Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.

BACKGROUND: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. OBJECTIVE: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. DESIGN: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SETTING: A national collaboration of pediatric health systems (PEDSnet). PARTICIPANTS: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. INTERVENTION: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. MEASUREMENTS: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. RESULTS: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. LIMITATION: Observational study design and potentially undocumented infection. CONCLUSION: This study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. PRIMARY FUNDING SOURCE: National Institutes of Health.

Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial.

BACKGROUND & AIMS: Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. METHODS: Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. RESULTS: Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. CONCLUSIONS: Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. CLINICALTRIALS: gov, Number: NCT02772965.

Assessing Alternative Approaches for Wound Closure in a National Pediatric Learning Health System.

INTRODUCTION: Our objective was to perform a feasibility study using real-world data from a learning health system (LHS) to describe current practice patterns of wound closure and explore differences in outcomes associated with the use of tissue adhesives and other methods of wound closure in the pediatric surgical population to inform a potentially large study. METHODS: A multi-institutional cross-sectional study was performed of a random sample of patients <18 y-old who underwent laparoscopic appendectomy, open or laparoscopic inguinal hernia repair, umbilical hernia repair, or repair of traumatic laceration from January 1, 2019, to December 31, 2019. Sociodemographic and operative characteristics were obtained from 6 PEDSnet (a national pediatric LHS) children's hospitals and OneFlorida Clinical Research Consortium (a PCORnet collaboration across 14 academic health systems). Additional clinical data elements were collected via chart review. RESULTS: Of the 692 patients included, 182 (26.3%) had appendectomies, 155 (22.4%) inguinal hernia repairs, 163 (23.6%) umbilical hernia repairs, and 192 (27.8%) traumatic lacerations. Of the 500 surgical incisions, sutures with tissue adhesives were the most frequently used (n = 211, 42.2%), followed by sutures with adhesive strips (n = 176, 35.2%), and sutures only (n = 72, 14.4%). Most traumatic lacerations were repaired with sutures only (n = 127, 64.5%). The overall wound-related complication rate was 3.0% and resumption of normal activities was recommended at a median of 14 d (interquartile ranges 14-14). CONCLUSIONS: The LHS represents an efficient tool to identify cohorts of pediatric surgical patients to perform comparative effectiveness research using real-world data to support medical and surgical products/devices in children.

One-shot distributed algorithms for addressing heterogeneity in competing risks data across clinical sites.

OBJECTIVE: To characterize the interplay between multiple medical conditions across sites and account for the heterogeneity in patient population characteristics across sites within a distributed research network, we develop a one-shot algorithm that can efficiently utilize summary-level data from various institutions. By applying our proposed algorithm to a large pediatric cohort across four national Children's hospitals, we replicated a recently published prospective cohort, the RISK study, and quantified the impact of the risk factors associated with the penetrating or stricturing behaviors of pediatric Crohn's disease (PCD). METHODS: In this study, we introduce the ODACoRH algorithm, a one-shot distributed algorithm designed for the competing risks model with heterogeneity. Our approach considers the variability in baseline hazard functions of multiple endpoints of interest across different sites. To accomplish this, we build a surrogate likelihood function by combining patient-level data from the local site with aggregated data from other external sites. We validated our method through extensive simulation studies and replication of the RISK study to investigate the impact of risk factors on the PCD for adolescents and children from four children's hospitals within the PEDSnet, A National Pediatric Learning Health System. To evaluate our ODACoRH algorithm, we compared results from the ODACoRH algorithms with those from meta-analysis as well as those derived from the pooled data. RESULTS: The ODACoRH algorithm had the smallest relative bias to the gold standard method (-0.2%), outperforming the meta-analysis method (-11.4%). In the PCD association study, the estimated subdistribution hazard ratios obtained through the ODACoRH algorithms are identical on par with the results derived from pooled data, which demonstrates the high reliability of our federated learning algorithms. From a clinical standpoint, the identified risk factors for PCD align well with the RISK study published in the Lancet in 2017 and other published studies, supporting the validity of our findings. CONCLUSION: With the ODACoRH algorithm, we demonstrate the capability of effectively integrating data from multiple sites in a decentralized data setting while accounting for between-site heterogeneity. Importantly, our study reveals several crucial clinical risk factors for PCD that merit further investigations.

Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation.

BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.

Associations between neighborhood characteristics and child well-being before and during the COVID-19 pandemic: A repeated cross-sectional study in the Environmental influences on Child Health Outcomes (ECHO) program.

The corona virus disease (COVID-19) pandemic disrupted daily life worldwide, and its impact on child well-being remains a major concern. Neighborhood characteristics affect child well-being, but how these associations were affected by the pandemic is not well understood. We analyzed data from 1039 children enrolled in the Environmental influences on Child Health Outcomes Program whose well-being was assessed using the Patient-Reported Outcomes Measurement Information System Global Health questionnaire and linked these data to American Community Survey (ACS) data to evaluate the impacts of neighborhood characteristics on child well-being before and during the pandemic. We estimated the associations between more than 400 ACS variables and child well-being t-scores stratified by race/ethnicity (non-Hispanic white vs. all other races and ethnicities) and the timing of outcome data assessment (pre-vs. during the pandemic). Network graphs were used to visualize the associations between ACS variables and child well-being t-scores. The number of ACS variables associated with well-being t-scores decreased during the pandemic period. Comparing non-Hispanic white with other racial/ethnic groups during the pandemic, different ACS variables were associated with child well-being. Multiple ACS variables representing census tract-level housing conditions and neighborhood racial composition were associated with lower well-being t-scores among non-Hispanic white children during the pandemic, while higher percentage of Hispanic residents and higher percentage of adults working as essential workers in census tracts were associated with lower well-being t-scores among non-white children during the same study period. Our study provides insights into the associations between neighborhood characteristics and child well-being, and how the COVID-19 pandemic affected this relationship.

The Caregiver Burden of Helmet Therapy following Endoscopic Strip Craniectomy: A Phenomenological Qualitative Study.

INTRODUCTION: This cohort study aimed to elucidate the caregiver burden of helmet therapy (HT), following endoscopic strip craniectomy (ESC) to treat craniosynostosis, in an effort to inform clinicians and future caregivers navigating this therapeutic option. METHODS: Fourteen caregivers of children with positional plagiocephaly (6) and craniosynostosis treated by ESC (8) undergoing HT at a single center were recruited via convenience sampling. Using a phenomenological qualitative approach, semi-structured interviews were conducted to understand the experience of HT for caregivers. Data collection and analysis were iterative and conducted until thematic saturation was reached. RESULTS: Emerging themes revealed five domains of caregiver burden: emotional, cognitive, physical, psychosocial, and financial. No caregiver felt the therapy was too burdensome to complete. Caregivers of both groups also expressed positive aspects of HT related to support from the team, the noninvasive nature of treatment, and the outcomes of therapy. Furthermore, caregivers report overall satisfaction with the process, stating willingness to repeat the treatment with subsequent children if required. CONCLUSION: HT is associated with five major domains of caregiver burden; however, none of the caregivers regret choosing this treatment option, nor was the burden high enough to encourage treatment cessation. This study will inform future prospective analyses that will quantify real-time caregiver burden throughout HT.

Do respiratory virus infections modify associations of asthma exacerbation with aeroallergens or fine particulate matter? A time series study in Philadelphia PA.

Respiratory virus infections are related to over 80% of childhood asthma exacerbations. They enhance pro-inflammatory mediator release, especially for sensitized individuals exposed to pollens/molds. Using a time-series study design, we investigated possible effect modification by respiratory virus infections of the associations between aeroallergens/PM2.5 and asthma exacerbation rates. Outpatient, emergency department (ED), and inpatient visits for asthma exacerbation among children with asthma (28,540/24,444 [warm/cold season]), as well as viral infection counts were obtained from electronic health records of the Children's Hospital of Philadelphia from 2011 to 2016. Rate ratios (RRs, 90th percentile vs. 0) for late-season grass pollen were 1.00 (0.85-1.17), 1.04 (0.95-1.15), and 1.12 (0.96-1.32), respectively, for respiratory syncytial virus (RSV) counts within each tertile. However, similar trends were not observed for weed pollens/molds or PM2.5. Overall, our study provides little evidence supporting effect modification by respiratory viral infections.

