What is the effect of a decision aid in potentially vulnerable parents? Insights from the head CT choice randomized trial.

ObjectiveTo test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust.MethodsThis was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy-two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site.ResultsThe decision aid did not increase knowledge more in parents with high numeracy (P for interaction [Pint ] = 0.14) or physician trust more in parents with low health literacy (Pint  = 0.34). The decision aid decreased decisional conflict more in non-white parents (decisional conflict scale, -8.14, 95% CI: -12.33 to -3.95; Pint  = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35-14.83; Pint  = 0.04).ConclusionsUse of the Head CT Choice decision aid resulted in less decisional conflict in non-white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents

The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes

Immunoglobulins, antigens and complement can assemble to form immune complexes (IC). ICs can be detrimental as they propagate inflammation in autoimmune diseases. Like ICs, submicron extracellular vesicles termed microparticles (MP) are present in the synovial fluid from patients affected with autoimmune arthritis. We examined MPs in rheumatoid arthritis (RA) using high sensitivity flow cytometry and electron microscopy. We find that the MPs in RA synovial fluid are highly heterogeneous in size. The observed larger MPs were in fact MP-containing ICs (mpICs) and account for the majority of the detectable ICs. These mpICs frequently express the integrin CD41, consistent with platelet origin. Despite expression of the Fc receptor FcγRIIa by platelet-derived MPs, we find that the mpICs form independently of this receptor. Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs. Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene production by neutrophils. Taken together, our data suggest a unique role for platelet MPs as autoantigen-expressing elements capable of perpetuating formation of inflammatory ICs

A177: Program Evaluation of the ACR/CARRA Inter‐Institutional Mentoring Program (AMIGO) in Pediatric Rheumatology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106776/1/art38603.pd

Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis

A bacterial etiology of rheumatoid arthritis (RA) has been suspected since the beginnings of modern germ theory. Recent studies implicate mucosal surfaces as sites of disease initiation. The common occurrence of periodontal dysbiosis in RA suggests that oral pathogens may trigger the production of disease-specific autoantibodies and arthritis in susceptible individuals. We used mass spectrometry to define the microbial composition and antigenic repertoire of gingival crevicular fluid in patients with periodontal disease and healthy controls. Periodontitis was characterized by the presence of citrullinated autoantigens that are primary immune targets in RA. The citrullinome in periodontitis mirrored patterns of hypercitrullination observed in the rheumatoid joint, implicating this mucosal site in RA pathogenesis. Proteomic signatures of several microbial species were detected in hypercitrullinated periodontitis samples. Among these, Aggregatibacter actinomycetemcomitans (Aa), but not other candidate pathogens, induced hypercitrullination in host neutrophils. We identified the pore-forming toxin leukotoxin-A (LtxA) as the molecular mechanism by which Aa triggers dysregulated activation of citrullinating enzymes in neutrophils, mimicking membranolytic pathways that sustain autoantigen citrullination in the RA joint. Moreover, LtxA induced changes in neutrophil morphology mimicking extracellular trap formation, thereby releasing the hypercitrullinated cargo. Exposure to leukotoxic Aa strains was confirmed in patients with RA and was associated with both anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF). The effect of HLA-DRB1 shared epitope alleles on autoantibody positivity was limited to RA patients that were exposed to Aa. These studies identify the periodontal pathogen Aa as a candidate bacterial trigger of autoimmunity in RA

Aseptic Meningitis in Children: Analysis of 506 Cases

BACKGROUND: Non-polio human enteroviruses are the leading cause of aseptic meningitis in children. The role of enterovirus PCR for diagnosis and management of aseptic meningitis has not been fully explored. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was conducted to determine the epidemiological, clinical, and laboratory characteristics of aseptic meningitis and to evaluate the role of enterovirus PCR for the diagnosis and management of this clinical entity. The medical records of children who had as discharge diagnosis aseptic or viral meningitis were reviewed. A total of 506 children, median age 5 years, were identified. The annual incidence rate was estimated to be 17/100,000 children less than 14 years of age. Most of the cases occurred during summer (38%) and autumn (24%). The dominant clinical symptoms were fever (98%), headache (94%) and vomiting (67%). Neck stiffness was noted in 60%, and irritation in 46% of the patients. The median number of CSF cell count was 201/mm(3) with polymorphonuclear predominance (>50%) in 58.3% of the cases. Enterovirus RNA was detected in CSF in 47 of 96 (48.9%) children tested. Children with positive enterovirus PCR had shorter hospitalization stay as compared to children who had negative PCR or to children who were not tested (P = 0.01). There were no serious complications or deaths. CONCLUSIONS: Enteroviruses accounted for approximately one half of cases of aseptic meningitis. PCR may reduce the length of hospitalization and plays important role in the diagnosis and management of children with aseptic meningitis

Implicit Review Instrument to Evaluate Quality of Care Delivered by Physicians to Children in Emergency Departments

