bluuebunny/crossref_metadata_2025_split huggingface dataset:
A122: Metabolomic Analysis of Breath Volatile Organic Compounds Reveals Unique Breathprints in Children With Juvenile Idiopathic Arthritis
Authors: Zeft Andrew , Costanzo Denise , Alkhouri Naim , Patel Nishaben , Grove David , Spalding Steven J. , Dweik Raed 
Published: March 2014

Background/Purpose:Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by synovial inflammation and is the most common rheumatic complaint in children. Breath testing is becoming an important diagnostic method to evaluate many disease states. The aim of this study was to analyze exhaled volatile organic compounds (VOCs) to evaluate for the presence of a unique breath pattern to differentiate pediatric patients with JIA from healthy controls.Methods:This was a prospective cross‐sectional, single‐center study that included pediatric JIA patients and healthy controls (age range, 5–21 years). The diagnosis of JIA was determined using standard clinical criteria. Exhaled breath was collected and analyzed using a selective ion flow tube (SIFT‐MS) to identify new markers of JIA.Results:76 patients were included in the study (21 with JIA and 55 healthy controls). JIA phenotype was as follows: 12 polyarticular RF negative, 2 persistent oligoarticular, 4 extended oligoarticular, 2 psoriatic, and 1‐ enthesitis‐related arthritis. Routinely analyzed VOCs for SIFT‐MS quantification showed significant differences in 13 VOCs peaks between JIA patients and healthy controls. Discriminant analysis via stepwise variable selection of mass scanning ion peak data demonstrated that 4 VOCs can classify patients with JIA or as healthy controls with only three misclassifications; p < 0.001. Further analysis revealed that breath 1‐decene, 1‐octene, and 3‐methyhexane (all markers of oxidative stress) were significantly higher in the JIA group compared to controls (11.5 ± 6.7 ppb vs. 2.1 ± 0.2 for 1‐decene; 10.5 ± 2.2 vs. 4.5 ± 0.7 for 1‐octene; and 17.5 ± 3.7 vs. 10.4 ± 1.4 for 3‐methyhexane, p value < 0.001 for all).Conclusion:Exhaled breath analysis is a promising non‐invasive method to distinguish children with JIA from healthy children. We provide pilot data to support the hypothesis that a unique breathprint can be demonstrated for JIA in the exhaled metabolome.
A130: Is the CCR5‐delta32 Mutation Protective Against Systemic‐Onset Juvenile Idiopathic Arthritis?
Authors: Chasnyk Vyacheslav , Fedorova Elena , Egorov Andrey , Ammosova Tatiana , Nekhai Sergei , Kostik Mikhail , Santimov Andrei , Dubko Margarita , Kalashnikova Olga , Masalova Vera , Likhacheva Tatyana , Snegireva Ludmila , Grom Alexei 
Published: March 2014

Background/Purpose:The CCR5 protein is a chemokine receptor, and is known to be expressed on T cells, macrophages, dendritic and microglia cells. It is believed that different prevalence of HLA and CCR5‐ delta32—a 32 base pair deletion in the coding region—in various ethnic groups is associated with the severity and prevalence of chemokine‐mediated autoimmune diseases, systemic‐onset Juvenile Idiopathic Arthritis (soJIA) being among them (Del Rincon et al., 2003). Since the end of the last century the protective role of the CCR5‐delta32 mutation against JIA is discussed (Hinks et al., 2010), though it seems the role of this mutation is less simple than was hitherto thought. The purposes of the study was to compare the prevalence of the CCR5‐delta32 mutation in children with and without soJIA, to assess the association of this mutation with the severity of the disease and thus to evaluate its protective role.Methods:234 children (193 of European origin, 25–Hispanic or Latino, 14–Afro‐Americans, 3–of Asian origin) with soJIA living in the USA and in the Northwestern part of Russia were enrolled in the study. Genomic DNA was isolated from blood samples using QIAamp Mini Kit and amplified by PCR. The following oligonucleotide primers were used to detect CCR5 d32: CCR5‐ Δ32‐F: 5′CTTCATTACACCTGCAGTC3′, CCR5‐Δ32‐R: 5′TGAAGATAAGCCTCACAGCC3′ by following condition: 95°–5′×1; 95°–15″→55°–15″→72°–60″×40; 72°–10′×3→4°–∞; the resulting PCR products were separated on 2% agarose gel by electrophoresis and visualized by Gel Doc XR Plus.Results:Mutation was revealed only in children of European origin. Though the prevalence of the heterozygous CCR5‐delta32 mutation being 16% and 21% in the USA and in Russia correspondingly didn't excel from its prevalence in populations in total (10–18% for Northwestern Russia, Kofiady, 2008; 11,8%– for white American group, Downer et al, 2002), some laboratory and clinical signs of soJIA proved to be related to the mutation (see ). Heterozygous CCR5‐delta32 genotype was associated with milder so‐JIA course and predominance of the articular features over systemic.