Ureteral Stent Placement Prior to Definitive Stone Treatment Is Associated With Higher Postoperative Emergency Department Visits and Opioid Prescriptions for Youth Having Ureteroscopy or Shock Wave Lithotripsy.

PURPOSE: Little is known about the impact of ureteral stents on youth having stone surgery. We evaluated the association of ureteral stent placement before or concurrent with ureteroscopy and shock wave lithotripsy with emergency department visits and opioid prescriptions among pediatric patients. MATERIALS AND METHODS: We conducted a retrospective cohort study of individuals aged 0-24 years who underwent ureteroscopy or shock wave lithotripsy from 2009-2021 at 6 hospitals in PEDSnet, a research network that aggregates electronic health record data from children's health systems in the United States. The exposure, primary ureteral stent placement, was defined as a stent placed concurrent with or within 60 days before ureteroscopy or shock wave lithotripsy. Associations between primary stent placement and stone-related ED visits and opioid prescriptions within 120 days of the index procedure were evaluated with mixed-effects Poisson regression. RESULTS: Two-thousand ninety-three patients (60% female; median age 15 years, IQR 11-17) had 2,477 surgical episodes; 2,144 were ureteroscopy and 333 were shock wave lithotripsy. Primary stents were placed in 1,698 (79%) ureteroscopy episodes and 33 (10%) shock wave lithotripsy episodes. Ureteral stents were associated with a 33% higher rate of emergency department visits (IRR 1.33; 95% CI 1.02-1.73) and a 30% higher rate of opioid prescriptions (IRR 1.30; 95% CI 1.10-1.53). The magnitudes of both associations were greater for shock wave lithotripsy. Results were similar for age <18 and were lost when restricted to concurrent stent placement. CONCLUSIONS: Primary ureteral stent placement was associated with more frequent emergency department visits and opioid prescriptions, driven by pre-stenting. These results support elucidating situations where stents are not necessary for youth with nephrolithiasis.

Leveraging Serologic Testing to Identify Children at Risk For Post-Acute Sequelae of SARS-CoV-2 Infection: An Electronic Health Record-Based Cohort Study from the RECOVER Program.

Using an electronic health record-based algorithm, we identified children with Coronavirus disease 2019 (COVID-19) based exclusively on serologic testing between March 2020 and April 2022. Compared with the 131 537 polymerase chain reaction-positive children, the 2714 serology-positive children were more likely to be inpatients (24% vs 2%), to have a chronic condition (37% vs 24%), and to have a diagnosis of multisystem inflammatory syndrome in children (23% vs <1%). Identification of children who could have been asymptomatic or paucisymptomatic and not tested is critical to define the burden of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection in children.

Patient-Reported Outcomes Over 24 Months in Pediatric CKD: Findings From the MyKidneyHealth Cohort Study.

