First name
Timothy
Middle name
G
Last name
Brandon

Title

Patient Reported Outcomes Measurement Information System® (PROMIS(®) ) Tools for Collecting Patient-Reported Outcomes in Children with Juvenile Arthritis.

Year of Publication

2016

Date Published

2016 May 9

ISSN Number

2151-4658

Abstract

OBJECTIVE: To evaluate the precision and construct validity of pediatric Patient Reported Outcomes Measurement Information System(®) (PROMIS(®) ) instruments in a population of juvenile idiopathic arthritis (JIA) patients and parent proxies.

METHODS: A convenience sample of JIA patients and parents of JIA patients completed PROMIS instruments for eight domains: anger, anxiety, depressive symptoms, fatigue, mobility, pain interference, peer relationships, and upper extremity function. Short form and computerized adaptive test (CAT) scores were derived from item bank responses. Raw scores were translated to standardized T-scores with corresponding standard errors (SEs). Discrimination between inactive versus active disease was evaluated as an indicator of each measures' construct validity. SEs were plotted to evaluate each instrument's relative precision. Patient-parent concordance was assessed using intraclass correlations (ICC).

RESULTS: 228 patients and 223 parents participated, providing 71-78 responses per domain. Patient- and parent-reported anger, fatigue, mobility, and pain interference scores significantly differed between those with inactive and active disease. Anxiety, depressive symptoms, and peer relationships differed by disease activity levels for parent-report only. Short forms and CATs provided comparable reliability to the full item banks across the full range of each outcome. Patient-parent agreement ranged from ICC=0.3 to 0.8. CAT did not reduce the number of items for any domain compared to the short form.

CONCLUSION: Precision and discriminatory abilities of PROMIS instruments depend on health domain and report type (self-report versus parent proxy-report) for children with JIA. Varying levels of patient-parent concordance reinforces the importance of considering both perspectives in comprehensive health outcomes assessments. This article is protected by copyright. All rights reserved.

DOI

10.1002/acr.22937

Alternate Title

Arthritis Care Res (Hoboken)

PMID

27159889

Title

Incidence Rates of Psoriasis in Children with Inflammatory Bowel Disease and Juvenile Arthritis Treated with TNFi Agents and DMARDs.

Year of Publication

2022

Date Published

2022 Apr 15

ISSN Number

0315-162X

Abstract

<p><strong>OBJECTIVE: </strong>To estimate the differential effect of tumor necrosis factor inhibitor (TNFi) therapies and presence/absence of conventional synthetic disease-modifying antirheumatic drug (DMARD) on the incidence of psoriasis in children with inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and chronic nonbacterial osteomyelitis (CNO).</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study from 2008 to 2020. TNFi and DMARD exposures were dichotomized as ever/never. The primary outcome was incident psoriasis. Incidence rates (IRs) of psoriasis were stratified by underlying diagnosis, TNFi agent, and DMARD use. Poisson regression was used to assess the IR ratios (IRR) between exposure groups.</p>

<p><strong>RESULTS: </strong>5088 children met inclusion criteria - 3794 (75%) had IBD, 1189 (23%) had JIA, and 105 (2%) had CNO. 613 (30%) and 1410 (70%) had TNFi exposure with or without a DMARD, respectively. IRR of developing psoriasis in patients exposed to adalimumab was 2.70 times higher (95% CI: 1.52-4.75; p&lt;0.001) than those who did not receive any TNFi treatment, when controlling for DMARD, sex, and family history of psoriasis. IRR was lower, but not significantly different, for patients exposed to infliximab (IRR=2.34; 95% CI: 1.56-3.51; p&lt;0.001) and etanercept (IRR=2.22; 95% CI: 1.17-4.21; p=0.006) compared to TNFi unexposed patients. IRR of TNFi exposure was lower by 0.25 (p&lt;0.001) in DMARD exposed patients compared to non- DMARD exposed patients.</p>

<p><strong>CONCLUSION: </strong>IRR of TNFi-induced psoriasis was not significantly different amongst adalimumab, infliximab, and etanercept. However, for patients with exposure to any of the TNFi evaluated, the IRR was significantly lower in those also exposed to a DMARD.</p>

DOI

10.3899/jrheum.211359

Alternate Title

J Rheumatol

PMID

35428721

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

Changes over time in inflammatory and structural lesions at the sacroiliac joint in children with spondyloarthritis exposed and unexposed to tumor necrosis factor inhibitor.

