First name
Joyce
Middle name
C
Last name
Chang

Title

Use of renin angiotensin aldosterone system inhibitors in children with lupus and time to glucocorticoid discontinuation.

Year of Publication

2022

Number of Pages

395-404

Date Published

05/2022

ISSN Number

1523-1755

Abstract

There is little data to inform use of renin angiotensin aldosterone system (RAAS) inhibitors in pediatric patients with systemic lupus erythematosus (SLE). Here, we sought to characterize RAAS inhibitor use in pediatric SLE and determine whether early RAAS inhibitor initiation among children with incident lupus nephritis is associated with decreased duration of chronic glucocorticoid exposure. A retrospective cohort study was performed of children (ages 5-18) with SLE and/or lupus nephritis in the Truven MarketScan™ Medicaid and Commercial databases (2013-2018) and estimated RAAS inhibitor use. Among incident nephritis cases, we used competing risk hazard models with inverse probability of treatment weighting to estimate the association between RAAS inhibitor initiation less than 180 days after diagnosis and time to glucocorticoid discontinuation with kidney failure as a competing event. Among 592 children with nephritis and 1407 children with non-kidney SLE, 67% and 15% ever received RAAS inhibitors, respectively. Median duration of RAAS inhibitor use among 323 incident users was 14 and 9 months in children with and without nephritis, respectively. Medicaid enrollment was independently associated with greater likelihood of RAAS inhibitor use, irrespective of nephritis. Among 158 incident nephritis cases, early RAAS inhibitor initiation was significantly associated with a faster rate of glucocorticoid discontinuation (adjusted sub-distribution hazard ratio 1.81, 95% confidence interval [1.09 - 3.00]). Thus, early initiation of RAAS inhibitors may have a role in children newly diagnosed with lupus nephritis; not only those with refractory proteinuria after induction therapy. Hence, integrated health systems data could be leveraged to confirm these findings and optimize adjunctive therapies in pediatric lupus.

DOI

10.1016/j.kint.2022.04.023

Alternate Title

Kidney Int

PMID

35618096

Title

Clinical features, treatment patterns and short-term outcomes of children with inflammatory bowel disease evaluated in rheumatology clinic.

Year of Publication

2022

Date Published

2022 Mar 09

ISSN Number

0392-856X

Abstract

<p><strong>OBJECTIVES: </strong>This study evaluated the clinical features, treatment patterns, and short-term outcomes of children with inflammatory bowel disease (IBD)-associated musculoskeletal manifestations.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study of children with IBD evaluated for joint complaints in a paediatric rheumatology clinic from 2015 to 2020. The index visit was the date of initial rheumatology evaluation. Clinical features were evaluated using standard descriptive statistics. Differences in outcomes over time were compared using rank-sum tests. Univariate logistic regression was used to test associations between clinical features and persistent arthritis or enthesitis.</p>

<p><strong>RESULTS: </strong>Seventy-five patients met inclusion criteria. 61% had active arthritis or enthesitis at initial evaluation, 1/3 of whom were not yet diagnosed with IBD. Of those with known IBD, over half with joint complaints had arthritis or enthesitis. Active joint disease was common even among patients already receiving tumour necrosis factor (TNF) inhibitors or other immunomodulatory medications for IBD and despite inactive gastrointestinal disease. Treatment escalation was often needed to control articular disease, which included changes in immunomodulatory therapy and NSAIDs. Treatment outcomes for arthritis were good and significant improvements in functional mobility were observed (p&lt;0.01), while enthesitis often persisted at follow-up (11/28, 39%). Moreover, a significant proportion of patients with pain at the index visit reported persistent pain at follow-up (29/44, 65%).</p>

<p><strong>CONCLUSIONS: </strong>This study provides several findings relevant to the multidisciplinary care of children with IBD, including high rates of active arthritis and enthesitis despite ongoing use of immunomodulatory medications for the management of IBD, responses to treatment, and pain management.</p>

Alternate Title

Clin Exp Rheumatol

PMID

35349409

Title

Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis: Development and Validation of Computable Phenotypes.

