bluuebunny/crossref_metadata_2025 huggingface dataset:
A62: GO‐KIDS Imaging Substudy: MRI Treatment Response to 30 mg/m2 Q4W Subcutaneous (SC) Injections of Golimumab (GLM) and Placebo in Children With Polyarticular JIA (pJIA)—Preliminary Results of the Placebo Controlled Portion (Week 48)
Authors: Tzaribachev Nikolay , Tzaribachev Catrin , Mehrwald Marret , Koos Bernd
Published: March 2014

Background/Purpose:

The GO‐KIDS trial is a double blind placebo controlled Phase III trial, where patients 2–17 yrs of age with pJIA received open label SC GLM 30 mg/m2 every 4 weeks until W16, followed by 1:1 randomization to placebo or GLM from W16 to W48 for children achieving ACR Pedi 30 response at W16 with resumption of GLM in PBO randomized subjects upon flare. Primary endpoint is % of children who did not experience flares of JIA between W16 and 48. 173 patients were enrolled globally.

Methods:

Patients participating in the GO‐KIDS trial at a single center could voluntarily participate in the GO‐KIDS Imaging substudy after obtaining separate informed consent. Gadolinium enhanced MRI examinations of a reference peripheral joint region were obtained at Weeks 0, 16, 28, 48 (primary endpoint). MRI was scored (grade 0–3) for synovitis (S) and synovial hypertrophy (SH). Statistical analysis used Shapiro‐Wilk‐W‐test, non‐parametric Wilcoxon rank‐sum test.

Results:

From the 17 children with complete data sets at W16 (10 female) with a median age of 9 (7–17) years at study inclusion in the Imaging substudy, 14 of the 17 children reached W48 in the substudy (8 GLM, 6 PBO). Discontinuations through W48 were due to 2 clinical non‐responders at W16 and 1 possible allergic reaction to GLM before W48. At W16 and W48 the MRI was significantly improved compared to W0 both for S and SH (p < 0.001 for W16, p < 0.0001 for W48) for the peripheral joints.

After unblinding, 6 patients were on placebo (PBO) where 4 demonstrated through W48 both inactive disease on MRI and clinical improvement above ACR Ped 30 compared to baseline. One of the 4 patients flared after W48, while the remaining 3 do not show residual disease activity on MRI beyond W72. The remaining 2 patients, who were randomized to PBO at W16, flared and resumed GLM treatment. MRI at W28 predicted clinical flare in both patients with evidence of recurrent synovitis. One of the 2 patients responded to reintroduction of GLM showing inactive disease on MRI at W48. The other patient did not respond clinically or by MRI to GLM reintroduction.

Changes in synovitis (S) on Gd enhanced MRI were a significant. Data presented as mean, mininal and maximal values.

image

Conclusion:

At the primary endpoint of the GO‐KIDS trial, overall, children with pJIA demonstrated significant improvement on MRI measurements of synovitis and synovial hypertrophy between W0 and W48 during the GO‐KIDS Imaging substudy, particularly children randomized to continued GLM between W16 and W48. In 4/6 patients randomized to placebo at W16, GLM treatment from W0 to W12 alone induced inactivity on MRI through W48. MRI predicted clinical flare in 2 patients randomized to PBO.
A63: Treatment of Arthritis in Animal Models of the Mucopolysaccharidoses Using a Novel Anti‐Inflammatory Drug, Pentosan Polysulfate
Authors: Simonaro Calogera , Frohbergh Michael , Ge Yi , Meng Fanli , Schuchman Edward
Published: March 2014

Background/Purpose:

The mucopolysaccharidoses (MPS) comprise a group of 11 lysosomal storage disorders (LSDs) due to inherited deficiencies of glycosaminoglycan (GAG) degrading enzymes. Naturally occurring animal models exist for most of these disorders, providing excellent systems in which to study disease pathogenesis and treatment. We have previously shown that GAG storage in MPS leads to activation of the TLR4/TNF‐alpha inflammatory pathway, and that inflammation is a major contributor to the degenerative cartilage disease occurring in MPS patients. The pattern of inflammatory changes in MPS closely resembles that occurring in arthritis, and the MPS animals also represent excellent, naturally occurring genetic models of arthritis. Various treatment approaches have been investigated for MPS, and we recently identified one FDA‐approved drug, pentosan polysulfate (PPS), that resulted in remarkable clinical improvements in a rat model of MPS type VI (Schuchman et al., PLoS One, 2013).

