Children's Hospital Medical Center Research Articles

Development of a multimodal geomarker pipeline to assess the impact of social, economic, and environmental factors on pediatric health outcomes.

We sought to create a computational pipeline for attaching geomarkers, contextual or geographic measures that influence or predict health, to electronic health records at scale, including developing a tool for matching addresses to parcels to assess the impact of housing characteristics on pediatric health. We created a geomarker pipeline to link residential addresses from hospital admissions at Cincinnati Children's Hospital Medical Center (CCHMC) between July 2016 and June 2022 to place-based data. Linkage methods included by date of admission, geocoding to census tract, street range geocoding, and probabilistic address matching. We assessed 4 methods for probabilistic address matching. We characterized 124244 hospitalizations experienced by 69842 children admitted to CCHMC. Of the 55684 hospitalizations with residential addresses in Hamilton County, Ohio, all were matched to 7 temporal geomarkers, 97% were matched to 79 census tract-level geomarkers and 13 point-level geomarkers, and 75% were matched to 16 parcel-level geomarkers. Parcel-level geomarkers were linked using our exact address matching tool developed using the best-performing linkage method. Our multimodal geomarker pipeline provides a reproducible framework for attaching place-based data to health data while maintaining data privacy. This framework can be applied to other populations and in other regions. We also created a tool for address matching that democratizes parcel-level data to advance precision population health efforts. We created an open framework for multimodal geomarker assessment by harmonizing and linking a set of over 100 geomarkers to hospitalization data, enabling assessment of links between geomarkers and hospital admissions.

Bivalirudin Monitoring in Pediatric Ventricular Assist Device and Extracorporeal Membrane Oxygenation: Analysis of Single-Center Retrospective Cohort Data 2018-2022.

The activated partial thromboplastin time (aPTT) is the most frequently used monitoring assay for bivalirudin in children and young adults on mechanical circulatory support including ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO). However, intrinsic variability of the aPTT complicates management and risks bleeding or thrombotic complications. We evaluated the utility and reliability of a bivalirudin-calibrated dilute thrombin time (Bival dTT) assay for bivalirudin monitoring in this population. Retrospective analysis of clinical data (including aPTT, dilute thrombin time [dTT]) and results of residual plasma samples from VAD patients were assessed in two drug-calibrated experimental assays. One assay (Bival dTT) was validated for clinical use in VAD patients, and subsequently used by clinicians in ECMO patients. Pearson correlation and simple linear regression were used to determine R2 correlation coefficients between the different laboratory parameters using Statistical Package for Social Sciences (Armonk, NY). ICUs at Cincinnati Children's Hospital Medical Center. Children on VAD or ECMO support anticoagulated with bivalirudin. None. One hundred fifteen plasma samples from 11 VAD patients were analyzed. Both drug-calibrated experimental assays (anti-IIa and Bival dTT) showed excellent correlation with each other (R2 = 0.94) and with the dTT (R2 = 0.87), but poor correlation with aPTT (R2 = 0.1). Bival dTT was selected for validation in VAD patients. Subsequently, clinically ordered results (105) from 11 ECMO patients demonstrated excellent correlation between the Bival dTT and the standard dTT (R2 = 0.86) but very poor correlation with aPTT (R2 = 0.004). APTT is unreliable and correlates poorly with bivalirudin's anticoagulant effect in ECMO and VAD patients. A drug-calibrated Bival dTT offers superior reliability and opportunity to standardize results across institutions. Additional studies are needed to determine an appropriate therapeutic range and correlation with clinical outcomes.

Reprint of: How He Did It – The James S. Tweddell Approach to Single Ventricle Palliation in Patients With Hypoplastic Left Heart Syndrome

This article will detail Dr. James Tweddell's operative technique and considerations for 26 all three stages of SVP in patients with HLHS. This will include the Norwood Procedure with 27 Right-Ventricle-to-Pulmonary-Artery Conduit (Sano Modification), Bidirectional Glenn 28 (Superior Cavopulmonary Connection), and Extracardiac, Fenestrated Fontan Completion (Total 29 Cavopulmonary Connection). These techniques are the culmination of over 20 years of experience 30 and represent the final techniques he employed at both Children's Hospital of Wisconsin and 31 Cincinnati Children's Hospital Medical Center.

