Taking the pressure off in the Emergency Department: evaluation of the prophylactic application of a low shear, soft silicon sacral dressing on high risk medical patients.

Pressure injuries are key clinical indicators of care standard. In Australia, pressure injuries increase length of hospital stay by 4.31 and cost $285 million annually. This pilot study examined the effectiveness of sacral dressing in reducing the prevalence of pressure injuries in older, high-risk patients. A non randomised one-sample experimental design was used in this study comprising of four phases. Of the 51 patients recruited to the study, one patient developed a sacral pressure injury compared to six patients identified in a known group with similar demographics who were not approached to participate in the study. The results indicated that patients in the known group were 5.4 times more likely to develop a pressure injury than the intervention group. Findings suggest that applying a protective sacral dressing with a low shear backing as part of a simple standardised prevention injury prevention regime commencing in the Emergency Department was beneficial in the prevention of pressure injury in older 'at high risk' medical patients.

Profiling anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis.

BACKGROUND: Anti-citrullinated protein/peptide antibodies (ACPA), have high specificity for rheumatoid arthritis (RA). Some children with juvenile idiopathic arthritis (JIA), phenotypically resemble RA and test positive for rheumatoid factor (RF) a characteristic biomarker of RA. We investigated the prevalence of ACPA and its relationship to other serologic markers associated with RA in a well-characterized JIA cohort. METHODS: Cases were 334 children with JIA, 30 of whom had RF + polyarticular JIA. Sera from all cases and 50 healthy pediatric controls were investigated by ELISA at a single time point for anti-cyclic citrullinated peptide (anti-CCP) IgG, RF IgM, IgA and IgG, anti-RA33 IgG, and antinuclear antibodies (ANA). Comparisons between cases and controls were made using Chi-square or Fisher exact tests and T-tests. RESULTS: The prevalence of RF was 8% among controls, and 12% among cases (ns). The prevalence of ACPA was 2% in controls and 14.3% in cases (OR 8.2, p <0.01). Children who were ACPA-positive and RF-negative (n = 23) had a significantly earlier onset-age (4.6 years vs. 12.1 years, p <0.00001) and had fewer HLA-DRB1 shared epitope alleles than those positive for both RF and ACPA (n = 25). Prevalence of anti-RA33 was not different between cases and controls. CONCLUSIONS: ACPAs are detectable in 14% of children with JIA. Children with positive ACPA but negative RF are frequent, and may define a distinct subset of children with JIA. ACPA testing should be included in the classification of JIA.

Quantification of the familial contribution to juvenile idiopathic arthritis.

OBJECTIVE: We previously demonstrated that there is familial aggregation of juvenile idiopathic arthritis (JIA). Using a large JIA cohort, we sought to identify additional clusters of JIA cases and to calculate robust estimates of the relative risk (RR) of JIA in the siblings and cousins of JIA probands. We also estimated the population attributable risk (PAR) of familial factors in JIA. METHODS: A probabilistic record-linking analysis was performed by matching the records of 862 patients with JIA with the records of approximately 7 million individuals in the Utah Population Database (UPDB), a computerized genealogic database. For each patient, 5 control subjects matched for birth year and sex were selected from the UPDB. Specialized software was used to test for familial aggregation of disease, to estimate the magnitude of familial risks, and to identify families at high risk of disease. RESULTS: We identified 22 founders who had significantly more descendants with JIA than expected (5-13 descendants; P values ranged from <0.0001 to <0.008). The PAR of familial factors for JIA was approximately 13%. The RR of JIA in the siblings of patients was significantly increased (11.6, 95% confidence interval [95% CI] 4.9-27.5, P < 2.59 x 10(-8)). The RR of JIA in first cousins was also increased (5.82, 95% CI 2.5-13.8, P < 6.07 x 10(-5)). CONCLUSION: We have identified the largest sets of JIA pedigrees described to date. Approximately 13% of cases of JIA can be attributed to familial factors. Siblings and first cousins of probands with JIA have an increased risk of JIA. The observed decline in the magnitude of risk between siblings and cousins suggests that JIA is influenced by shared genetic factors.

Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis.

OBJECTIVE: Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors. METHODS: Cases were 445 children with JIA, and controls were 643 healthy adults. Using the TaqMan assay, subjects were genotyped for 8 single-nucleotide polymorphisms in 7 loci including rs10499194 and rs6920220 in the TNFAIP3 locus, rs6679677 in the RSBN1 locus, rs17696736 in the C12orf30 locus, rs3761847 in the TRAF1/C5 locus, rs2104286 in the IL2RA locus, rs7574865 in the STAT4 locus, and rs2542151 in the PTPN2 locus. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The strongest associations with JIA risk or protection were observed for TNFAIP3 variants rs10499194 (OR 0.74 [95% CI 0.61-0.91], P < 0.004) and rs6920220 (OR 1.30 [95% CI 1.05-1.61], P = 0.015). We also observed associations between JIA and both STAT4 (OR 1.24 [95% CI 1.02-1.51], P = 0.029) and C12orf30 (OR 1.20 [95% CI 1.01-1.43], P = 0.041) variants. The PTPN2 variant rs2542151 deviated from Hardy-Weinberg equilibrium and was excluded from analyses. Variants in IL2RA, TRAF1/C5, and RSBN1 were not associated with JIA. After stratification by JIA subtype, the TNFAIP3 and C12orf30 variants were associated with oligoarticular JIA, while the STAT4 variant was associated primarily with polyarticular JIA. CONCLUSION: We have demonstrated associations between JIA and variants in the TNFAIP3, STAT4, and C12orf30 regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors.