Year of Publication

2021

Number of Pages

167

Date Published

2021 Dec 02

ISSN Number

1546-0096

Abstract

<p><strong>BACKGROUND: </strong>The objective of this work was to describe magnetic resonance imaging (MRI) changes over time in inflammatory and structural lesions at the sacroiliac joint (SIJ) in children with spondyloarthritis (SpA) exposed and unexposed to tumor necrosis factor inhibitor (TNFi).</p>

<p><strong>METHODS: </strong>This was a retrospective, multicenter study of SpA patients with suspected or confirmed sacroiliitis who underwent at ≥2 pelvic MRI scans. Images were reviewed independently by 3 radiologists and scored for inflammatory and structural changes using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ inflammation score (SIS) and structural score (SSS). Longitudinal, quantitative changes in patient MRI scans were measured using descriptive statistics and stratified by TNFi exposure. We used an average treatment effects (ATE) regression model to explore the average effect of TNFi exposure over time on inflammatory and structural lesions, adjusting for baseline lesion scores.</p>

<p><strong>RESULTS: </strong>Forty-six subjects were evaluated using the SIS (n&nbsp;= 45) and SSS (n&nbsp;= 18). Median age at baseline imaging was 13.6 years, 63% were male and 71% were white. Twenty-three subjects (50%) were TNFi exposed between MRI studies. The median change in SIS in TNFi exposed and unexposed subjects with a baseline SIS ≥0 was - 20.7 and - 14.3, respectively (p&nbsp;= 0.09). Eleven (85%) TNFi exposed and 8 (89%) unexposed subjects with a baseline SIS ≥0 met the SIS minimal clinically important difference (MCID; ≥2.5). Using the ATE model adjusted for baseline SIS, the average effect of TNFi on SIS in patients with a baseline SIS ≥2 was - 14.5 (p&nbsp;&lt; 0.01). Unadjusted erosion change score was significantly worse in TNFi unexposed versus exposed subjects (p&nbsp;= 0.03) but in the ATE model the effect of TNFi was not significant.</p>

<p><strong>CONCLUSION: </strong>This study quantitatively describes how lesions in the SIJs on MRI change over time in patients exposed to TNFi versus unexposed. Follow-up imaging in TNFi exposed patients showed greater improvement than the unexposed group by most metrics, some of which reached statistical significance. Surprisingly, a majority of TNFi unexposed children with a baseline SIS≥2 met the SIS MCID. Additional studies assessing the short and long-term effects of TNFi on inflammatory and structural changes in juvenile SpA are needed.</p>

DOI

10.1186/s12969-021-00647-6

Alternate Title

Pediatr Rheumatol Online J

PMID

34857002

Title

Feasibility of T2 Mapping of the Sacroiliac Joints in Healthy Control Subjects and Children and Young Adults with Sacroiliitis.

Year of Publication

2021

Date Published

2021 Nov 10

ISSN Number

2578-5745

Abstract

<p><strong>OBJECTIVE: </strong>To assess the feasibility of T2 mapping for evaluating pediatric SIJ cartilage at 3 Tesla (T) magnetic resonance imaging (MRI).</p>

<p><strong>METHODS: </strong>Healthy control subjects and adolescents with sacroiliitis underwent a 3T MRI dedicated pelvic protocol that included a T2 mapping sequence consisting of multislice, multiecho acquisition. Healthy control subjects were prospectively recruited from our primary care practices as part of a larger imaging study, whereas adolescents with sacroiliitis were recruited specifically for this study. Regions of interest (ROIs) were hand-drawn by a senior pediatric radiologist twice and a radiology fellow twice to calibrate and test reliability using the intraclass correlation coefficient (ICC). T2 relaxation time between control subjects and cases was compared using univariate linear regression. We tested the association of T2 relaxation time in adolescents with sacroiliitis with patient-reported outcomes and the Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) inflammation and structural scores using Pearson correlation coefficients.</p>

<p><strong>RESULTS: </strong>Fourteen subjects were evaluable (six control subjects: median age 13.7 years [interquartile range (IQR): 12.2-15.5], 67% male patients; eight cases: median age 17.4 years [IQR: 12.5-20], 88% male patients]. Acquisition time for T2 mapping sequences was approximately 6 minutes, and segmenting the ROI for each SIJ took approximately 3 minutes. The intrarater and inter-rater ICCs were 0.67 and 0.46, respectively, indicating good to fair reliability. There was a trend, albeit statistically insignificant, in longer median T2 relaxation time in cases (43.04 ms; IQR: 41.25-49.76 ms) versus healthy control subjects (40.0 ms; IQR: 38.9-48.6 ms). Although not statistically significant, cases with longer T2 relaxation time tended to occur with poorer patient-reported outcomes. Correlations with the SIJ inflammation and structural lesion scores were weak.</p>

