confidence intervals (CI) were pooled using the random-effects model (METAN package, Stata v16.1). Heterogeneity and publication bias were assessed. RESULTS: Thirty-two studies using US and MRI comprising 1,350 and 638 participants respectively were included. While only grey-scale synovitis (GSS) associated with AUSCAN-pain (pooled Regression coefficient (95% CI): 0.46 (0.13-0.79); 0-20 scale for AUSCAN-pain), US-detected osteophytes, GSS and power Doppler (PD) [pooled ORs (95% CI): 2.68(2.16-3.33), 2.38(1.74-3.26) and 2.04 (1.45-2.88)] as well as MRI-detected bone marrow lesions (BMLs), synovitis, osteophytes, and central bone erosions (CBEs) associated with joint tenderness [pooled ORs (95% CI): 2.59(2.12-3.18), 2.17(1.85-2.54), 2.15(1.55-2.99), and 2.41 (1.45-4.02)] respectively. US-detected GSS and PD associated with radiographic progression of CBEs [pooled ORs 5.37, 5.08], osteophytes [pooled ORs 5.17, 6.45], and joint space narrowing (pooled ORs 4.28, 4.36) whilst MRI-detected synovitis and BMLs associated with increasing KL grades with pooled ORs 2.92, 2.54 respectively. CONCLUSIONS: US and MRI-detected structural and inflammatory changes associate with tenderness, whilst articular inflammation and subchondral bone damage associate with radiographic hand OA progression. There was inconsistent relationship between these changes and pain.

Get a Grip on Factors Related to Grip Strength in Persons With Hand Osteoarthritis: Results From an Observational Cohort Study.

OBJECTIVE: To compare levels of grip strength in individuals with hand osteoarthritis (OA) with normative values, and to examine how hand OA severity and other biopsychosocial factors are associated with grip strength. METHODS: Levels of grip strength across age groups were compared with normative values from the general population in sex-stratified analyses using 2-sample t-tests. Associations between radiographic hand OA severity (Kellgren/Lawrence sum score) in different joint groups and grip strength of the same hand were examined in 300 individuals from the Nor-Hand study using linear regression. Analyses were repeated using markers of pain, demographic factors, comorbidities, and psychological and social factors as independent variables. We adjusted for age, sex, and body mass index. RESULTS: Individuals with hand OA had lower grip strength than the general population, especially in individuals age <60 years. In thumb base joints, increasing radiographic severity (range 0-8) and the presence of pain were associated with lower grip strength (ß = -0.83 [95% confidence interval (95% CI) -1.12, -0.53] and ß = -2.15 [95% CI -3.15, -1.16], respectively). Negative associations with grip strength were also found for women, low education, higher comorbidity index, and higher resting heart rate. CONCLUSION: Individuals with hand OA have lower grip strength than the general population. Our results support the idea that studies on thumb base OA should include grip strength as an outcome measure. However, other biopsychosocial factors should also be considered when the grip strength is being interpreted, because other factors such as sex, socioeconomic factors, physical fitness, and comorbidities are negatively associated with grip strength.

Effects of Neurodynamic Mobilizations on Pain Hypersensitivity in Patients With Hand Osteoarthritis Compared to Robotic Assisted Mobilization: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of the neurodynamic mobilization techniques compared with passive robotic physiologic movement in patients with hand osteoarthritis (OA). METHODS: We conducted a randomized controlled trial. A total of 72 patients (mean ± SD age 71 ± 11 years) with dominant symptomatic hand OA were randomized in 2 groups, and both received 12 treatment sessions over 4 weeks. The experimental group received neurodynamic mobilization of the median, radial, and ulnar nerves, and the control group received robotic-assisted passive movement treatment. Both groups also participated in a program of hand stability exercises. Outcome measures included pain intensity, pressure pain thresholds (PPTs), and strength measurements. Group-by-time effects were compared using mixed-model analyses of variance. RESULTS: After the intervention, the experimental group had statistically significant, higher PPTs than the control group at the thumb carpometacarpal joint by 0.7 kg/cm2 (95% confidence interval [95% CI] 0.6, 0.8), the median nerve by 0.7 kg/cm2 (95% CI 0.6, 0.7), and the radial nerve by 0.5 kg/cm2 (95% CI 0.3, 0.6); however, the difference was not statistically significant at 3 months postintervention. Although mean values in the experimental group were higher than in the control group at all PPT sites at both assessments, these differences were not statistically significant. The experimental group experienced a statistically significant reduction in pain immediately postintervention, but this was not present at the 3-month follow-up. There were no statistically significant differences in pinch or grip strength between groups. CONCLUSION: We found that neurodynamic mobilizations decreased hypersensitivity in patients with hand OA immediately after the intervention; however, differences were no longer present at 3 months. The results suggest that these techniques may have some limited value in the short term but do not have lasting effects.

Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).

BACKGROUND: Colchicine may offer relief in osteoarthritis. This has never been investigated for hand osteoarthritis. OBJECTIVES: To investigate the effect of 1 mg daily colchicine vs placebo on hand pain and function over 12 weeks in older adults with hand osteoarthritis. METHODS: Community-dwelling adults with diagnosed osteoarthritis of the hand aged 40-80 years were randomised to receive colchicine (0.5 mg twice daily) or matching placebo. Primary outcome measure was VAS hand pain score (0-100 mm). Secondary outcome measures included tender and swollen joint count, grip strength, C-reactive protein, and Michigan Hand Questionnaire total, function and pain scores. In an exploratory assessment, we compared synovial grade and power Doppler. All outcome measures were obtained at baseline and week 12. Stata v16 was used to perform constrained longitudinal data analysis models. RESULTS: 64 adults (54 females, 10 males) aged 48-79 years of age were enrolled. 59 participants completed the study (N = 28 colchicine, N = 31 placebo) (withdrawal rate 8%). Adverse reactions to the study medication occurred in nine patients. VAS score was not significantly different at baseline (61 ± 17 mm in the colchicine, 64 ± 17 mm in the placebo group). Between-group difference for VAS score at week 12 was 7.6 mm (95% CI -3.5-18.7, p-value 0.18). There were no significant differences between groups for any secondary outcomes at baseline or week 12. CONCLUSIONS: 1 mg colchicine daily for 12 weeks was not effective for reducing pain, tender and swollen joint count or increasing grip strength in symptomatic hand osteoarthritis. Our results do not support the use of colchicine in hand osteoarthritis.

Factors Associated With Functional Decline in Hand and Hip/Knee Osteoarthritis After One Year: Data From a Population-Based Study.

OBJECTIVE: To investigate factors that together with hand or hip/knee osteoarthritis (OA) could contribute to functional decline over a year's time in elderly individuals. METHODS: The data of 1,886 individuals between ages 65 and 85 years in a prospective, observational population-based study with 12-18 months of follow-up in the context of the European Project on Osteoarthritis were analyzed. The outcome measures were self-reported hand and hip/knee functional decline, evaluated using a minimum clinically important difference of 4 on the Australian/Canadian Hand OA Index and of 2 on the Western Ontario and McMaster Universities Osteoarthritis Index hip/knee physical function subscales, both normalized to 0-100. Using regression models adjusted for sex, age, country, and education level, the baseline factors considered were clinical hand or hip/knee OA, pain, analgesic/antiinflammatory medications, comorbidities, social isolation, income, walking time, grip strength, physical activity time, and medical/social care. RESULTS: After a year, 453 participants were identified as having worse hand functionality and 1,389 as not worse. Hand OA, anxiety, walking time, and grip strength were risk factors for hand functional decline; pain was a confounder of the effect of hand OA. Analgesic/antiinflammatory medications mediated the combined effect of hip/knee OA plus pain on functional decline in the 554 individuals classified as having worse hip/knee functionality and the 1,291 persons who were not worse. Peripheral artery disease, obesity, and cognitive impairment were other baseline risk factors. CONCLUSION: Study findings showed that together with emotional status and chronic physical and cognitive conditions, OA affects hand and hip/knee functional decline.