RATIONALE & OBJECTIVE: The lived experience of children with chronic kidney disease (CKD) is poorly characterized. We examined the associations between patient-reported outcome (PRO) scores measuring their fatigue, sleep health, psychological distress, family relationships, and global health with clinical outcomes over time in children, adolescents, and younger adults with CKD and investigated how the PRO scores of this group compare with those of other children, adolescents, and younger adults. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 212 children, adolescentss, and adults aged 8 to 21 years with CKD and their parents recruited from 16 nephrology programs across North America. PREDICTORS: CKD stage, disease etiology, and sociodemographic and clinical variables. OUTCOME: PRO scores over 2 years. ANALYTICAL APPROACH: We compared PRO scores in the CKD sample with a nationally representative general pediatric population (ages 8 to 17 years). Change of PROs over time and association of sociodemographic and clinical variables with PROs were assessed using multivariable regression models. RESULTS: For all time points, 84% of the parents and 77% of the children, adolescents, and younger adults completed PRO surveys . The baseline PRO scores for the participants with CKD revealed a higher burden of fatigue, sleep-related impairment, psychological distress, impaired global health, and poorer family relationships compared with the general pediatric population, with median score differences≥1 SD for fatigue and global health. The baseline PRO scores did not differ by CKD stage or glomerular versus nonglomerular etiology. Over 2 years, PROs were stable with a<1-point annual change on average on each measure and intraclass correlation coefficients ranging from 0.53 to 0.79, indicating high stability. Hospitalization and parent-reported sleep problems were associated with worse fatigue, psychological health, and global health scores (all P<0.04). LIMITATIONS: We were unable to assess responsiveness to change with dialysis or transplant. CONCLUSIONS: Children with CKD experience a high yet stable burden of impairment across numerous PRO measures, especially fatigue and global health, independent of disease severity. These findings underscore the importance of assessing PROs, including fatigue and sleep measures, in this vulnerable population. PLAIN-LANGUAGE SUMMARY: Children with chronic kidney disease (CKD) have many treatment demands and experience many systemic effects. How CKD impacts the daily life of a child is poorly understood. We surveyed 212 children, adolescents, and younger adults with CKD and their parents over 24 months to assess the participants' well-being over time. Among children, adolescents, and younger adults with CKD we found a very high and persistent burden of psychological distress that did not differ by degree of CKD or type of kidney disease. The participants with CKD endorsed greater impairment in fatigue and global health compared with healthy children, adolescents, and younger adults, and parent-reported sleep problems were associated with poorer patient-reported outcome (PRO) scores across all domains. These findings emphasize the importance of including PRO measures, including fatigue and sleep measures, into routine clinical care to optimize the lived experience of children with CKD.

Patterns of Morbidity Across the Lifespan: A Population Segmentation Framework for Classifying Health Care Needs for All Ages.

BACKGROUND: Classification systems to segment such patients into subgroups for purposes of care management and population analytics should balance administrative simplicity with clinical meaning and measurement precision. OBJECTIVE: To describe and empirically apply a new clinically relevant population segmentation framework applicable to all payers and all ages across the lifespan. RESEARCH DESIGN AND SUBJECTS: Cross-sectional analyses using insurance claims database for 3.31 Million commercially insured and 1.05 Million Medicaid enrollees under 65 years old; and 5.27 Million Medicare fee-for-service beneficiaries aged 65 and older. MEASURES: The "Patient Need Groups" (PNGs) framework, we developed, classifies each person within the entire 0-100+ aged population into one of 11 mutually exclusive need-based categories. For each PNG segment, we documented a range of clinical and resource endpoints, including health care resource use, avoidable emergency department visits, hospitalizations, behavioral health conditions, and social need factors. RESULTS: The PNG categories included: (1) nonuser, (2) low-need child, (3) low-need adult, (4) low-complexity multimorbidity, (5) medium-complexity multimorbidity, (6) low-complexity pregnancy, (7) high-complexity pregnancy, (8) dominant psychiatric/behavioral condition, (9) dominant major chronic condition, (10) high-complexity multimorbidity, and (11) frailty. Each PNG evidenced a characteristic age-related trajectory across the full lifespan. In addition to offering clinically cogent groupings, large percentages (29%-62%) of patients in two pregnancy and high-complexity multimorbidity and frailty PNGs were in a high-risk subgroup (upper 10%) of potential future health care utilization. CONCLUSIONS: The PNG population segmentation approach represents a comprehensive measurement framework that captures and categorizes available electronic health care data to characterize individuals of all ages based on their needs.

Safety of intravenous lacosamide in hospitalized children and neonates.

