Digitally augmented, parent-led CBT versus treatment as usual for child anxiety problems in child mental health services in England and Northern Ireland: a pragmatic, non-inferiority, clinical effectiveness and cost-effectiveness randomised controlled trial.

BACKGROUND: Anxiety problems are common in children, yet few affected children access evidence-based treatment. Digitally augmented psychological therapies bring potential to increase availability of effective help for children with mental health problems. This study aimed to establish whether therapist-supported, digitally augmented, parent-led cognitive behavioural therapy (CBT) could increase the efficiency of treatment without compromising clinical effectiveness and acceptability. METHODS: We conducted a pragmatic, unblinded, two-arm, multisite, randomised controlled non-inferiority trial to evaluate the clinical effectiveness and cost-effectiveness of therapist-supported, parent-led CBT using the Online Support and Intervention (OSI) for child anxiety platform compared with treatment as usual for child (aged 5-12 years) anxiety problems in 34 Child and Adolescent Mental Health Services in England and Northern Ireland. We examined acceptability of OSI plus therapist support via qualitative interviews. Participants were randomly assigned (1:1) to OSI plus therapist support or treatment as usual, minimised by child age, gender, service type, and baseline child anxiety interference. Outcomes were assessed at week 14 and week 26 after randomisation. The primary clinical outcome was parent-reported interference caused by child anxiety at week 26 assessment, using the Child Anxiety Impact Scale-parent report (CAIS-P). The primary measure of health economic effect was quality-adjusted life-years (QALYs). Outcome analyses were conducted blind in the intention-to-treat (ITT) population with a standardised non-inferiority margin of 0·33 for clinical analyses. The trial was registered with ISRCTN, 12890382. FINDINGS: Between Dec 5, 2020, and Aug 3, 2022, 706 families (706 children and their parents or carers) were referred to the study information. 444 families were enrolled. Parents reported 255 (58%) child participants' gender to be female, 184 (41%) male, three (<1%) other, and one (<1%) preferred not to report their child's gender. 400 (90%) children were White and the mean age was 9·20 years (SD 1·79). 85% of families for whom clinicians provided information in the treatment as usual group received CBT. OSI plus therapist support was non-inferior for parent-reported anxiety interference on the CAIS-P (SMD 0·01, 95% CI -0·15 to 0·17; p<0·0001) and all secondary outcomes. The mean difference in QALYs across trial arms approximated to zero, and OSI plus therapist support was associated with lower costs than treatment as usual. OSI plus therapist support was likely to be cost effective under certain scenarios, but uncertainty was high. OSI plus therapist support acceptability was good. No serious adverse events were reported. INTERPRETATION: Digitally augmented intervention brought promising savings without compromising outcomes and as such presents a valuable tool for increasing access to psychological therapies and meeting the demand for treatment of child anxiety problems. FUNDING: Department for Health and Social Care and United Kingdom Research and Innovation Research Grant, National Institute for Health and Care (NIHR) Research Policy Research Programme, Oxford and Thames Valley NIHR Applied Research Collaboration, Oxford Health NIHR Biomedical Research Centre.

Association between Markers of Synovial Inflammation, Matrix Turnover and Symptoms in Knee Osteoarthritis: A Cross-Sectional Study.

To investigate the association between markers of synovial inflammation and matrix turnover (MRI-based and serum biomarkers) and knee symptoms in established knee osteoarthritis (KOA). This cross-sectional study utilised data from a randomised, multicentre placebo-controlled trial (UK-VIDEO) of vitamin D therapy in symptomatic KOA. Data on serum biomarkers, type III collagen degradation (C3M), metabolite of C-reactive protein (CRPM) and cartilage oligomeric matrix protein (COMP), were available at baseline whilst contrast-enhanced (CE) MRI data were acquired in a subsample at baseline and annually. Knee symptoms were assessed using WOMAC at all visits. We examined the cross-sectional association between knee symptoms and three MRI-based and three serum markers of synovitis and matrix turnover, respectively. A total of 447 participants were included in the serum and 136 participants in the MRI analyses. MRI-defined medial perimeniscal synovitis was positively associated with knee pain and, suprapatellar and medial perimeniscal synovitis with knee function in multivariate analysis. We observed a statistically significant, negative association between a higher concentration of serum C3M and CRPM and knee pain, respectively. Furthermore, the highest CRPM quartile was negatively associated with knee function. Our findings suggest that, in established painful radiographic KOA, MRI-defined medial perimeniscal and suprapatellar synovitis were positively associated with knee symptoms. Serum-based C3M and CRPM markers were negatively associated with knee symptoms. Pain fluctuations are common in KOA and a better understanding of the relationship between markers of synovitis and matrix turnover and knee symptoms would facilitate a more accurate assessment of temporal changes in disease progression.