Sign
CCR5‐delta32 (+)Mediana (frst quartile; thrd quartile)
CCR5‐delta32 (–) Mediana (frst quartile; thrd quartile)
p

AST, U/l
30.5 (25.1; 36.5)
50.6 (36.1; 69.0)
0.003

LDH, U/l
386.0 (382.0; 543.0)
1049.0 (635.0; 1086.0)
0.02

Total protein, g/l
76.5 (73.1; 82.5)
67.0 (65.0; 70.0)
0.01

Ferritin, µg/l
1200.0 (1200.0; 1200.0)
1278.0 (117.0; 2629.0)
0.0000001

Polyarticular course, (%)
100.0
20.0
0.015Conclusion:The results of the study may be considered rather not supporting the idea of the protective role of the CCR5‐delta32 mutation against soJIA, though the revealed associations—most of them related to the signs of the Macrophage Associated Syndrome—can be the basis for a more sophisticated research.
A131: Associations of Short–Term Pollution Exposures With Childhood Autoimmune Disease
Authors: Zeft Andrew , Pope C. Arden 
Published: March 2014

Background/Purpose:Fine particulate matter (aerodynamic diameter less than or equal to a 2.5–mm cut point, PM2.5) is a measurable component of ambient urban pollution. Our preliminary data suggests that short‐term PM2.5 exposures are associated with the clinical presentation of Juvenile idiopathic Arthritis (JIA) in young children (). In this EPA funded project, we are further testing the hypothesis that clinical autoimmune disease presentation and exacerbation is associated with exposures to short–term pollution, focusing on PM2.5. We are establishing associations between short–term PM2.5 exposure and the clinical onset of systemic onset Juvenile Idiopathic Arthritics (soJIA) and Kawasaki Disease (KD) and the clinical exacerbation of Henoch Schonlein Purpura (HSP).Methods:Cases are from existing physician operated SoJIA and KD datasets diagnosed in United States and Canadian metropolitan regions. Cases of HSP arise from a US national hospital database (Children's Hospital Association). The study utilizes a case–crossover study design to define associations of short‐term PM2.5 with the event dates of symptom onset of soJIA and KD (fever onset) and of hospitalization for HSP exacerbation from metropolitan regions, stratified by parameters of disease activity.Results:We have assembled PM2.5 exposure measurements from urban monitors and have carefully imputed PM2.5 to provide day–to–day temporal variability and resolution for reliable time series indexes of pollution exposures for each metropolitan area (Philadelphia, Boston, Toronto, Chicago, Atlanta, Cincinnati, San Diego, Salt Lake City, Denver, Cleveland). To date, case–crossover analysis results establishing risk of the event dates of clinical symptom onset and hospitalization exacerbation for the pediatric rheumatic diseases under study are preliminary.Conclusion:Well–constructed, environmental epidemiology studies examining the triggers of disease onset and exacerbation in pediatric rheumatic diseases are few and far between. Findings from this Environmental Protection Agency funded project will have a significant impact on the field of particulate induced environmental epidemiology research of autoimmune disease.
A132: Farber Disease Explains Subset of Juvenile Idiopathic Arthritis
Authors: Schuchman Edward 
Published: March 2014