Year of Publication

2021

Date Published

2021 Nov 03

ISSN Number

1555-905X

Abstract

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Performing adequately powered clinical trials in pediatric diseases, such as SLE, is challenging. Improved recruitment strategies are needed for identifying patients.</p>

<p><strong>DESIGN, SETTING, PARTICIPANTS, &amp; MEASUREMENTS: </strong>Electronic health record algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single-center electronic health record data to develop computable phenotypes composed of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled database of patients with SLE. The highest-performing phenotypes were then evaluated across institutions in PEDSnet, a national health care systems network of &gt;6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases (=350) and noncases (=350).</p>

<p><strong>RESULTS: </strong>Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included two or more in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, one or more hydroxychloroquine exposures, and either three or more qualifying diagnosis codes separated by ≥30 days or one or more diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 100% (95% confidence interval [95% CI], 99 to 100), specificity was 92% (95% CI, 88 to 94), positive predictive value was 91% (95% CI, 87 to 94), and negative predictive value was 100% (95% CI, 99 to 100). Lupus nephritis diagnostic criteria included either three or more qualifying lupus nephritis diagnosis codes (or SLE codes on the same day as glomerular/kidney codes) separated by ≥30 days or one or more SLE diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 90% (95% CI, 85 to 94), specificity was 93% (95% CI, 89 to 97), positive predictive value was 94% (95% CI, 89 to 97), and negative predictive value was 90% (95% CI, 84 to 94). Algorithms identified 1508 children with SLE at PEDSnet institutions (537 with lupus nephritis), 809 of whom were seen in the past 12 months.</p>

<p><strong>CONCLUSIONS: </strong>Electronic health record-based algorithms for SLE and lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions.</p>

DOI

10.2215/CJN.07810621

Alternate Title

Clin J Am Soc Nephrol

PMID

34732529

Title

Determinants of disease activity change over time in Enthesitis related arthritis: effect of structured outcome monitoring and clinical decision support.

Year of Publication

2020

Number of Pages

79

Date Published

2020 Oct 15

ISSN Number

1546-0096

Abstract

<p><strong>BACKGROUND: </strong>We aimed to test if standardized point-of-care outcome monitoring and clinical decision support (CDS), as compared to standard care, improves disease activity and patient-reported pain in children with enthesitis-related arthritis (ERA).</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study of outcomes of children with ERA after phased implementation of I) standardized outcome monitoring with CDS for polyarticular JIA, and II) CDS for ERA, compared to a pre-intervention group of historical controls. We used multivariable mixed-effects models for repeated measures to test whether implementation phase or other disease characteristics were associated with change over time in disease activity, as measured by the clinical juvenile arthritis disease activity score (cJADAS), and pain.</p>

<p><strong>RESULTS: </strong>One hundred fifty-two ERA patients (41% incident cases) were included with a median age of 14.9 years. Implementation of standardized outcome monitoring or ERA-specific CDS did not result in significant differences in cJADAS or pain over time compared to the pre-intervention cohort. Higher cJADAS at the index visit, pain and more tender entheses were significantly associated with higher cJADAS scores over time (all p &lt; 0.01), while biologic use was associated with lower cJADAS (p = 0.02). Regardless of intervention period, incident ERA cases had a greater rate of cJADAS improvement over time compared to prevalent cases (p &lt; 0.01), but pain persisted over time among both incident and prevalent cases.</p>

<p><strong>CONCLUSIONS: </strong>There was no significant effect of point-of-care outcome monitoring or CDS interventions on disease activity or pain over time in children with ERA in this single center study. Future efforts to improve disease outcomes using standardized outcome monitoring and CDS will need to consider the importance of addressing pain as a target in addition to spondyloarthritis-specific disease activity metrics.</p>

DOI

10.1186/s12969-020-00472-3

Alternate Title

Pediatr Rheumatol Online J

PMID

33059694

Title

Longitudinal assessment of racial disparities in juvenile idiopathic arthritis disease activity in a treat-to-target intervention.