Designing A Model for Production of Children's Health Information Content in Radiology Centers: A Case Study

Background: In contemporary healthcare systems, there is a growing emphasis on promoting self-care, patient empowerment, and informed decision-making. The creation of health information content is recognized as a vital tool for enhancing the health literacy of patients. Objectives: This study aimed to explore the components of children's health information in radiology centers to develop a model for producing health information content tailored to their needs. Methods: This qualitative exploratory case study involved 71 participants, including 25 children aged 6 - 14 years, 25 parents of children aged 0 - 14 years, and 23 staff members (radiology technicians and doctors) from the Radiology Department at Children's Medical Center Hospital in Tehran, Iran. Semi-structured and in-depth interviews were conducted to collect data, which were then analyzed using qualitative content analysis and selective-axial coding. Results: The developed model comprised two main dimensions: Health information content and health information format. The dimension of health information content included process information, emotional information, and self-regulating information. The dimension of health information format encompassed various formats such as informational brochures, books, educational animations, applications, and oral explanations. Conclusions: Creating health information content that aligns with children's interests and preferences can enhance their cooperation and participation in radiology examinations.

Impact of inflammation and steroids on anti-coagulation in children supported on a ventricular assist device.

Critically ill pediatric patients supported on ventricular assist devices (VADs) are increasingly being anticoagulated on bivalirudin, but with difficulty monitoring anticoagulation. Activated partial thromboplastin time (aPTT) has recently been shown to poorly correlate with bivalirudin plasma concentrations, while dTT had excellent correlation. However, aPTT is the more common monitoring test and dTT testing is rarely used. In addition, effects of frequent clinical VAD scenarios (such as inflammation) on the accuracy of aPTT and dTT testing remains uncertain. We reviewed the effects of clinical scenarios (infection/inflammation, chylothorax, and steroids administration) on anticoagulation monitoring in 10 pediatric VAD patients less than 3years at Cincinnati Children's Hospital Medical Center from 10/27/2020 to 5/6/2022 using bivalirudin for anticoagulation. There were 16 inflammation/infection, 3 chylothorax, and 6 steroids events. Correlation between dTT and aPTT was significantly lower after infection/inflammation, with dTT increasing prior to inflammation/infection while aPTT remained unchanged. In addition, steroids are administered to VAD patients to reduce inflammation and thus additionally stabilize anticoagulation. However, this anticoagulation stabilization effect was reflected more accurately by dTT compared to aPTT. In children requiring VAD support utilizing bivalirudin anticoagulation, inflammation/infection is a common occurrence resulting in anticoagulation changes that may be more accurately reflected by dTT as opposed to aPTT.

The society for craniofacial genetics and developmental biology 46th annual meeting.

The Society for Craniofacial Genetics and Developmental Biology (SCGDB) held its 46th Annual Meeting at Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio on October 10th-12th, 2023. On the first day of the meeting, Drs. Sally Moody and Justin Cotney were each honored with the SCGDBDistinguished Scientist Awards for their exceptional contributions to the field of craniofacial biology. The following two days of the meeting featured five sessions that highlighted new discoveries in signaling and genomic mechanisms regulating craniofacial development, human genetics, translational and regenerative approaches, and clinical management of craniofacial differences. Interactive workshops on spatial transcriptomics and scientific communication, as well as a poster session facilitated meaningful interactions among the 122 attendees representing diverse career stages and research backgrounds in developmental biology and genetics, strengthened the SCGDB community.

The Application of Umbilical Cord Blood-derived Platelet Gel for Skin Ulcers Associated With Chronic Graft-Versus-Host Disease in Pediatrics: A Randomized Trial

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative strategy against a variety of malignant and nonmalignant disorders. However, acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) commonly complicate this approach, culminating in substantial morbidities, and mortalities. The integumentary system is the preponderant organ involved in cGVHD, and its response to existing treatments, including well-versed immunosuppressants and novel targeted therapies, is not desirable. Despite the rarity, ulcers of sclerotic skin cGVHD are treatment-refractory and associated with significant morbidities and an exaggerated risk of infectious complications. Platelet-rich plasma (PRP) and its derivatives are endowed with growth factors and proangiogenic molecules and hold regenerative potential. To assess the safety and efficacy of the application of platelet gel-containing dressing for the management of ulcerative skin cGVHD in pediatric patients. This randomized trial is conducted at the hematopoietic stem cell transplantation unit of the Children's Medical Center Hospital in Tehran, Iran. Twenty-one pediatric patients (aged between 5 and 15 years) were initially enrolled, and 16 met the inclusion criteria. All cases (4 females) were recipients of allo-HSCT who had been complicated with symmetrically or near-symmetrically ulcerative sclerotic skin cGVHD. Fresh umbilical cord blood (UCB) was obtained from healthy donors and underwent centrifugation using a novel PRP preparation kit in a single-step process. Platelet gel was produced by adding thrombin to the isolated buffy coat layer. Two similar ulcers of each patient were randomized to receive either conventional dressing or platelet gels up to 6 times. At each time point evaluation, ulcer size and its relative reduction compared to the basal size were recorded. Included patients received a total of 80 platelet gel-containing dressings. While the mean sizes of randomized ulcers at the beginning of the study were similar, their differences became significant 15 days after the initiation of intervention (P = .019). In addition, the mean reduction in the ulcers’ surface area (in comparison to their baseline values) was significantly higher for the intervention arm at all evaluation points (P = .001 for day 5 and P < .001 for subsequent time points). At the end of the trial, the number of ulcers with a more than 50% reduction in size was 14 (87.5%) in the intervention arm (including 6 completely healed ulcers) versus 1 (6.25%, which was not completely healed) in the control arm (P < .001). None of the patients exhibited any localized or systemic treatment-related adverse events. In this study, using a relatively large number of cases, we showed that UCB-derived platelet gel is a safe, feasible, and effective curative approach for skin ulcers of sclerotic skin cGVHD in pediatric patients. Designing upcoming trials on the efficacy of this therapeutic approach for ocular, mucosal, and acute skin GVHD is prudent. Retrospectively registered at the Iranian Registry of Clinical Trials (registration number IRCT20190101042197N1) on August 24, 2020.

