The Role of Musculoskeletal Ultrasound in the Rheumatoid Arthritis Continuum

Purpose of Review: Rheumatoid arthritis (RA) is no longer considered a fixed phenotype but rather a disease continuum. This review outlines the current and potential value of applying ultrasound (US) along this continuum: from the prediction of progression to RA in at-risk individuals, to confirmation of the early diagnosis of RA, as well as the consideration of differential diagnoses, and the use in disease monitoring and defining remission. Recent Findings: In individuals at-risk of RA (i.e., positive autoantibodies with symptoms but without synovitis), US has shown a promising predictive value for the development of clinical arthritis, providing the opportunity to improve risk stratification (and disease prevention) of these individuals. The detection of inflammation on US in patients with early undifferentiated arthritis, in which a definite diagnosis cannot be reached, could predict evolution to persistent arthritis, mostly RA. This, in addition to the US potential ability to identify disease specific patterns for different rheumatic conditions, might facilitate early diagnosis and, therefore, improve the management of patients with RA, or other types of inflammatory arthritides. US has also demonstrated the capability to predict radiographic progression, and relapse risk after treatment discontinuation, in RA patients in remission according to the clinical instruments, raising implications in the management, including therapy discontinuation, of these patients. Summary: US has an undeniable value in the management of patients at different stages along the RA continuum. Further research is needed to identify which groups of patients benefit the most from US imaging

Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis

Objective: To determine the clinical outcomes for patients with new-onset undifferentiated arthritis (UA), not fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) classification criteria, and the clinical and imaging predictors of disease progression in these patients. Methods: A prospective observational study was conducted in treatment-naïve UA patients. Baseline ultrasound involved semiquantitative assessment of grey scale (GS) synovitis and power Doppler activity (PD) at 26 joints. Outcomes were fulfilment of 2010 RA criteria (joint involvement determined clinically) and initiation of methotrexate over 12 months. Cox proportional hazards analysis was used to investigate predictors of outcome. Results: Of 60 patients, 13(22%) progressed to RA and 32(53%) ever received methotrexate. Analyses of predictors of outcome were conducted in the subgroup (n=41) of patients with complete baseline data. The presence of GS was associated with progression to RA and methotrexate use: HRs (95% CI) were 1.25(1.07 to 1.45) and 1.16(1.02 to 1.32), respectively, for the number of joints with GS≥ grade 2 after adjustment for swollen joints. PD was not predictive in the low levels at which it was observed. Progression to RA was also associated with fulfilment of the 2010 criteria using ultrasound synovitis for enumerating joint involvement, higher baseline disability and radiographic erosion. Conclusions: This is the first report of ultrasound findings in early UA (defined by presence of clinical synovitis and non-fulfilment of 2010 RA criteria). A significant proportion of patients with UA progressed to RA and/or required methotrexate. GS synovitis was predictive of disease progression

Reduction in stiffness of proximal leg muscles during the first 6 months of glucocorticoid therapy for giant cell arteritis: A pilot study using shear wave elastography.

Aim: To investigate muscle stiffness changes in patients treated for giant cell arteritis (GCA) with high‐dose oral glucocorticoids. Methods: Using ultrasound elastography, shear wave velocity (SWV) was measured in the quadriceps, hamstrings and biceps brachii muscles of 14 patients with GCA (4 male, mean age ± SD, 68.2 ± 4.3 years) within the first 2 weeks of initiating glucocorticoid treatment (baseline) and repeated after 3 and 6 months treatment. Muscle strength and performance tests were performed at each visit. Baseline measures were compared with those from 14 healthy controls. Linear mixed models were used to test for change in patient measures over time. Results: At baseline, muscle SWV in patients was not significantly different from controls. With glucocorticoid treatment, there was a reduction in SWV in the leg but not the arm muscles. SWV decreased by a mean of 14% (range 8.3%‐17.3%; P = .001) after 3 months and 18% (range 10.2%‐25.3%; P < .001) after 6‐months in the quadriceps and hamstrings during the resting position. The baseline, 3 and 6 months mean SWV (±SD) for the vastus lateralis were 1.62 ± 0.16 m/s, 1.40 ± 0.10 m/s and 1.31 ± 0.06 m/s, respectively (P < .001). In the patient group as a whole, there was no significant change in muscle strength. However, there were moderate correlations (r = .54‐.69) between exhibiting weaker muscle strength at follow‐up visits and a greater reduction in SWV. Conclusion: Glucocorticoid therapy in patients with GCA was associated with a significant reduction in proximal leg muscle stiffness during the first 6 months. Future research should study a larger sample of patients for a longer duration to investigate if diminished muscle stiffness precedes signs of glucocorticoid‐induced myopathy