Background/Purpose:Farber Lipogranulomatosis (Farber Disease; FD) is an ultra‐;rare lysosomal storage disorder due to the inherited deficiency of the enzyme acid ceramidase, and the resultant accumulation of the lipid substrate, ceramide. Ceramide is a proinflammatory and pro‐;apoptotic lipid that has been implicated in the pathogenesis of cartilage disorders. Farber Disease has a heterogeneous presentation ranging from a severe phenotype with respiratory and CNS involvement with an average life expectancy of 1.3 years (Type 1) to a moderate phenotype which generally includes joint swelling, contractures and pain (Type 3). Awareness of FD in the pediatric arthritis community is limited due to the rarity of the disease. The clinical similarity between the moderate Farber phenotype and Juvenile Idiopathic Arthritis (JIA) suggests that moderate Farber Disease cases would be classified as JIA cases.Methods:To test the hypothesis that moderate Farber Disease is diagnosed as Juvenile Idiopathic Arthritis, we conducted a literature search of Farber Disease case studies since 1990 using search terms “Farber Disease,” “Farber's Disease” and “Farber lipogranulomatosis” in PubMed published in English. Moderate Farber Disease patients were defined as surviving into their third year of life without hepatosplenomegally or significant neurological involvement. Cases where idiopathic arthritis was suspected were noted.Results:The literature search identified 84 unique papers with 35 comprising Farber Disease case studies. Of the overall case studies, 14 or 40% described patients with moderate disease. Five or 36% of these patients were diagnosed as having Juvenile Idiopathic Arthritis.Conclusion:A high percentage of moderate Farber Disease patients are diagnosed as having Juvenile Idiopathic Arthritis. Several of the patients described were referred to secondary or tertiary centers for treatment, which suggests that this percentage may be understated. Given this finding, it is important to increase the awareness of Farber Disease in the pediatric rheumatology community. Differential diagnosis can be made by accounting for the comparatively early onset of FD, the progressive severity of arthritis in FD, the presence of subcutaneous nodules in the joints, scalp and/or spine of FD patients and an unusual, hoarse cry or voice in FD patients, whichi is due to nodule formation on the larynx. Plexcera Therapeutics LLC is a new company focused on developing acid ceramidase enzyme therapy for disorders with ceramide accumulation (www.plexcera.com). Based on experience with bone marrow transplant in Farber Disease patients, enzyme replacement therapy could resolve arthritis phenotype in patients. We propose that FD can account for specific cases of JIA, and that genetic screening of the JIA population will reveal FD patients that will benefit from future treatment with rhAC.
A135: Final Year Undergraduate Medical Student Use and Acceptability of an e‐Learning Module in Pediatric Rheumatology
Authors: Southwood Taunton R. , Rainger Peter , Hussain Dabir , Couperthwaite John , Perryer Giles 
Published: March 2014

Background/Purpose:Traditional medical student learning and teaching methods, such as lectures and bedside teaching, maybe inadequate for providing core knowledge and clinical skills in paediatrics, with reduction in undergraduate time allocated to paediatrics and increasing medical student numbers. To supplement paediatric knowledge and improve access to essential clinical skills, we developed an e‐;learning module, “paediatric rheumatolog‐e”, within a Canvas(c) learning management system. The design promoted revision of basic sciences (e.g. musculoskeletal anatomy, inflammation and immunological processes), in the context of clinical sciences (e.g. pharmacology, rheumatology and child development). Learning content comprised videos of patient and family narratives, clinical skills and layered information on 4 key learning outcomes: joint swelling, limb pain, back pain and the limping child. Optional information on juvenile idiopathic arthritis was provided. Core knowledge was consolidated using interaction, reflection and formatively assessed case‐based quizzes.Purpose: The aim of this study was to assess final year medical student use and acceptabilty of an e‐learning module in paediatric rheumatology.Methods:341 final year medical students were notified of the e‐learning module by email at the beginning of the academic year, and again 3 months later. Students beginning their paediatric rotation were reminded in the introductory lecture and written course materials. Use of the module was assessed 4 months into the academic year, after 3 blocks of medical students (193 students, 53% of the year) had undertaken a paediatric rotation. Canvas(c) embedded in‐course analytics were used and acceptability was ascertained through online feedback and an email questionnaire.Results:187 students (55%) accessed the e‐learning module (a mean of 14.8 pages per student, range 1–270, 28% >3); of these 20 (11%) answered at least one clinical quiz. Higher median quiz scores were found in the joint swelling quiz and back pain quiz. There was a preference for accessing the module during a paediatric rotation (74/193 students to date, 62%). Time for completion of the module was 1–1.5 hours. Student acceptability was high, with comments such as “thorough” and “engaging”, and requests for more e‐learning modules.Conclusion:An e‐learning module in a paediatric speciality was widely used and found to be acceptable by final year medical students.
A136: Assessing the Efficacy of Pediatric Rheumatology Video‐based Curriculum
Authors: Modica Renee 
Published: March 2014