Correlation Between Lung Clearance Index (LCI) and Forced Expiratory Volume (FEV1) in Children with Cystic Fibrosis (CF): A Cross-Sectional Study

Background: The Lung Clearance Index (LCI) serves as a non-uniform ventilation index utilized for monitoring pulmonary function in patients with cystic fibrosis (CF). Lung Clearance Index exhibits higher sensitivity compared to forced expiratory volume in 1 second (FEV1) for early detection of lung disease and does not necessitate active patient cooperation, as required for FEV1 measured through spirometry. Presently, FEV1 is the standard parameter employed for monitoring lung function in CF patients. Objectives: The objective of this study was to assess the correlation between LCI and FEV1 in patients with cystic fibrosis. Methods: This cross-sectional study enrolled children aged 6 to 18 years with confirmed CF diagnosis, who were referred to the CF clinic at Children's Medical Center Hospital (Tehran, Iran). Participants completed consent forms and subsequently underwent pulmonary function tests. Lung Clearance Index was calculated using the exhaling-D device via the Multiple Breath Washout (MBW) method, followed by FEV1 assessment through spirometry. Results: The study included 52 patients with an average age of 12 years, among whom 52% were males. The mean ± standard deviation of FEV1 and LCI were 80.2% ± 25.3 and 8.9 ± 2.8, respectively. A significant inverse relationship was observed between these two parameters in the study (r = -0.49, P = 0.001). Conclusions: These findings further underscore the potential utility of LCI, which offers ease of administration and demonstrates high reliability and accuracy compared to FEV1 for monitoring pulmonary function in CF patients.

Learning competing risks across multiple hospitals: one-shot distributed algorithms.

To characterize the complex interplay between multiple clinical conditions in a time-to-event analysis framework using data from multiple hospitals, we developed two novel one-shot distributed algorithms for competing risk models (ODACoR). By applying our algorithms to the EHR data from eight national children's hospitals, we quantified the impacts of a wide range of risk factors on the risk of post-acute sequelae of SARS-COV-2 (PASC) among children and adolescents. Our ODACoR algorithms are effectively executed due to their devised simplicity and communication efficiency. We evaluated our algorithms via extensive simulation studies as applications to quantification of the impacts of risk factors for PASC among children and adolescents using data from eight children's hospitals including the Children's Hospital of Philadelphia, Cincinnati Children's Hospital Medical Center, Children's Hospital of Colorado covering over 6.5 million pediatric patients. The accuracy of the estimation was assessed by comparing the results from our ODACoR algorithms with the estimators derived from the meta-analysis and the pooled data. The meta-analysis estimator showed a high relative bias (∼40%) when the clinical condition is relatively rare (∼0.5%), whereas ODACoR algorithms exhibited a substantially lower relative bias (∼0.2%). The estimated effects from our ODACoR algorithms were identical on par with the estimates from the pooled data, suggesting the high reliability of our federated learning algorithms. In contrast, the meta-analysis estimate failed to identify risk factors such as age, gender, chronic conditions history, and obesity, compared to the pooled data. Our proposed ODACoR algorithms are communication-efficient, highly accurate, and suitable to characterize the complex interplay between multiple clinical conditions. Our study demonstrates that our ODACoR algorithms are communication-efficient and can be widely applicable for analyzing multiple clinical conditions in a time-to-event analysis framework.

Impact of a relocation to a new critical care building on pediatric safety events.

