Diagnostic Accuracy Study of the Pediatric-Specific Ultrasound Scoring System for the Knee Joint in Children With Juvenile Idiopathic Arthritis.

OBJECTIVE: We undertook this study to validate the Pediatric Arthritis Ultrasound Scoring System for the knee joint (PAUSS-knee) in children with juvenile idiopathic arthritis (JIA). METHODS: Children with JIA were enrolled to prospectively receive a musculoskeletal ultrasound (MSUS) examination of the knee and a physical examination to determine presence/absence of clinical arthritis. MSUS images were scored using the PAUSS-knee, a semiquantitative MSUS scoring system (0-3, normal to severe) for B-mode and power Doppler mode. In addition to MSUS, a subset of participants also received magnetic resonance imaging (MRI) of the knee, which was scored according to the combined Juvenile Arthritis MRI Scoring (JAMRIS) system. Spearman's correlations (rs ) were used to calculate associations between variables. Test characteristics of the PAUSS-knee were calculated with MRI as the reference standard. Inflammatory biomarkers were assessed in synovial fluid from involved knees. RESULTS: Eighty children with JIA contributed 112 MSUSs and 25 MRIs of the knee. Of the knees, 41% (n = 46) had clinical evidence of arthritis. The B-mode PAUSS-knee score moderately correlated with clinically determined arthritis (rs = 0.54, P < 0.001) and strongly correlated with the JAMRIS score (rs = 0.75, P < 0.001). Compared with MRI, the area under the curve for the B-mode PAUSS-knee was 0.92. For a cutoff of >1, the B-mode PAUSS-knee had a sensitivity of 83% and specificity of 82%. Biomarker analysis indicates that interleukin-2R levels correlate with PAUSS score. CONCLUSION: Our data indicate that the PAUSS-knee has excellent accuracy for the diagnosis of arthritis when compared with MRI. The PAUSS-knee has the potential to effectively inform JIA medical decision-making in real time.

Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.

OBJECTIVE: Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes. METHODS: This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. RESULTS: We enrolled 41 patients with SJIA-LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow-up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty-four percent of patients carried the HLA-DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA-LD also showed markedly elevated serum interleukin-18 (IL-18), variable C-X-C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti-IL-1/6 biologics and addition of other immunomodulatory treatments and lung-directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. CONCLUSION: Patients with SJIA-LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.

A Rapid Review of Uses and Outcomes of Telehealth Care in Rural and Remote Regions in the United States.

As telehealth expands and becomes an increasingly important provision of palliative care and hospice services, the understanding of the uses and outcomes of this care delivery platform in rural communities is warranted. This rapid review aims to highlight the practice, policy, and research implications of telehealth in rural regions. Using a systematic approach for accessing and synthesizing available publications, this review included 22 articles published between January 2020 and January 2023. Telehealth was used with adult and pediatric populations diagnosed with serious illnesses. Acceptance of this type of care delivery was noted in adults and children, but not all found telehealth a valuable mechanism for care. Telehealth services included but were not limited to direct communication between the provider and the patient/caregiver, medication management, and a peer-to-peer consultant role for rural palliative care and hospice teams. Of those studies addressing provider-centered outcomes, noise level, interruptions, missed appointments, and challenges with providing emotional support were reported. Organizational barriers, such as the lack of financial support, were noted for pediatric hospices. Individuals living in rural communities require more frequent, immediate, and specialized attention over their illness trajectory. Practice, policy, and research implications are identified to consider the next steps for telehealth delivery of palliative care.

Usefulness of the lupus low disease activity state as a treatment target in childhood-onset SLE.