Evaluation of the content validity index of the Australian/Canadian osteoarthritis hand index, the patient-rated wrist/hand evaluation and the thumb disability exam in people with hand arthritis.

BACKGROUND: The Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Patient-Rated Wrist/Hand Evaluation (PRWHE) and the Thumb Disability Exam (TDX) are patient-reported outcome measures (PROM) designed to assess pain and hand function in patients with hand arthritis, hand pain and disability, or thumb pathology respectively. This study evaluated the content validity of AUSCAN, PRWHE and TDX in people with hand arthritis. METHODS: This study enrolled participants with hand arthritis to rate the items of all 3 PROM in terms of relevance and clarity. The Content Validity Index (CVI) was computed for each item in each scale (I-CVI) as well as for the overall scale (S-CVI). Kappa was used to determine the inter-rater agreement among the raters. RESULTS: Overall, 64 individuals with hand arthritis (27% with OA, 67% with rheumatoid arthritis and 6% with psoriatic arthritis) participated in the study. The I-CVI for all items and all scales were very high (I-CVI > 0.76) and the modified Kappa agreement among the raters demonstrated excellent agreement (k > 0.76). The S-CVI for all PROMs was very high for relevance (AUSCAN = 0.92, 95% CI 0.90 to 0.94; PRWHE = 0.85, 95% CI 0.82 to 0.88 and TDX = 0.87, 95% CI 0.85 to 0.89) and for clarity (AUSCAN = 0.99, 95% CI 0.98 to 1.00; PRWHE = 0.95, 95% CI 0.93 to 0.97 and TDX = 0.91, 95% CI 0.89 to 0.94), respectively. CONCLUSIONS: This study demonstrated very high content validity indices for the AUSCAN, PRWHE and TDX; with strong consensus across raters. This augments prior studies demonstrating appropriate statistical measurement properties, to provide confidence that all three measures assess important patient concepts of pain and disability.

Altered Lymphatic Vessel Anatomy and Markedly Diminished Lymph Clearance in Affected Hands of Patients With Active Rheumatoid Arthritis.

OBJECTIVE: To assess differences between lymphatic function in the affected hands of rheumatoid arthritis (RA) patients with active synovitis and that of healthy controls, using indocyanine green (ICG) dye and near-infrared (NIR) imaging. METHODS: NIR imaging of the hands of 8 patients with active RA and 13 healthy controls was performed following web space injection of 0.1 ml of 100 µM ICG. The percentage of ICG retention in the web spaces was determined by NIR imaging at baseline and at 7 days (±1 day) after the initial injections; image analysis provided contraction frequency. ICG+ lymphatic vessel (LV) length and branching architecture were assessed. RESULTS: Retention of ICG in RA hands was higher compared to controls (P < 0.01). The average contraction frequency of ICG+ LVs in RA patients and in controls did not differ (mean ± SD 0.53 ± 0.39 contractions/minute versus 0.51 ± 0.35 contractions/minute). Total ICG+ LV length in RA hands was lower compared to healthy controls (58.3 ± 15.0 cm versus 71.4 ± 16.1 cm; P < 0.001), concomitant with a decrease in the number of ICG+ basilic LVs in the hands of RA patients (P < 0.05). CONCLUSION: Lymphatic drainage in the hands of RA patients with active disease was reduced compared to controls. This reduction was associated with a decrease in total length of ICG+ LVs on the dorsal surface of the hands, which continued to contract at a similar rate to that observed in controls. These findings provide a plausible mechanism for exacerbation of synovitis and joint damage, specifically the accumulation and retention of inflammatory cells and catabolic factors in RA joints due to impaired efferent lymphatic flow. NIR/ICG imaging of RA hands is feasible and warrants formal investigation as a primary outcome measure for arthritis disease severity and/or persistence in future clinical trials.

GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

Incidence and progression of hand osteoarthritis in a large community-based cohort: the Johnston County Osteoarthritis Project.