OBJECTIVE: Seizures are common in critically ill children and neonates, and these patients would benefit from intravenous (IV) antiseizure medications with few adverse effects. We aimed to assess the safety profile of IV lacosamide (LCM) among children and neonates. METHODS: This retrospective multicenter cohort study examined the safety of IV LCM use in 686 children and 28 neonates who received care between January 2009 and February 2020. RESULTS: Adverse events (AEs) were attributed to LCM in only 1.5% (10 of 686) of children, including rash (n = 3, .4%), somnolence (n = 2, .3%), and bradycardia, prolonged QT interval, pancreatitis, vomiting, and nystagmus (n = 1, .1% each). There were no AEs attributed to LCM in the neonates. Across all 714 pediatric patients, treatment-emergent AEs occurring in >1% of patients included rash, bradycardia, somnolence, tachycardia, vomiting, feeling agitated, cardiac arrest, tachyarrhythmia, low blood pressure, hypertension, decreased appetite, diarrhea, delirium, and gait disturbance. There were no reports of PR interval prolongation or severe cutaneous adverse reactions. When comparing children who received a recommended versus a higher than recommended initial dose of IV LCM, there was a twofold increase in the risk of rash in the higher dose cohort (adjusted incidence rate ratio = 2.11, 95% confidence interval = 1.02-4.38). SIGNIFICANCE: This large observational study provides novel evidence demonstrating the tolerability of IV LCM in children and neonates.

Patient-reported outcomes for measuring sleep disturbance in pediatric atopic dermatitis: Cross-sectional study of the Patient Reported Outcomes Measurement Information System pediatric sleep measures and actigraphy.

BACKGROUND: Most children with atopic dermatitis (AD) experience sleep disturbance, but reliable and valid assessment tools are lacking. OBJECTIVES: To test the Patient-Reported Outcomes Measurement Information System (PROMIS) sleep measures in pediatric AD and to develop an algorithm to screen, assess, and intervene to reduce sleep disturbance. METHODS: A cross-sectional study was conducted with children with AD ages 5 to 17 years and 1 parent (n = 61), who completed sleep, itch, and AD-specific questionnaires; clinicians assessed disease severity. All children wore actigraphy watches for a 1-week objective sleep assessment. RESULTS: PROMIS sleep disturbance parent proxy reliability was high (Cronbach α = 0.90) and was differentiated among Patient-Oriented Eczema Measure (POEM)-determined disease severity groups (mean ± standard deviation in mild vs moderate vs severe was 55.7 ± 7.5 vs 59.8 ± 10.8 vs 67.1 ± 9.5; P < .01). Sleep disturbance correlated with itch (numeric rating scale, r = 0.48), PROMIS sleep-related impairment (r = 0.57), and worsened quality of life (Children's Dermatology Life Quality Index, r = 0.58), with all P values less than .01. Positive report on the POEM sleep disturbance question has high sensitivity (95%) for PROMIS parent proxy-reported sleep disturbance (T-score ≥ 60). An algorithm for screening and intervening on sleep disturbance was proposed. LIMITATIONS: This was a local sample. CONCLUSIONS: Sleep disturbance in pediatric AD should be screened using the POEM sleep question, with further assessment using the PROMIS sleep disturbance measure or objective sleep monitoring if needed.

Clinical course and management of children with IgA vasculitis with nephritis.

BACKGROUND: IgA vasculitis is the most common vasculitis in children and is often complicated by acute nephritis (IgAVN). Risk of chronic kidney disease (CKD) among children with IgAVN remains unknown. This study aimed to describe the clinical management and kidney outcomes in a large cohort of children with IgAVN. METHODS: This observational cohort study used the PEDSnet database to identify children diagnosed with IgAV between January 1, 2009, and February 29, 2020. Demographic and clinical characteristics were compared among children with and without kidney involvement. For children followed by nephrology, clinical course, and management patterns were described. Patients were divided into four categories based on treatment: observation, renin-angiotensin-aldosterone system (RAAS) blockade, corticosteroids, and other immunosuppression, and outcomes were compared among these groups. RESULTS: A total of 6802 children had a diagnosis of IgAV, of whom 1139 (16.7%) were followed by nephrology for at least 2 visits over a median follow-up period of 1.7 years [0.4,4.2]. Conservative management was the most predominant practice pattern, consisting of observation in 57% and RAAS blockade in 6%. Steroid monotherapy was used in 29% and other immunosuppression regimens in 8%. Children receiving immunosuppression had higher rates of proteinuria and hypertension compared to those managed with observation (p < 0.001). At the end of follow-up, 2.6 and 0.5% developed CKD and kidney failure, respectively. CONCLUSIONS: Kidney outcomes over a limited follow-up period were favorable in a large cohort of children with IgAV. Immunosuppressive medications were used in those with more severe presentations and may have contributed to improved outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evaluation of evidence for interaction between PM2.5 and aeroallergens on childhood asthma exacerbation in Philadelphia, PA, 2011 to 2016.