Methods:

In our previous work we reported the effects of daily oral PPS treatment in MPS VI rats, and here we compare these effects with weekly subcutaneous (subQ) injections. Four groups of MPS VI rats were treated with weekly subQ PPS at human equivalent doses of 1, 2 and 4 mg/kg, and with a combination of 2 mg/kg PPS and 1 mg/kg enzyme replacement therapy (ERT; Naglazyme®).

Results:

The most efficacious subQ PPS dose was 2 mg/kg. Among the four groups of treated rats the best results were found in animals treated with a combination of PPS and ERT. Treatment of all MPS VI rats with weekly subQ PPS for up to 6 months was safe.

Conclusion:

We propose that weekly subQ injections of PPS will be efficacious and safe in MPS patients, and a phase 1/2 clinical study is planned. We also propose that PPS could be effective in arthritis, and might provide a cost‐effective, safe alternative to existing TNF‐alpha drugs.
A67: Factors That Contribute to Classification of Children as Having Undifferentiated Juvenile Idiopathic Arthritis
Authors: Chan Mercedes O. , Petty Ross E. , Oen Kiem , Duffy Ciarán M. , Tucker Lori B. , Yeung Rae SM , Guzman Jaime ,   The ReACCh Out Investigators
Published: March 2014

Background/Purpose:

According to the ILAR criteria, undifferentiated juvenile idiopathic arthritis (U‐JIA) includes children who fail to meet criteria for 1 of the other 6 categories or who meet criteria in more than 1 category. Classification requires category‐specific application of 5 exclusion criteria: 1. Psoriasis in the patient or a 1st degree relative; 2. Arthritis beginning after the 6th birthday in an HLA‐B27 + male; 3. HLAB27 associated disease in a 1st degree relative; 4. Rheumatoid factor positivity (RF+) on 2 occasions; and 5. The presence of systemic JIA (SoJIA).

A pilot single‐centre study (n=21) revealed that psoriasis in a 1st degree relative was the most common reason for classifying patients as U‐JIA; disregarding this criterion would allow re‐classification of most U‐JIA patients and had no impact on the classification of JPsA patients (Chan et al., 2011). We aimed to determine the most frequent reasons for classifying children as U‐JIA from a large multicenter prospective cohort of children with JIA (n=1104).

Methods:

Two investigators reviewed data on patients diagnosed with UJIA extracted from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh‐Out) database. They identified by consensus the reasons for classifying patients as U‐JIA and the JIA category they would fall in if the following two changes were made: disregarding psoriasis in a 1st degree relative, considering patients as RF negative when only a single positive RF test was recorded.

Results:

84 patients (51 female), were classified as U‐JIA for the reasons shown in the .

Exclusion criteria
1st degree relative with psoriasis (n=57)
B27 male>6 years + arthritis (n=4)
RF+ on 2 occasions (n=1)
RF+ on 1 occasion only (n=17)
1st degree relative with B27 related disease (n=4)
SoJIA (n=0)
Fulfills criteria for 2 categories (n=2)

Revised category if exclusion criteria disregarded

Oligo
25

9
2

Poly RF−
13

2

Poly RF+
5 (1 RF+x2, 4 RF+x1)

ERA
12

5

Systemic
2

1

JPsA

4

1

U‐JIA

1
1

2 (JPsA + ERA)

If the criterion of having a 1st degree relative with psoriasis was disregarded, 25 patients would be classified as oligo JIA, 13 poly RF−, 5 poly RF+, 12 ERA and 2 SoJIA. If a single positive RF test was considered to be insufficient to meet the ILAR criterion of RF positivity, 9 patients would be re‐classified as oligo JIA, 5 ERA, 1 SoJIA, 1 JPsA and 1 would remain U‐JIA.