OBJECTIVE: Treat-to-target (T2T) strategies are advocated to improve prognosis in childhood-onset SLE (cSLE). Proposed T2T states include SLEDAI score of <4 (SLEDAI-LD), limited corticosteroid use (low-CS), and lupus low disease activity state (LLDAS). We sought to compare T2T states for their association with cSLE prognosis under consideration of relevant disease characteristics such as pre-existing damage, race and lupus nephritis (LN). METHODS: Longitudinal data from 165 patients enrolled in the Cincinnati Lupus Registry were included. LN presence was based on renal biopsy, and patients were followed up until 18 years of age. RESULTS: The 165 patients (LN: 45, white: 95) entered the registry within a median of 0 (IQR: 0-1) year post diagnosis and were followed up for a median of 4 (IQR: 2-5) years during which 80%, 92% and 94% achieved LLDAS, low-CS and SLEDAI-LD. Patients with LN were significantly less likely to achieve any T2T state (all p<0.03) and required a significantly longer time to reach them (all p<0.0001). Over the study period, patients maintained low-CS, SLEDAI-LD or LLDAS for a median of 76% (IQR: 48%-100%), 86% (IQR: 55%-100%) or 39% (IQR: 13%-64%) of their follow-up. Significant predictors of failure to maintain LLDAS included LN (p≤0.0062), pre-existing damage (p≤0.0271) and non-white race (p≤0.0013). There were 22%, 20% and 13% of patients who reached SLEDAI-LD, CS-low and LLDAS and nonetheless acquired new damage. Patients with LN had a higher risk of new damage than patients without LN even if achieving low-CS (p=0.009) or LLDAS (p=0.04). CONCLUSIONS: Patients with LN and pre-existing damage are at higher risk of increased future damage acquisition, even if achieving a T2T state such as LLDAS. Among proposed common T2T states, the LLDAS is the hardest to achieve and maintain. The LLDAS may be considered the preferred T2T measure as it conveys the highest protection from acquiring additional disease damage.

Musculoskeletal Ultrasound and the Assessment of Disease Activity in Juvenile Idiopathic Arthritis.

OBJECTIVE: To determine the frequency of subclinical synovitis on musculoskeletal ultrasonography (MSUS) in juvenile idiopathic arthritis (JIA) and correlate patient- and provider-reported outcome measures with MSUS synovitis. METHOD: JIA patients with an active joint count (AJC) of >4 underwent a 42-joint MSUS performed at baseline and 3 months. B-mode and power Doppler images were obtained and scored (range 0-3) for each of the 42 joints. Outcomes evaluated included physician global assessment of disease activity (PhGA), patient global assessment of disease activity (PtGA), patient pain, Childhood Health Assessment Questionnaire (C-HAQ), and AJC. Subclinical synovitis was defined as synovitis detected by MSUS only. Generalized estimation equations were used to test the relationship between clinical arthritis (positive/negative) and subclinical synovitis (positive/negative). Spearman's correlation coefficients (rs ) were calculated to determine the association between MSUS synovitis and patient- and physician-reported outcomes. RESULTS: In 30 patients, subclinical synovitis was detected in 30% of joints. Clinical arthritis of the fingers, wrists, and knee joints was significantly associated with MSUS synovitis in these joints. PtGA and the C-HAQ had a moderate (rs  = 0.44, P = 0.014) to weak (rs  = 0.37, P = 0.045) correlation with MSUS synovitis. There was a statistically significant strong correlation between MSUS synovitis and PhGA (rs  = 0.61, P = 0.001), but a weak correlation with AJC (rs  = 0.37, P = 0.048) at the follow-up visit. CONCLUSION: Subclinical synovitis was commonly observed in this cohort of JIA patients. The fair-to-moderate correlation of MSUS synovitis with patient- and provider-reported outcomes suggests that MSUS assesses a different, possibly more objective, domain not determined by traditional JIA outcome measurements.

Alternative Biologic Therapy in Children Failing Conventional TNFα Inhibitors for Refractory, Noninfectious, Chronic Anterior Uveitis.

PURPOSE: A significant number of children with noninfectious, chronic anterior uveitis (CAU) fail to respond to conventional therapy; however, successful alternative biologic treatments (ABT) have not been well described. This study aims to review the clinical and treatment characteristics of children with CAU who require ABT. DESIGN: Retrospective, nonrandomized clinical study. METHODS: Setting: Tertiary center. STUDY POPULATION: Children with noninfectious CAU. OBSERVATION PROCEDURES: Clinical characteristics, uveitis course, complications, and treatment were compared among patients treated with methotrexate (MTX) monotherapy, conventional TNFα inhibitors (cTNFi), and ABT for >3 months. MAIN OUTCOME MEASURE: Success of ABT (abatacept, tocilizumab, and/or golimumab) in children failing conventional treatment. RESULTS: Of the 52 children with CAU, 75% had juvenile idiopathic arthritis. CAU was controlled in 15 children receiving MTX monotherapy, 28 receiving cTNFi, and 9 receiving ABT (n = 1, abatacept; n = 3, tocilizumab; n = 5, golimumab). Patients in the ABT group had a greater number of total ocular complications per person before ABT than those in the control groups (3.4 vs 0.7 [MTX], P < .001, and 1.5 [cTNFi], P < .001, respectively). In all 9 children on ABT, treatment led to control of CAU and topical glucocorticoids tapered to ≤2 drops/d with no new ocular complications. CONCLUSIONS: In this study, alternative biologics (abatacept, golimumab, and tocilizumab) were useful for treating CAU in children who fail MTX and cTNFi therapy. Patients who were controlled on ABT had more disease activity, ocular complications, and anti-cTNFi neutralizing antibodies (before ABT) than those managed with conventional therapy. Larger studies are required to confirm these findings.