Cincinnati Children's Hospital Medical Center (CCHMC) relocated the pediatric, cardiac, and neonatal intensive care units (PICU, CICU and NICU) to a newly constructed critical care building (CCB) in November 2021. Simulation and onboarding sessions were implemented before the relocation, aimed at mitigating latent safety threats. To evaluate the impact of ICU relocation to the CCHMC CCB on patient safety as measured by the quantity, rate, severity score, and category of safety reports. This retrospective, cross-sectional, observational study compared safety reports filed in a 90-day period before and following the CCB relocation. The primary outcome was pre- and postrelocation safety report rates per 100 patient-days. Secondary outcomes included safety report severity, category, and rate of hospital acquired conditions (HACs). Total safety report incidence increased by 16% across all ICUs postrelocation with no difference in post- versus prerelocation odds ratio between ICUs. Three isolated instances of special cause variation were found, one in NICU and two in CICU. No special cause variation was found in the PICU. There were no statistical differences in assigned safety report severity pre- to postrelocation for all ICUs, and only lab specimen/test related safety reports showed a statistically significant increase postrelocation. Overall rates of HACs were low, with six occurring prerelocation and eight postrelocation. All three ICUs were relocated to the new CCB with minimal changes in the incidence, severity, or category of safety reports filed, suggesting staff training and preparations ahead of the relocation mitigated latent safety threats.

The molecular epidemiology and clinical implication of methicillin-resistant Staphylococcus aureus (MRSA) sequence types in pediatric bacteremia: a restrospective observational study, 2016-2021.

While there is a high burden of methicillin-resistant Staphylococcus aureus (MRSA) infections among pediatric patients, studies on the molecular epidemiology of MRSA infections in Korean children since the 2010s are lacking. This study aimed to investigate the molecular genotypes and clinical characteristics of MRSA isolates from children with MRSA bacteremia at Asan Medical Center Children's Hospital from 2016 to 2021. Clinical data were retrospectively reviewed, and the molecular types of MRSA were determined using multilocus sequence typing (MLST) and Staphylococcal cassette chromosome mec (SCCmec) typing. The overall methicillin resistance rate of S. aureus bacteremia was 44.8% (77/172); 49.5% in the period 2016-2018 (period 1) and 37.3% in the period 2019-2021 (period 2) (P = 0.116). Community-acquired infections accounted for only 3.9% of cases. The predominant ST group was ST72 group (67.6%), followed by ST5 group (18.9%) and ST1 group (5.4%). The proportion of ST5 was significantly lower in period 2 compared to period 1 (P = 0.02). Compared to the ST5 and ST1 groups, the ST72 group exhibited lower overall antibiotic resistance and multidrug-resistant (MDR) rates (12.0% [6/50] in ST72 group vs. 100.0% [14/14] in ST5 group vs. 50.0% [2/4] in ST1 group; P < 0.001). In the multivariate analysis, the ST1 group was an independent risk factor for 30-day all-cause mortality (aOR, 44.12; 95% CI, 3.46-562.19). The ST72-MRSA strain remained the most frequently isolated genotype in Korean children, while the ST1 group emerged as an independent risk factor for 30-day all-cause mortality in pediatric MRSA bacteremia. Ongoing efforts to uncover the evolving epidemiology of MRSA are essential for developing effective strategies for prevention and treatment.

Incidence, risk factors, and management following cardiac catheterization via carotid and axillary artery approaches: A single-center experience on pseudoaneurysms in young infants.

Use of alternate access for complex neonatal interventions has gained acceptance with carotid and axillary artery access being used for ductal and aortic interventions. This study was a retrospective, single-center study at Cincinnati Children's Hospital Medical Center. The study included infants, aged ≤90 days, who underwent cardiac catheterization with either carotid or axillary artery access between 2013 and 2022. Data encompassing demographics, clinical information, catheterization data, and the incidence of pseudoaneurysm as a procedural complication were collected. Among 29 young infants (20 males, 69%), 4 out of 15 patients (27%) who underwent the carotid approach developed pseudoaneurysms, while 1 out of 14 patients (7.1%) who underwent the axillary approach developed one. Two patients required transcatheter intervention due to enlargement of pseudoaneurysms, involving the placement of transarterial flow-diverting stent and occlusion of left common carotid artery. Longer sheath in-to-out time (135 vs. 77 min, p = 0.001), and higher closing activated clotting times (ACT) (268 vs. 197 s, p = 0.021) were observed among patients with pseudoaneurysms compared to those without. Young infants with alternative access via the carotid and axillary arteries may be at risk of pseudoaneurysm formation during longer procedures and with higher ACTs for closure. Ultrasound-guided compression can be employed to prevent the progression and in resolution of these lesions.