Conclusion:

Psoriasis in a 1st degree relative is the most common factor contributing to the classification of a child as having U‐JIA and removing it from the existing criteria should be considered. The presence of a single positive test for RF was the second most common reason resulting in a classification of U‐JIA. Definitive RF testing (two tests) should be maintained to satisfy the criterion of “RF positivity”.
A69: Lupus Nephritis and Autoantibody Characteristics of a Single Center Cohort of Male Pediatric SLE Patients
Authors: Wenderfer Scott E. , Canter Debra , DeGuzman Marietta , Muscal Eyal
Published: March 2014

Background/Purpose:

Males represent 4–22% of all SLE patients, but it is unclear if gender should influence management. A number of studies of mostly adult patients suggest genetic, hormonal and environmental aspects of gender differences contribute to differences in presentation, clinical course and outcome, including a positive association between male gender and nephritis and a negative association with disease activity and outcome. While differences may exist, these findings are supported by limited evidence, particularly for children and adolescents with SLE.

Methods:

We retrospectively reviewed records of the nearly 200 pediatric SLE patients actively followed in the TCH rheumatology and renal clinics between 2011 and 2013 to identify males with SLE. Characteristic autoantibody features and renal disease were defined.

Results:

We identified 25 males (48% Hispanic, 16% Black, 16% Asian). The mean age of onset of disease was 11.5 ± 0.6 yo. Comorbid autoimmune diseases were identified in 46% of patients and 31% had a positive family history of autoimmune disease. Hypocomplementemia was seen at least once in 54% of patients. The cumulative incidence of positive autoantibodies included 50% anti‐dsDNA, 54% with antiphospholipid abs, 42% with anti‐RNP, 38% with anti‐Ro (SS‐A), 19% with anti‐Smith, 15% with anti‐La (SS‐B), and 8% with RF. Only 35% (9) of male SLE patients developed lupus nephritis (LN), the majority of whom had class IV lesions (77%). Class V lesions were seen in 3 patients, including one with mixed histopathology (IV/V). LN was a presenting symptom in all 9 patients. Of these, 33% had acute kidney injury and 22% had crescentic disease on biopsy. The proportion of boys with LN and anti‐dsDNA antibodies was not significantly different from boys without LN (66% vs. 50%, p = 0.67); however, a significantly higher proportion of boys with LN had anti‐RNP abs (77% vs. 29%, p = 0.04).

Conclusion:

Although SLE predominately affects females, males with SLE represent an important subset of patients about which little is known. In our male cohort, rates of autoantibody positivity were similar to those published for females, but rates of kidney invovlement seem lower than expected. In addition, autoantibody profiling may not be as useful in predicting kidney involvement in boys. Additional research is of upmost importance to improve the diagnosis, quality of care, and outcomes of male SLE patients.
A72: Predicting Progression From Oligoarticular to Polyarticular Juvenile Arthritis
Authors: Rumsey Dax , Rezaei Elham , Karunanayake Chandima , Oen Kiem , Rosenberg Alan M. , Shiff Natalie
Published: March 2014

Background/Purpose:

It has been previously shown that early involvement of wrist and ankle are risk factors for extension of oligoarticular onset juvenile arthritis (oligoJA). Our objective was to determine whether early wrist, ankle, upper limb, or lower limb involvement are risk factors for extension to a polyarticular course in a cohort of paediatric patients with oligoJA.