Fine particulate matter (PM2.5) and aeroallergens (i.e., pollen, molds) are known triggers of asthma exacerbation. Despite mechanistic evidence suggesting synergistic effects between PM2.5 and asthma exacerbation, little epidemiologic work has been performed in children, which has exhibited inconsistency. We conducted a time-series study to explore their interactions using electronic health records (EHR) data in Philadelphia, PA, for asthma diagnoses in outpatient, emergency department [ED], and inpatient settings. Daily asthma exacerbation cases (28,540 asthma exacerbation case encounters) were linked to daily ambient PM2.5 and daily aeroallergen levels during the aeroallergen season of a six-year period (mid-March to October 2011-2016). Asthma exacerbation counts were modeled using quasi-Poisson regression, where PM2.5 and aeroallergens were fitted with distributed lag non-linear functions (lagged from 0 to 14-days), respectively, when modeled as the primary exposure variables. Regression models were adjusted for mean daily temperature/relative humidity, long-term and seasonal trends, day-of-week, and major U.S. holidays. Increasing gradient of RR estimates were observed for only a few primary exposure risk factors [PM2.5 (90th vs. 5th percentile)/aeroallergens (90th percentile vs. 0)], across different levels of effect modifiers. For example, RRs for the association between late-season grass pollen (lag1) and asthma exacerbation were higher at higher levels of PM2.5, 5-days preceding the exacerbation event (low PM2.5: RR = 1.01, 95% CI: 0.93-1.09; medium PM2.5: 1.04, 95% CI: 0.96-1.12; high PM2.5: 1.09, 95% CI: 1.01-1.19). However, most of the highest RRs for aeroallergens were instead observed for days with low- or medium- PM2.5 levels; likewise, when PM2.5 was modeled as the primary exposure with aeroallergens as the effect modifier. Most of the RR estimates did not exhibit gradients that suggested synergism, and were of relatively high imprecision. Overall, our study suggested no evidence for interactions between PM2.5 and aeroallergens in their relationships with childhood asthma exacerbation.

The real world experience of pediatric primary hyperoxaluria patients in the PEDSnet clinical research network.

The rarity of primary hyperoxaluria (PH) challenges our understanding of the disease. The purpose of our study was to describe the course of clinical care in a United States cohort of PH pediatric patients, highlighting health service utilization. We performed a retrospective cohort study of PH patients < 18 years old in the PEDSnet clinical research network from 2009 to 2021. Outcomes queried included diagnostic imaging and testing related to known organ involvement of PH, surgical and medical interventions specific to PH-related renal disease, and select PH-related hospital service utilization. Outcomes were evaluated relative to cohort entrance date (CED), defined as date of first PH-related diagnostic code. Thirty-three patients were identified: 23 with PH type 1; 4 with PH type 2; 6 with PH type 3. Median age at CED was 5.0 years (IQR 1.4, 9.3 years) with the majority being non-Hispanic white (73%) males (70%). Median follow-up between CED and most recent encounter was 5.1 years (IQR 1.2, 6.8). Nephrology and Urology were the most common specialties involved in care, with low utilization of other sub-specialties (12%-36%). Most patients (82%) had diagnostic imaging used to evaluate kidney stones; 11 (33%) had studies of extra-renal involvement. Stone surgery was performed in 15 (46%) patients. Four patients (12%) required dialysis, begun in all prior to CED; four patients required renal or renal/liver transplant.    Conclusion: In this large cohort of U.S. PH children, patients required heavy health care utilization with room for improvement in involving multi-disciplinary specialists. What is Known: • Primary hyperoxaluria (PH) is rare with significant implications on patient health. Typical involvement includes the kidneys; however, extra-renal manifestations occur. • Most large population studies describe clinical manifestations and involve registries. What is New: • We report the clinical journey, particularly related to diagnostic studies, interventions, multispecialty involvement, and hospital utilization, of a large cohort of PH pediatric patients in the PEDSnet clinical research network. • There are missed opportunities, particularly in that of specialty care, that could help in the diagnosis, treatment, and even prevention of known clinical manifestations.

