Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.

Cannabidiol (CBD) Use among children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is common and difficult to treat. Cannabidiol (CBD) is now widely available, but no studies to date have investigated the use of CBD for JIA. METHODS: We performed a chart review to identify patients with JIA at a Midwestern medical institution between 2017 and 2019. We surveyed primary caregivers of JIA patients using an anonymous, online survey with questions on caregiver knowledge and attitudes towards CBD. We compared respondents with no interest in CBD use vs. those contemplating or currently using CBD using descriptive statistics. RESULTS: Of 900 reviewed charts, 422 met inclusion criteria. Of these, 236 consented to be sent a survey link, and n=136 (58%) completed surveys. Overall, 34.5% (n=47) of respondents reported no interest in using a CBD product for their child's JIA, while 54% (n=79) reported contemplating using CBD and 7% (n=10) reported currently giving their child CBD. Only 2% of respondents contemplating or actively using a CBD product learned about CBD from their child's rheumatologist, compared with television (70%) or a friend (50%). Most respondents had not talked to their child's rheumatologist about using CBD. Of those currently using CBD, most used oral or topical products, and only 10% of respondents (n=1) knew what dose they were giving their child. CONCLUSIONS: Our results show infrequent use but a large interest in CBD among caregivers of children with JIA. Given CBD's unknown safety profile in children with JIA, this study highlights a need for better studies and education around CBD for pediatric rheumatologists.

Telemedicine in pediatric rheumatology: this is the time for the community to embrace a new way of clinical practice.

BACKGROUND: The use of telemedicine in pediatric rheumatology has been historically low. The current COVID 19 global pandemic has forced a paradigm shift with many centers rapidly adopting virtual visits to conduct care resulting in rapid expansion of use of telemedicine amongst practices. BODY: This commentary discusses practical tips for physicians including guidance around administrative and governance issues, preparation for telemedicine, involving the multidisciplinary care team, and teaching considerations. We also outline a standard proforma and smart phrases for the electronic health record. A proposed variation of the validated pediatric gait arms legs spine examination (pGALS) called the video pGALS (VpGALS) as a means of conducting virtual pediatric rheumatology physical examination is presented. CONCLUSION: This commentary provides a starting framework for telemedicine use in pediatric rheumatology and further work on validation and acceptability is needed.

Medical education in pediatric rheumatology-unique challenges and opportunities.

Pediatric rheumatology faces workforce shortages in both developed and developing regions of the world resulting in suboptimal care of children with chronic rheumatic diseases. In addition to outlining the structure of formal rheumatology training programs in North America and Europe, we attempt to summarize various strategies being implemented with success in several parts of the world to help close the gap via innovative learning strategies. We discuss the important role of professional organizations in leading this effort.

Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis.

BACKGROUND: Juvenile dermatomyositis (JDM) is an auto-immune muscle disease which presents with skin manifestations and muscle weakness. At least 10% of the patients with JDM present with acquired lipodystrophy. Laminopathies are caused by mutations in the lamin genes and cover a wide spectrum of diseases including muscular dystrophies and lipodystrophy. The p.T10I LMNA variant is associated with a phenotype of generalized lipodystrophy that has also been called atypical progeroid syndrome. CASE PRESENTATION: A previously healthy female presented with bilateral proximal lower extremity muscle weakness at age 4. She was diagnosed with JDM based on her clinical presentation, laboratory tests and magnetic resonance imaging (MRI). She had subcutaneous fat loss which started in her extremities and progressed to her whole body. At age 7, she had diabetes, hypertriglyceridemia, low leptin levels and low body fat on dual energy X-ray absorptiometry (DEXA) scan, and was diagnosed with acquired generalized lipodystrophy (AGL). Whole exome sequencing (WES) revealed a heterozygous c.29C > T; p.T10I missense pathogenic variant in LMNA, which encodes lamins A and C. Muscle biopsy confirmed JDM rather than muscular dystrophy, showing perifascicular atrophy and perivascular mononuclear cell infiltration. Immunofluroscence of skin fibroblasts confirmed nuclear atypia and fragmentation. CONCLUSIONS: This is a unique case with p.T10I LMNA variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that LMNA, and possibly p.T10I, may have a pathogenic role in not only the occurrence of generalized lipodystrophy, but also juvenile dermatomyositis. Careful phenotypic characterization of additional patients with laminopathies as well as individuals with JDM is warranted.