Year of Publication

2020

Number of Pages

88

Date Published

2020 Nov 13

ISSN Number

1546-0096

Abstract

<p><strong>BACKGROUND: </strong>We sought to evaluate racial disparities in disease outcomes among children with polyarticular juvenile idiopathic arthritis (JIA) during a treat-to-target (TTT) intervention with clinical decision support (CDS).</p>

<p><strong>METHODS: </strong>This was a retrospective analysis of a TTT-CDS strategy integrated into clinical practice for children with polyarticular JIA at a single center from 2016 to 2019. The primary outcome was the clinical Juvenile Arthritis Disease Activity Score (cJADAS-10). We used multivariable linear regression to assess racial differences in disease outcomes at the index visit (first visit after implementation). The effect of race on disease outcomes over time was estimated using linear mixed-effects models, stratified by incident or prevalent disease.</p>

<p><strong>RESULTS: </strong>We included 159 children with polyarticular JIA, of which 74, 13 and 13% were white, black, and Asian/other, respectively. cJADAS-10 improved significantly over time for all race categories, while the rates of improvement did not differ by race in incident (p = 0.53) or prevalent cases (p = 0.58). cJADAS-10 over time remained higher among black children compared to white children (β 2.5, p &lt; 0.01 and β 1.2, p = 0.08 for incident and prevalent cases, respectively). Provider attestation to CDS use at ≥50% of encounters was associated with a 3.9 greater reduction in cJADAS-10 among black children compared to white children (p = 0.02).</p>

<p><strong>CONCLUSION: </strong>Despite similar rates of improvement over time by race, disparities in JIA outcomes persisted throughout implementation of a TTT-CDS approach. More consistent CDS use may have a greater benefit among black children and needs to be explored further.</p>

DOI

10.1186/s12969-020-00485-y

Alternate Title

Pediatr Rheumatol Online J

PMID

33187519

Title

Echocardiographic strain analysis reflects impaired ventricular function in youth with pediatric-onset systemic lupus erythematosus.

Year of Publication

2020

Date Published

2020 Oct 03

ISSN Number

1540-8175

Abstract

<p><strong>BACKGROUND: </strong>Strain analysis with speckle-tracking echocardiography shows promise as a screening tool for silent myocardial dysfunction in pediatric-onset systemic lupus erythematosus (pSLE). We compared left ventricular (LV) systolic deformation (measured by strain) in children and adolescents with pSLE to controls, and assessed the relationship between strain, disease activity, and other noninvasive measures of cardiovascular health.</p>

<p><strong>METHODS: </strong>Twenty pSLE subjects ages 9-21 underwent comprehensive cardiovascular testing, including 2D speckle-tracking echocardiography, ambulatory blood pressure monitoring (ABPM), peripheral endothelial function testing, pulse wave velocity and analysis, and carotid ultrasound. Longitudinal apical-4 chamber (LS ) and midpoint circumferential strain (CS ) were compared to that of 70 healthy controls using multivariable linear regression. Among pSLE subjects, Pearson correlation coefficients were calculated to evaluate relationships between global longitudinal or circumferential strain and other measures of cardiovascular health.</p>

<p><strong>RESULTS: </strong>Average SLE disease duration was 3.2&nbsp;years (standard deviation [SD] 2.1). 2/20 pSLE subjects had persistent disease activity, and only one met criteria for hypertension by ABPM. LS was significantly reduced in pSLE subjects compared to controls (mean -18.3 [SD 3.2] vs -21.8% [SD 2.2], P-value &lt;.001). There was no significant difference in CS (-24.8 [SD 3.7] vs -25.7% [SD 3.4], P&nbsp;=&nbsp;.29). Among pSLE subjects, decreased nocturnal blood pressure dipping on ABPM was associated with reduced global circumferential strain (r -0.59, P&nbsp;=&nbsp;.01).</p>

<p><strong>CONCLUSIONS: </strong>Longitudinal myocardial deformation is impaired in pSLE patients despite clinical remission and may represent early myocardial damage. Strain analysis should be considered in addition to standard echocardiographic assessment during follow-up of patients with pSLE.</p>

DOI

10.1111/echo.14872

PMID

33009676

Title

The Impact of Psychiatric Diagnosis and Treatment on Medication Adherence in Youth with Systemic Lupus Erythematosus.

