Nationwide Children's Hospital Research Articles

The changing profile of infective endocarditis: A multi-year retrospective study for dentists.

Infective endocarditis (IE) has high morbidity and mortality and is often attributed to dental procedures. This study characterized variables related to paediatric IE in a paediatric hospital cohort. A retrospective review of medical records, from January 1, 2008, to January 1, 2020, to examine demographic, medical and dental history, and risk factors associated with children diagnosed with IE at Nationwide Children's Hospital. Of the 242 patients who were admitted with tentative IE diagnoses, 67 met the inclusion criteria: 46 (69%) had underlying cardiac conditions and 21 (31%) had not. One-third had an infection with S. aureus and viridans streptococci. Age was significantly associated with intracardiac devices in children with IE. Mean hospitalization was 25 days, and the mortality was 6 (9%); 41(61%) required surgery for causative defects, and 24 (32%) had dental consultation during admission. Although cardiac-related conditions were present in most cases, IE occurred in patients without cardiac factors.

Toxin-neutralizing Abs are associated with improved T cell function following recovery from Staphylococcus aureus infection.

BACKGROUNDT cell responses are impaired in Staphylococcus aureus-infected children, highlighting a potential mechanism of immune evasion. This study tested the hypotheses that toxin-specific antibodies protect immune cells from bacterial killing and are associated with improved T cell function following infection.METHODSS. aureus-infected and healthy children (N = 33 each) were prospectively enrolled. During acute infection and convalescence, we quantified toxin-specific IgG levels by ELISA, antibody function using a cell killing assay, and functional T cell responses by ELISPOT.RESULTSThere were no differences in toxin-specific IgG levels or ability to neutralize toxin-mediated immune cell killing between healthy and acutely infected children, but antibody levels and function increased following infection. Similarly, T cell function, which was impaired during acute infection, improved following infection. However, the response to infection was highly variable; up to half of children did not have improved antibody or T cell function. Serum from children with higher α-hemolysin-specific IgG levels more strongly protected immune cells against toxin-mediated killing. Importantly, children whose serum more strongly protected against toxin-mediated killing also had stronger immune responses to infection, characterized by more elicited antibodies and greater improvement in T cell function following infection.CONCLUSIONThis study demonstrates that, despite T cell impairment during acute infection, S. aureus elicits toxin-neutralizing antibodies. Individual antibody responses and T cell recovery are variable. These findings also suggest that toxin-neutralizing antibodies protect antigen-presenting cells and T cells, thereby promoting immune recovery. Finally, failure to elicit toxin-neutralizing antibodies may identify children at risk for prolonged T cell suppression.FUNDINGNIH National Institute of Allergy and Infectious Diseases R01AI125489 and Nationwide Children's Hospital.

Assessment of ISTH-BAT Scores in a Primary Care Clinic Population of Menstruating Adolescents

Background Accurate assessment of bleeding severity is critical for timely diagnosis and appropriate management of inherited bleeding disorders. To achieve standardized and reliable evaluation, the International Society on Thrombosis and Haemostasis (ISTH) developed the Bleeding Assessment Tool (BAT). The ISTH-BAT is a comprehensive questionnaire designed to systematically evaluate bleeding symptoms in both children and adults. A crucial aspect of utilizing the ISTH-BAT in clinical practice is determining the normal range of bleeding scores in the general population. Defining this baseline aids in distinguishing abnormal bleeding tendencies from variations within the healthy population. The ISTH-BAT Merging Project established a normal range of BAT scores for children age <18 years as 0-2 and for adult females age ≥18 years as 0-5. However, the normal range of BAT scores for adolescent females remains undetermined. This population is unique because they have undergone the bleeding challenge of menarche but are less likely to have experienced childbirth or multiple surgeries. Furthermore, while prior studies have shown age-related increases in BAT scores in individuals with von Willebrand Disease, there are limited data on the effect of aging on BAT scores in a healthy adolescent population. This study aims to determine the range of BAT scores in a diverse menstruating adolescent population, compare bleeding scores to published reference ranges from the ISTH-BAT Merging Project and assess potential age-related variations in BAT scores. Methods In an ongoing large population study, 10-20 year-old menstruating adolescents presenting for routine care are recruited from primary care clinics across Nationwide Children's Hospital (Columbus, OH, USA). Patients with a prior diagnosis of a bleeding disorder are excluded. The ISTH-BAT is administered by trained study personnel. Data analyses were completed using nonparametric methods such as Wilcoxon signed-rank or rank sum tests and Spearman's correlation. Means and 95% confidence intervals (CI) were calculated and compared to historical estimates. Results In a preliminary analysis of the first 150 participants, the median age was 15 years (IQR: 13-18). Participants represented a diverse range of backgrounds, with 69% of participants identifying as Black/African American, 19% as White, and 12% as other races. 94% identified as non-Hispanic, while 6% identified as Hispanic/Latino. The mean BAT score was 1.06 (95% CI: 0.87-1.25), with scores ranging from 0-5. The data exhibited a non-normal distribution, with most scores concentrated at 0 or 1, accounting for 72% of the dataset. The mean BAT score is significantly higher than the ISTH-BAT Merging Project pediatric mean score of 0.34 (p<0.0001), but not significantly different from the adult female mean of 1.28 (p=0.99). When analyzed by age group, participants aged 10-17 years had a mean BAT score of 0.96, significantly higher than the published pediatric mean (p<0.0001) but similar to the published adult mean (p=0.99). Similarly, participants aged 18-20 years had a mean BAT score of 1.33. To assess if BAT score increased with age, we compared participants aged 10-14 years to adolescents 15-20 years, and identified a small, but significant increase in mean BAT score with age (p=0.001). Participants aged 10-14 years had a mean score of 0.69 (95% CI: 0.45-0.94), falling between the published pediatric and adult means, with no significant difference from either one (p=0.003 and p=0.99, respectively) (Figure 1). However, participants aged 15-20 had a mean BAT score of 1.30 (95% CI: 1.03-1.56), which remained significantly higher than the published pediatric mean (p<0.0001) but still showed no significant difference from the published adult mean (p=0.81). There was a weak, but statistically significant positive correlation between age and bleeding score, indicating that as age increases, bleeding scores tend to rise (Spearman's correlation r s= 0.21, p=0.001) (Figure 2). Similarly, a weak positive relationship exists between years post-menarche and bleeding score (r s=0.23, p=0.005). Conclusion This study provides insight on ISTH-BAT scores in a population of healthy menstruating adolescent females, suggesting that after the onset of menstruation, the adult female bleeding score range may be more suitable for adolescents than the pediatric range.