Methods:

This is a retrospective cohort study of children with oligoJA presenting to paediatric rheumatology clinics at the two Canadian paediatric centres from 1981 to 2010. OligoJA was defined as ≤4 joints at the first and 6 month visits. Risk factors for extension from oligoJA to polyarthritis (>5 joints) by 2 and 5 years after diagnosis were modelled using logistic regression while controlling for sex, ever having used DMARDs, or intraarticular corticosteroid injections. Time to extension was assessed using Cox proportional hazard analysis.

Results:

420 patients met eligibility criteria. 56% were female. The median time from disease onset to diagnosis was 136 days (IQR 55.5 days, 365.0 days); 15 patients in the logistic regression models extended by 2 years (n=280, of which 5.4% extended) and 27 by 5 years (n=339, of which 8.0% extended). At 2 years after diagnosis the odds of extension was 6.1 times higher (95% CI 1.9, 24.3) in those with initial wrist involvement than in those without, and at 5 years it was 3.1 times higher (95% CI 1.0, 8.0). The OR of extension in those with initial upper limb involvement versus those without was 7.0 (95% C.I. 2.3, 21.6) at 2 years and 6.3 (95% C.I. 2.5, 15.8) at 5 years. Cox proportional hazard modelling showed a HR of 2.3 (95% CI 1.2, 4.5) in patients with upper limb involvement compared to without upper limb involvement indicating that extension was 2.3 times more likely to occur in the former group. The likelihood ratio was 68.7, p value < 0.0001, degrees of freedom (d.f) = 4, and events per variable = 9.8.

Conclusion:

This study independently confirms previous published findings that wrist and upper limb arthritis in the first 6 months after diagnosis of oligoJA is a risk factor for extension. Unlike previous reports, we did not find an increased probability of extension in patients with early ankle arthritis. Patients with upper limb arthritis in the first 6 months after diagnosis were more likely to extend sooner than those without early upper limb arthritis.
A97: Endothelial Function in Children With a History of Henoch‐Schonlein Purpura
Authors: Aviel Yonatan butbul , Dafna Lotem , Brik Riva , Pilar Giora
Published: March 2014

Background/Purpose:

Few reports have focused on vascular endothelial function in children with Henoch‐Schönlein purpura (HSP). The purpose of the present study was to assess the long term effect of HSP on endothelial function, in children and adolescents.

Methods:

Patients between 6–20 years old, who were diagnosed as having HSP according to ACR Criteria, were included in the study. All patients were followed by the rheumatologic clinic at Meyer children's hospital Israel. The time interval between diagnosis of HSP and endothelial study was at least 6 months.

Endothelial function evaluation was assessed by a noninvasive technology named peripheral arterial tonometry, using an ENDO_PAT device. The device measures blood flow in the limb, in response to arterial occlusion as an index of endothelial function, Reactive Hyperemic Index (RHI). Endothelial function was compared to known normal values of existing control group consisting of 23 healthy children and adolescents.

Results:

Nineteen children and adolescents (M:F 8/11) age (3.9 ± 13.5 years) with history of HSP were included in the study. Endothelial function was compared to that of a known control group comprising of 23 healthy children and adolescents of the same age group and M:F ratio.

There was no difference in RHI levels between the children with diagnosis of HSP and the control group (1.8 ± 0.7 vs. 1.9 ± 0.35 p = 0.7).

For patients with HSP we used multi variant regression models to evaluate relation between RHI and different variables the final model include smoking that have negative effect (β = (−1.042), P = 0.31) and, period of time from diagnosis to time of evaluation that have positive effect (β = 0.139, P = 0.003) (R2 = 0.476).

When we excluded two patients with exceptional level of RHI from the study a higher correlation was found between those variables and RHI (R2 = 0.76).

RHI levels were significantly higher in patients that endothelial function was measured more than 6 years after diagnosis of HSP compared to the rest of the group (1.98 ± 0.74 vs 1.38 ± 0.43 P = 0.037).

Conclusion:

These results suggest that HSP cause endothelial dysfunction that improves with time.