OBJECTIVE: To describe the incidence and progression of radiographic and symptomatic hand osteoarthritis (rHOA and sxHOA) in a large community-based cohort. DESIGN: Data were from the Johnston County OA Project (1999-2015, 12 ± 1.2 years follow-up, age 45+). Participants had bilateral hand radiographs each visit, read for Kellgren-Lawrence grade (KLG) at 30 joints. We defined rHOA as KLG ≥2 in ≥1 joint. SxHOA was defined in a hand/joint with rHOA and self-reported symptoms or tenderness on exam. Incidence was assessed in those without, while progression was assessed in those with, baseline rHOA. Proportions or medians are reported; differences by sex and race were assessed using models appropriate for dichotomous or continuous definitions, additionally adjusted for age, education, body mass index (BMI), and weight change. RESULTS: Of 800 participants (68% women, 32% African American, mean age 60 years), 327 had baseline rHOA and were older, more often white and female, than those without rHOA (n = 473). The incidence of HOA was high, for rHOA (60%) and for sxHOA (13%). Women were more likely than men to have incident HOA, particularly for distal interphalangeal joint radiographic osteoarthritis (DIP rOA) (adjusted odds ratios (aOR) 1.60 95% confidence intervals (95% CI) [1.03, 2.49]) and sxHOA (aOR 2.98 [1.50, 5.91]). Progressive HOA was more similar by sex, although thumb base rOA progressed more frequently in women than in men (aOR 2.56 [1.44, 4.55]). Particularly HOA incidence, but also progression, was more frequent among whites compared with African Americans. CONCLUSION: This study provides much needed information about the natural history of HOA, a common and frequently debilitating condition, in the general population.

Impact of thumb osteoarthritis on pain, function, and quality of life: a comparative study between erosive and non-erosive hand osteoarthritis.

OBJECTIVE: The study was aimed to compare the impact of thumb base osteoarthritis (TBOA) on pain, function, and quality of life in patients with erosive or non-erosive hand osteoarthritis (HOA). METHODS: This observational retrospective study included 232 patients: 64 with erosive HOA (EHOA) and concomitant TBOA, 36 with isolated EHOA, 97 with non-erosive HOA (non-EHOA) and TBOA, and 35 with isolated non-EHOA. Hand pain by a visual analogue scale (VAS), Functional Index for Hand Osteoarthritis (FIHOA) score, Health Assessment Questionnaire (HAQ), the Medical Outcomes Study 36-Item Short Form (SF-36), and the possible correlations between VAS and FIHOA with radiological score were assessed. RESULTS: No differences were found between EHOA with TBOA and isolated EHOA in VAS and FIHOA scores; opposite, there was a significant difference in VAS (p < 0.01) and FIHOA (p < 0.001) between subjects with non-EHOA and TBOA and patients with only non-EHOA. VAS and FIHOA values resulted slightly higher in patients with EHOA and TBOA vs non-EHOA and TBOA; they were significantly more elevated in EHOA and TBOA group compared to isolated non-EHOA (p ≤ 0.001) and in isolated EHOA vs isolated non-EHOA (p < 0.01 and p < 0.001, respectively). HAQ, SF-36 resulted significantly better in isolated non-EHOA patients compared to the other groups. Finally, we observed a significant correlation between FIHOA and all the Kallman scales in EHOA patients with TBOA and between FIHOA and Kallman's thumb score in non-EHOA-TBOA group. CONCLUSIONS: EHOA has a more severe clinical burden than non-EHOA; the presence of TBOA appeared an important determinant of pain and disability in non-EHOA.Key Points• Each subset of HOA can have a different impact on pain and functionality, with EHOA determining more severe effects on hand symptoms and disability than non-EHOA.• The presence of TBOA appeared an important determinant of pain and disability in non-EHOA, but not in EHOA.• Our findings support the need for an individualized therapy for each phenotype of hand osteoarthritis.

Extracorporal shock wave therapy for the treatment of arthrodesis non-unions.