Differences in Observed Toxicities for Adolescent and Young Adult Patients with Aggressive Mature B-Cell Lymphomas Treated at Adult Versus Pediatric Cancer Center - a Comparative Cohort Study

Introduction: Standard treatment regimens for pediatric and adult patients with mature B-cell lymphomas vary significantly. For adolescent or young adult (AYA) patients, who may be candidates for either pediatric or adult regimens, limited data are available regarding comparative toxicities and efficacy for adult versus pediatric therapies. Methods: A retrospective review was completed for individuals aged 12-39 years at diagnosis with aggressive mature B-cell lymphomas seen between 2011 to 2023 at Ohio State University Comprehensive Care Center (adult cohort) and Nationwide Children's Hospital (pediatric cohort). Diagnoses included diffuse large B cell lymphoma (DLBCL), double hit lymphoma (DHL), Burkitt lymphoma (BL), primary mediastinal B cell lymphoma (PMBCL), grey zone lymphoma (GZL), and unclassifiable high-grade B cell lymphoma (HGBCL). Progression free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by log-rank test. Differences between adult and pediatric cohort were compared using Fisher's exact test and Chi-squared test. Cox regression model was used to identify prognostic factors for PFS. Results: Among 180 eligible AYA patients, 156 were treated at the adult center and 24 at the pediatric center. The median age was 30 years (median 15 pediatric [range 12-18] and 31 adult [range 21-39; p<0.001]). Other characteristics included male sex in 75% of pediatric vs 65% adult patients (p=0.3), stage 4 disease in 25% vs 47%(p<0.001), CNS involvement in 8.3% vs 5.4% (p=0.6), and LDH >2x upper limit of normal in 21% vs 31% (p=0.2). The overall median follow-up was 4.8 years (4.5 vs 4.8, p=0.7). Adult center histology included DLBCL (95); DHL (9); BL (8); PMBCL (31); GZL (4); and HGBCL (9). Pediatric diagnoses were DLBCL (13); BL (8); PMBCL (2); and HGBCL (1). The most common treatments included R-CHOP (57), R-EPOCH (56), RM-CHOP (20), and R-CODOX-M/R-IVAC (16) at the adult center and CCG5961 (7), ANHL1131 (15), and ANHL0221 (1) protocols at the pediatric center. CCG5961 Group B protocol includes pre-phase, induction, and consolidation phases of COP, COPADM, and CYM. Group C includes the same pre-phase and induction, except for higher doses of MTX, with CYVE consolidation with high-dose MTX and randomization to 1 or 4 cycles of maintenance. ANHL1131 protocol was like CCG5961; major differences include randomization to receive rituximab during induction and consolidation and 2 cycles of maintenance for group C patients. ANHL0221, a PTLD protocol, involves 2 cycles of cyclophosphamide, prednisone, and rituximab followed by 4 cycles of cyclophosphamide and prednisone. A greater incidence of unplanned hospitalization (79% pediatric vs 50% adult, p=0.007), grade 3 mucositis (38% vs 12%, p=0.005), febrile neutropenia (67% vs 44%, p=0.035), and fungal infections (25% vs 3%, p<0.001) were observed for the pediatric cohort (Table 1). Patients in the adult cohort were more likely to receive radiation therapy (26% vs 0%, p=0.004) and experience neuropathy at last follow-up (22% v 0%, p=0.009). Among all patients, other adverse events during follow-up included diagnosis of depression/anxiety (93), heart failure (16), impaired renal function (20), and secondary malignancy (6) (Table 1). For the total population, 2-year PFS was 78% (88% pediatric vs 77% adult, p=0.35), and 2-year OS was 93% (96% vs 92%, p=0.31). For patients with DLBCL or DHL, there was a trend towards improved PFS in the pediatric versus adult cohort (p=0.06, Figure 1), and on univariable analysis a trend towards lower risk for progression with receipt of a more intensive regimen compared with R-CHOP/R-MCHOP (hazard ratio 0.46, 95% confidence interval 0.2-1.1, p=0.07). Conclusions: We observed a higher incidence of short-term adverse effects including severe mucositis, febrile neutropenia, and fungal infection, but lower rates of radiation consolidation and ongoing neuropathy in AYA patients with aggressive mature B-cell lymphoma treated with pediatric versus adult regimens. Relatively higher dose intensity (compared to adult treatments), standard use of CNS prophylaxis, and lower dosage of vinca-alkaloids likely account for the greater incidence of short-term adverse effects and lower rates of neuropathy seen in patients treated at pediatric centers. Further study is needed to evaluate differences in efficacy between treatment approaches in AYA patients with DLBCL/DHL.