The influence of the endothelial dysfunction on the long term chances of developing atherosclerosis has still to be determined.
A104: Aggressive Erosive Synovitis in Juvenile Idiopathic Arthritis
Authors: Chédeville Gaëlle , Azouz Michel , Scuccimarri Rosie
Published: March 2014

Background/Purpose:

Plain radiographs (x‐rays) are useful in the evaluation of children with JIA. Bone erosions are one of the finding that can be seen on x‐rays. However, they are most often reported in the polyarticular RF+ subtype of JIA and are rare in most other subtypes.

Methods:

Herein 3 patients with JIA are presented whose diagnoses were questioned after plain x‐rays were obtained. MRI later revealed significant erosive disease in these patients.

Results:

Case 1: A 14 yo male presented with a monoarthritis of the left wrist. Initial x‐rays were normal. His work‐up was unremarkable. His inflammatory markers were normal. He was thus diagnosed with JIA–oligoarthritis. After 6 months in remission, after the use of an NSAID, he flared in the same joint. Repeat x‐rays showed a radiolucent area with associated sclerosis in the scaphoid of unclear etiology. An MRI was thus requested. It revealed synovitis associated with erosive disease. Post gadolinium injection, a geode in the scaphoid bone with marked synovial enhancement visible within this erosion was detected. He underwent a joint injection which put him into remission. Repeat x‐rays one year later, revealed unchanged findings likely corresponding to the non‐healed erosion.

Case 2: An 11 yo HLA B27 + male diagnosed with ERA with polyarthritis of the lower limbs and sacroiliac joints was treated with methotrexate and an NSAID. Investigations ruled out IBD and the arthritis was felt to be well controlled despite persistently elevated inflammatory markers of unclear etiology. He presented with a severe flare in his knees and ankles. X‐rays revealed well‐defined lytic lesions in the anterior aspect of the proximal tibial metaphysis just below the growth plate bilaterally. Given the concern of an infiltrative process, an MRI was obtained. Post gadolinium injection, a large erosion of the tibial plateau with marked synovial enhancement within this erosion was seen, as well as a knee synovitis. Etanercept was started.

Case 3: An 8 yo male presented with a monoarthritis of the right wrist evolving for five months after an initial minor trauma. X‐rays revealed advanced bone maturation of the right wrist as well as a sclerotic lesion of the hamate. Given the initial trauma, an MRI was obtained which demonstrated very extensive bone marrow edema, synovitis, tenosynovitis and a large erosion within the hamate. A diagnosis of JIA–oligoarthritis was made. He underwent a joint injection with good disease control.

Conclusion:

Large erosions are not typical for some JIA subtypes such as oligoarthritis and ERA. Findings on x‐rays led the treating physicians to question the underlying diagnosis however, MRI revealed very aggressive synovitis of the wrist and knee in these patients. MRI was useful to demonstrate the presence of synovial enhancement within the eroded bone and helped rule out another diagnosis. Awareness of this type of aggressive arthritis is needed so that patients are not over‐investigated and prompt treatment can be offered.
A105: Late Cardiac Assessment in Children Who Were Diagnosed With Post Streptococcal Reactive Arthritis—A Long Term Study
Authors: Perl Liat , Kvint Ifat , Matityahu Avraham , Levi Alex , Uziel Yosef , Barash Judit
Published: March 2014

Background/Purpose:

In different from rheumatic fever (RF), the association of post streptococcal reactive arthritis (PSRA) and carditis is controversial. Currently the American Heart Association recommends anti‐streptococcal prophylaxis for PSRA for one year, repeat echocardiogram and discontinuation of prophylaxis if normal (level 2, C evidence).

Aim—To examine whether there is late cardiac involvement in a cohort of children with PSRA.

Methods:

Children with defined PSRA who were followed at the pediatric rheumatology units in Meir and Kaplan hospitals had echocardiography, done by pediatric cardiologists, at least 1 year following diagnosis.