The Phenotype of a Bone Marrow Transplant Nurse: Survival of the Fittest

There is a need for proficient nursing practice in specialized critical care settings, such as a pediatric Bone Marrow Transplant (BMT) Unit. The staffing crisis continues to be problematic for areas around the country. Nursing tenure has been positively correlated with improving patient outcomes and confidence in giving care, so efforts must be made to retain pediatric BMT nurses. The purpose of this study was to investigate factors of resilience and how it pertains to the retention of pediatric BMT nurses through 1) Understanding current BMT nursing turnover and trend why nurses are leaving; 2) Measure resilience throughout BMT nursing cohort, covering all tenure of nurses; and 3) Interview senior nurses within the cohort to identify themes relating to retention and resilience using grounded theory methodology. This research was carried out in the Bone Marrow Transplant (BMT) Unit at Cincinnati Children's Hospital Medical Center (CCHMC). The study spanned from 2014 to 2019, during which researchers gathered extensive data to evaluate the turnover risk among BMT nurses. A detailed follow-up was conducted in 2019 to further assess this risk. To measure resilience levels, a group of 115 nurses in the unit completed the Connor Davidson Resilience Scale (CD-RISC). Additionally, in-depth interviews were conducted with nine senior nurses in the cohort, continuing until theoretical saturation was reached, ensuring a comprehensive understanding of the factors influencing nurse turnover in the unit. Researchers looked retrospectively at nursing turnover from 2014-2019. Investigators determined the risk of new nurses leaving was between 22 and 24 months (HR 0.025). Further, follow-up was conducted for data points between 2019-present time, which showed a drastic change in the hazard rate curvature. However, the risk remained relatively the same at 22-24 months (HR 0.03). There was no statistical significance found between CD-RISC results and age (p=0.465), gender (p=0.725), working experience (p=0.15), or education (p=0.14). Through a constant comparative process, several themes were identified as positive, negative, and ambiguous contributions to the retention of nurses. The risk of nurses leaving after two years decreases significantly; therefore, we determined that a nurse with a commitment to pediatric BMT occurs with two years' experience. Although our initial hypothesis was that senior nurses had greater resilience than less tenured nurses, there was no statistical significance as the effect of resilience is small. However, we identified several additional factors pertinent to the pediatric BMT field which may be associated with nursing retention.

Characterization of Ceftriaxone-Resistant Haemophilus influenzae Among Korean Children.

Haemophilus influenzae is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant H. influenzae at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in H. influenzae, with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and β-lactamase production. Among H. influenzae isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of β-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via ftsI gene sequencing. Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant H. influenzae isolates, eighteen were non-typeable H. influenzae, and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L. The emergence of ceftriaxone-resistant H. influenzae with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in H. influenzae isolated from pediatric patients in Korea.

Red cell abnormalities characterized by ektacytometry in children with cholestasis.

Spur-cell anemia sometimes accompanies cholestasis. We postulated that even in the absence of spur-cells, cholestasis might alter red blood cell (RBC) osmotic fragility and deformability. Therefore, we assessed these RBC measures by ektacytometry in pediatric patients. We conducted a single center, prospective, cross-sectional investigation of RBC membrane characteristics by ektacytometry in pediatric patients with intra- and extrahepatic cholestasis followed at Cincinnati Children's Hospital Medical Center. We measured red cell membrane fragility and deformability in 17 patients with cholestasis and 17 age-matched controls without cholestasis. Patients with cholestasis had decreased RBC osmotic fragility compared to controls, with a significant left shift in Omin, indicating increased RBC surface-to-volume ratio. One showed spur cell morphology. However, the other 16 had no spurring, indicating that ektacytometry is a sensitive method to detect RBC membrane abnormalities. Left shift of Omin positively correlated with serum conjugated bilirubin levels and even more negatively with serum vitamin E concentration. This study suggests that subclinical red blood cell membrane abnormalities exist in most pediatric patients with cholestasis, increasing risk for hemolysis when subjected to oxidative stress. Hence minimizing pro-oxidants exposure and maximizing antioxidant exposure is advisable for this group. NCT05582447 https://clinicaltrials.gov/ct2/show/NCT05582447?cond=Cholestasis&cntry=US&state=US%3AOH&city=Cincinnati&draw=2&rank=2 . Spur cell anemia due to decreased red cell osmotic fragility and decreased deformability has been reported among patients with cholestasis. Ektacytometry is a reliable, reproducible method to measure red cell osmotic fragility and deformability. Few data describe red cell osmotic fragility or deformability in patients with cholestasis who may or may not have spur cell anemia. Ektacytometry shows that red cell osmotic fragility and deformability are decreased in many children with cholestasis even when spur cell anemia has not yet occurred. Factors associated with decreased osmotic fragility include elevated serum bilirubin, elevated serum bile acids, and decreased serum vitamin E.