INTRODUCTION: Non-union is a regular complication of arthrodeses. Standard treatment includes revision surgery with frequent need for re-revision due to persistent non-union. Particularly patients with concomitant diseases are at risk of secondary complications. There is a need for evaluation of alternative treatment options. The aim of this study is to provide first evidence on union-rate and pain course after focussed extracorporeal shock-wave therapy of arthrodesis non-unions. PATIENTS AND METHODS: In a retrospective single-centre study, 25 patients with non-union following arthrodesis received one session of focussed extracorporeal shock-wave therapy (energy flux density 0.36 mJ/mm2, 3000 impulses, 23 kV, 4 Hz). Radiographic and clinical results were recorded 6, 12 and 24 weeks after treatment. RESULTS: 24 patients were followed-up. After 24 weeks arthrodeses of the hand healed in 80%, of the upper ankle in 50%, of subtalar joint in 27.2% and of the midfoot in 0% of the cases. Pain decreased from 4.8 (± 2.8) points on the visual analogue scale to 3.4 (± 2.3), 2.9 (± 2.5) and 2.4 (± 2.8) points after 6, 12 and 24 weeks, respectively (p < 0.0001). CONCLUSION: Our data indicate that the effect of focussed, high-energy shock wave therapy depends on body region and is effective for the treatment of non-unions of the hand as well as for pain relief. LEVEL OF EVIDENCE: Level IV.

Associations Between Radiographic and Ultrasound-Detected Features in Hand Osteoarthritis and Local Pressure Pain Thresholds.

OBJECTIVE: Pain sensitization contributes to the complex osteoarthritis (OA) pain experience. The relationship between imaging features of hand OA and clinically assessed pain sensitization is largely unexplored. This study was undertaken to examine the association of structural and inflammatory features of hand OA with local pressure pain thresholds (PPTs) in the Nor-Hand study. METHODS: The cross-sectional relationship of severity of structural radiographic features of hand OA (measured according to the Kellgren/Lawrence scale [grade 0-4] and the absence or presence of erosive joint disease) as well as ultrasound-detected hand joint inflammation (assessed by gray-scale synovitis [grade 0-3] and the absence or presence of power Doppler activity) to the PPTs of 2 finger joints was examined by multilevel regression analyses adjusted for age, sex, and body mass index, using beta values with 95% confidence intervals (95% CIs). RESULTS: A total of 570 joints in 285 participants included in the Nor-Hand study were assessed. Greater structural and inflammatory severity was associated with lower PPTs, with adjusted beta values of -0.5 (95% CI -0.6, -0.4) per Kellgren/Lawrence grade increase, -1.4 (95% CI -1.8, -0.9) for erosive versus non-erosive joints, -0.7 (95% CI -0.9, -0.6) per gray-scale synovitis grade increase, and -1.5 (95% CI -1.8, -1.1) for joints with power Doppler activity on ultrasound versus those without. CONCLUSION: Greater severity of structural pathologic features and hand joint inflammation was associated with lower PPTs in the finger joints of patients with hand OA, indicating pain sensitization. Our results indicate that pain sensitization might be driven by structural and inflammatory pathology in hand OA.

Self-reported painful joint count and assessor-reported tender joint count as instruments to assess pain in hand osteoarthritis.

OBJECTIVES: To evaluate self-reported and assessor-reported joint counts for pain and their value in measuring pain and joint activity in hand OA patients. METHODS: A total of 524 patients marked painful joints on hand diagrams. Nurses assessed tenderness upon palpation. Pain was measured with a visual analogue scale pain and the Australian/Canadian hand OA index subscale pain. Synovitis and bone marrow lesions in right hand distal/proximal interphalangeal joints on MRI served as measure of joint activity. Agreement was assessed on the patient (intraclass correlation coefficient, Bland-Altman plot) and joint level (percentage absolute agreement). Correlations with measures of pain and joint activity were analysed, and joint level associations with synovitis/bone marrow lesions were calculated. RESULTS: Self-reported painful joint count (median 8, interquartile range 4-13) was consistently higher than assessor-reported tender joint count (3, 1-7). Agreement between patients and nurses on overall scores was low. Percentage absolute agreement on the joint level was 61-89%. Joint counts correlated similarly but weakly with measures of pain and joint activity (r = 0.14-0.38). On the joint level, assessor-reported tenderness was more strongly associated with synovitis/bone marrow lesions than self-reported pain. CONCLUSION: In hand OA, self- and assessor-reported joint counts cannot be used interchangeably, and measure other pain aspects than questionnaires. Assessor-reported tenderness was most closely related to MRI-defined joint activity.