Parent perceptions of their child’s and their own physical activity after treatment for childhood cancer

Purpose: Parents are important facilitators of physical activity for children, yet little is known about the perceptions of parents of childhood cancer survivors. We investigated parent perceptions of their own and their child’s physical activity levels after cancer treatment and examined associations with clinical, demographic, and psychosocial factors. Methods: We conducted a cross-sectional survey among 125 parents and 125 survivors. Parents reported on the perceived importance of their child being physically active and concerns regarding exercising after cancer treatment. Results: Parents and survivors self-reported median (range) of 127.5 (0–1260) and 220 (0–1470) min/week of moderate-to-vigorous physical activity. Most parents (n = 109, 98%) believed that physical activity was highly important for their child. Some parents (n = 19, 17%) reported concerns, most commonly regarding exercise safety (n = 7, 22%). Parents were more likely to perceive that their child should increase physical activity if their child was an adolescent and had high body fat percentage. Conclusions: Physical activity levels varied widely among survivors, reflecting factors including parents’ lifestyles, limited understanding of exercise benefits and perceptions of risk. Given survivors’ insufficient physical activity levels and sedentary behaviour among families, embedding physical activity promotion into health systems and follow-up support could benefit the entire family unit

A Digital Educational Intervention With Wearable Activity Trackers to Support Health Behaviors Among Childhood Cancer Survivors: Pilot Feasibility and Acceptability Study

Background: Childhood cancer survivors are at increased risk of cardiometabolic complications that are exacerbated by poor health behaviors. Critically, many survivors do not meet physical activity guidelines. Objective: The primary aim was to evaluate the feasibility and acceptability of iBounce, a digital health intervention for educating and engaging survivors in physical activity. Our secondary aims were to assess the change in survivors’ physical activity levels and behaviors, aerobic fitness, and health-related quality of life (HRQoL) after participating in the iBounce program. Methods: We recruited survivors aged 8 to 13 years who were ≥12 months post cancer treatment completion. The app-based program involved 10 educational modules, goal setting, and home-based physical activities monitored using an activity tracker. We assessed objective physical activity levels and behaviors using cluster analysis, aerobic fitness, and HRQoL at baseline and after the intervention (week 12). Parents were trained to reassess aerobic fitness at home at follow-up (week 24). Results: In total, 30 participants opted in, of whom 27 (90%) completed baseline assessments, and 23 (77%) commenced iBounce. Our opt-in rate was 59% (30/51), and most (19/23, 83%) of the survivors completed the intervention. More than half (13/23, 57%) of the survivors completed all 10 modules (median 10, IQR 4-10). We achieved a high retention rate (19/27, 70%) and activity tracker compliance (15/19, 79%), and there were no intervention-related adverse events. Survivors reported high satisfaction with iBounce (median enjoyment score 75%; ease-of-use score 86%), but lower satisfaction with the activity tracker (median enjoyment score 60%). Parents reported the program activities to be acceptable (median score 70%), and their overall satisfaction was 60%, potentially because of technological difficulties that resulted in the program becoming disjointed. We did not observe any significant changes in physical activity levels or HRQoL at week 12. Our subgroup analysis for changes in physical activity behaviors in participants (n=11) revealed five cluster groups: most active, active, moderately active, occasionally active, and least active. Of these 11 survivors, 3 (27%) moved to a more active cluster group, highlighting their engagement in more frequent and sustained bouts of moderate-to-vigorous physical activity; 6 (56%) stayed in the same cluster; and 2 (18%) moved to a less active cluster. The survivors’ mean aerobic fitness percentiles increased after completing iBounce (change +17, 95% CI 1.7-32.1; P=.03) but not at follow-up (P=.39). Conclusions: We demonstrated iBounce to be feasible for delivery and acceptable among survivors, despite some technical difficulties. The distance-delivered format provides an opportunity to engage survivors in physical activity at home and may address barriers to care, particularly for regional or remote families. We will use these pilot findings to evaluate an updated version of iBounce

