Evidence describing paediatric COVID-19 and influenza co-infection is limited because influenza circulation was minimal during the early COVID-19 pandemic. We used the National Clinical Cohort Collaborative, a multicentre electronic health record repository, to describe the characteristics and clinical outcomes of paediatric COVID-19 and influenza co-infections in the United States from March 2020-April 2024. We defined co-infection as COVID-19 and influenza identified <7 days apart. We reported demographics, pre-existing diagnoses, and clinical outcomes and used generalized estimating equation models. We defined clinical outcomes as Severe/Moderate disease (hospitalization, critical care, or death) versus emergency department/outpatient encounters. We repeated analyses using varying co-infection definitions to assess robustness of findings. Among 1.53 million patients, 10,277 were co-infected, and 647 (6%) were hospitalized. Co-infections occurred predominantly among children aged <12 years. The most common pre-existing diagnoses were obesity (24%), asthma (10%), and congenital/genetic conditions (5%). The risk for Severe/Moderate disease was greatest among persons aged 0-4 years (adjusted risk ratio (aRR) 3.05; 95% confidence interval (CI): 2.35-3.97) and those with ≥2 pre-existing diagnoses (aRR 2.89; 95% CI: 2.43-3.43). Similar distributions of disease severity were observed across varying co-infection definitions. This study provides a large-scale epidemiological characterization of paediatric COVID-19 and influenza co-infection and successfully implemented a practical EHR-based co-infection case definition for future analyses.

Directed acyclic graph of the potential associations between rurality at time of diagnosis and survivors with Passport for Care

Purpose: Cardiovascular risk factors (CVRFs) later in life potentiate risk for late cardiovascular disease (CVD) from cardiotoxic treatment among survivors. This study evaluated the association of baseline CVRFs and CVD in the early survivorship period. Methods: This analysis included patients ages 0-29 at initial diagnosis and reported in the institutional cancer registry between 2010 and 2017 (n = 1228). Patients who died within 5 years (n = 168), those not seen in the oncology clinic (n = 312), and those with CVD within one year of diagnosis (n = 17) were excluded. CVRFs (hypertension, diabetes, dyslipidemia, and obesity) within 1 year of initial diagnosis were constructed and extracted from the electronic health record based on discrete observations, ICD9/10 codes, and RxNorm codes for antihypertensives. Results: Among survivors (n = 731), 10 incident cases (1.4%) of CVD were observed between 1 and 5 years after the initial diagnosis. Public health insurance (p = 0.04) and late effects risk strata (p = 0.01) were positively associated with CVD. Among survivors with public insurance (n = 495), two additional cases of CVD were identified from claims data with an incidence of 2.4%. Survivors from rural areas had a 4.1 times greater risk of CVD compared with survivors from urban areas (95% CI: 1.1-15.3), despite adjustment for late effects risk strata. Conclusion: Clinically computable phenotypes for CVRFs among survivors through informatics methods were feasible. Although CVRFs were not associated with CVD in the early survivorship period, survivors from rural areas were more likely to develop CVD.

Rural-Urban Commuting Area (RUCA) codes, definitions, and categories (adapted from https://www.ers.usda.gov/data-products/rural-urban-commuting-area-codes/ and https://depts.washington.edu/uwruca/ruca-uses.php)

Modeling for the association between rurality, with subanalysis for non-Oklahoma City urban areas, and the risk of suboptimal subspecialty follow-up care five to seven years after initial diagnosis using Modified Poisson Regression with robust error variance. (n=449)

This study aimed to evaluate whether a custom warmer height improves the quality and consistency of chest compressions (CCs) compared with a standard warmer height during simulated neonatal resuscitation. Cross-over study using simulated neonatal resuscitation. A controlled research environment equipped with a 12-camera motion capture system, four in-floor multi-axis force plates, a neonatal manikin, and resuscitation equipment. Biomechanical assessments were recorded every 2 minutes during a 20-minute simulation for each condition. Twenty Neonatal Resuscitation Program (NRP)-trained providers. Each participant performed two 20-minute CC sessions—one with the warmer at the standard 100 cm height and one at a custom height selected by the participant. CC depth, force, and rate; participant back angle, heart rate, and self-reported exertion, were analyzed at 2-minute intervals. Compared with the standard height, the custom height resulted in greater and more consistent CC depth and force while maintaining compression rate. Participants also exhibited a greater back angle, and lower heart rate, and reported reduced exertion under the custom height condition. Allowing NRP-trained providers to adjust warmer heights led to improved CC quality and consistency, suggesting that customizable warmer heights may enhance neonatal resuscitation performance. Key Points

Geographic distribution of survivors with Passport for Care

Directed acyclic graph of the potential associations between rurality at time of diagnosis and optimal subspecialty follow-up among childhood cancer survivors.