ALTERED PROFILES OF EXTRACELLULAR MITOCHONDRIAL DNA IN IMMUNOPARALYZED PEDIATRIC PATIENTS AFTER THERMAL INJURY.

Background: Thermal injury is a major cause of morbidity and mortality in the pediatric population worldwide with secondary infection being the most common acute complication. Suppression of innate and adaptive immune function is predictive of infection in pediatric burn patients, but little is known about the mechanisms causing these effects. Circulating mitochondrial DNA (mtDNA), which induces a proinflammatory signal, has been described in multiple disease states but has not been studied in pediatric burn injuries. This study examined the quantity of circulating mtDNA and mtDNA mutations in immunocompetent (IC) and immunoparalyzed (IP) pediatric burn patients. Methods: Circulating DNA was isolated from plasma of pediatric burn patients treated at Nationwide Children's Hospital Burn Center at early (1-3 days) and late (4-7 days) time points postinjury. These patients were categorized as IP or IC based on previously established immune function testing and secondary infection. Three mitochondrial genes, D loop, ND1, and ND4, were quantified by multiplexed qPCR to assess both mtDNA quantity and mutation load. Results: At the early time point, there were no differences in plasma mtDNA quantity; however, IC patients had a progressive increase in mtDNA over time when compared with IP patients (change in ND1 copy number over time 3,880 vs. 87 copies/day, P = 0.0004). Conversely, the IP group had an increase in mtDNA mutation burden over time. Conclusion: IC patients experienced a significant increase in circulating mtDNA quantity over time, demonstrating an association between increased mtDNA release and proinflammatory phenotype in the burn patients. IP patients had significant increases in mtDNA mutation load likely representative of degree of oxidative damage. Together, these data provide further insight into the inflammatory and immunological mechanisms after pediatric thermal injury.

Mobile Application Measurement of Menstrual Cycle Characteristics and Their Association with Dysmenorrhea and Activity Limitation in Early Adolescents

Presentation: The study was accepted for an oral presentation at the Hemostasis and Thrombosis Research Society Scientific Symposium, Orlando, FL, 11th March, 2023. Authorship: N.S.B. participated in data collection, analysis and interpretation and wrote the manuscript. S.K.V. assisted in study design, analyzed the data and critically reviewed the manuscript. A.E.B assisted in study design and critically reviewed the manuscript. J.C.C and C.B assisted in data collection and critically reviewed the manuscript. E.S. and K.M. critically reviewed the manuscript. S.H.O. conceptualized and designed the study, interpreted data and assisted in writing the manuscript. Study Site: Nationwide Children's Hospital, Columbus, Ohio, United States.

Multidisciplinary Care for Pediatric Patients With Psychogenic Nonepileptic Seizures May Be Associated With Decreased Health Care Utilization.