Results:

146 PSRA patients fulfilled the study criteria. Of these, 69 had undergone echocardiography 1–6.9 years from diagnosis. All had normal major parameters. 20 patients had minimal findings: 5 (7.2%) mild mitral insufficiency; 12 (17.4%) minimal mitral insufficiency; 2 (2.9%) mild tricuspid insufficiency and one patient (1.4%) had very mild aortic insufficiency. All were consistent as non significant findings. Of the 77 patients who did not complete echocardiography, 31 were randomly excluded from the study, 26 refused to undergo echocardiography, and 20 were lost to followup, all were asymptomatic according to their medical record or telephone questionnaire. There were no statistically significant differences between the group that had completed echocardiography to the group that had not.

Conclusion:

No late cardiac involvement was found in our pediatric PSRA patients. Therefore, different approaches to antibiotic prophylaxis for PSRA and RF are probably justified. A prospective, double blind placebo controlled study is needed to definitively assess the necessity of prophylaxis in PSRA.
A107: Dream Doctors—Medical Clowns Increase the Effect of Nitrous Oxide Sedation in Intra‐Articular Corticosteroid Injection for Juvenile Idiopathic Arthritis
Authors: Uziel Yosef , Weintraub Yael , Rabinowicz Noa , Hanuka Penny , Rothschild Michal , Kotzki Shulamit
Published: March 2014

Background/Purpose:

Intra‐articular corticosteroid injection (IASI), a common procedure in juvenile idiopathic arthritis (JIA), is usually associated with anxiety and pain.

In previous study we concluded that nitrous oxide (NO) provides effective and safe sedation for such procedures. The efficacy in reducing pain was associated with the level of the child's anxiety even before starting the procedure.

Following the introduction of “Dream Doctors” in our hospital, we added medical clown as an important integral part of the team doing IASI.

Aim:

To prospectively evaluate how a medical clown affects pain perception during IASI in JIA using NO conscious sedation.

Methods:

Patients scheduled for IASI first met and interacted with the medical clown. During the procedure, the rheumatologist and the medical clown worked in parallel to create distraction. NO was administered. The patient, parent, physician, medical clown and nurse completed a visual analog scale (VAS ‐ (0–10) for pain. Change in heart rate (HR) ≥15% was recorded to examine physiologic response to pain and stress.

Results:

46 procedures were performed in 32 children: 23 girls, 9 boys, with a mean age of 10.87 ± 3.58 yrs. The median VAS pain score for the patients, parents, physicians, medical clown and nurses was 2, 2, 1, 1, and 1, respectively. 5 patients had increased HR, and experienced increased pain. In our previous study using only NO, the median pain score was 3.

Conclusion:

Active participation of a medical clown during IASI with NO for JIA further decreasing pain, stress, and induces a pleasant patient experience.
A114: Methylprednisolone‐Induced Inhibition of miR‐155 Expression Increases SOCS1‐Driven Suppression of Cytokine Signaling
Authors: Davis Trevor E. , Kis‐Toth Katalin , Tsokos George C.
Published: March 2014

Background/Purpose:

MicroRNA (miRNA, miR) are short RNA species (20–23 nt) that act post‐transcriptionally modulating messenger RNA (mRNA) translation or stability. They control many biological processes including cell differentiation and homeostasis. Abnormal levels of miRNA have been implicated in cancers and autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Steroids are first line anti‐inflammatory medications that act through transcriptional or posttranscriptional gene regulation. In multiple instances steroids cause mRNA destabilization indicating a potential role for miRNA.

Previously, using high‐throughput microarray analysis, we found that methylprednisolone (MP) decreased miR‐155 expression in CD4+ T cells in vitro. miR‐155 is highly expressed in immune cells and influential in cell differentiation. This influence may in part be mediated through suppression of cytokine signaling 1 (SOCS1), a known target of miR‐155. SOCS1 inhibits multiple JAK/STAT pathways, which may inhibit cell proliferation and differentiation. Steroids have also been shown to inhibit proliferation, differentiation and the JAK/STAT pathways. Steroids through blocking the IL‐12/STAT4 pathway inhibit Th1 differentiation. This pathway is in part controlled by SOCS1, which should be under the control of miR‐155. Following our previous work here we explore the potential mechanism of action of miR‐155 during MP treatment of T cells.