Subanalysis and geographical map for Oklahoma City Urban, non-Oklahoma City urban, large town, and small town/isolated rural areas in Oklahoma.

Objective The U.S. opioid epidemic has been characterized by increases in opioid misuse, overdose deaths, and neonatal opioid withdrawal syndrome. Research suggests that marijuana legalization has contributed to decreased use of opiates, although many studies had methodological weaknesses and failed to address the pregnant population. Implementation of medical cannabis laws has the potential to reduce maternal opioid use and, therefore, neonatal exposure to the drugs. This study aimed to examine the association between Oklahoma's implementation of state medical marijuana laws and the neonatal exposure to opioids.Study Design Electronic medical records at two sites (Oklahoma City and Lawton) were searched for results of cord, urine, and meconium screens to detect amphetamines, barbiturates, benzodiazepines, cocaine, ethanol, opiates, phencyclidine, and tetrahydrocannabinol (THC). Two study periods were compared: 19 months before Oklahoma's medical marijuana law took effect and 19 months after legalization began.Results A total of 16,804 babies were born alive at the two sites during the study period. The rate of positive THC tests per 1,000 liveborn infants significantly increased from 16.2 per 1,000 during the prelaw period to 22.2 per 1,000 during the postlaw period ( p = 0.004). Neonatal opioid exposure incidence showed a nonsignificant decrease from 7.6 positive tests per 1,000 liveborn infants to 6.8 per 1,000 from prelaw to postlaw period ( p = 0.542). The number of positive tests for THC and concomitant use of opioids doubled from the prelaw period ( n = 4) to postlaw ( n = 9), but there were too few cases for statistical significance. Infants at the more rural site had significantly higher rates for amphetamines, benzodiazepines, and THC, with a trend toward higher rates for opiates.Conclusion Marijuana legalization was related to significant increases in positive test rates for THC, but no significant change/association was noted for neonatal exposure to opioids.

Aim:Neonatal resuscitation guidelines promote the laryngeal mask (LM) interface for positive pressure ventilation (PPV), but little is known about how the LM is used among Neonatal Resuscitation Program (NRP) Providers and Instructors. The study aim was to characterize the training, experience, confidence, and perspectives of NRP Providers and Instructors regarding LM use during neonatal resuscitation at birth.Methods:A voluntary anonymous survey was emailed to all NRP Providers and Instructors. Survey items addressed training, experience, confidence, and barriers for LM use during resuscitation. Associations between respondent characteristics and outcomes of both LM experience and confidence were assessed using logistic regression.Results:Between 11/7/22-12/12/22, there were 5,809 survey respondents: 68% were NRP Providers, 55% were nurses, and 87% worked in a hospital setting. Of these, 12% had ever placed a LM during newborn resuscitation, and 25% felt very or completely confident using a LM. In logistic regression, clinical or simulated hands-on training, NRP Instructor role, professional role, and practice setting were all associated with both LM experience and confidence.The three most frequently identified barriers to LM use were insufficient experience (46%), preference for other interfaces (25%), and failure to consider the LM during resuscitation (21%). One-third (33%) reported that LMs are not available where they resuscitate newborns.Conclusion:Few NRP providers and instructors use the LM during neonatal resuscitation. Strategies to increase LM use include hands-on clinical training, outreach promoting the advantages of the LM compared to other interfaces, and improving availability of the LM in delivery settings.