Domains rated as important by patients with hand osteoarthritis.

BACKGROUND: No data exist on patient participation in the selection of core domains for clinical trials of hand osteoarthritis (HOA). We aim to explore HOA patients' perspectives in the relative importance of domains. METHODS: Seven domains affecting patients' lives were derived from a prior qualitative study. We recruited consecutive patients with symptomatic HOA to rate on 11-point numeric rating scales for each domain, from 0 representing "not important at all" to 10 representing "most important", with consideration in two scenarios: (a) how important the domains are in affecting their current lives; and (b) how important the domains are when there are treatments for HOA (eg exercise or drugs). RESULTS: Forty-five patients (91% female; mean age ± standard deviation 64.3 ± 7.5 years) with mild HOA symptoms were included. Of these, 31%-42% rated current impact of HOA in various domains as highly important. Seven domains with rated scores of ≥7/10 in importance were endorsed for clinical trials in the following order: pain and HOA symptoms (endorsed by 77.8% of patients), physical function (66.7%), ability to participate in social roles (64.4%), ability to participate in social activities (62.2%), work productivity (62.2%), emotional health (60%), and appearance of fingers (55.6%). CONCLUSION: The preliminary important domains as endorsed by patients with HOA for inclusion into clinical trials were explored. Apart from pain and physical function, further research is needed to refine other domains of impact, such as participation, emotional health and aesthetic concerns, as core domain sets for HOA.

Association between body composition and osteoarthritis: A systematic review and meta-analysis.

OBJECTIVES: To examine the association between body composition and osteoarthritis (OA). METHODS: An extensive literature review was performed to identify studies that examined the association between body composition and OA. The mean difference (MD), odds ratio (OR), relative risk (RR) and corresponding 95% confidence intervals (CIs) were determined using RevMan statistical software. RESULTS: A total of 19 studies were included. The combined MD showed the fat mass of the subjects with knee OA was higher than that of the control group (MD 4.38, 95% CI: 2.84-5.92). Both fat mass and fat mass percentage were positively associated with knee OA (ORs ranged from 1.49, 95% CI: 1.15-1.92, to 2.37, 95% CI: 1.18-4.74). Similar findings were observed in hip and hand joints as well (ORs ranged from 1.20, 95% CI: 1.08-1.32, to 1.87, 95% CI: 1.11-3.15), and such results were also confirmed by most cohort studies of knee and hip OA (RRs ranged from 0.98, 95% CI: 0.95-1.01, to 3.60, 95% CI: 2.60-5.00). Lean mass was also positively associated with knee OA (OR 1.48, 95% CI: 1.13-1.94). However, lean mass percentage was negatively associated with knee OA (OR 0.65, 95% CI: 0.46-0.92). CONCLUSIONS: Both fat mass and fat mass percentage were likely to be risk factors for knee, hip and hand OA. Similarly, lean mass also seemed to be a risk factor for knee OA, while lean mass percentage seemed to be a protective factor.

Investigating causal mechanisms in randomised controlled trials.

INTRODUCTION: In some randomised trials, the primary interest is in the mechanisms by which an intervention exerts its effects on health outcomes. That is, clinicians and policy-makers may be interested in how the intervention works (or why it does not work) through hypothesised causal mechanisms. In this article, we highlight the value of understanding causal mechanisms in randomised trials by applying causal mediation analysis to two randomised trials of complex interventions. MAIN BODY: In the first example, we examine a potential mechanism by which an exercise programme for rheumatoid arthritis of the hand could improve hand function. In the second example, we explore why a rehabilitation programme for ankle fractures failed to improve lower-limb function through hypothesised mechanisms. We outline critical assumptions that are required for making valid causal inferences from these analyses, and provide results of sensitivity analyses that are used to assess the degree to which the estimated causal mediation effects could have been biased by residual confounding. CONCLUSION: This paper demonstrates how the application of causal mediation analyses to randomised trials can identify the mechanisms by which complex interventions exert their effects. We discuss methodological issues and assumptions that should be considered when mediation analyses of randomised trials are used to inform clinical practice and policy decisions.

