Greater efficacy of a combination of conservative therapies for thumb base OA in individuals with lower radial subluxation - a pre-planned subgroup analysis of the COMBO trial.

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

Radial subluxation in relation to hand strength and radiographic severity in trapeziometacarpal osteoarthritis.

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

Clinimetrics of ultrasound pathologies in osteoarthritis: systematic literature review and meta-analysis.

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

Ferromagnetism in Ga(1-x)Mn(x)P: evidence for inter-Mn exchange mediated by localized holes within a detached impurity band.

We report an energy gap for hole photoexcitation in ferromagnetic Ga(1-x)Mn(x)P that is tunable by Mn concentration (x < or = 0.06) and by compensation with Te donors. For x approximately 0.06, electrical transport is dominated by excitation across this gap above the Curie temperature (TC) of 60 K and by thermally activated hopping below TC. Magnetization measurements reveal a moment of 3.9 +/- 0.4 muB per substitutional Mn while the large anomalous Hall signal demonstrates that the ferromagnetism is carrier mediated. In aggregate these data indicate that ferromagnetic exchange is mediated by holes localized in a Mn-derived band that is detached from the valence band.