Psychogenic nonepileptic seizures (PNES) are paroxysmal events that resemble epileptic seizures but have psychological underpinnings. Patients with PNES have high health care utilization. We hypothesize that appropriate care would lead to decreases in utilization. The aim of this study was to measure the impact of a multidisciplinary PNES clinic in reducing health care utilization (HCU) in youth with PNES referred to the clinic. We reviewed the frequency of visits to the emergency department (ED), urgent care (UC), planned and unplanned hospitalizations, neurodiagnostic studies, and total charges associated with these encounters 12 months before and 12 months after initial referral to the clinic. Manual chart review of all patients referred from November 2017 to March 2020 was performed. Two hundred and twelve unique patients were included in this retrospective study. Patient sex was identified as 71% female, 28% male, and 1% other, with an average age of 14 years at diagnosis. These patients visited the ED a total of 410 times before being seen in the PNES clinic, which decreased to 187 visits after (75% reduction). All measures of HCU decreased in the 12 months after the visit, and statistically significant differences were observed in all measures of HCU except for head MRIs, leading to an estimated potential cost savings of $7,978,447. Patients with PNES were found to have decreased health care utilization in the 12 months after referral to the Nationwide Children's Hospital multidisciplinary clinic, including significant decreases in emergency services and unnecessary diagnostic testing, in the 12 months after the referral.

Quality Tool School: Improving the Delivery of Quality Improvement Education in a Children's Hospital.

In 2013, Nationwide Children's Hospital's (NCH) Quality Tool School (QTS) was created as an initial Quality Improvement educational series, composed of three separate classes, totaling 5.5 hours of hands-on QI training. QTS complemented the NCH 40-hour Quality Improvement Essentials course. Over 10 years, the series went through three phases of aims: Phase 1: develop and implement three core courses (Project Tools, Excel, and Control Charts); Phase 2: have participants complete the entire series of all three classes; Phase 3: have participants who complete the entire series of all three classes demonstrate the application of learning through involvement in a quality improvement project. Since initiation, QTS has provided an educational entry point for 1428 NCH employees to participate in QI projects and teams. QTS has shown statistically significant improvement in 2 of the 3 principal aims. The Phase 1 metric of average monthly one-class participation completion percentage showed a statistically significant centerline shift from 9 to 16 students in October 2018. The Phase 3 metric Percentage of QTS participants completing the QTS series of classes and then participating in a QI team began in 2016 with a baseline of 42%. A centerline shift from 42% to 63% occurred in Q4 2018. QTS can provide QI education to healthcare system employees using limited resources. Organizations that strategically integrate a culture of QI into core beliefs can realize substantial improvement gains.

The Risk of Developmental Dysplasia of the Hip in Premature Infants with Breech Presentation at Birth.

This article evaluates the risk (defined here as incidence per 1,000 infants) of developmental dysplasia of the hip (DDH) in premature infants undergoing hip ultrasound (HUS) for breech presentation only compared with other indications. Retrospective study of infants born between January 1, 2009 and December 31, 2018 at <37 weeks' gestation with a HUS obtained in the first year of life, at Nationwide Children's Hospital, the only available facility for pediatric radiology and orthopaedic services in central Ohio. We calculated risk differences and odds ratios of DDH by the indication of HUS. From 2,397 infants reviewed, 89% underwent HUS for breech presentation only. The local incidence of DDH for infants undergoing HUS for breech-only indication was 15 per 1,000 compared with 155 per 1,000 for infants undergoing HUS for other indications. The odds ratio of DDH diagnosis was 12.1 (95% confidence interval: 7.5, 19.6) for infants undergoing HUS for an indication other than breech presentation only relative to infants undergoing HUS for the indication of breech presentation only. The risk of DDH diagnosis in premature infants undergoing HUS for breech presentation is much lower than those undergoing HUS for clinical concerns and other risk factors. Screening these infants with physical examination may be sufficient. · Breech presentation is the most common indication for hip ultrasound in premature infants.. · The risk of DDH is lower in premature infants with breech presentation compared with premature infants with other clinical concerns.. · The risk of DDH is higher in infants born at 33 to 36 weeks of gestation compared with those born at an earlier gestation..

Efficacy of an expanded preoperative survey during perioperative care to identify illicit substance use in teenagers and adolescents.

As illicit substance use can present several perioperative concerns, effective means to identify such practices are necessary to ensure patient safety. Identification of illicit substance use in pediatric patients may be problematic as screening may rely on parental reporting. The current study compares answers regarding use of illicit substances between a survey completed by the patient and the preoperative survey completed by parents or guardians. The study included patients presenting for surgery at Nationwide Children's Hospital, ranging in age from 12 to 21 years. After consent, patients completed a survey of six drop-down questions using an iPad. The six questions involved the patient's history of alcohol, tobacco, marijuana, vaping, and opioid use. The results were compared to the answers obtained from the parents during a preoperative phone call. The study cohort included surveys from 250 patients with a median age of 16 years. Survey data showed a statistically higher reporting of substance use or abuse from the patient study survey in comparison to the routine parental preoperative survey. Alcohol report rates were highest with 69 (27.6%) patients reporting use compared to only 5 parental reports (2%). There was a similar discrepancy in reported rates of vaping use (40 patient reports, 16.0% vs. 11 parental reports, 4.4%) and illicit substance use including marijuana (52 patient reports, 20.8% vs. 11 parental reports, 4.4%). Reported rates of tobacco use were lowest among the survey responses with 12 patient reports (4.8%) and 5 parental reports (2.0%). Identifying illicit substance and tobacco use via a phone survey of parents is inaccurate and does not allow for proper identification of use of these substances in patients ≤21 years of age presenting for surgery. An anonymous 2-min survey completed by the patient more correctly identifies these issues.