<p><strong>CONCLUSION: </strong>T2 mapping of the SIJ cartilage in children was feasible and reliable. Larger controlled and longitudinal assessments are needed to assess the validity and utility of these measurements for routine clinical practice and trials.</p>

DOI

10.1002/acr2.11354

Alternate Title

ACR Open Rheumatol

PMID

34757697

Title

Development and validation of the juvenile spondyloarthritis disease flare (JSpAflare) measure: Ascertaining flare in patients with inactive disease.

Year of Publication

2021

Date Published

2021 Aug 07

ISSN Number

2151-4658

Abstract

<p><strong>OBJECTIVE: </strong>Our objective was to develop and validate a composite disease flare definition for juvenile spondyloarthritis that would closely approximate the clinical decision made to reinitiate/not reinitiate systemic therapy after therapy de-escalation.</p>

<p><strong>METHODS: </strong>Retrospective chart reviews of children with spondyloarthritis who underwent systemic therapy de-escalation of biologic or conventional disease-modifying antirheumatic drugs (bDMARDs; cDMARDs) were used to develop and validate the flare outcome. Independent cohorts for development (1 center) and validation (4 centers) were collected from large tertiary healthcare systems. Core measure thresholds and candidate disease flare outcomes were assessed using sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and area under the receiver operating characteristic (AUROC) curve with physician assessment of "active disease" plus re-initiation of standard dose of systemic therapy as the reference standard.</p>

<p><strong>RESULTS: </strong>Of the candidate definitions, clinically meaningful worsening in ≥3 of the following five core measures performed best: caregiver/patient assessment of well-being, physician assessment of disease activity, caregiver/patient assessment of pain, physical function, and active joint count. AUROC was 0.91, PPV 87.5%, NPV 98.1%, sensitivity 82.4%, and specificity 98.7%. Cronbach's α was 0.81, signifying internal consistency and factor analysis demonstrated the outcome measured one construct. "JSpAflare" had face validity according to 21 surveyed pediatric rheumatologists. JSpAflare had AUROC 0.85, PPV 92.3%, and NPV 96.8% in the validation cohort.</p>

<p><strong>CONCLUSIONS: </strong>There is initial support for the validity of JSpAflare as a tool to identify disease flare in juvenile spondyloarthritis patients de-escalating therapy and is potentially applicable in clinical practice, observational studies, and therapeutic trials.</p>

DOI

10.1002/acr.24763

Alternate Title

Arthritis Care Res (Hoboken)

PMID

34363343

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

Juvenile Spondyloarthritis: focus on uveitis.

Year of Publication

2020

Number of Pages

70

Date Published

2020 Sep 10

ISSN Number

1546-0096

Abstract

<p><strong>BACKGROUND: </strong>Juvenile spondyloarthritis (JSpA) represents a group of inflammatory arthritides with several distinctive features (enthesitis, involvement of spine and sacroiliac joint, HLA-B27 association and development of uveitis). There are limited data on the course of uveitis in children with JSpA. This study aims to estimate the prevalence of uveitis and to look at the presence of HLA-B27 in relation to uveitis occurrence and ocular symptoms in a cohort of JSpA patients.</p>

<p><strong>FINDINGS: </strong>This is a cross sectional/retrospective study involving patients with JSpA followed in a tertiary referral hospital. Two hundred twenty-three patients were enrolled in the study. The prevalent diagnosis was enthesitis-related arthritis (ERA) (62%) followed by juvenile psoriatic arthritis (PsA), undifferentiated arthritis (UA), and the arthropathies associated with inflammatory bowel disease (IBD-A) (18, 14, 6%, respectively). Uveitis was reported in twenty-four patients (11%) of the JSpA cohort (JSpA-U). ERA patients had the highest uveitis prevalence (ERA-U) (13%) with similar prevalences in UA, PsA and in IBD-A (7% each). The prevalence of HLA-B27 positivity was similar amongst the entire JSpA-U cohort (N&nbsp;= 22, 45%) and those with ERA-U (N&nbsp;= 8, 44%). The overall prevalence of symptomatic uveitis was 79%. Neither the likelihood of uveitis, nor of symptomatic uveitis, varied by HLA-B27 status either in the entire cohort nor in those with ERA.</p>

<p><strong>CONCLUSIONS: </strong>About one-tenth of patients developed uveitis, the majority of which was symptomatic. Fewer than half of the patients with uveitis were HLA-B27 positive. HLA-B27 status was not statistically associated with either the development of uveitis or symptomaticity of uveitis.</p>

DOI

10.1186/s12969-020-00463-4

Alternate Title

Pediatr Rheumatol Online J

PMID

32912296

Title

Normal hip joint fluid volumes in healthy children of different ages, based on MRI volumetric quantitative measurement.