Year of Publication

2020

Date Published

2020 Sep 16

ISSN Number

2151-4658

Abstract

<p><strong>OBJECTIVE: </strong>Youth with systemic lupus erythematosus (SLE) experience high rates of psychiatric comorbidities, which may affect medication adherence. We examined the association between psychiatric disorders and hydroxychloroquine adherence and determined whether psychiatric treatment modifies this association.</p>

<p><strong>METHODS: </strong>We identified incident hydroxychloroquine users among youth with SLE (ages 10-24 years) using de-identified U.S. commercial insurance claims in Optum Clinformatics® Data Mart (2000-2016). Adherence was estimated using medication possession ratios (MPR) over a 365-day interval. Multivariable linear regression models were used to estimate the effect of having any psychiatric disorder on MPR, as well as the independent effects of depression, anxiety, adjustment and other psychiatric disorders. We tested for interactions between psychiatric diagnoses and treatment with psychotropic medications or psychotherapy.</p>

<p><strong>RESULTS: </strong>Among 873 subjects, 20% had a psychiatric diagnosis, most commonly depression. Only adjustment disorders were independently associated with decreased MPRs (β -0.12, p=0.05). We observed significant crossover interactions, in which psychiatric disorders had opposite effects on adherence depending on the receipt of psychiatric treatment. Among youth with any psychiatric diagnosis, psychotropic medication use was associated with a 0.15 increase in MPR compared with no psychotropic medication (p=0.02 for interaction). Among youth with depression or anxiety, psychotherapy was also associated with a higher MPR compared with no psychotherapy (p=0.05 and p&lt;0.01 for interaction, respectively).</p>

<p><strong>CONCLUSION: </strong>The impact of psychiatric disorders on medication adherence differed by whether youth had received psychiatric treatment. Improving recognition and treatment of psychiatric conditions may increase adherence in youth with SLE.</p>

DOI

10.1002/acr.24450

Alternate Title

Arthritis Care Res (Hoboken)

PMID

32937032

Title

Nocturnal blood pressure dipping as a marker of endothelial function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus.

Year of Publication

2020

Number of Pages

129

Date Published

2020 Jun 03

ISSN Number

1478-6362

Abstract

<p><strong>BACKGROUND: </strong>Loss of the normal nocturnal decline in blood pressure (BP), known as non-dipping, is a potential measure of cardiovascular risk identified by ambulatory blood pressure monitoring (ABPM). We sought to determine whether non-dipping is a useful marker of abnormal vascular function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus (pSLE).</p>

<p><strong>METHODS: </strong>Twenty subjects 9-19 years of age with pSLE underwent ABPM, peripheral endothelial function testing, carotid-femoral pulse wave velocity/analysis for aortic stiffness, and carotid intima-media thickness. We assessed the prevalence of non-dipping and other ABPM abnormalities. Pearson or Spearman rank correlation tests were used to evaluate relationships between nocturnal BP dipping, BP load (% of abnormally elevated BPs over 24-h), and vascular outcome measures.</p>

<p><strong>RESULTS: </strong>The majority (75%) of subjects had inactive disease, with mean disease duration of 3.2 years (± 2.1). The prevalence of non-dipping was 50%, which occurred even in the absence of nocturnal or daytime hypertension. Reduced diastolic BP dipping was associated with poorer endothelial function (r 0.5, p = 0.04). Intima-media thickness was significantly greater in subjects with non-dipping (mean standard deviation score of 3.0 vs 1.6, p = 0.02). In contrast, higher systolic and diastolic BP load were associated with increased aortic stiffness (ρ 0.6, p = 0.01 and ρ 0.7, p &lt; 0.01, respectively), but not with endothelial function or intima-media thickness.</p>

<p><strong>CONCLUSION: </strong>In a pSLE cohort with low disease activity, isolated nocturnal BP non-dipping is prevalent and associated with endothelial dysfunction and atherosclerotic changes. In addition to hypertension assessment, ABPM has a promising role in risk stratification and understanding heterogeneous mechanisms of cardiovascular disease in pSLE.</p>

DOI

10.1186/s13075-020-02224-w

Alternate Title

Arthritis Res. Ther.

PMID

32493472

Title

A population-based study of risk factors for heart failure in pediatric and adult-onset systemic lupus erythematosus.