Piloting a parent and patient decision aid to support clinical trial decision making in childhood cancer

Objective: Families of a child with cancer can find the decision to enrol in a clinical trial challenging and often misunderstand key concepts that underpin trials. We pilot tested “Delta,” an online and booklet decision aid for parents with a child with cancer, and adolescents with cancer, deciding whether or not to enrol in a clinical trial. Methods: We developed Delta in accordance with the International Patient Decision Aid Standards. We conducted a pre-post pilot with parents with a child, and adolescents, who had enrolled in a paediatric phase III clinical trial for newly diagnosed acute lymphoblastic leukaemia. Parents (n = 37) and adolescents (n = 3) completed a questionnaire before and after using Delta (either the website or booklet, based on their preference). Results: Twenty-three parents (62.2%) and three adolescents (100%) reviewed the Delta website. Parents rated Delta as highly acceptable in regard to being clearly presented, informative, easy to read, useful, visually appealing, and easy to use. All participants reported that they would recommend Delta to others and that it would have been useful when making their decision. Parents' subjective (Mdiff=10.8, SDdiff = 15.69, P <.001) and objective (OR = 2.25, 95% CI, 1.66-3.04; P <.001) clinical trial knowledge increased significantly after reviewing Delta. Conclusions: To our knowledge, Delta is the first reported decision aid, available online and as a booklet, for parents and adolescents deciding whether or not to enrol in a paediatric oncology clinical trial. Our study suggests that Delta is acceptable, feasible, and potentially useful

Ultrasound erosions in the feet best predict progression to inflammatory arthritis in anti-CCP positive at-risk individuals without clinical synovitis

Objectives To investigate, in anti-cyclic citrullinated peptide antibody positive (CCP+) at-risk individuals without clinical synovitis, the prevalence and distribution of ultrasound (US) bone erosions (BE), their correlation with subclinical synovitis and their association with the development of inflammatory arthritis (IA). Methods Baseline US scans of 419 CCP+ at-risk individuals were analysed. BE were evaluated in the classical sites for rheumatoid arthritis damage: the second and fifth metacarpophalangeal (MCP2 and MCP5) joints, and the fifth metatarsophalangeal (MTP5) joints. US synovitis was defined as synovial hypertrophy (SH) ≥2 or SH ≥1+power Doppler signal ≥1. Subjects with ≥1 follow-up visit were included in the progression analysis (n=400). Results BE were found in ≥1 joint in 41/419 subjects (9.8%), and in 55/2514 joints (2.2%). The prevalence of BE was significantly higher in the MTP5 joints than in the MCP joints (p1 joint 10.6 (95% CI 1.9 to 60.4, p<0.01) and BE and synovitis in ≥1 MTP5 joint 5.1 (95% CI 1.4 to 18.9, p=0.02). In high titre CCP+ at-risk individuals, with positive rheumatoid factor and BE in ≥1 joint, the OR increased to 16.9 (95% CI 2.1–132.8, p<0.01). Conclusions In CCP+ at-risk individuals, BE in the feet appear to precede the onset of clinical synovitis. BE in >1 joint, and BE in combination with US synovitis in the MTP5 joints, are the most predictive for the development of clinical arthritis

Pragmatic randomised controlled trial of very early etanercept and MTX versus MTX with delayed etanercept in RA: the VEDERA trial

Objectives: We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. Methods: Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/−anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. Results: We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. Conclusions: Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested. Trial registration number: NCT0243318

Families as support and burden: a mixed methods exploration of the extent to which family identification and support predicts reductions in stress among disadvantaged neighbourhood residents

Stronger family relationships predict positive health outcomes: a relationship that is partially due to the range of emotional, practical and informational support that families can provide. Yet not all families possess these resources. A survey study in a disadvantaged community in Nottingham, UK (N=142) demonstrated that family identification positively predicts ability to cope with financial stress, but that this relationship is moderated by whether family support is present or absent. Semi-structured interviews with 10 members of different families from the same community shed further light upon the nature of this relationship: individuals report that they tend to turn to their family rather than friends or community services in times of financial hardship, even though their family are unlikely to be able to support them effectively, and that this is often due to feelings of embarrassment or finance-related stigma. Our findings highlight the complex role that families can play in finance-related issues, as well as the need to encourage individuals to seek financial support from sources which provide effective (rather than emotionally comfortable) assistance