Automated prediction of cardiorespiratory deterioration in patients with single-ventricle parallel circulation: A multicenter validation study

ObjectivesPatients with single-ventricle physiology have a significant risk of cardiorespiratory deterioration between their first- and second-stage palliation surgeries. Detection of deterioration episodes may allow for early intervention and improved outcomes. MethodsA prospective study was executed at Nationwide Children's Hospital, Children's Hospital of Philadelphia, and Children's Hospital Colorado to collect physiologic data of subjects with single ventricle physiology during all hospitalizations between neonatal palliation and II surgeries using the Sickbay software platform (Medical Informatics Corp). Timing of cardiorespiratory deterioration events was captured via chart review. The predictive algorithm previously developed and validated at Texas Children's Hospital was applied to these data without retraining. Standard metrics such as receiver operating curve area, positive and negative likelihood ratio, and alert rates were calculated to establish clinical performance of the predictive algorithm. ResultsOur cohort consisted of 58 subjects admitted to the cardiac intensive care unit and stepdown units of participating centers over 14 months. Approximately 28,991 hours of high-resolution physiologic waveform and vital sign data were collected using the Sickbay. A total of 30 cardiorespiratory deterioration events were observed. the risk index metric generated by our algorithm was found to be both sensitive and specific for detecting impending events one to two hours in advance of overt extremis (receiver operating curve = 0.927). ConclusionsOur algorithm can provide a 1- to 2-hour advanced warning for 53.6% of all cardiorespiratory deterioration events in children with single ventricle physiology during their initial postop course as well as interstage hospitalizations after stage I palliation with only 2.5 alarms being generated per patient per day.

1153-P: Postprandial Increase in Inflammation Is Not Affected by Glycemic Index in Children and Adolescent with Type 1 Diabetes

Patients with type 1 diabetes (T1D) have lower life expectancy than individuals without diabetes. Most of this reduction is due to cardiovascular disease, the major cause of death in patients with T1D. Post-prandial inflammation after high glycemic index (GI) meals may cause cardiovascular disease in adults. Differences in postprandial inflammatory responses between high and low GI foods have not been studied in children and adolescents with T1D. Twelve non-obese children and adolescents, 10-18 years old, with type 1 diabetes were recruited from the Diabetes Clinic of Nationwide Children's Hospital. A randomized cross-over design for their two subsequent visits was used. Baseline blood sample were taken (plasma glucose, triglyceride, IL-6, CRP, and TNF-α), rapid acting insulin was given to cover meal carbohydrate without glucose correction, and blood samples were repeated (30, 60, 90, and 120 minutes) after an overnight fast. Visits 1 and 2 were identical except for the GI of the given meal. Visits were rescheduled if the fasting glucose was greater than 200 mg/dl. Glucose response were significantly greater following high GI meal (Δglucose: high 52±12 vs low 6±5 mg/dl, mean±SE, repeated measures ANOVA, p&amp;lt;0.001), as expected. TNF-α (High 0 min: 0.86±0.08, 30 min: 1.83±0.08; Low 0 min: 0.82±0.06, 30 min 1.81±0.06 ng/ml) and IL-6 (High 0 min: 0.38±0.06, 120 min: 0.68±0.25; Low 0 min: 0.49±0.11, 120 min 0.71±0.14 ng/ml) increased following both high and low GI meals (p &amp;lt;0.001 and p=0.008, respectively), but there were no statistically significant differences between the two groups. CRP did not increase with either type of meal. Children and adolescent with T1D have post prandial inflammation, as indicated by increased TNFα and IL-6 levels. The post-prandial inflammation is not different between high and low GI meals in spite of higher glucose levels with the former. Disclosure C.P.Damilano: None. R.P.Hoffman: None. Funding Abigail Wexner Research Institute; University of Ohio

Feasibility and Acceptability of Biofeedback-Based Virtual Reality System Use in Children and Adolescents Undergoing Surgery: Phase 1 of a Pilot Observational Study.

