Improving outcomes of pediatric lupus care delivery with provider goal setting activities and multidisciplinary care models.

2023

04/2023

2151-4658

OBJECTIVES: Using an electronic health record (EHR)-enabled pediatric lupus registry, we evaluated high-quality care delivery in the context of provider goal-setting activities and a multidisciplinary care model. We then determined associations between care quality and prednisone use among youth with systemic lupus erythematosus (SLE).

METHODS: We implemented standardized EHR documentation tools to auto-populate a SLE registry. We compared pediatric lupus care index (p-LuCI) performance (range 0.0-1.0; 1.0 representing perfect metric adherence) and timely follow-up a) before vs. during provider goal-setting activities and population management, and b) in multidisciplinary lupus nephritis vs. rheumatology clinic. We estimated associations between p-LuCI and subsequent prednisone use, adjusted for time, current medication, disease activity, clinical features, and social determinants of health.

RESULTS: We analyzed 830 visits by 110 patients (median 7 visits/patient [IQR 4-10]) over 3.5 years. The provider-directed activity was associated with improved p-LuCI performance (adjusted β 0.05, 95%CI [0.01-0.09]; mean 0.74 vs. 0.69). Patients with nephritis in multidisciplinary clinic had higher p-LuCI (adjusted β 0.06, 95%CI [0.02-0.10]) and likelihood of timely follow-up than those in rheumatology (adjusted RR 1.27, 95%CI [1.02-1.57]). p-LuCI ≥0.50 was associated with 0.72-fold lower adjusted risk of subsequent prednisone use (95%CI [0.53-0.93]). Minoritized race, public insurance, and living in areas with greater social vulnerability were not associated with reduced care quality or follow-up, but public insurance was associated with higher risk of prednisone use.

CONCLUSION: Greater attention to quality metrics associates with better outcomes in childhood SLE. Multidisciplinary care models with population management may additionally facilitate equitable care delivery. This article is protected by copyright. All rights reserved.

10.1002/acr.25134

Arthritis Care Res (Hoboken)

37070611

Improving outcomes of pediatric lupus care delivery with provider goal setting activities and multidisciplinary care models.

2023

04/2023

2151-4658

OBJECTIVES: Using an electronic health record (EHR)-enabled pediatric lupus registry, we evaluated high-quality care delivery in the context of provider goal-setting activities and a multidisciplinary care model. We then determined associations between care quality and prednisone use among youth with systemic lupus erythematosus (SLE).

METHODS: We implemented standardized EHR documentation tools to auto-populate a SLE registry. We compared pediatric lupus care index (p-LuCI) performance (range 0.0-1.0; 1.0 representing perfect metric adherence) and timely follow-up a) before vs. during provider goal-setting activities and population management, and b) in multidisciplinary lupus nephritis vs. rheumatology clinic. We estimated associations between p-LuCI and subsequent prednisone use, adjusted for time, current medication, disease activity, clinical features, and social determinants of health.

RESULTS: We analyzed 830 visits by 110 patients (median 7 visits/patient [IQR 4-10]) over 3.5 years. The provider-directed activity was associated with improved p-LuCI performance (adjusted β 0.05, 95%CI [0.01-0.09]; mean 0.74 vs. 0.69). Patients with nephritis in multidisciplinary clinic had higher p-LuCI (adjusted β 0.06, 95%CI [0.02-0.10]) and likelihood of timely follow-up than those in rheumatology (adjusted RR 1.27, 95%CI [1.02-1.57]). p-LuCI ≥0.50 was associated with 0.72-fold lower adjusted risk of subsequent prednisone use (95%CI [0.53-0.93]). Minoritized race, public insurance, and living in areas with greater social vulnerability were not associated with reduced care quality or follow-up, but public insurance was associated with higher risk of prednisone use.

CONCLUSION: Greater attention to quality metrics associates with better outcomes in childhood SLE. Multidisciplinary care models with population management may additionally facilitate equitable care delivery. This article is protected by copyright. All rights reserved.

10.1002/acr.25134

Arthritis Care Res (Hoboken)

37070611

Proteomic Profiling of MIS-C Patients Reveals Heterogeneity Relating to Interferon Gamma Dysregulation and Vascular Endothelial Dysfunction.

2021

2021 Apr 20

<p>Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. We performed a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesized that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. Protein signatures demonstrated overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is a key marker of MIS-C that associates with TMA. We found that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.</p>

10.1101/2021.04.13.21255439

medRxiv

33907759

Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations.

2020

6051-6063

2020 12 08

2473-9537

<p>Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P &lt; .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.</p>

10.1182/bloodadvances.2020003471

Blood Adv

33290544

Distinguishing Multisystem Inflammatory Syndrome in Children From Kawasaki Disease and Benign Inflammatory Illnesses in the SARS-CoV-2 Pandemic.