BACKGROUND:Managing critically ill neonates has unique challenges, and the transport team plays an important role in stabilizing and facilitating the transfer of these neonates from lower-level nurseries to tertiary centers, and the use of telemedicine in transport (tele-transport) can potentially benefit patient care. We conducted a multicenter study to assess the readiness for utilizing telemedicine as an adjunct to guide the care of critically ill neonates among physicians and transport team members (TTMs). This is the first multicenter study that explored physicians' and TTMs' perceptions of telemedicine usage and its value in neonatal transport. METHODS:A confidential, voluntary survey on pre-implementation attitudes toward telemedicine usage during neonatal transport was conducted as part of a quality improvement initiative. This survey involved physicians and TTMs from four academic institutions whose responses were entered into an online survey using REDCap®. The survey inquired about satisfaction with the current practice of phone consultation and the perception of using telemedicine to optimize the management of neonates during transport. RESULTS:The overall response rate for the survey was 60.1%; 82 of 127 (64.6%) physicians and 64 of 116 (55.2%) TTMs responded to the surveys. Half of the physicians and less than one-fourth of the TTMs had prior experience with telemedicine other than that used on neonatal transport. TTMs expressed greater concern about the inconvenience of video (55% vs. physicians 35% agree or strongly agree) and its time consumption (84% vs. physicians 50%). More than 70% of physicians and less than half of TTMs endorsed the potential for added value and quality improvement with video capability. Almost half of TTMs reported concern about video calls reducing their autonomy in patient care. Physicians expressed confidence in management decisions they would make after video calls (72% confident or very confident) and less confidence (49%) about both the phone assessment by TTMs and their decisions based on phone assessment. In contrast, TTMs were confident or very confident (94%) in both sharing their assessment over the phone and executing patient management after a phone call, compared with 70% for decisions made after video calls. CONCLUSIONS:Physicians and TTMs had distinct opinions on the use of telemedicine during neonatal transport. Physicians were more likely than TTMs to agree with statements about the potential for improving quality of care, while TTMs were more likely than physicians to say video calls would be time-consuming and inconvenient. We speculate some differences may stem from the TTMs' concern about losing their autonomy. Therefore, during implementation, it is critical for physicians and TTMs to agree on a shared mental model of indications for telemedicine during transport and its value to the patient care.

Background : Inflammation plays a complex, incompletely understood role in the pathogenesis of acute COVID-19 and Post-Acute Sequelae of SARS-CoV-2 infection (PASC or “Long COVID”). Systemic acute inflammation resulting in cytokine storm, hypercoagulability and endothelial damage is thought to be a central mechanism for severe morbidity and mortality in acute COVID-19. Anti-inflammatory medications taken routinely for chronic conditions prior to contracting COVID-19 (“background medications”) may modulate acute COVID-19 outcomes.  Methods : Using data from the National COVID Cohort Collaborative (N3C) enclave, we estimated effects of six classes of background medications on acute COVID outcomes. Medication classes included aspirin, celecoxib, other NSAIDS, steroids, immune suppressants, and antidepressants. Acute COVID outcomes included probability of hospital admission, inpatient mortality, and mortality among diagnosed COVID patients. Each medication class was compared to benzodiazepines (excluding midazolam) which served as a comparator/control. Only adult COVID patients with pre-existing osteoarthritis and without any diagnosed autoimmune disease were included in the analyses. Random effects logistic regression models were used to adjust for covariates and data contributing organization. Medication effects also were estimated for COVID negative cases.  Results : Non-aspirin NSAIDS were associated with mortality among diagnosed COVID-19 patients: adjusted Odds Ratio (aOR)=0.32 (p=.032) for celecoxib; aOR=0.51 (p<.001) for NSAIDS other than aspirin and celecoxib. For inpatient mortality: aOR=0.34 (p=.060) for celecoxib and aOR=0.74 (p=.200) for other non-aspirin NSAIDS. Similar effects were observed for COVID negative cases, including for inpatient mortality: aOR=0.21 (p<.001) for celecoxib and aOR=0.34 (p<.001) for other non-aspirin NSAIDS. Secondary analyses examined alternative explanations for results.  Discussion : Protective effects were observed for non-aspirin NSAIDS, especially celecoxib. However, those estimated effects implicitly assume the medication classes did not differ on the probability a true COVID-19 case was diagnosed. The similarity of COVID positive and COVID negative results suggests possible missing covariates. However, such similarity plausibly could stem from a medication having both “direct” and “indirect” effects on COVID outcomes. Adjudicating among the alternative interpretations would require data beyond those available. However, the effects observed for non-aspirin NSAIDS, while possibly biased, rationalize further investigation using study designs constructed to overcome the limitations of existing datasets. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Pennington Biomedical Research Center’s IRB (20211-016-PBRC) and the N3C Data Access Committee (RP-504BA5) approved the study COVID-19 Treatments Associated with Lower Mortality. N3C operates under the authority of the National Institutes of Health IRB, with Johns Hopkins University serving as the central IRB (IRB00249128). No informed consent was obtained from individual patients because the study used a limited data set already stripped of direct identifiers in compliance with the HIPAA Privacy Rule. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data cannot be shared because The N3C Data Enclave is managed under the authority of the NIH information can be found at https://ncats.nih.gov/n3c/resources.