Patient characteristics associated with response to NSAID monotherapy in children with systemic juvenile idiopathic arthritis.

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is an auto-inflammatory disease characterized by fever, arthritis, and ≥1 of rash, generalized lymphadenopathy, hepato/splenomegaly, and serositis. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the initial treatments of sJIA, but there is currently no evidence indicating which children should undergo a trial of NSAID monotherapy and which should not. Our objective is to identify presentation characteristics which are associated with response and lack of response to a trial of NSAID monotherapy. METHODS: This is a retrospective single-center cohort study of children diagnosed with sJIA from 2000 to 2014. Patient demographics and disease characteristics were investigated to identify predictors of response to NSAID monotherapy. RESULTS: Eighty-seven children were newly diagnosed with sJIA 2000-2014. Thirteen of the 51 children who received NSAID monotherapy achieved clinically inactive disease (CID) without other medications. Age at presentation (≤8 years old), initial joint count (≤5), and C-reactive protein (CRP) (≤13 mg/dL) at diagnosis were associated with achievement of CID on NSAIDs alone. Physicians were less likely to trial NSAID monotherapy if the patient had either serositis or macrophage activation syndrome (MAS) at diagnosis. Ultimate achievement of CID and time to CID were not significantly affected by whether the patient received a trial of NSAID monotherapy. CONCLUSIONS: While a subset of children with sJIA can achieve CID with NSAID monotherapy, we recommend against a trial in patients who are >8 years old, with >5 joints involved, or with CRP > 13 mg/dL. Patients who undergo a trial of NSAID monotherapy should follow up within 2-4 weeks to evaluate for possible need for drug escalation. Clinical trials are necessary to confirm these findings.

Evidence for Updating the Core Domain Set of Outcome Measures for Juvenile Idiopathic Arthritis: Report from a Special Interest Group at OMERACT 2016.

OBJECTIVE: The current Juvenile Idiopathic Arthritis (JIA) Core Set was developed in 1997 to identify the outcome measures to be used in JIA clinical trials using statistical and consensus-based techniques, but without patient involvement. The importance of patient/parent input into the research process has increasingly been recognized over the years. An Outcome Measures in Rheumatology (OMERACT) JIA Core Set Working Group was formed to determine whether the outcome domains of the current core set are relevant to those involved or whether the core set domains should be revised. METHODS: Twenty-four people from the United States, Canada, Australia, and Europe, including patient partners, formed the working group. Guided by the OMERACT Filter 2.0 process, we performed (1) a systematic literature review of outcome domains, (2) a Web-based survey (142 patients, 343 parents), (3) an idea-generation study (120 parents), (4) 4 online discussion boards (24 patients, 20 parents), and (5) a Special Interest Group (SIG) activity at the OMERACT 13 (2016) meeting. RESULTS: A MEDLINE search of outcome domains used in studies of JIA yielded 5956 citations, of which 729 citations underwent full-text review, and identified additional domains to those included in the current JIA Core Set. Qualitative studies on the effect of JIA identified multiple additional domains, including pain and participation. Twenty-one participants in the SIG achieved consensus on the need to revise the entire JIA Core Set. CONCLUSION: The results of qualitative studies and literature review support the need to expand the JIA Core Set, considering, among other things, additional patient/parent-centered outcomes, clinical data, and imaging data.

Efficacy of an Interinstitutional Mentoring Program Within Pediatric Rheumatology.