Stakeholder outcome prioritization in the Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA) trial.

BACKGROUND: The Biologic Abatement and Capturing Kids' Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA) study is a randomized, pragmatic trial investigating different tumour necrosis factor inhibitor de-escalation strategies for children with sustained inactive disease. In this project, we elicited concept rankings that aided in the selection of the patient-reported outcome (PRO) measures that should be examined as part of the BACK-OFF JSpA trial. METHODS: We conducted a discrete choice experiment to evaluate individuals' preferences regarding PROs. Stakeholders assessed a discrete list of 21 outcome concepts, each of which had a Patient-Reported Outcome Measurement Information System (PROMIS) measure associated with it. PROMIS measures are self- or proxy-reported instruments that are universally applicable to the general population and all chronic conditions. Stakeholders were required to make choices instead of expressing the strength of a preference. RESULTS: Fourteen caregivers, 12 patients (9-22 years old), 16 rheumatologists and three executives from health insurance companies completed the exercise, which took approximately 10 min. The discrete choice experiment resulted in an estimate of the relative importance of each outcome and rank. All stakeholder groups agreed that the primary PRO should be 'Pain Interference', a measure that evaluates the effect of pain on a child's everyday activities, including its impact on social, emotional, mental and physical functioning. Patients and caregivers were mostly aligned in their top priorities, with patients valuing physical health (50% of the top 10) whereas caregivers were more interested in mental health (60% of the top 10). Rheumatologists and health insurance executives were most interested in physical health outcomes, which were ranked 80% and 60% of their top 10 PROs, respectively. Overall, the patients had the most diverse set of prioritized outcomes, including at least one of each category in their top 10 rank order of importance. Patients were also the only stakeholders to prioritize 'social' health. CONCLUSIONS: Patients and caregivers were mostly aligned in their outcome priority rankings. The rank-order list directly informed the creation of a profile of PRO measures for our upcoming trial. PATIENT OR PUBLIC CONTRIBUTION: Stakeholder partners helped with acquisition of data and lead parent partners helped interpret data.

Skeletal Outcomes in Children and Young Adults with Glomerular Disease.

BACKGROUND: Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking. METHODS: This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed >3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours. RESULTS: We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5). CONCLUSIONS: Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

Evaluation of Research Diagnostic Criteria in Craniofacial Microsomia.

Characteristics of patients with craniofacial microsomia (CFM) vary in type and severity. The diagnosis is based on phenotypical assessment and no consensus on standardized clinical diagnostic criteria is available. The use of diagnostic criteria could improve research and communication among patients and healthcare professionals. Two sets of phenotypic criteria for research were independently developed and based on multidisciplinary consensus: the FACIAL and ICHOM criteria. This study aimed to assess the sensitivity of both criteria with an existing global multicenter database of patients with CFM and study the characteristics of patients that do not meet the criteria. A total of 730 patients with CFM from were included. Characteristics of the patients were extracted, and severity was graded using the O.M.E.N.S. and Pruzansky-Kaban classification. The sensitivity of the FACIAL and ICHOM was respectively 99.6% and 94.4%. The Cohen's kappa of 0.38 indicated a fair agreement between both criteria. Patients that did not fulfill the FACIAL criteria had facial asymmetry without additional features. It can be concluded that the FACIAL and ICHOM criteria are accurate criteria to describe patients with CFM. Both criteria could be useful for future studies on CFM to create comparable and reproducible outcomes.