Patterns of Nonadherence to Hydroxyurea in Pediatric Sickle Cell Disease

Background: Sickle cell disease (SCD) affects an estimated 100,000 American children and adults (CDC, 2017). Hydroxyurea is the first-line disease-modifying treatment for SCD. Daily oral hydroxyurea significantly reduces the frequency of pain and serious medical complications associated with SCD, including dactylitis and acute chest syndrome (Wang et al., 2011). However, adherence to hydroxyurea is less than optimal at 74% among pediatric patients, with 20% of children who are prescribed hydroxyurea taking less than 50% of their prescribed doses (Louiselle et al., 2016). Suboptimal hydroxyurea adherence is associated with increased risk for medical complications, diminished quality of life, and higher health care costs and utilization (e.g., Badawy et al., 2017; Thornburg et al., 2010). Factors associated with hydroxyurea nonadherence in pediatric SCD include female sex, older age, more adherence barriers (e.g., difficulty obtaining refills), lower socioeconomic status, and lower parent treatment knowledge. Purpose: This study aims to characterize trajectories of pediatric hydroxyurea adherence to identify subgroups that may be at highest risk for hydroxyurea nonadherence (e.g., sociodemographic factors), critical time periods for adherence support interventions (e.g., adolescence), and minimal adherence thresholds to optimize hydroxyurea efficacy. Methods: Retrospective chart review across two institutions (i.e., Cincinnati Children's Hospital Medical Center and Nemours Children's Hospital, Delaware) are ongoing. Participants will include patients with SCD ages 2 to 21 years who were prescribed hydroxyurea from March 2007 to February 2017. Researchers are extracting the following data from patient electronic medical records (EMRs) to estimate hydroxyurea adherence: hemoglobin F levels (HbF), mean corpuscular volume (MCV), and absolute neutrophil count (ANC). Additional clinical information will be extracted from patient EMRs including demographic information, SCD genotype, SCD complications, acute care utilization, medical and social complexity, and concomitant medication use. Descriptive statistics will be used to summarize demographic and clinical characteristics of the sample. MCV will be the primary measure of hydroxyurea adherence and Hgb F and ANC will be secondary measures. If the final sample size is sufficiently large, we will conduct group-based trajectory modeling (GBTM) to analyze patterns of hydroxyurea adherence changes over time and identify hydroxyurea adherence trajectory subgroups. Multinomial logistic regression analyses will be used to analyze potential predictors of hydroxyurea adherence trajectory subgroup membership. Results: Preliminary results revealed that as of February 2017, 88% of eligible patients (based on age) were prescribed hydroxyurea.Data from the first 30 completed chart reviews indicates that half of the sample was female (sex assigned at birth), all identified as Black or African American, all but two participants had HbSS, and the mean age 13.0 years ( SD=8.0, range=2.47 to 26.81). Average MCV across an average of 21 time points ( SD=14.2, range=5-74) was 94.3 ( SD=11.2, range=58.4-114.2). As of February 2017, 53% of individuals had MCV values at or above 100. Specifically, 60% of 5-9 year olds, 47% of 10-15 year olds, and 46% of 16+ year olds had MCV values at or above 100. Average Hgb F across an average of 21 time points ( SD=15.3, range=3-81) was 22.9 ( SD=9.3, range=2.6-44.8). As of February 2017, 50% of individuals had HbF values at or above 20.0. Specifically, 55% of 5-9 year olds, 32% of 10-15 year olds, and 55% of 16+ year olds had HbF values at or above 20.0. Average ANC (at non-ill visits) across an average of 20.0 time points ( SD=13.6, range=5-71) was 3,965 ( SD=1,227; range=1,600-6,910). As of February 2017, 31% of individuals had ANC values less than 3,000. Specifically, 20% of 5-9 year olds, 34% of 10-15 year olds, and 30% of 16+ year olds had ANC values less than 3,000. Discussion:Results from this study have the potential to help researchers and clinicians better understand patterns and correlates of hydroxyurea adherence in pediatric SCD patients that can be targeted in future interventions.