2020

2020 Sep 22

1535-1815

<p><strong>OBJECTIVE: </strong>The aim of the study was to compare presenting clinical and laboratory features among children meeting the surveillance definition for multisystem inflammatory syndrome in children (MIS-C) across a range of illness severities.</p>

<p><strong>METHODS: </strong>This is a retrospective single-center study of patients younger than 21 years presenting between March 1 and May 15, 2020. Included patients met the Centers for Disease Control and Prevention criteria for MIS-C (inflammation, fever, involvement of 2 organ systems, lack of alternative diagnoses). We defined 3 subgroups by clinical outcomes: (1) critical illness requiring intensive care interventions; (2) patients meeting Kawasaki disease (KD) criteria but not requiring critical care; and (3) mild illness not meeting either criteria. A comparator cohort included patients with KD at our institution during the same time frame in 2019.</p>

<p><strong>RESULTS: </strong>Thirty-three patients were included (5, critical; 8, 2020 KD; 20, mild). The median age for the critical group was 10.9 years (2.7 for 2020 KD; 6.0 for mild, P = 0.033). The critical group had lower median absolute lymphocyte count (850 vs 3005 vs 2940/uL, P = 0.005), platelets (150 vs 361 vs 252 k/uL, P = 0.005), and sodium (129 vs 136 vs 136 mmol/L, P = 0.002), and higher creatinine (0.7 vs 0.2 vs 0.3 mg/dL, P = 0.002). In the critical group, 60% required vasoactive medications, and 40% required mechanical ventilation. Clinical and laboratories features were similar between the 2020 and 2019 KD groups.</p>

<p><strong>CONCLUSIONS: </strong>We describe 3 groups with inflammatory syndromes during the SARS-CoV-2 pandemic. The initial profile of lymphopenia, thrombocytopenia, hyponatremia, and abnormal creatinine may help distinguish critically ill MIS-C patients from classic/atypical KD or more benign acute inflammation.</p>

10.1097/PEC.0000000000002248

Pediatr Emerg Care

32970023

Convalescent plasma for pediatric patients with SARS-CoV-2-associated acute respiratory distress syndrome.

2020

e28693

2020 Sep 04

1545-5017

<p>There are no proven safe and effective therapies for children who develop life-threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2, but has theoretical risks.We present the first report of CP in children with life-threatening coronavirus disease 2019 (COVID-19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody-dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.</p>

10.1002/pbc.28693

Pediatr Blood Cancer

32885904

Human Adenovirus 7-Associated Hemophagocytic Lymphohistiocytosis-Like Illness: Clinical and Virological Characteristics in a Cluster of Five Pediatric Cases.

2020

2020 Aug 31

1537-6591

<p><strong>BACKGROUND: </strong>Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking.</p>

<p><strong>METHODS: </strong>We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018-2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed.</p>

<p><strong>RESULTS: </strong>All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identified as genomic variant 7d. Adenovirus type 7 DNA was detected in the fifth case. Phylogenetic analysis of genome sequences identified two clusters - one related to strains implicated in 2016-2017 outbreaks in Pennsylvania and New Jersey, the other related to a 2009 Chinese strain.</p>

<p><strong>CONCLUSIONS: </strong>It can be challenging to determine whether HLH is the result of an infectious pathogen alone or genetic predisposition triggered by an infection. We describe 5 children from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infection. None of the patients were found to have a genetic predisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH.</p>

10.1093/cid/ciaa1277

Clin. Infect. Dis.

32866230

Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2.

2020

2020 Jul 30

1558-8238

<p><strong>BACKGROUND: </strong>Initial reports from the Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to Coronavirus Disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed Multisystem Inflammatory Syndrome in Children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.</p>

<p><strong>METHODS: </strong>We prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8 and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. Cts and burr cells on blood smears also differentiated between patients with severe COVID-19 and those with MIS-C.</p>

<p><strong>CONCLUSION: </strong>Pediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and severe COVID-19.</p>

10.1172/JCI140970

J. Clin. Invest.

32730233

Multisystem Inflammatory Syndrome in Children during the COVID-19 pandemic: a case series.

2020

2020 May 28

2048-7207

<p>We present a series of six critically ill children with Multisystem Inflammatory Syndrome in Children (MIS-C). Key findings of this syndrome include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes.</p>

10.1093/jpids/piaa069

J Pediatric Infect Dis Soc

32463092

Patient-reported Outcomes across Categories of Juvenile Idiopathic Arthritis.

2015

1914-21

2015 Oct

0315-162X

<p><strong>OBJECTIVE: </strong>Although there is increasing reliance on patient-reported outcomes (PRO) for disease management, there is little known about the differences in PRO across juvenile idiopathic arthritis (JIA) categories. The purpose of our study was to assess PRO across JIA categories, including pain, quality of life, and physical function, and to determine clinical factors associated with differences in these measures across categories.</p>

<p><strong>METHODS: </strong>This was a longitudinal cohort study of patients with JIA at a tertiary care pediatric rheumatology clinic. Subjects, PRO, and clinical variables were identified by querying the electronic medical record. Mixed-effects regression assessed pain, quality of life, and function.</p>

<p><strong>RESULTS: </strong>Subjects with enthesitis-related arthritis (ERA) and undifferentiated JIA had significantly more pain, poorer quality of life, and poorer physical function. The ERA and undifferentiated JIA categories, physician's global disease activity assessment, female sex, and nonsteroidal antiinflammatory drug use were significantly associated with more pain, poorer quality of life, and poorer function. In models limited to ERA, female sex and tender enthesis count were significant predictors of decreased function.</p>

<p><strong>CONCLUSION: </strong>ERA and undifferentiated JIA categories had poorer PRO than other JIA categories. Further work is needed to address ways to improve PRO in children with JIA, with a special focus on children with ERA and undifferentiated JIA.</p>

10.3899/jrheum.150092

J. Rheumatol.

26329337