OBJECTIVE: The small size of many pediatric rheumatology programs translates into limited mentoring options for early career physicians. To address this problem, the American College of Rheumatology (ACR) and the Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed a subspecialty-wide interinstitutional mentoring program, the ACR/CARRA Mentoring Interest Group (AMIGO). We sought to assess the impact of this program on mentoring within pediatric rheumatology. METHODS: In a longitudinal 3-year study, participant ratings from the AMIGO pilot program were compared with those after the program was opened to general enrollment. Access to mentoring as a function of career stage was assessed by surveys of the US and Canadian pediatric rheumatologists in 2011 and 2014, before and after implementation of AMIGO. RESULTS: Participants in the pilot phase (19 dyads) and the general implementation phase (112 dyads) reported comparable success in establishing mentor contact, suitability of mentor-mentee pairing, and benefit with respect to career development, scholarship, and work-life balance. Community surveys showed that AMIGO participation as mentee was high among fellows (86%) and modest among junior faculty (31%). Implementation correlated with significant gains in breadth of mentorship and in overall satisfaction with mentoring for fellows but not junior faculty. CONCLUSION: AMIGO is a career mentoring program that serves most fellows and many junior faculty in pediatric rheumatology across the US and Canada. Program evaluation data confirm that a subspecialty-wide interinstitutional mentoring program is feasible and can translate into concrete improvement in mentoring, measurable at the level of the whole professional community.

Prescription patterns for children with juvenile idiopathic arthritis in Michigan Medicaid: a comparison by prescriber type.

BACKGROUND: Due to a limited number and disparate distribution of pediatric rheumatologists in the US, a variety of physician types provide care to children with rheumatologic diseases. However, little is known about how that care may differ across prescribing physician groups. Our objective was to compare medication claims for children with juvenile idiopathic arthritis (JIA) by type of prescribing physician. METHODS: We performed a retrospective cohort study of children with JIA using Michigan Medicaid data for 7/1/2005-6/30/2007, employing descriptive and bivariate analyses by age, medication type, and prescriber type. RESULTS: Among 397 children, there was no difference in the frequency of medication claims for children with internist versus pediatric rheumatologist prescribers. Children with non-rheumatologist prescribers were less likely to have claims for disease modifying anti-rheumatic drugs (DMARDs) and biologic agents. CONCLUSION: Differential use of DMARDs and biologic agents by rheumatologists indicates the importance of referring children with JIA for specialty care.

Noncompletion in pediatric rheumatology fellowships.

BACKGROUND: One challenge facing the health care workforce is a paucity of pediatrics subspecialists. No prior studies have investigated fellowship noncompletion as an influence of the subspecialty workforce. OBJECTIVE: We sought to determine the noncompletion rate for pediatric rheumatology fellowships and to identify demographic characteristics associated with noncompletion. METHODS: A retrospective cohort study of all trainees entering US pediatric rheumatology fellowship programs between 1997 and 2007 was performed. American Board of Pediatrics tracking data were used to determine completion status (completer or noncompleter) for each trainee. Completers were compared with noncompleters, using the independent variables sex, medical school location, and age. The noncompletion rate was calculated overall and individually. Program size was examined as a predictor of nonompletion rate. Data analysis used χ(2) tests, Kruskal-Wallis tests, and Spearman correlation. RESULTS: The cohort included 182 trainees from 28 pediatric rheumatology fellowship programs. Program size ranged from 1 to 18 trainees. The overall noncompletion rate was 16%. Male fellows, especially male international medical graduates, were more likely to be noncompleters. Noncompletion rates varied among programs: 15 programs had noncompletion rates of 0% and 4 programs had noncompletion rates of 50% or higher. Program size was not associated with noncompletion rate. CONCLUSIONS: During the study period, 1 of 6 pediatric rheumatology fellows did not complete training. Noncompletion was concentrated in a small number of programs. Further research should investigate noncompletion across specialties, identifying the causes of noncompletion at the individual, program, and specialty levels to inform future interventions to improve fellowship completion.

Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis.

OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin-1 (IL-1) and IL-6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients. METHODS: Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. RESULTS: The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL-1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti-IL-1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications. CONCLUSION: PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.

Remediation in the context of the competencies: a survey of pediatrics residency program directors.