Attitudes of Hematologists in the Midwestern United States Toward Evaluating and Managing Thrombosis Risk in Transgender Youth Starting Gender Affirming Hormone Therapy

Background: Transgender and gender nonconforming (TG) youth who are at increased risk of thrombosis may be evaluated by a hematologist to discuss thromboprophylaxis prior to starting gender-affirming hormone therapy (GAHT). However, in the absence of guidelines to inform the delivery of hematologic care to such youth, variations in practice patterns may lead to suboptimal care for these individuals. Aim: Determine hematologists' recommendations about which TG youth should be considered at higher risk of thrombosis, laboratory evaluation and medical management of such youth, and which youth should be referred for hematologic evaluation prior to starting GAHT. Methods: From 6/2022-2/2023, we recruited hematologists caring for patients 13-22 years-old and practicing in the Midwestern U.S. for individual semi-structured interviews. Hematologists were recruited from the institutions in the footprint of the Midwest Transgender Research Collaborative. Interviews assessed demographics, practice characteristics, comfort recommending and prescribing thromboprophylaxis to TG youth, and recommendations for 1) which youth TG youth would be considered at higher risk of thrombosis; 2) laboratory evaluation; 3) recommended thromboprophylactic medication and duration; and 4) which TG youth should undergo hematologic evaluation prior to GAHT. Transcripts were analyzed using team-based framework analysis. The study was IRB approved; informed consent was obtained. Results: Eleven hematologists from 4 academic centers participated. Mean age was 50.5 years (SD 7.2); 9 participants identified as white; 2 were Latino/a. Ten participants had provided care to TG adolescents (13-17 years-old); all 11 had provided care to TG young adults (18-22 years-old). Participants reported on average 2.8 (SD 3.3) TG adolescents and 2.5 (SD 2.9) TG young adults in their practices. Ten participants reported comfort with recommending and prescribing thromboprophylaxis to patients at higher risk of thrombosis starting estrogen for GAHT; counseling about knowledge gaps and engaging in shared decision making were important elements in the process. One participant reported preference for non-medication interventions, such as compression stockings and using lower doses or transdermal formulations of estrogen. There was less consensus around attitudes toward prophylaxis for youth starting testosterone for GAHT: 4 participants reported lower likelihood of recommending thromboprophylaxis due to low risk of thrombosis with testosterone use; 3 participants discussed risk of erythrocytosis/polycythemia due to testosterone use (although there was no consensus on whether prophylaxis would be recommended); 3 participants reported comfort prescribing prophylaxis to youth starting testosterone; and 2 participants reported insufficient knowledge about the thrombotic risks of testosterone. Hematologists reported various factors that would lead to TG youth being considered high risk, as well as recommended lab testing (Table 1). If prophylaxis is needed, 10 participants would recommend a direct anticoagulant, while 1 would recommend aspirin. Five participants anticipated that long term prophylaxis would be needed for the duration of GAHT, while 6 reported duration would be individualized. Ten participants would not recommend against estrogen due to thrombosis risk, emphasizing the importance of gender care and the role of the hematologist in making GAHT as safe as possible. No participant would recommend against testosterone. Participants offered recommendations for which TG youth should be evaluated by a hematologist prior to starting GAHT (Table 2). Conclusion: Overall, hematologists voiced comfort with recommending and prescribing thromboprophylaxis to TG youth at higher risk of thrombosis starting estrogen. However, there was lack of consensus about evaluation of youth at higher risk of thrombosis starting testosterone and whether mitigation of risk would be needed. Developing guidance for gender care teams for which youth should be considered at higher risk of thrombosis and referred for hematologic evaluation would help optimize the safe delivery of gender-affirming hormone care. Additional data and guidance about the thrombosis risks associated with GAHT is needed to better inform hematologic care. Funding: NIH R01HL161153; Cincinnati Children's Hospital Medical Center Gap Funding

Association between sputum culture results and pulmonary changes in children with cystic fibrosis.

Despite the significant improvement in the prognosis of cystic fibrosis (CF), it is still regarded as the most common life-shortening genetic disease in Caucasian populations. This disease is the most important cause of chronic lung disease and exocrine pancreatic insufficiency in infancy and childhood. The aim of our study was to assess the potential association between bacterial colonization detected by sputum cultures and pulmonary structural and functional changes in Iranian children with CF. In this cross-sectional study, 76 CF children ≥6 years old registered in the CF Foundation of Children's Medical Center Hospital, Tehran, Iran, who underwent high resolution CT scan (HRCT), pulmonary function test, and sputum cultures within a month of each other during the study period were included. For each patient, demographic characteristics (age and sex), results of sputum cultures, forced expiratory volume in 1st second (FEV1), and chest HRCT findings based on the Bhalla scoring system were recorded in a check list. Sixty seven percent of the patients had positive sputum cultures, with the most commonly isolated microorganism being Pseudomonas aeruginosa (mucoid strain). Based on categorization of Bhalla scores, none of the patients had severe pulmonary involvement. FEV1 was mainly >70%. There was a statistically significant correlation between colonization with mucoid P. aeruginosa and lower Bhalla scores in children aged 14-16 years (P=0.001). Colonization with mucoid P. aeruginosa was also significantly associated with patient's age (P=0.020) and FEV-1 (P=0.001). Severity of lung involvement in CF children is clearly dependent to mucoid P. aeruginosa colonization in airways and this notorious bacterium is the most prevalent one in Iranian CF children. Prompt identification and eradication by proper nebulized and systemic antibiotics can have valueless effects on patients' quality of life and prevent lifelong destructive complications such as bronchiectasis. Timely lung CT scan wisely advised by expert CF treatment team can meticulously detect injuries and it seems to act more efficacious than -still helpful-clinical scores and pulmonary function tests.