The Impact of a Gamified Curriculum Using Kahoot! on Musculoskeletal Knowledge and Skill Acquisition Among Pediatric Residents.

OBJECTIVE: To determine whether a musculoskeletal curriculum involving gamification via Kahoot! (an online classroom response system) was acceptable and more effective at teaching pediatric residents musculoskeletal knowledge and skills than a nongamified curriculum. METHODS: A prospective, randomized controlled trial was conducted at an urban, academic pediatric clinic. All participants received a curriculum that included brief didactics and knowledge questions. The knowledge questions were delivered via Kahoot! to the intervention group and administered via paper to the control group. The primary outcome was knowledge and skill acquisition following curriculum participation. RESULTS: A total of 73 of 85 (86%) residents completed the study (intervention group: 46; control group: 27). Following participation in the curriculum, intervention and control residents demonstrated an improvement in musculoskeletal knowledge (P < .05) measured via questionnaire, as well as an improvement in physical exam skills during a standardized patient encounter (P < .05). There was no difference in knowledge or skill improvement between groups. Intervention participants indicated positive attitudes toward Kahoot!. CONCLUSIONS: Our musculoskeletal curriculum demonstrated improvements in knowledge and skills among residents, though inclusion of Kahoot! did not enhance the experimental effect. Further research is needed to identify strategies to optimize gamification for learning.

Maintaining Hepatitis B Protection in Immunocompromised Pediatric Rheumatology and Inflammatory Bowel Disease Patients.

OBJECTIVE: Hepatitis B virus (HBV) infection remains a significant public health challenge, particularly for immunocompromised patients. Our aim was to evaluate the serologic immunity in immunocompromised rheumatology and inflammatory bowel disease (IBD) patients, assess factors for serologic nonimmunity, and evaluate their response to 1 HBV booster dose. METHODS: Immunocompromised rheumatology and IBD patients with completed HBV screening were identified. A chart review was performed to collect demographics, clinical information, baseline HBV serology results, and serologic response to booster vaccination. Serologic nonimmunity was defined as a negative/indeterminate hepatitis B surface antibody (anti-HBs) level. RESULTS: Among 580 patients, 71% were nonimmune. The highest portion of nonimmune patients were 11-18 years old (P = 0.004). There was no significant difference between immune and nonimmune patients with regards to diagnosis (P = 0.34), age at diagnosis (P = 0.64), duration of treatment (P = 0.07), or type of medications (P = 0.08). Sixty-two percent of those who received a booster vaccine were rescreened, and most (68%) seroconverted. In those 18 years or older, only half seroconverted. CONCLUSION: Results of this study support the benefit of HBV screening in immunosuppressed patients. Beginning at age 11 years, most patients lacked serologic immunity to HBV. Seroconversion for most patients 11-18 years occurred after 1 booster vaccine. Thus, for immunocompromised patients without recent HBV serologic data, obtaining the HBV serology beginning at age 11 years might be considered. Those 18 years and older were least likely to seroconvert after 1 booster, indicating that they may benefit from receiving the 3-dose HBV vaccine series.

Feasibility and acceptability of an innovative adherence intervention for young adults with childhood-onset systemic Lupus Erythematosus.