Methods:

Total or naive CD4+ T cells were isolated from peripheral blood of healthy donors and activated by anti‐CD3/anti‐CD28 antibodies for up to 5 days with or without Th1 polarizing conditions (10 nM IL‐12 and 5 mM anti‐IL‐4 neutralizing antibody) and with or without exposure to 10−6 M of methylprednisolone. Some cells were first transfected with mimic miR‐155, control mimic miR, anti‐miR‐155, or control anti‐miR by electroporation. Effects on miR‐155, SOCS1, STAT phosphorylation, IFNg production and Th1 differentiation were monitored using flow cytometry, RNA quantification by PCR, and protein quantification by ELISA or western blot analysis.

Results:

Activated T cells treated with MP decrease miR‐155 expression and increase SOCS1 expression. In turn, SOCS1 decreases JAK/STAT signaling and inhibits response to cytokines, notably IL‐12, resulting in decreased IFNg production by activated T cells.

Conclusion:

We found that the anti‐inflammatory effects of MP, at least in part, act through decreasing miR‐155 in T cells by inhibiting JAK/STAT signaling and cytokine production through modulating SOCS1 expression. Based on our findings we propose that miR‐155 inhibition could be utilized to suppress inflammation without the myriad of side effects currently inherent in chronic steroid therapy.
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.
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‐test

Conclusion:

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 < 0.1

Conclusion:

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.
A163: Alternative Mechanisms of Care Delivery in Pediatric Rheumatology: To What Extent Do They Expand the Reach of Pediatric Rheumatologists?
Authors: Riebschleger Meredith P. , Tootoo Joshua , Mroczek Amanda , Clark Sarah
Published: March 2014

Background/Purpose:

Pediatric rheumatology (PR) practitioners are concentrated in academic centers, rather than being evenly distributed throughout the US. Alternative mechanisms of care delivery, such as secondary clinic sites and telemedicine, may function as a bridge between PR practitioners and children who live far from academic centers. The objective of this study was to determine the prevalence and distribution of alternative mechanisms of care delivery in US PR practices.

Methods:

PR practices were identified using the American College of Rheumatology member directory and the Children's Hospital Association hospital directory. Practice websites were reviewed to obtain data regarding secondary clinic sites and use of telemedicine. Practices were then called to confirm website data and obtain data not available on websites. Distance between each main and secondary clinic site was calculated. Geographic information system (GIS) was used to integrate study data with census data.

Results:

77/90 PR practices participated in phone calls and were included in analyses. 46 practices (60%) reported using secondary clinic sites; the number of secondary sites per practice ranged from 1–6 (total 96 sites). Frequency of clinics at secondary sites ranged from weekly to once per year; >80% of sites held clinics at least once each month. Distance from the main practice site to secondary clinic sites ranged from 6.2 to 2265 miles, with 65% (62/96) <60 miles from the main practice site and almost half (47/96) <30 miles from the main practice site. Census data indicate that 39% of US children live >60 miles from a main practice site and 30% of US children live >60 miles from any PR clinic site. Of the 12 states without a PR practice, 3 were served by secondary clinic sites. Seven practices (9%) reported telemedicine capability, but only 3 (4%) reported ever using it.

Conclusion:

Though most PR practices utilize secondary clinic sites, nearly 2/3 of those sites are <60 miles from the main practice site and nearly 1/3 of US children live far (>60 miles) from any PR clinic site. Few practices currently use telemedicine. Therefore, it is not clear that secondary clinic sites and telemedicine, as currently employed, significantly expand the reach of PR practitioners. Future studies should investigate the efficiency and effectiveness of alternative mechanisms of care delivery, to determine how best to serve children who live far from academic centers.