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144238/1/hesr12800_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144238/2/hesr12800.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144238/3/hesr12800-sup-0001-AppendixSA1.pd

Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2)

BACKGROUND Deficiency of adenosine deaminase 2 (DADA2) is a syndrome with pleiotropic manifestations including vasculitis and hematologic compromise. A systematic definition of the relationship between ADA2 mutations and clinical phenotype remains unavailable. OBJECTIVE We tested whether the impact of ADA2 mutations on enzyme function correlates with clinical presentation. METHODS DADA2 patients with severe hematologic manifestations were compared with vasculitis-predominant patients. Enzymatic activity was assessed using expression constructs reflecting all 53 missense, nonsense, insertion and deletion genotypes from 152 patients across the DADA2 spectrum. RESULTS We identified DADA2 patients presenting with pure red cell aplasia (PRCA, n = 5) or bone marrow failure syndrome (BMF, n = 10). Most patients did not exhibit features of vasculitis. Recurrent infection, hepatosplenomegaly and gingivitis were common in patients with BMF, of whom half died from infection. Unlike DADA2 patients with vasculitis, patients with PRCA and BMF proved largely refractory to tumor necrosis factor inhibitors. ADA2 variants associated with vasculitis predominantly reflected missense mutations with at least 3% residual enzymatic activity. By contrast, PRCA and BMF were associated with missense mutations with minimal residual enzyme activity, nonsense variants, and insertions / deletions resulting in complete loss of function. CONCLUSION Functional interrogation of ADA2 mutations reveals an association of subtotal function loss with vasculitis, typically responsive to TNF blockade, whereas more extensive loss is observed in hematologic disease which may be refractory to treatment. These findings establish a genotype-phenotype spectrum in DADA2

IL-17RA Signaling Amplifies Antibody-Induced Arthritis

Objective: To investigate the role of IL-17RA signaling in the effector phase of inflammatory arthritis using the K/BxN serumtransfer model. Methods: Wild-type and Il17ra 2/2 mice were injected with serum isolated from arthritic K/BxN mice and their clinical score was recorded daily. Mice were also harvested on days 12 and 21 and ankles were analyzed for cytokine and chemokine mRNA expression by qPCR on day 12 and for bone and cartilage erosions by histology on day 21, respectively. The induction of cytokine and chemokine expression levels by IL-17A in synovial-like fibroblasts was also analyzed using qPCR. Results: Il17ra 2/2 mice were partially protected from clinical signs of arthritis and had markedly fewer cartilage and bone erosions. The expression of several pro-inflammatory mediators, including the chemokines KC/CXCL1, MIP-2/CXCL2, LIX/ CXCL5 MIP-1c/CCL9, MCP-3/CCL7, MIP-3a/CCL20, the cytokines IL-1b, IL-6, RANKL and the matrix metalloproteinases MMP2, MMP3, and MMP13 were decreased in the ankles of Il17ra 2/2 mice compared to wild-type mice. Many of these proinflammatory genes attenuated in the ankles of Il17ra 2/2 mice were shown to be directly induced by IL-17A in synovial fibroblasts in vitro. Conclusions: IL-17RA signaling plays a role as an amplifier of the effector phase of inflammatory arthritis. This effect is likel

Patientâ level Factors and the Quality of Care Delivered in Pediatric Emergency Departments

ObjectiveQuality of care delivered to adult patients in the emergency department (ED) is often associated with demographic and clinical factors such as a patient’s race/ethnicity and insurance status. We sought to determine whether the quality of care delivered to children in the ED was associated with a variety of patientâ level factors.MethodsThis was a retrospective, observational cohort study. Pediatric patients (<18 years) who received care between January 2011 and December 2011 at one of 12 EDs participating in the Pediatric Emergency Care Applied Research Network (PECARN) were included. We analyzed demographic factors (including age, sex, and payment source) and clinical factors (including triage, chief complaint, and severity of illness). We measured quality of care using a previously validated implicit review instrument using chart review with a summary score that ranged from 5 to 35. We examined associations between demographic and clinical factors and quality of care using a hierarchical multivariable linear regression model with hospital site as a random effect.ResultsIn the multivariable model, among the 620 ED encounters reviewed, we did not find any association between patient age, sex, race/ethnicity, and payment source and the quality of care delivered. However, we did find that some chief complaint categories were significantly associated with lower than average quality of care, including fever (â 0.65 points in quality, 95% confidence interval [CI] = â 1.24 to â 0.06) and upper respiratory symptoms (â 0.68 points in quality, 95% CI = â 1.30 to â 0.07).ConclusionWe found that quality of ED care delivered to children among a cohort of 12 EDs participating in the PECARN was high and did not differ by patient age, sex, race/ethnicity, and payment source, but did vary by the presenting chief complaint.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142981/1/acem13347_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142981/2/acem13347-sup-0001-DataSupplementS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142981/3/acem13347.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142981/4/acem13347-sup-0002-DataSupplementS2.pd