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research, such as small sample sizes, reliance on manual record review, and limited analytic methods, that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite, retrospective registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases, 10th Revision (ICD-10) code-defined hypertension disorder on or after January 1, 2015, and age < 19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, US Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to reduce CVD burden across the life course and establish gold-standard biomedical informatics methods for youth with hypertension disorders.

Purpose Rural communities are among the most underserved and resource-scarce populations in the United States. However, there are limited data on COVID-19 outcomes in rural America. This study aims to compare hospitalization rates and inpatient mortality among SARS-CoV-2-infected persons stratified by residential rurality. Methods This retrospective cohort study from the National COVID Cohort Collaborative (N3C) assesses 1,033,229 patients from 44 US hospital systems diagnosed with SARS-CoV-2 infection between January 2020 and June 2021. Primary outcomes were hospitalization and all-cause inpatient mortality. Secondary outcomes were utilization of supplemental oxygen, invasive mechanical ventilation, vasopressor support, extracorporeal membrane oxygenation, and incidence of major adverse cardiovascular events or hospital readmission. The analytic approach estimates 90-day survival in hospitalized patients and associations between rurality, hospitalization, and inpatient adverse events while controlling for major risk factors using Kaplan-Meier survival estimates and mixed-effects logistic regression. Findings Of 1,033,229 diagnosed COVID-19 patients included, 186,882 required hospitalization. After adjusting for demographic differences and comorbidities, urban-adjacent and nonurban-adjacent rural dwellers with COVID-19 were more likely to be hospitalized (adjusted odds ratio [aOR] 1.18, 95% confidence interval [CI], 1.16-1.21 and aOR 1.29, CI 1.24-1.1.34) and to die or be transferred to hospice (aOR 1.36, CI 1.29-1.43 and 1.37, CI 1.26-1.50), respectively. All secondary outcomes were more likely among rural patients. Conclusions Hospitalization, inpatient mortality, and other adverse outcomes are higher among rural persons with COVID-19, even after adjusting for demographic differences and comorbidities. Further research is needed to understand the factors that drive health disparities in rural populations.

Background: Glioblastoma is a high-grade aggressive neoplasm whose outcomes have not changed in decades. In the current treatment pathway, tumour growth continues and remains untreated for several weeks post-diagnosis. Intensified upfront therapy could target otherwise untreated tumour cells and improve the treatment outcome. POBIG will evaluate the safety and feasibility of single-fraction preoperative radiotherapy for newly diagnosed glioblastoma, assessed by the maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV). Methods: POBIG is an open-label, dual-centre phase I dose and volume escalation trial that has received ethical approval. Patients with a new radiological diagnosis of glioblastoma will be screened for eligibility. This is deemed sufficient due to the high accuracy of imaging and to avoid treatment delay. Eligible patients will receive a single fraction of preoperative radiotherapy ranging from 6 to 14 Gy followed by their standard of care treatment comprising maximal safe resection and postoperative chemoradiotherapy (60 Gy/30 fr) with concurrent and adjuvant temozolomide). Preoperative radiotherapy will be directed to the part of the tumour that is highest risk for remaining as postoperative residual disease (hot spot). Part of the tumour will remain unirradiated (cold spot) and sampled separately for diagnostic purposes. Dose/volume escalation will be guided by a Continual Reassessment Method (CRM) model. Translational opportunities will be afforded through comparison of irradiated and unirradiated primary glioblastoma tissue. Discussion: POBIG will help establish the role of radiotherapy in preoperative modalities for glioblastoma. Trial registration: NCT03582514 (clinicaltrials.gov).

Abstract Background: Children with cancer from rural and nonurban areas face unique challenges. Health equity for this population requires attention to geographic disparities in optimal survivorship-focused care. Methods: The Oklahoma Childhood Cancer Survivor Cohort was based on all patients reported to the institutional cancer registry and ≤ 18 years old at diagnosis between January 1, 2005, and September 24, 2014. Suboptimal follow-up was defined as no completed oncology-related clinic visit five to 7 years after their initial diagnosis (survivors were 7–25 years old at end of the follow-up period). The primary predictor of interest was rurality. Results: Ninety-four (21%) of the 449 eligible survivors received suboptimal follow-up. There were significant differences (P = 0.01) as 36% of survivors from large towns (n = 28/78) compared with 21% (n = 20/95) and 17% (n = 46/276) of survivors from small town/isolated rural and urban areas received suboptimal follow-up, respectively. Forty-five percent of adolescents at diagnosis were not seen in the clinic compared with 17% of non-adolescents (P < 0.01). An adjusted risk ratio of 2.2 (95% confidence interval, 1.5, 3.2) was observed for suboptimal follow-up among survivors from large towns, compared with survivors from urban areas. Seventy-three percent of survivors (n = 271/369) had a documented survivorship care plan with similar trends by rurality. Conclusions: Survivors from large towns and those who were adolescents at the time of diagnosis were more likely to receive suboptimal follow-up care compared with survivors from urban areas and those diagnosed younger than thirteen. Impact: Observed geographic disparities in survivorship care will inform interventions to promote equitable care for survivors from nonurban areas.