Carbonic anhydrase inhibitors limit complications in X-linked retinoschisis.

Carbonic anhydrase inhibitors (CAIs) reduce macular schisis in patients with X-linked retinoschisis (XLRS). The purpose of this study was to determine if CAIs reduce the incidence of complications from XLRS, including macular atrophy, retinal tears, and retinal detachment (RD), the most common causes of vision loss in patients with XLRS. For this retrospective interventional case series, a chart review of patients examined at Cincinnati Children's Hospital Medical Center [CCHMC] and Cincinnati Eye Institute [CEI] between 1/1/2015 and 1/16/2023 was performed. Male patients were included based on genetically-confirmed RS1 or typical clinical presentation with known family history of XLRS with at least two follow-up visits. Twenty-eight patients (56 eyes) with XLRS were included. There were 10 RS1 variants among the 21 genotyped patients. Median age at clinical diagnosis was 10.4 years old (range: 0.4-55.7 years) with median follow-up time of 4.7 years (range: 0.2-38.3 years). Median presenting Snellen visual acuity was 20/60 (logMAR 0.48, range: 0.18-3). In 26 eyes of 15 patients treated with CAIs, median CST pre-treatment was 416 microns (range: 198-701 microns), and median percentage decrease in CST on treatment was 21.8% (range: 0-74.5%) from highest pre-treatment CST. Reduction in CST with CAI use was statistically significant (p = 0.02), but not logMAR VA (p = 0.64). There was no significant difference in CST between patients treated with topical vs. oral CAI (p = 0.95) or between patients with partial or complete CAI adherence (p = 0.60). Ten eyes of seven patients had an RD requiring surgical intervention. No treated eyes developed new macular atrophy, peripheral retinoschisis, retinal tears, or RD; two eyes on topical CAIs had spontaneous resolution of bullous peripheral retinoschisis. During the follow-up period, patients taking CAIs reduced macular schisis and did not experience new complications of macular atrophy, retinal tears, or RD. This is a relatively large cohort with long-term follow-up periods for patients with XLRS. Reduced macular schisis may not require perfect adherence with CAIs. A large, prospective, randomized, controlled clinical trial is needed to determine the potential of CAIs to improve visual function, reduce retinoschisis, and prevent RD.

Genetic counseling clinic model expansion: Impact on access for general genetics clinic.

Cincinnati Children's Hospital Medical Center (CCHMC) implemented a Genetic Counseling Clinic (GCC), where the appointment for a general genetics indication is conducted solely by a genetic counselor (GC). We conducted a retrospective chart review of 211 patient encounters scheduled in the GCC between January 1, 2022 and June 30, 2022 and collected patient demographics, wait time, appointment characteristics, referral indication, and clinical recommendations. To study impact on patient access, we compared patient demographics and appointment characteristics with 912 patient encounters scheduled in the General Genetics Clinic with a geneticist during the same time period. We found that there were not significant differences in patient demographics scheduled in the GCC as compared with the General Genetics Clinic with the exception of insurance type, where patients scheduled in the GCC were more likely to have private insurance. Patients scheduled in the GCC had a significantly shorter wait time, were more likely to complete their appointment, were more often new to the genetics division, and were more likely to be seen via telehealth (audio plus video or audio-only) as compared with patients scheduled in the General Genetics Clinic. The most common indications for patients scheduled in the GCC were post-test counseling (36.0%) followed by pre-test counseling and coordination of testing (22.3%), and first-line testing for autism, intellectual disability, and developmental delay (13.7%). Completed appointments in the GCC often resulted in the GC ordering genetic testing (67.5%). After genetic testing results were received, most patients (72.7%) did not require subsequent follow-up with the genetics division, thereby reducing burden to the medical genetics team. Our GCC increased access to genetic services and allowed GCs and clinical geneticists to better work at the top of their scope of practice.