Background/Purpose:Musculoskeletal complaints are common in pediatrics. Practitioners are often under‐skilled in performing the musculoskeletal exam and deficient in basic knowledge regarding rheumatologic diseases. We sought to determine if learning the pediatric musculoskeletal exam and rheumatic conditions in a video‐enriched case‐based lecture series will improve their knowledge of rheumatic diseases.Methods:This prospective pre/post test single group design study was conducted at a pediatric tertiary care center with a pediatric residency. A convenience sample of students attending a monthly lecture series was included in this study. We designed a video case‐based curriculum; Pediatric Rheumatology Video‐based Curriculum (PRVC), using a disease specific video/image timeline to demonstrate abnormal physical findings. Novel features included: “voice over” explanation of findings while the patient is being examined, split screen display of abnormal vs. normal findings, graphics to highlight subtle findings seen in rheumatic diseases and evolution of physical exam with treatment. A single experimental group was administered a pretest prior to being exposed to the PRVC. After each intervention, effectiveness was assessed with a posttest. The primary outcome measure was measured by improvement on pre‐/post‐ intervention questionnaires using a paired t‐test. Secondary outcome measure was learner satisfaction assessed by a 5‐point Likert questionnaire.Results:Over a 10‐month period, 8 (1 hour) lectures were given to audiences consisting of medical students and pediatric residents. Eleven to 28 listeners performed an assessment pre and post‐test for each lecture. Based on pre‐test and post‐test results from each lecture, each lecture demonstrated statistically significant improvement for the learner (Table ). Similarly, respondents expressed overall satisfaction with an average score of 4.8 on a 5‐point Likert scale.

Results for pre/post‐test improvement for each lecture

Lecture Topic
n
Pre‐test (%)
Post‐test (%)
p value

MSK (Musculoskeletal Exam)
15
66.7
80
0.01

JIA (Juvenile Idiopathic Arthritis)
24
44.2
78.6
<0.0001

ERA (Enthesitis Related Arthritis)
20
61.5
85.8
<0.0001

JDMS (Juvenile Dermatomyositis)
11
50
78.8
0.0005

SCL (Juvenile Scleroderma)
14
52.5
80.4
<0.0001

SARC (Juvenile Sarcoidosis)
28
53
96.4
<0.0001

SLE (Systemic Lupus)
18
51.4
78.2
0.0002

PFS (Periodic Fever Syndromes)
11
50
92.2
<0.0001

Overall
141
53.6
83.5
<0.00001

p value calculated using paired t‐testConclusion:The PRVC is a unique curriculum that demonstrated effectiveness and satisfaction as assessed by the learners.
A138: Clinical Decision Support to Improve Preventive Care in Pediatric Systemic Lupus Erythematosus
Authors: Nelson Brittany 
Published: March 2014

Background/Purpose:Quality indicators, such as infection and cardiovascular disease (CVD) preventive care, for patients with systemic lupus erythematosus (SLE) have recently been published and can be utilized for assessing quality of care. Implementation of tools such as clinical decision support (CDS) within the electronic health record (EHR) can be utilized in quality care improvement efforts. The purpose of this quality improvement study is to test the chronic care model to study the relationship between CDS and rates of compliance with infection and CVD preventive care quality indicators for pediatric SLE patients at an outpatient rheumatology clinic.Methods:The study is a pilot retrospective design with a convenience sample. Documentation in the EHR of up to date vaccinations and lipid screen was measured before and after implementation of an electronic documentation template. Data for the comparative hypothesis was analyzed using Chi‐square test.Results:Baseline data was collected from 48 (70%) patient charts and post‐CDS data were collected from 20 (30%) patient charts. Before intervention, 15 (31.3%) patients received pneumonia vaccine and 17 (81.0%) of patients received vaccine after intervention. Sixteen (33.3%) patients received influenza vaccine before intervention and 20 (95.2%) received vaccine after intervention. Before intervention, 12 (25.0%) patients received lipid panels and 16 (76.2%) patients received lipid panels after intervention. All three differences were significantly different (Fisher's Exact p < 0.001). Patents were 9 times more likely to receive the pneumococcal vaccination and lipid panels and 40 times more likely to receive the influenza vaccination post intervention than before intervention.
Baseline QI rates, Post‐intervention QI rates, and statistical differences between groups