BACKGROUND: In Childhood-Onset Systemic Lupus Erythematosus (cSLE), poor medication adherence rates are very high. Interventions targeting this problem in cSLE are limited thus effective interventions are needed. The objective of this study is to examine the feasibility and acceptability an intervention (automated digital reminders + personalized prescribed treatment plan (pPTP)) to improve medication adherence in young adults with cSLE over 3 months. METHOD: This is a proof-of-concept randomized controlled study. All participants received SimpleMed+ pillboxes that track adherence. The treatment group received a pPTP, and in month 2, preselected digital reminders for missed doses. Reminders were discontinued after 30 days and adherence data collected. Data analysis was done using t-tests. RESULTS: Twenty-one participants were approached and nineteen consented to participate, yielding a recruitment rate of 86%. Participants were on average 20.5 years, mostly black (58%) and female (84%). Of the nineteen consented, eleven were randomized to control (57%) and eight to treatment (42%) groups respectively. All participants in the treatment group rated the pillbox as easy to use, notably; none reported boredom with the pillbox or reminders. Also, 88% of participants in the treatment group rated the pillbox as helpful, however, only 50% reported the pPTP taught them new information about lupus or made them more interested in their lupus management. CONCLUSIONS: This is the first use of an electronic pillbox to track adherence to multiple medications in cSLE. The high rating of the pillbox makes it an acceptable method of measuring adherence. Feasibility and acceptability ratings for the intervention were mixed suggesting a there is a subset of cSLE patients for whom this intervention would be beneficial. Future research should focus on a larger trial.

The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis.

BACKGROUND: Serum phagocyte-derived alarmins S100A8/9 and S100A12 are considered useful for the assessment of inflammatory diseases. Our study evaluated the use of S100 proteins in a pediatric clinical setting for estimating disease activity and supporting diagnosis. METHODS: Patients (n = 136) who had S100 proteins tested as part of clinical care were included in this study and relevant information obtained from the medical record: C-reactive protein (CRP), disease activity status (inactive: = 0 joint; active: > 0 active joint), systemic symptoms in systemic JIA (sJIA), and symptoms of flare of other autoinflammatory and fever syndromes. Patients were categorized as: sJIA, non-systemic JIA (nsJIA), other defined autoinflammatory syndromes (AID) and systemic undifferentiated recurring fever syndromes (SURFS). RESULTS: Patients with sJIA (n = 21) had significantly higher levels of S100A8/9 and S100A12 compared to patients with nsJIA (n = 49), other AIDs (n = 8) or SURFS (n = 14) (all p < 0.0001). Compared to CRP [area under the receiver operating characteristics curve (AUC) = 0.7], S100 proteins were superior in differentiating sJIA from AID and SURFS [AUC = 0.9]. S100A8/9 and S100A12 levels were not associated with disease activity in nsJIA, AID or SURFS. S100A8/9 and S100A12 levels were significantly higher in active sJIA compared to inactive (p = 0.0002 and p = 0.0002 respectively). CONCLUSION: Compared to other autoinflammatory and fever syndromes, sJIA patients have markedly higher levels of S100A8/9 and S100A12 proteins which may assist with diagnosis. S100 levels slightly outperformed CRP in distinguishing sJIA from other diagnoses and in sJIA disease activity. S100 proteins may aid in monitoring disease activity in sJIA patients.

Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease: Characterization and Risk Factors.

OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is associated with a recently recognized, albeit poorly defined and characterized, lung disease (LD). The objective of this study was to describe the clinical characteristics, risk factors, and histopathologic and immunologic features of this novel inflammatory LD associated with systemic JIA (designated SJIA-LD). METHODS: Clinical data collected since 2010 were abstracted from the medical records of patients with systemic JIA from the Cincinnati Children's Hospital Medical Center. Epidemiologic, cellular, biochemical, genomic, and transcriptional profiling analyses were performed. RESULTS: Eighteen patients with SJIA-LD were identified. Radiographic findings included diffuse ground-glass opacities, subpleural reticulation, interlobular septal thickening, and lymphadenopathy. Pathologic findings included patchy, but extensive, lymphoplasmacytic infiltrates and mixed features of pulmonary alveolar proteinosis (PAP) and endogenous lipoid pneumonia. Compared to systemic JIA patients without LD, those with SJIA-LD were younger at the diagnosis of systemic JIA (odds ratio [OR] 6.5, P = 0.007), more often had prior episodes of macrophage activation syndrome (MAS) (OR 14.5, P < 0.001), had a greater frequency of adverse reactions to biologic therapy (OR 13.6, P < 0.001), and had higher serum levels of interleukin-18 (IL-18) (median 27,612 pg/ml versus 5,413 pg/ml; P = 0.047). Patients with SJIA-LD lacked genetic, serologic, or functional evidence of granulocyte-macrophage colony-stimulating factor pathway dysfunction, a feature that is typical of familial or autoimmune PAP. Moreover, bronchoalveolar lavage (BAL) fluid from patients with SJIA-LD rarely demonstrated proteinaceous material and had less lipid-laden macrophages than that seen in patients with primary PAP (mean 10.5% in patients with SJIA-LD versus 66.1% in patients with primary PAP; P < 0.001). BAL fluid from patients with SJIA-LD contained elevated levels of IL-18 and the interferon-γ-induced chemokines CXCL9 and CXCL10. Transcriptional profiling of the lung tissue from patients with SJIA-LD identified up-regulated type II interferon and T cell activation networks. This signature was also present in SJIA-LD human lung tissue sections that lacked substantial histopathologic findings, suggesting that this activation signature may precede and drive the lung pathology in SJIA-LD. CONCLUSION: Pulmonary disease is increasingly detected in children with systemic JIA, particularly in association with MAS. This entity has distinct clinical and immunologic features and represents an uncharacterized inflammatory LD.

Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti-Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy.

OBJECTIVE: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). METHODS: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. RESULTS: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36). CONCLUSION: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.

Validation of the Cutaneous Lupus Erythematosus Disease Area and Severity Index and pSkindex27 for use in childhood-onset systemic lupus erythematosus.

OBJECTIVE: To determine the measurement properties of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the paediatric adaptation of the Skindex29 (pSkindex27) when used in childhood-onset SLE (cSLE). METHODS: Patients with mucocutaneous involvement of cSLE were evaluated at the study entry and 6 months later. Besides the CLASI and pSkindex27, the Pediatric Quality of Life Inventory Generic Core scale (PedsQL-GC), its Rheumatology Module (PedsQL-RM), the SLE Disease Activity Index (SLEDAI) and the SLE Damage Index (SDI) were completed. RESULTS: The CLASI and pSkindex27 had high internal consistency (both Cronbach α >0.82). Children were able to complete the pSkindex27, with self-report and caregiver proxy-reports showing excellent agreement (intraclass correlation coefficient=0.97). The CLASI Activity Score (CLASI-A) was strongly correlated with the mucocutaneous domain score of the SLEDAI as was the CLASI Damage Score (CLASI-D) with that of the SDI (both: Spearman correlation coefficients (rs) >0.68). pSkindex27 summary scores were moderately correlated with those of the PedsQL-GC and PedsQL-RM (all: rs >|0.51|), the CLASI-A and CLASI-D (both: rs > 0.64), respectively. Patients who experienced a >50% improvement of the CLASI-A between study visits had significantly higher PedsQL-GC and pSkindex27 scores than those without improvement of mucocutaneous features. CONCLUSION: Both CLASI and pSkindex27 are useful assessment tools in cSLE, active and chronic mucocutaneous lesions and their changes over time can be measured using the CLASI and the pSkindex27 can capture the impact of mucocutaneous involvement on patient health-related quality of life.

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.

Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared with the non-risk allele of rs11889341. We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.

Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease.

OBJECTIVE: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. METHODS: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. RESULTS: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). CONCLUSION: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.

Measuring Disease Damage and Its Severity in Childhood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: To describe the frequency and types of disease damage occurring with childhood-onset systemic lupus erythematosus (SLE) as measured by the 41-item Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and to assess the SDI's ability to reflect damage severity. METHODS: Information for the SDI was prospectively collected from 1,048 childhood-onset SLE patients. For a subset of 559 patients, physician-rated damage severity measured by visual analog scale (MD VAS damage) was also available. Frequency of SDI items and the association between SDI summary scores and MD VAS damage were estimated. Finally, an international consensus conference, using nominal group technique, considered the SDI's capture of childhood-onset SLE-associated damage and its severity. RESULTS: After a mean disease duration of 3.8 years, 44.2% of patients (463 of 1,048) already had an SDI summary score >0 (maximum 14). The most common SDI items scored were proteinuria, scarring alopecia, and cognitive impairment. Although there was a moderately strong association between SDI summary scores and MD VAS damage (Spearman's r = 0.49, P < 0.0001) in patients with damage (SDI summary score >0), mixed-effects analysis showed that only 4 SDI items, each occurring in <2% of patients overall, were significantly associated with MD VAS damage. There was consensus among childhood-onset SLE experts that the SDI in its current form is inadequate for estimating the severity of childhood-onset SLE-associated damage. CONCLUSION: Disease damage as measured by the SDI is common in childhood-onset SLE, even with relatively short disease durations. Given the shortcomings of the SDI, there is a need to develop new tools to estimate the impact of childhood-onset SLE-associated damage.