BACKGROUND: The 6 competencies defined by the Accreditation Council for Graduate Medical Education provide the framework of assessment for trainees in the US graduate medical education system, but few studies have investigated their impact on remediation. METHODS: We obtained data via an anonymous online survey of pediatrics residency program directors. For the purposes of the survey, remediation was defined as "any form of additional training, supervision, or assistance above that required for a typical resident." Respondents were asked to quantify 3 groups of residents: (1) residents requiring remediation; (2) residents whose training was extended for remediation purposes; and (3) residents whose training was terminated owing to issues related to remediation. For each group, the proportion of residents with deficiencies in each of the 6 competencies was calculated. RESULTS: In all 3 groups, deficiencies in medical knowledge and patient care were most common; deficiencies in professionalism and communication were moderately common; and deficiencies in systems-based practice and practice-based learning and improvement were least common. Residents whose training was terminated were more likely to have deficiencies in multiple competencies. CONCLUSION: Although medical knowledge and patient care are reported most frequently, deficiencies in any of the 6 competencies can lead to the need for remediation in pediatrics residents. Residents who are terminated are more likely to have deficits in multiple competencies. It will be critical to develop and refine tools to measure achievement in all 6 competencies as the graduate medical education community may be moving further toward individualized training schedules and competency-based, rather than time-based, training.

Perspective: beyond counting hours: the importance of supervision, professionalism, transitions of care, and workload in residency training.

The medical education community's conversations about residents' duty hours have long focused solely on the number of those hours. In July 2011, the Accreditation Council for Graduate Medical Education (ACGME) enacted its most recent iteration of standards regarding duty hours. Those standards, as well as a 2008 Institute of Medicine report, look beyond the quantity of duty hours to address their quality as well. Indeed, the majority of the 2011 ACGME standards specify requirements for the qualitative components of residents' working and learning environments, including supervision of residents; professionalism, personal responsibility, and patient safety; transitions of care; and clinical responsibilities (including workload). The authors believe that focusing on these qualitative (rather than quantitative) components of the resident's working and learning environment provides the greatest promise for balancing patient care with resident education, thus optimizing the safety and effectiveness of both. For each of the four qualitative components that the authors discuss (enhancing supervision, nurturing professionalism and personal responsibility, ensuring safe transitions of care, and optimizing workloads and cognitive loads), they offer agendas for faculty development, educational program planning, and research. Thus, the authors call on the medical education community to expand its discussion beyond counting duty hours to focus on these critical issues that ensure quality resident education and patient care and to implement necessary strategies to address them.

Hospitalizations for intussusception before and after the reintroduction of rotavirus vaccine in the United States.

OBJECTIVE: To determine whether hospital discharges for intussusception in children younger than 1 year have changed since the reintroduction of rotavirus vaccine in the United States. DESIGN: Serial cross-sectional analysis. SETTING: US hospitals. PARTICIPANTS: Children younger than 1 year with a discharge diagnosis of intussusception identified in the Kids' Inpatient Database, a series of nationally representative data sets of pediatric hospital discharges in the United States with 4 available years prior to vaccine reintroduction (1997, 2000, 2003, and 2006) and 1 year after (2009). MAIN EXPOSURES: Hospital discharge before vs after rotavirus vaccine reintroduction. OUTCOME MEASURES: Total number and rate of hospital discharges for infants younger than 1 year with a diagnosis of intussusception (International Classification of Diseases, Ninth Revision, Clinical Modification code 560.0). RESULTS: From 1997 to 2006, there was no change in the total number of hospital discharges for intussusception, with a small decrease in the rate of intussusception discharges (41.6 [95% CI, 36.7-46.5] to 36.5 [95% CI, 31.7-41.2] per 100,000 infants). Based on the trend, the predicted rate of discharges for intussusception in 2009 was 36.0 (95% CI, 30.2-41.8) per 100,000 infants. The measured rate of hospital discharges for intussusception in 2009 was 33.3 (95% CI, 29.0-37.6) per 100,000 infants. CONCLUSION: The reintroduction of rotavirus vaccine since 2006 has not resulted in a detectable increase in the number of hospital discharges for intussusception among US infants.