PVX Vaccine
Influenza Vaccine
Lipid Panel

Baseline patients meeting QI, n (%)
15 (31.3)
16 (33.3)
12 (25)

Post CDS patients meeting QI, n (%)
17 (81)
20 (95)
16 (76)

Fischer's Exact test significance
.000
.000
.000

Cramer's V
.459
.570
.480

Odds Ratio (95% CI)
9.35 (2.683–32.587)
40 (4.917–325.378)
9.6 (2.897–31.810)

Pretest n = 48 (70%), poster intervention n = 20 (30%); p value < 0.1Conclusion:Use of EHR CDS was associated with improved rates of preventive care for pSLE patients in the Pediatric Rheumatology outpatient setting. Our results suggested that patients were more likely to receive a screening lipid panel, influenza vaccination and pneumococcal vaccination if the health care provider used the EHR template with CDS.
A159: The Autoimmune Genetic Architecture of Childhood Onset Rheumatoid Arthritis
Authors: Prahalad Sampath , Marion Miranda C. , Cobb Joanna , Sudman Marc , Hinks Anne , Pichavant Mina , Ponder Lori , Reed Ann M. , Wallace Carol , Becker Mara L. , Yeung Rae S. M. , Rosenberg Alan M. , Punaro Marilynn G. , Mellins Elizabeth D. , Nelson J. Lee , Videm Vibeke , Rygg Marite , Nordal Ellen , Brown Matthew A. , Cutler David , Bohnsack John F. , Thomson Wendy , Thompson Susan D. , Langefeld Carl D. 
Published: March 2014

Background/Purpose:Genome‐wide association studies have identified susceptibility loci for many autoimmune diseases, including rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). About 5% of children with JIA have rheumatoid factor positive arthritis that is phenotypically similar to adult seropositive RA, thus representing childhood onset RA (CORA). To understand the genetic architecture of CORA risk relative to other autoimmune diseases, we genotyped CORA cases and controls on the Immunochip, a custom array designed by the Immunochip Consortium to fine map autoimmune disease‐associated loci shared across 11 autoimmune phenotypes.Methods:Genotyping was completed on 340 CORA cases (mean onset age: 10.2 ± 4.2 yrs) and 11624 controls. Standard SNP and sample QC was performed (e.g., removing samples with call rate <98%, admixture outliers). To test for SNP association with CORA a logistic regression model was computed with Caucasian admixture proportions (ADMIXTURE) as covariates (SNPLash). False discovery rate (FDR) adjusted p‐values (PFDR) are reported to account for the actual number of tests computed.Results:SNP rs3129769, near HLA DRB1 was the most significantly associated (PFDR <3×10‐25), and is in linkage disequilibrium with the HLA DRB1 SNP reported in RA (rs660895, PFDR <1×10‐24). Outside the HLA region, 28 regions had ≥1 SNP meeting genome‐wide significance (PFDR<0.05). The best signal of association was on 22q13 (rs9610687, OR = 0.57, PFDR < 0.0002) near IL2RB, followed by the PTPN22 locus (rs6679677, OR = 1.83, PFDR < 0.0005), an intergenic SNP on chromosome 4 (rs970036, OR = 1.78, PFDR < 0.002) and an intronic SNP (19p13, rs3787016 PFDR < 0.002) in the POLR2E gene, which encodes a subunit of RNA polymerase II. Some loci which have previously been implicated in RA had evidence of association including MMEL (rs751358 PFDR < 0.003), IRF5 (rs4731531 PFDR < 0.006) and CCR6 (rs11575078 PFDR < 0.03). In addition using the FDR‐based threshold we identified several potential SNPs (rs10918214, 1q23; rs28491312, 14q31) not previously implicated in RA.Conclusion:Immunochip analysis of the largest cohort of CORA investigated to date has confirmed the HLA DRB1 association and identified several other loci associated with CORA. Comparisons among loci associated with CORA and those identified in RA and other forms of JIA are underway and will help delineate the unique genetic factors for CORA susceptibility.