Improving health maintenance supervision in a paediatric IBD clinic.

BACKGROUND: Previsit planning (PVP) has been an integral part of clinical care for paediatric patients with inflammatory bowel disease (IBD) at Cincinnati Children's Hospital Medical Center since 2007. Over the past years, we have adopted several programmes to improve health maintenance supervision for our paediatric patients with IBD but did not have a sustainable way to provide health maintenance updates for every patient at every encounter that was concise and complete in the setting of an increasing patient population and fewer support staff to complete the work. METHODS: Using quality improvement methods, we completed several Plan-Do-Study-Act (PDSA) cycles aimed at improving our centre's ability to provide complete health maintenance 'bundle' recommendations from 0% to 90% of patients over a period of 11 months. RESULTS: First steps included consensus gathering and summarising evidence into guidelines suitable for the group. PDSAs centred on consensus building from standardised guidelines, using empty checklists for simulated and real patients, and use of autofilled checklists. After several PDSA cycles, we have improved our ability to provide complete health maintenance PVP from 0% to nearly 100% with very little variation. CONCLUSION: Using the health maintenance PVP process, we can now sustainably provide health maintenance guidance for all outpatient clinic visits. We have begun to scale up this work and anticipate over the coming months that we will be able to expand the health maintenance PVP to provide complete PVP for over 90% of patients for any scheduled encounter including biologic infusion visits. We anticipate that using this reliable process we can improve remission rates and reduce preventable infections for these at-risk patients.

Transancestral mapping and genetic load in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.

Improving a process to obtain hepatitis B serology among patients treated with infliximab at a large urban children's hospital.

BACKGROUND: Hepatitis B infection is a significant public health challenge despite improvements in vaccination efforts. Patients such as those on chronic immunosuppressive therapy for inflammatory bowel disease (IBD) or rheumatic disease may incur greater risk. The risk of reactivation of hepatitis B while on immunosuppressive therapy may have mortality rates up to 25%. These patients should be screened for acute or chronic infection and vaccinated if necessary. Our aim was to reliably complete hepatitis B screenings in patients receiving infliximab at Cincinnati Children's Hospital Medical Center (CCHMC). METHODS: Eligible patients included all patients with gastroenterology (GI) IBD and rheumatology receiving infliximab between October 2015 and March 2016. Using quality improvement methodology and the 'plan-do-study-act' (PDSA) approach, interventions centred around education of clinical providers, previsit planning and the development of 'talking points' for patients. RESULTS: An initial screen of the IBD population revealed that 48% of the IBD patient population had been screened for anti-HBs alone, but no patients from GI or rheumatology divisions had a complete set of hepatitis B serology prior to the intervention including anti-Hep B Core and Hep B Surface Antigen. Seven PDSA cycles were performed during the 32-week intervention period, resulting in an increase in patients screened from 0% to ~85%. By March 2016, a total of 251 patients (201 GI, 50 rheumatology) had up-to-date hepatitis B serology screening. Automated ordering of the hepatitis B serology and 'talking points' for the provider had the greatest impact on successful screening. CONCLUSIONS: We developed a method to obtain hepatitis B serology on at-risk patients on infliximab within two subspecialty divisions within a large children's hospital. Next steps will be to develop a process to reliably provide vaccines for patients who are seronegative, expand this process to all patients who are identified as immunocompromised within GI and rheumatology and then expand this process to other divisions at the CCHMC.

Adolescent Vaccination Strategies: Interventions to Increase Coverage.

While vaccines have decreased the burden of disease, many adolescents still remain under-immunized, particularly for human papillomavirus (HPV) and influenza. We review the most current data regarding adolescent immunizations in the United States and discuss proven strategies that work for increasing vaccination rates. Strategies that have been shown to improve rates include provider feedback, immunization information systems (or registries), and enhanced access outside of provider offices, such as school-based immunization programs. Overall, practices may want to consider multimodal quality improvement approaches to enhance practice vaccination rates. The public health and cost benefits of immunizing adolescents are well known, yet recent measles outbreaks in the United States have highlighted issues with state immunization laws and vaccine refusals. Providers should be clear in their advice regarding vaccines and use effective reminder strategies as parents commonly cite not having enough information or knowledge that a vaccine was needed for their adolescent. Additional research is needed regarding adolescent consent for vaccines, as well as adolescent and parental refusal, in order to design systems that will help inform families and allow for widespread vaccine availability.