10048 Background: Marked improvements in outcomes for children with cancer and robust cohort studies with longitudinal follow-up inform evidence-based guidelines for survivors at risk for late cardiomyopathy. Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management. Methods: The Oklahoma Childhood Cancer Survivor cohort was constructed from an institutional cancer registry of survivors diagnosed between 2005 and 2014 (n=382). Data elements (cumulative anthracycline, cumulative chest-directed radiotherapy, alkylator, and platinum exposures) were extracted from Passport for Care (PFC) to implement previously validated late cardiovascular risk prediction modeling from the Childhood Cancer Survivor Study (CCSS) for cardiomyopathy. Risk groups were compared to the Children’s Oncology Group (COG) Long-Term Follow-up Guidelines. Standard query language facilitated extraction of echocardiogram data from the electronic health record to determine adherence, defined as an echocardiogram within 27 months and 63 months from the last day of therapy for high and moderate risk survivors, respectively. Results: Sixty-nine percent (n=264) of survivors from the cancer registry were documented in PFC, of whom 29%, 56%, and 15% were classified as low, moderate, high risk, respectively, based on the CCSS late cardiomyopathy risk calculator. Concordance was modest for high and moderate risk groups (Kappa = 0.42 and 0.46, respectively) and good for the low risk group (Kappa = 0.77) compared to COG risk groups. There was excellent adherence to echocardiogram guidelines with 93% and 81% of moderate and high-risk survivors, respectively. There were significant differences based on risk group (p=0.02) and age at diagnosis (p<0.01). Conclusions: Clinical informatics tools represent a feasible approach to leverage discrete data elements regarding key treatment exposures from PFC to successfully implement previously validated late cardiovascular risk prediction models on a population health level. PFC promotes adherence to echocardiogram surveillance and serves as a platform for future interoperability to generate real-world data to improve survivorship-focused care. [Table: see text]

Background:One in three high-risk prostate cancer patients treated with radiotherapy recur. Detection of lymph node metastasis and microscopic disease spread using conventional imaging is poor, and many patients are under-treated due to suboptimal seminal vesicle or lymph node irradiation. We use Image Based Data Mining (IBDM) to investigate association between dose distributions, and prognostic variables and biochemical recurrence (BCR) in prostate cancer patients treated with radiotherapy. We further test whether including dose information in risk-stratification models improves performance.Method:Planning CTs, dose distributions and clinical information were collected for 612 high-risk prostate cancer patients treated with conformal hypo-fractionated radiotherapy, intensity modulated radiotherapy (IMRT), or IMRT plus a single fraction high dose rate (HDR) brachytherapy boost. Dose distributions (including HDR boost) of all studied patients were mapped to a reference anatomy using the prostate delineations. Regions where dose distributions significantly differed between patients that did and did-not experience BCR were assessed voxel-wise using 1) a binary endpoint of BCR at four-years (dose only) and 2) Cox-IBDM (dose and prognostic variables). Regions where dose was associated with outcome were identified. Cox proportional-hazard models with and without region dose information were produced and the Akaike Information Criterion (AIC) was used to assess model performance.Results:No significant regions were observed for patients treated with hypo-fractionated radiotherapy or IMRT. Regions outside the target where higher dose was associated with lower BCR were observed for patients treated with brachytherapy boost. Cox-IBDM revealed that dose response was influenced by age and T-stage. A region at the seminal vesicle tips was identified in binary- and Cox-IBDM. Including the mean dose in this region in a risk-stratification model (hazard ratio=0.84, p=0.005) significantly reduced AIC values (p=0.019), indicating superior performance, compared with prognostic variables only. The region dose was lower in the brachytherapy boost patients compared with the external beam cohorts supporting the occurrence of marginal misses.Conclusion:Association was identified between BCR and dose outside of the target region in high-risk prostate cancer patients treated with IMRT plus brachytherapy boost. We show, for the first-time, that the importance of irradiating this region is linked to prognostic variables.