Anakinra for systemic juvenile arthritis: the Rocky Mountain experience.

BACKGROUND: Poor outcomes in systemic juvenile arthritis have been associated with persistent thrombocytosis, increased sedimentation rates, anemia, polyarthritis, and prolonged steroid use. Off-label treatment with recombinant interleukin-1 receptor antagonist therapy (anakinra) has become more common since reports of its association with reduced systemic symptoms and arthritis scores, improved laboratory parameters of inflammation, and decreased corticosteroid requirements. OBJECTIVE: To examine the efficacy and safety of anakinra in a regional cohort of systemic juvenile arthritis patients. METHODS: We performed a retrospective case series of systemic juvenile arthritis patients (n = 33) treated with anakinra at 3 Pediatric Rheumatology centers. The effect of anakinra on corticosteroid dose, sedimentation rate, platelet count, albumin, hemoglobin, arthritis joint counts, and height Z score was determined using the paired t test. We evaluated differences in change in these variables between patient groups within the sample determined by: age of onset, anakinra dose, and duration from diagnosis until anakinra treatment. RESULTS: Treatment was associated with decreases in corticosteroid dosage and sedimentation rate and increases in hemoglobin and albumin (P < 0.02). There were decreases in large joint arthritis counts (P < 0.04) but not small joint counts after 3 to 4 months. There were greater decreases in sedimentation rates from pre to post (1-2 months) in patients on high versus low dose anakinra (P < 0.001). Fever and rash, present in 7 cases before treatment, was resolved. Eight patients had periods of arthritis, 1 developed macrophage activation syndrome, and another Epstein Barr virus. Over half of patients reported localized pain or swelling at their injection site. CONCLUSIONS: Treatment with anakinra was associated with short-term improvements in large joint counts and laboratory parameters of active disease. Higher anakinra doses may be more efficacious in treating the systemic inflammatory response in systemic onset juvenile idiopathic arthritis patients. A subset of patients had periods of arthritis during treatment, and local side-effects were frequent. Our experience supports the continued use of interleukin-1 inhibition in systemic juvenile arthritis and the search for more effective and more tolerable forms of interleukin-1 inhibition.

Elevated serum levels of soluble CD154 in children with juvenile idiopathic arthritis.

OBJECTIVE: Cytokines play important roles in mediating inflammation in autoimmunity. Several cytokines are elevated in serum and synovial fluid samples from children with Juvenile Idiopathic Arthritis (JIA). Soluble CD154 (sCD154) is elevated in other autoimmune disorders, but has not been characterized in JIA. Our objectives were to determine if sCD154 is elevated in JIA, and to examine correlations between sCD154 and other inflammatory cytokines. METHODS: Serum from 77 children with JIA and 81 pediatric controls was analyzed for interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, sCD154, interferon-gamma (IFNgamma), soluble IL2 receptor (sIL2R), and tumor necrosis factor-alpha (TNFalpha), using the Luminex Multi-Analyte Profiling system. Differences in levels of cytokines between cases and controls were analyzed. Logistic regression was also performed. RESULTS: sCD154 was significantly elevated in cases compared to controls (p < 0.0001). IL1beta, IL5, IL6, IL8, IL13, IFNgamma, sIL2R, and TNFalpha were also significantly elevated in JIA. Levels of sCD154 were highly correlated with IL1beta, IL6, IL8, and TNFalpha (p < 0.0001). Logistic regression analysis suggested that IL6 (odds ratio (OR): 1.4, p < 0.0001), sCD154 (OR: 1.1, p < 0.0001), and TNFalpha (OR: 1.1, p < 0.005) were positively associated with JIA, while IL10 (OR: 0.5, p < 0.002) was protective. sCD154 was elevated in all JIA subtypes, with highest levels among more severe subtypes. IL1beta, IL6, IL8, sIL2R and TNFalpha were also elevated in several JIA subtypes. CONCLUSION: Serum levels of sCD154, IL1beta, IL6, IL8, sIL2R and TNFalpha are elevated in most JIA subtypes, suggesting a major role for sCD154, and these cytokines and cytokine receptors in the pathogenesis of JIA.