Minimal clinically important decline in physical function over one year: EPOSA study.

BACKGROUND: The Australian/Canadian hand Osteoarthritis Index (AUSCAN) and the Western Ontario and McMaster Universities knee and hip Osteoarthritis Index (WOMAC) are the most commonly used clinical tools to manage and monitor osteoarthritis (OA). Few studies have as yet reported longitudinal changes in the AUSCAN index regarding the hand. While there are published data regarding WOMAC assessments of the hip and the knee, the two sites have always evaluated separately. The current study therefore sought to determine the minimal clinically important difference (MCID) in decline in the AUSCAN hand and WOMAC hip/knee physical function scores over 1 year using anchor-based and distribution-based methods. METHODS: The study analysed data collected by the European Project on Osteoarthritis, a prospective observational study investigating six adult cohorts with and without OA by evaluating changes in the AUSCAN and WOMAC physical function scores at baseline and 12-18 months later. Pain and stiffness scores, the performance-based grip strength and walking speed and health-related quality of life measures were used as the study's anchors. Receiver operating characteristic curves and distribution-based methods were used to estimate the MCID in the AUSCAN and WOMAC physical function scores; only the data of those participants who possessed paired (baseline and follow up-measures) AUSCAN and WOMAC scores were included in the analysis. RESULTS: Out of the 1866 participants who were evaluated, 1842 had paired AUSCAN scores and 1845 had paired WOMAC scores. The changes in the AUSCAN physical function score correlated significantly with those in the AUSCAN pain score (r = 0.31). Anchor- and distribution-based approaches converged identifying 4 as the MCID for decline in the AUSCAN hand physical function. Changes in the WOMAC hip/knee physical function score were significantly correlated with changes in both the WOMAC pain score (r = 0.47) and the WOMAC stiffness score (r = 0.35). The different approaches converged identifying two as the MCID for decline in the WOMAC hip/knee physical function. CONCLUSIONS: The most reliable MCID estimates of decline over 1 year in the AUSCAN hand and WOMAC hip/knee physical function scores were 4 and 2 points, respectively.

Two weeks versus four weeks of antibiotic therapy after surgical drainage for native joint bacterial arthritis: a prospective, randomised, non-inferiority trial.

OBJECTIVE: The optimal duration of postsurgical antibiotic therapy for adult native joint bacterial arthritis remains unknown. METHODS: We conducted a prospective, unblinded, randomised, non-inferiority study comparing either 2 or 4 weeks of antibiotic therapy after surgical drainage of native joint bacterial arthritis in adults. Excluded were implant-related infections, episodes without surgical lavage and episodes with a follow-up of less than 2 months. RESULTS: We enrolled 154 cases: 77 in the 4-week arm and 77 in the 2-week arm. Median length of intravenous antibiotic treatment was 1 and 2 days, respectively. The median number of surgical lavages was 1 in both arms. Recurrence of infection was noted in three patients (2%): 1 in the 2-week arm (99% cure rate) and 2 in the 4-week arm (97% cure rate). There was no difference in the number of adverse events or sequelae between the study arms. Of the overall 154 arthritis cases, 99 concerned the hand and wrist, for which an additional subgroup analysis was performed. In this per-protocol subanalysis, we noted three recurrences: one in the 2-week arm (97 % cure); two in the 4-week arm (96 % cure) and witnessed sequelae in 50% in the 2-week arm versus 55% in the 4-week arm, of which five (13%) and six (13%) needed further interventions. CONCLUSIONS: After initial surgical lavage for septic arthritis, 2 weeks of targeted antibiotic therapy is not inferior to 4 weeks regarding cure rate, adverse events or sequelae and leads to a significantly shorter hospital stay, at least for hand and wrist arthritis. TRIAL REGISTRATION NUMBER: NCT03615781.