Quantitative and semi-quantitative assessment of synovitis on MRI and the relationship with symptoms in symptomatic knee osteoarthritis.

OBJECTIVES: Synovitis in symptomatic knee OA (KOA) is common and is associated with joint symptoms. Optimal synovial measurement on MRI is, however, unclear. Our aims were to examine the relationship between MRI measures of synovitis and knee symptoms in symptomatic KOA. METHODS: Data from a randomized, multicentre, placebo-controlled trial (UK-VIDEO) of vitamin-D therapy in symptomatic KOA were utilized. Participants reported knee symptoms using WOMAC at baseline and annually. On contrast-enhanced (CE) MRI, synovial thickness was measured using established, semi-quantitative methods whilst synovial tissue volume (STV) was assessed as absolute STV (aSTV) and relative to the width of femoral condyle (rSTV). STV of the infrapatellar region was also assessed. Associations between synovial measures and symptoms were analysed using multiple linear regression modelling. RESULTS: No linear association was observed between knee symptoms and synovitis thickness scores. Whole-joint aSTV (0.88, 95% CI: 0.17, 1.59) and infrapatellar aSTV (5.96, 95% CI: 1.22, 10.7) were positively associated with knee pain. Whole-joint rSTV had a stronger association with pain (7.96, 95% CI: 2.60, 13.33) and total scores (5.63, 95% CI: 0.32, 10.94). Even stronger associations were found for infrapatellar rSTV with pain (55.47, 95% CI: 19.99, 90.96), function (38.59, 95% CI: 2.1, 75.07) and total scores (41.64, 95% CI: 6.56, 76.72). CONCLUSIONS: Whole-joint and site-specific infrapatellar STV measures on CE-MRI were associated with knee pain, respectively. Volumes relative to the size of the femoral condyle may be promising outcome measures in KOA trials.

Dominant vs. non-dominant hip comparison in bone mineral density in young sporting athletes.

To explore differences in bone mineral density (BMD) between dominant and non-dominant hip within levels of sport impact. BMD was higher in the non-dominant hip in high-impact sports, whereas the dominant hip had increased BMD for low-impact sports. The side-to-side differences were relatively small and not clinically relevant. PURPOSE: It is unknown whether there is difference in BMD at the hip between dominant and non-dominant sides in young athletes. The aims of this study were to explore the dominant-non-dominant differences in hip BMD in young athletes participating in low- and high-impact sports and to assess the effect of ground force impact on BMD. METHODS: Data was collected on University of Oxford athletes and controls (CG) between 2016 and 2018. Athletes were classified into two groups: high-impact sports (HIG) and low-impact sports (LIG). Total and regional measurements of both hips' BMD were recorded using a dual-energy X-ray absorptiometry (DXA). Linear regression method was used to assess differences in BMD between and within groups. RESULTS: One hundred ninety-four athletes (HIG: n = 89, LIG: n = 105) and 48 controls were included in this study. Total hip and femoral neck BMD was higher in athletes compared to the CG (p < 0.01), with HIG recording highest levels of BMD. The BMD difference between the dominant and non-dominant sides was significant in the LIG, with BMD being higher in the dominant side. Conversly, BMD was higher in the non-dominant hip within the HIG. However, the hip asymmetries were not clinically relevant (%BMD difference < 3%). A significant interaction between side and sport group on BMD was observed. CONCLUSIONS: High-impact sports had significantly higher BMD compared with low-impact sports and CG. BMD in the dominant hip was significantly higher for the LIG and lower in the HIG; however, differences were not clinically relevant.