Biofeedback-based virtual reality (VR-BF) is a novel, nonpharmacologic method for teaching patients how to control their breathing, which in turn increases heart rate variability (HRV) and may reduce pain. Unlike traditional forms of biofeedback (BF), VR-BF is delivered through a gamified virtual reality environment, increasing the accessibility of BF. This is the first study to systematically integrate VR-BF use in the pediatric perioperative setting, with the ultimate goal of evaluating the efficacy of VR-BF to reduce pain, anxiety, and opioid consumption once feasibility and acceptability has been established. The primary objective was to develop a clinical trial protocol for VR-BF use in the pediatric perioperative setting, including preoperative education/training and postoperative application of VR-BF in children undergoing surgery. A secondary objective was to evaluate the patient/parent experience with VR-BF. A total of 23 patients (12-18 years of age) scheduled for surgery at Nationwide Children's Hospital were recruited using purposive sampling. Following training, participants independently completed a daily, 10-minute VR-BF session for seven days before surgery and during their inpatient stay. Participants could use VR-BF up to two weeks after hospital discharge. Patient and session-level data of VR-BF usage and achievement of target HRV parameters were measured to identify the optimal frequency and duration of sessions before and after surgery for this population. Standardized questionnaires and semi-structured interviews were conducted to obtain qualitative information about patients' experiences with VR-BF. Patient-level data indicated that the highest odds of achieving 1 session under target HRV parameters was after 4 sessions (OR 4 vs. 3 sessions=5.1, 95% CI 1.3-20.6; OR 3 vs. 2 sessions=16.6, 95% CI 1.2-217.0). Session-level data showed that a session duration of 9 to 10 minutes provided the greatest odds of achieving 1 session under target HRV parameters (OR 9 vs. 8 minutes=1.3, 95% CI 1.1-1.7; OR 8 vs. 7 minutes=1.4, 95% CI 1.1-1.8; OR 10 vs. 9 minutes=1.0, 95% CI 0.9-1.2). Qualitative data revealed patient satisfaction with the VR-BF technology, particularly in managing perioperative stress (n=17, 85%). Few patients reported VR-BF as beneficial for pain (n=8, 40%). Children and adolescents undergoing surgery successfully learned behavioral strategies with VR-BF with once-daily 10-minute sessions for 5 days. To integrate VR-BF as a therapeutic intervention in a subsequent clinical trial, patients will be instructed to complete three 10-minute sessions a day for 7 days after surgery. ClinicalTrials.gov; NCT04943874; https://clinicaltrials.gov/ct2/show/NCT04943874.

Schools at the center of a public health emergency: leveraging schools for pediatric COVID-19 vaccination.

The U.S. Food and Drug Administration's expansion of COVID-19 vaccine eligibility in 2021 to include children presented opportunities and challenges to ensure widespread access. Children, and especially adolescents, were a crucial target population to reduce community positivity rates and support a resumption of in-person academics. Though existing school-based vaccination programs have demonstrated success in improving vaccination rates on an individual school level, best practice strategies for employing mass vaccination programs quickly in response to public health emergencies have yet to be identified. Through established partnerships, School Health Services at Nationwide Children's Hospital led a collaborative effort to employ a rapid, onsite school vaccination strategy across Franklin County for all eligible students. This collaboration resulted in a significant increase in vaccine access carried out through on-site vaccination clinics established in 20 local public and private school districts. Key strategies identified through the process included collaboration with school districts, local hospitals, and the public health department; calibrating program size to each site and number of vaccines needed; and coordination of team member roles. At the same time, experience with the effort also underscored key challenges and opportunities that future programs should consider, especially when operating in public health emergencies. School-based community health approaches targeting adolescents can increase vaccination rates, and can be successfully led by children's health systems in concert with public health departments and schools. At the same time, entities undertaking such efforts must plan in advance to ensure that partnerships can be effectively established with clear protocols for efficient and open communication, which is essential for overcoming barriers in access to healthcare services.

Exploration of sleep disturbances in children and adolescents with and without autism in a paediatric sample referred for polysomnography.

The purpose of the study was to increase the body of knowledge related to sleep in children with autism. The specific aims were to (i) identify the subgroup of children with autism, ages 3-17 years, referred for polysomnography and (ii) describe types and frequency of clinical encounters for sleep problems in a sample of children ages 3-17 with and without the diagnosis of autism. The authors performed a secondary data analysis of the de-identified Nationwide Children's Hospital Sleep DataBank, a collection of encounters with children referred for polysomnography. The data were filtered for ages 3-17 years at the time of the participant's first sleep study, and further filtered for the presence of an autism diagnosis. In the sample, there were 2838 unique participants (M = 10.5 years) with a total of 172 167 encounters between 2017 and 2019. Of these, 198 (7%) were diagnosed with Autism Spectrum Disorder, Asperger's Syndrome, or Pervasive Developmental Disorder. Among all participants, the most common sleep problems were apnea, snoring, non-specified sleep disorders (including restless sleeper), circadian rhythm disorder (CRD), and insomnia. The subgroup of patients diagnosed with autism was noted to have higher frequency of several types of sleep problems, especially restless sleep, CRD and insomnia, compared to those without an autism diagnosis. Findings elucidate the increased presence of sleep problems in paediatric patients with autism, and the need for purposeful sleep evaluation and research given the potential impact on daytime function for these individuals and their families.