Year of Publication

2020

Date Published

2020 Jun 29

ISSN Number

1432-1998

Abstract

<p><strong>BACKGROUND: </strong>While magnetic resonance imaging (MRI) of the pelvis and hips is common in pediatric patients, to date there are no data on the quantification of normal hip joint fluid volume in this patient population.</p>

<p><strong>OBJECTIVE: </strong>We sought to assess the feasibility and reliability of quantitative hip joint fluid measurement in the pediatric population to estimate the normal volume of fluid in a pediatric hip joint.</p>

<p><strong>MATERIALS AND METHODS: </strong>Seventy healthy children ages 8-17&nbsp;years underwent a pelvic MRI including a large field of view coronal T2 fat-saturated sequence where hips were entirely imaged. Following 3 training sessions, 2 readers with experience in musculoskeletal imaging performed volumetric quantitative measurements of hip fluid (140 hips) using semiautomated pixel-based thresholding on custom MATLAB software.</p>

<p><strong>RESULTS: </strong>The mean processing time per hip was 2&nbsp;min, 41&nbsp;s. The mean volume of fluid in a hip joint was 2.1&nbsp;mL (range: 0.38-5.41&nbsp;mL), increasing slightly with age. Volumes were also greater in boys than in girls (P=0.004). Intra-observer and interobserver agreement were high (intra-class correlation coefficients 0.93 and 0.98, respectively), with mean volume differences of 0.04&nbsp;mL for intra-observer and 0.09&nbsp;mL for interobserver.</p>

<p><strong>CONCLUSION: </strong>A semiautomated pixel-based thresholding approach was feasible and reliable for measuring joint fluid in pediatric hip MRI. The average fluid volume of 2.1&nbsp;mL can represent a visually substantial quantity of fluid per MRI slice, particularly in small children, and should not be misinterpreted as a joint effusion.</p>

DOI

10.1007/s00247-020-04744-8

Alternate Title

Pediatr Radiol

PMID

32601743

Title

Variability in magnetic resonance imaging interpretation of the pediatric sacroiliac joint.

Year of Publication

2020

Date Published

2020 Apr 11

ISSN Number

2151-4658

Abstract

<p><strong>OBJECTIVE: </strong>Magnetic resonance imaging (MRI) is pivotal in the assessment of early sacroiliitis in children. We aimed to evaluate the agreement between local radiology reports and central imaging reviewers for active inflammation and structural damage at the sacroiliac joints (SIJs).</p>

<p><strong>METHODS: </strong>Eight hospitals each contributed up to 20 cases of consecutively imaged children and adolescents with juvenile idiopathic arthritis and suspected sacroiliitis. Studies were independently reviewed by 3 experienced musculoskeletal pediatric radiologists. Local assessments of global impression and lesions were coded from the local radiology reports by two study team members. Test properties of local reports were calculated using the central imaging team's majority as the reference standard.</p>

<p><strong>RESULTS: </strong>For 120 evaluable subjects, median age was 14 years, half of cases were male, and median disease duration at time of imaging was 0.8 years (IQR: 0-2). Sensitivity, 93.5% (95% CI: 78.6-99.2%), and specificity, 69.7% (95% CI: 59.0-79.0%), of local reports for inflammation were high and moderate, respectively, but positive predictive value (PPV) was low 51.8% (95% CI: 38.0-65.3%). Twenty-seven (23%) cases had active inflammation reported locally but rated normal centrally, nineteen (70%) with subsequent medication changes. Sensitivity of local reports detecting structural damage was low, 45.7% (95% CI: 28.8-63.4%), and specificity, 88.2% (95% CI: 79.4-94.2%), was high; PPV was low 61.5% (95% CI: 40.6-79.8%).</p>

<p><strong>CONCLUSION: </strong>Substantial variation exists in the interpretation of inflammatory and structural lesions at the SIJs in children. In order to reliably identify pathology, additional training in the MR appearance of the maturing SIJ is greatly needed.</p>

DOI

10.1002/acr.24206

Alternate Title

Arthritis Care Res (Hoboken)

PMID

32277735

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