Novel optical spectral transmission (OST)-guided versus conventionally disease activity-guided treatment: study protocol of a randomized clinical trial on guidance of a treat-to-target strategy for early rheumatoid arthritis.

BACKGROUND: Assessment of disease activity is a critical component of tight-control, treat-to-target treatment strategies of rheumatoid arthritis (RA). Recently, the HandScan has been validated as a novel method for objectively assessing RA disease activity in only 1.5 min, using optical spectral transmission (OST) in hands and wrists. We describe the protocol of a randomized controlled clinical trial (RCT) to investigate whether HandScan-guided treatment aimed at 'HandScan remission' (HandScan arm) is at least as effective as and more cost-effective than clinically guided treatment aimed at ACR/EULAR 2011 Boolean remission (DAS arm). METHODS/DESIGN: The study is a multi-center, double-blind, non-inferiority RCT of 18 months duration. Patients ≥ 18 years with newly diagnosed, disease-modifying antirheumatic drug (DMARD)-naïve RA according to the ACR 2010 classification criteria, will be randomized to the DAS arm or the HandScan arm. The efficacy of the arms will be compared by evaluating Health Assessment Questionnaire (HAQ) scores (primary outcome) after 18 months of DMARD therapy, aimed at remission. The equivalence margin in HAQ scores between study arms is 0.2. Secondary outcomes are differences in cost-effectiveness and radiographic joint damage between treatment arms. The non-inferiority sample size calculation to obtain a power of 80% at a one-sided p value of 0.05, with 10% dropouts, resulted in 61 patients per arm. In both arms, DMARD strategy will be intensified monthly according to predefined steps until remission is achieved; in both arms DMARDs and treatment steps are identical. If sustained remission, defined as remission that persists consistently over three consecutive months, is achieved, DMARD therapy will be tapered. DISCUSSION: The study protocol and the specifically designed decision-making software application allow for implementation of this RCT. To test a novel method of assessing disease activity and comparing (cost-)effectiveness with the contemporary method in treat-to-target DMARD strategies in early RA patients. TRIAL REGISTRATION: Dutch Trial Register, NTR6388. Registered on 6 April 2017 ( NL50026.041.14 ). Protocol version 3.0, 19-01-2017.

Joint Mobilization of the Hands of Patients With Rheumatoid Arthritis: Results From an Assessor-Blinded, Randomized Crossover Trial.

OBJECTIVE: The purpose of this study was to assess the clinical feasibility and effectiveness of manual mobilization of the hands of patients with rheumatoid arthritis (RA). METHODS: A total of 320 individual hand joints were evaluated after recruiting an experimental research group of 12 participants with RA and, for clinical comparability, 8 participants with hand osteoarthritis (OA). One hand per participant was randomized to receive weekly low-grade (I-II) Kaltenborn manual mobilization, using passive sustained stretch of the metacarpophalangeal (MCP) joints II to V by licensed manual therapists. After 2 weeks, the randomized treated hand was crossed over to control (untreated) during weeks 3 to 4 and vice versa. Final assessment was at 2 months, which was 1 month after the last treatment at week 4. Primary hand outcomes included pain by visual analog scale, tender or swollen joint count, and presence of Doppler signal or synovial fluid and radiographic joint space by musculoskeletal ultrasound. RESULTS: In the RA group, both the initially randomized treated hand and the contralateral hand improved significantly from baseline to crossover to follow-up at 2 months (pain outcomes and Doppler signal, P < .050; synovial fluid and MCP joint space, P ≤ .001). Hand pain and MCP joint space also improved significantly in OA. There were no dropouts or reported adverse events in either the RA or OA group. CONCLUSION: In this study, manual mobilization of the hands of patients with RA was shown to be feasible, safe, and effective to integrate into specialized healthcare.