The Impact of Medication Synchronization on Proportion of Days Covered within the Pediatric Setting.

Poor adherence to medication regimens accounts for the substantial worsening of disease, death, and increased healthcare costs of approximately $100 billion annually in the United States. Patients participating in medication synchronization had 3.4 to 6.1 times increased odds of adherence, depending on the drug class. Abundant literature supports medication synchronization within the adult population. This IRB-exempt, prospective quality improvement project is an example of implementing and assessing medication synchronization inclusive of the pediatric setting. This study is a single-center, prospective, quality improvement project for patients seen at Nationwide Children's Hospital (NCH) Complex Care Clinic that also fill prescriptions at NCH Outpatient Pharmacies. The project assessed patient medication adherence using the Proportion of Days Covered and the number of trips to the pharmacy 90 days before and 90 days postimplementation. We also assessed patient and pharmacy staff satisfaction 3 months after project implementation. There was a statistically significant increase in the number of days covered for patients 90 days postimplementation compared to 90 days before implementation (Difference: 3.60; 95% confidence interval: 1.87, 5.33; P = 0.001). Additionally, there was a statistically significant decrease in pharmacy trips pre- and postimplementation (Difference: 2.17; 95% confidence interval: 1.26, 3.07; P < 0.001). Overall, pharmacy staff and patients reported satisfaction with the service. Implementing a medication synchronization service improved medication adherence and decreased trips to the pharmacy within the pediatric population.

Real-world driving digital data reliably index MCI over time (S15.008)

<h3>Objective:</h3> Our objective is to detect age-related cognitive decline from driver behavior. The overarching goal is to develop real-world, digital biomarkers of early dementia, including Alzheimer’s disease (AD), to inform clinical care and intervention. <h3>Background:</h3> Cognitive decline affects driving abilities. Driver behavior patterns, in turn, index cognitive abilities. Roadway environments present varying challenges, revealing driver strategies accommodating challenges. Strategies map to cognitive decline, even in transitional dementia stages like mild cognitive impairment (MCI). <h3>Design/Methods:</h3> Real-world driving data (249,104 miles) were collected for 2, 3-month periods across 2 years (baseline/longitudinal) using sensors installed in participants’ vehicles. 74 participants (mean age = 75.1, 44 females) self-reported demographics and completed neuropsychological assessments relevant to aging, driving, and AD. Neuropsychological data were used to classify MCI at baseline (MCI: N = 14; Peterson, 2004). Mixed-effect linear regressions assessed changes in speed limit compliance (difference between vehicle speed and posted speed limit) across MCI class and roadway environment (residential/commercial/interstate roads [20–30/35–45/≥ 55 mph]). <h3>Results:</h3> Drivers with MCI drove further below the posted speed limit compared to controls (<i>b</i> = −0.235, <i>p</i> &lt; 0.001). Individual driver speed patterns correlated at baseline and longitudinal (r = 0.63). Commercial (<i>b</i> = −0.541, <i>p</i> &lt; 0.001) and residential (<i>b</i> = −0.647, <i>p</i> &lt; 0.001) roadways showed ability to detect differences in speed limit compliance based on driver MCI class. High-speed driving (interstate roadways) revealed greater differences in speed limit compliance for MCI drivers compared to those without MCI. <h3>Conclusions:</h3> Results demonstrate feasibility to detect early dementia stages, like MCI, from real-world, digital driving sensor data. Findings reveal key environments that show discriminative MCI utility. Data show longitudinal reliability across individuals suggesting utility of data to predict decline progression for AD intervention. Sensor-based digital health biomarkers hold promise to deliver clinicians timely, objective data on patient health and risk. <b>Disclosure:</b> Dr. Chang has nothing to disclose. Mr. Wu has nothing to disclose. The institution of Prof. Zhang has received research support from National Institute of Health. Prof. Zhang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant with Nationwide Children Hospital. The institution of Dr. Rizzo has received research support from NIH. Dr. Rizzo has a non-compensated relationship as a Chair with ABC that is relevant to AAN interests or activities. Jennifer Merickel has nothing to disclose.

Assessing the Relationship Between Infection Frequency and Risk of Post-Tonsillectomy Hemorrhage.

