Foot related impairments and disability in juvenile idiopathic arthritis persist despite modern day treatment paradigms

Background: Foot problems such as synovitis, growth disturbance and deformity are considered common in juvenile idiopathic arthritis (JIA) and have been previously reported in over 90% of cases. The medical management of JIA appears to have improved recently however little is known about the impact of new regimes on localised joints such as in the foot. This pilot study aimed to investigate the prevalence of foot related impairments and disability, and survey the medical and podiatric management of patients in a cohort of UK children with JIA. Methods: This study was a tertiary care based cross-sectional survey. Thirty consecutive JIA patients with a history of foot and ankle arthritis completed the juvenile arthritis foot disability index questionnaire (JAFI) (0-4 for each domain), child health assessment questionnaire (CHAQ) (0-3), and pain visual analogue scale (VAS) (0-100mm). Foot deformity score (0-38), active and limited joint counts (0-77) and walking speed (m/s) were measured also recorded. Foot care provision over the previous 12 months was determined from the medical records in 23/ 30 participants. Results were analysed using simple descriptive statistics and expressed as median (range). Results: Children received biologic agents in 35%, DMARDs in 65%, and 90% of participants had received multiple intra-articular cortico-steroid injections. Median (range) values for foot disease outcomes were JAFI impairment = 1 (0-3), JAFI activity limitation = 1 (0-4) JAFI participation restriction 1 (0-3), CHAQ = 0.38 (0-2), VAS pain = 22 (0-79), foot deformity = 6 (0-20), active joints = 0 (0-7), limited joints (0-31), walking speed = 1.09 (0.84- 1.38). The JAFI scores represent mild foot related impairment and disability. Gait defects, deformity or abnormal foot posture, and/or active foot disease were the main reasons for referral. 43% of children received specialist podiatry care comprising footwear advice, orthotic therapy, and silicone digital appliances together with intrinsic muscle strengthening exercises. Conclusions: Despite DMARD/biologic regimes and specialist podiatry, foot related impairment and disability persists in JIA children. Foot care appears to be in line with current recommendations. Further study is required to determine the long-term consequences of these changes found during childhood in the foot

Association of the CCR5 gene with juvenile idiopathic arthritis

The CC chemokine receptor 5 (CCR5) has been shown to be important in the recruitment of T-helper cells to the synovium, where they accumulate, drive the inflammatory process and the consequent synovitis and joint destruction. A 32 base-pair insertion/deletion variant (CCR5Δ32) within the gene leads to a frame shift and a nonfunctional receptor. CCR5Δ32 has been investigated for its association with juvenile idiopathic arthritis (JIA), with conflicting results. The aim of this study was to investigate whether CCR5Δ32 is associated with JIA in an UK population. CCR5Δ32 was genotyped in JIA cases (n=1054) and healthy controls (n=3129) and genotype and allele frequencies were compared. A meta-analysis of our study combined with previously published studies was performed. CCR5Δ32 was significantly associated with protection from developing JIA, in this UK data set (P(trend)=0.006, odds ratio (OR) 0.79 95% confidence interval (95% CI): 0.66-0.94). The meta-analysis of all published case-control association studies confirmed the protective association with JIA (P=0.001 OR 0.82 95% CI: 0.73-0.93). CCR5Δ32 is a functional variant determining the number of receptors on the surface of T cells, and it is hypothesized that the level of CCR5 expression could influence the migration of proinflammatory T cells into the synovium and thus susceptibility to JIA

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

Recent genetic studies have led to identification of numerous loci that are associated with susceptibility to autoimmune diseases. The strategy of using information from these studies has facilitated the identification of novel juvenile idiopathic arthritis (JIA) susceptibility loci, specifically, PTPN22 and IL2RA. Several novel autoimmune susceptibility loci have recently been identified, and we hypothesise that single-nucleotide polymorphisms (SNPs) within these genes may also be JIA susceptibility loci. Five SNPs within the genes AFF3, IL2/IL21, IL7R, CTLA4 and CD226, previously associated with multiple autoimmune diseases were genotyped, in a large data set of Caucasian JIA patients and controls, and tested for association with JIA. We identified two susceptibility loci for JIA, AFF3 and the IL2/IL21 region and additional weak evidence supporting an association with the CTLA4 and IL7R genes, which warrant further investigation. All results require validation in independent JIA data sets. Further characterisation of the specific causal variants will be required before functional studies can be performed

Confidence and competence with mathematical procedures

Confidence assessment (CA), in which students state alongside each of their answers a confidence level expressing how certain they are, has been employed successfully within higher education. However, it has not been widely explored with school pupils. This study examined how school mathematics pupils (N = 345) in five different secondary schools in England responded to the use of a CA instrument designed to incentivise the eliciting of truthful confidence ratings in the topic of directed (positive and negative) numbers. Pupils readily understood the negative marking aspect of the CA process and their facility correlated with their mean confidence with r = .546, N = 336, p < .001, indicating that pupils were generally well calibrated. Pupils’ comments indicated that the vast majority were positive about the CA approach, despite its dramatic differences from more usual assessment practices in UK schools. Some pupils felt that CA promoted deeper thinking, increased their confidence and had a potential role to play in classroom formative assessment