Year of Publication

2020

Number of Pages

527-533

Date Published

2020 May 03

ISSN Number

1532-866X

Abstract

<p><strong>OBJECTIVES: </strong>The increased relative risk of heart failure (HF) from systemic lupus erythematosus (SLE) is greatest at younger ages, but the etiology remains unclear. We identified risk factors for HF in children and adults with SLE and evaluated associations between SLE manifestations and HF.</p>

<p><strong>METHODS: </strong>Incident SLE cases without preceding HF were identified using Clinformatics DataMart® (OptumInsight, Eden Prairie, MN) US claims data (2000-2015), and categorized by age of SLE onset (children 5-17, young adults 18-24, adults 25-44 years old). The primary outcome was the first HF ICD-9-CM diagnosis code (428.x), categorized as early-onset (&lt; 6 months) or delayed-onset. Multivariable logistic regression was used to identify factors associated with early or delayed-onset HF. Cox proportional hazards regression was used to identify time-dependent associations between the onset of SLE manifestations and incident HF.</p>

<p><strong>RESULTS: </strong>There were 523 (2.3%) HF cases among 1,466 children, 2,163 young adults and 19,349 adults age 25-44 with SLE. HF in children and young adults was early-onset in 50% and 60% of cases, respectively, compared to 35% of cases in adults 25-44 years old. There was a temporal association between incident myopericarditis and valvular disease diagnoses and early-onset HF, whereas nephritis and hypertension were more strongly associated with delayed-onset HF. Black race remained independently associated with a 1.5-fold increased HF risk at any time.</p>

<p><strong>CONCLUSION: </strong>Hypertension remains an important traditional CV risk factor across all ages and should be managed aggressively even in younger patients with SLE. Cardiac dysfunction due to acute cardiac manifestations of SLE may contribute to the very high relative incidence of early HF diagnoses among younger SLE patients. Therefore, future prospective studies will need to address heterogeneity in the types and severity of heart failure in order to determine etiology and which patients should be monitored.</p>

DOI

10.1016/j.semarthrit.2020.03.019

Alternate Title

Semin. Arthritis Rheum.

PMID

32446021

Title

Patterns of Health Care Utilization and Medication Adherence Among Youth with Systemic Lupus Erythematosus During Transfer from Pediatric to Adult Care.

Year of Publication

2020

Date Published

2020 Feb 01

ISSN Number

0315-162X

Abstract

<p><strong>OBJECTIVE: </strong>Youth with systemic lupus erythematosus (SLE) transferring from pediatric to adult care are at risk for poor outcomes. We describe patterns of rheumatology/nephrology care and changes in health care utilization and medication adherence during transfer.</p>

<p><strong>METHODS: </strong>We identified youth ages 15-25 with SLE using US private insurance claims from Optum's de-identified Clinformatics® Data Mart. Rheumatology/nephrology visit patterns were categorized as 1) unilateral transfers to adult care within 12 months, 2) overlapping pediatric and adult visits, 3) lost to follow-up, or 4) continuing pediatric care. We used negative binomial regression and paired t-tests to estimate changes in health care utilization and medication possession ratios (MPR) after the last pediatric (index) visit. We compared MPRs between youth who transferred and age-matched peers continuing pediatric care.</p>

<p><strong>RESULTS: </strong>184 youth transferred out of pediatric care, of which 41.8% transferred unilaterally, 31.5% had overlapping visits over a median of 12 months before final transfer, and 26.6% were lost to follow-up. We matched 107 youth continuing pediatric care. Overall ambulatory utilization decreased among those lost to follow-up. Acute care utilization decreased across all groups. MPRs after the index date were lower in youth lost to follow-up (mean 0.24) compared to peers in pediatric care (0.57, p&lt;0.001).</p>

<p><strong>CONCLUSION: </strong>Youth with SLE with continuous private insurance coverage do not use more acute care after transfer to adult care. However, a substantial proportion fail to see adult subspecialists within 12 months and have worse medication adherence, placing them at higher risk for adverse outcomes.</p>

DOI

10.3899/jrheum.191029

Alternate Title

J. Rheumatol.

PMID

32007936

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