To determine the relationship between frequency of tonsillitis and the risk of post-tonsillectomy hemorrhage (PTH) in pediatric patients undergoing tonsillectomy for recurrent tonsillitis. After obtaining IRB approval from Nationwide Children's Hospital, charts for all patients who underwent a total tonsillectomy in 2017 for recurrent or chronic tonsillitis were retrospectively reviewed (n = 424). Patients were divided into 2 cohorts based on the frequency of tonsillitis prior to surgery: those meeting the 1-year criteria with 7 or more infections in the past year (n = 100), and those who did not meet criteria defined as those with fewer than 7 infections in the past year (n = 324). The primary outcome of interest was PTH. Comparison of cohorts and frequency of PTH were assessed using bivariate analyses. Kaplan-Meier curves were used to compare time to onset of hemorrhage between primary vs. secondary PTH. Generalized mixed and logistic regression models were used to evaluate risk of hemorrhage following tonsillectomy. Among a total cohort of 424 patients undergoing tonsillectomy, 23.58% (n = 100) met criteria while 76.42% (n = 324) did not. A total of 8.73% (n = 37) patients experienced PTH. Compared to those who did not meet criteria, those who met criteria had a higher odds of developing PTH; however, this was not significant (OR: 1.42 [95% CI: 0.67, 2.98], P = .3582). Estimated probability of developing PTH for those who met criteria was 11% [95% CI: 6.19, 18.81] compared to 8.03% [95% CI: 5.52, 11.54] for those who did not meet criteria. Among all PTH cases, 5.41% (n = 2) were primary hemorrhage while 94.59% (n = 35) were secondary hemorrhage with 50% of those with secondary PTH having experienced hemorrhage within 6 days [95% CI: 5, 7] of tonsillectomy. Patients with neuromuscular conditions had significantly higher odds of PTH (OR: 4.75 [95% CI: 1.19, 18.97], P = .0276). Patients who met the 1-year criteria for tonsillectomy did not have a significantly higher odds of PTH. Further research is needed to better evaluate the relationship between infection frequency and risk of PTH.

Outcomes following a multi-disciplinary pediatric-to-adult transition and transfer clinic at a level four epilepsy center.

Transition and transfer from the pediatric to adult care model is crucial to the continued long-term health and well-being of patients impacted by life-long diseases. This project explores the impact of a novel epilepsy transition collaboration between Nationwide Children's Hospital (NCH) and Ohio State University (OSU) Wexner Medical Center. We retrospectively analyzed the characteristics and outcomes of 56 consecutive patients transferred to an adult health care system. These patients were divided into two groups. A cohort of 23 patients transferred in 2019 prior to clinic implementation were compared to a cohort of 33 consecutive patients transferred in 2019 and early 2020 using the epilepsy transition and transfer clinic model. Data points of interest included demographic information, age at transfer, epilepsy diagnosis, pharmacoresistance of epilepsy, surgical history and compliance with follow-up. Patients transferred to OSU through the transition clinic were statistically more likely to be followed at OSU (p = .037) within 6 months (p = .013). Additionally, there was improved patient retention at OSU following transition clinic implementation (p = .037). Data demonstrating statistically significant improvement in care has not been reported for an epilepsy transition clinic. This study establishes that our novelapproach improves continuity of care in this at-risk population. Our clinic model also successfully transitioned and transferred medically complex patients, including those with pharmacoresistant and/or genetically mediated epilepsy. Additionally, this work suggests that this clinic structure has potential to foster the growth of associated adult epilepsy subspecialty practices. These findings are encouraging as they offer potential for improved health care in the youth and young adult epilepsy population.

Targeted Muscle Reinnervation for Limb Amputation to Avoid Neuroma and Phantom Limb Pain in Patients Treated at a Pediatric Hospital.

Patients undergoing major limb amputation with TMR were included with minimum one year follow-up and completed questionnaires. Primary clinical outcomes included incidence of symptomatic neuromas, PLP, residual limb pain, narcotic use, and neuromodulator use. A follow-up phone survey was conducted assessing five pediatric Patient Reported Outcomes Measurement Information System (PROMIS) metrics adapted to assess residual limb and PLP. Nine patients (seven male and two female patients, avg. age = 16.83 ± 7.16 years) were eligible. Average time between surgery and phone follow-up was 21.3 ± 9.8 months. Average PROMIS Pediatric t-scores for measures of pain behavior, interference, quality-affective, and quality-sensory for both PLP and residual limb pain were nearly 1 standard deviation lower than the United States general pediatric population. One patient developed a symptomatic neuroma 1 year after surgery. Compared with an adult patient sample reported by Valerio et al, our TMR patients at Nationwide Children's Hospital (NCH) showed similar PLP PROMIS t-scores in pain behavior (50.1 versus 43.9) and pain interference (40.7 versus 45.6). Both pediatric and adult populations had similar residual limb pain including PROMIS pain behavior (36.7 adult versus 38.6 pediatric) and pain interference (40.7 adult versus 42.7 pediatric). TMR at the time of amputation is feasible, safe, and should be considered in the pediatric population.