Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium.

OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children. DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry. SETTING: PICUs within U.S. CHAT Consortium participating centers. PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE. CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.

Effects of Cumulative Head Impact Exposure in Adolescent Male Contact and Collision Sport Student Athletes.

OBJECTIVE: This prospective cohort study aimed to investigate the association between head impact exposure (HIE) and neuropsychological sequelae in high school football and ice hockey players over 1 year. SETTING: Community sample. PARTICIPANTS: A cohort of 52 adolescent American football and ice hockey players were enrolled in the study, with a final study sample of 35 included in analyses. DESIGN: The study followed a prospective cohort design, with participants undergoing neuropsychological screening and accelerometer-based measurement of HIE over 1 season. MAIN MEASURES: Changes in cognition, emotions, behavior, and reported symptoms were assessed using standardized neuropsychological tests and self-reported questionnaires. RESULTS: Cumulative HIE was not consistently associated with changes in cognition, emotions, behavior, or reported symptoms. However, it was linked to an isolated measure of processing speed, showing inconsistent results based on the type of HIE. History of previous concussion was associated with worsened verbal memory recognition (ImPACT Verbal Memory) but not on a more robust measure of verbal memory (California Verbal Learning Test [CVLT]). Reported attention-deficit/hyperactivity disorder history predicted improved neurocognitive change scores. No associations were found between reported history of anxiety/depression or headaches/migraines and neuropsychological change scores. CONCLUSION: Overall, our findings do not support the hypothesis that greater HIE is associated with an increase in neuropsychological sequelae over time in adolescent football and ice hockey players. The results align with the existing literature, indicating that HIE over 1 season of youth sports is not consistently associated with significant neuropsychological changes. However, the study is limited by a small sample size, attrition over time, and the absence of performance validity testing for neurocognitive measures. Future studies with larger and more diverse samples, longer follow-up, and integration of advanced imaging and biomarkers are needed to comprehensively understand the relationship between HIE and neurobehavioral outcomes. Findings can inform guidelines for safe youth participation in contact sports while promoting the associated health and psychosocial benefits.

Comparison of Caregiver and Provider Food Insecurity Screening Preferences Within a Health System.

Food insecurity is a public health concern associated with poor health. Evidence guiding how to best implement screening for food insecurity across a pediatric health care system is lacking. We performed a single-center, multi-department, cross-sectional study of caregivers and health care providers in outpatient and inpatient settings to describe the beliefs, barriers, preferences, and preferred food insecurity screening location. Most providers and caregivers underestimated the pervasiveness of food insecurity while acknowledging the benefit of screening. Caregivers are overall receptive to food insecurity screening and disagree with feelings of discomfort or shame when disclosing food insecurity status. Providers acknowledged perceived caregiver discomfort, lack of community food resources, and lack of a validated screening tool as barriers to screening. Both caregivers and providers identified the primary care setting as the preferred screening setting.

Survival analysis for pediatric heart transplant patients using a novel machine learning algorithm: A UNOS analysis.

BACKGROUND: Impact of pretransplantation risk factors on mortality in the first year after heart transplantation remains largely unknown. Using machine learning algorithms, we selected clinically relevant identifiers that could predict 1-year mortality after pediatric heart transplantation. METHODS: Data were obtained from the United Network for Organ Sharing Database for years 2010-2020 for patients 0-17 years receiving their first heart transplant (N = 4150). Features were selected using subject experts and literature review. Scikit-Learn, Scikit-Survival, and Tensorflow were used. A train:test split of 70:30 was used. N-repeated k-fold validation was performed (N = 5, k = 5). Seven models were tested, Hyperparameter tuning performed using Bayesian optimization and the concordance index (C-index) was used for model assessment. RESULTS: A C-index above 0.6 for test data was considered acceptable for survival analysis models. C-indices obtained were 0.60 (Cox proportional hazards), 0.61 (Cox with elastic net), 0.64 (gradient boosting), 0.64 (support vector machine), 0.68 (random forest), 0.66 (component gradient boosting), and 0.54 (survival trees). Machine learning models show an improvement over the traditional Cox proportional hazards model, with random forest performing the best on the test set. Analysis of the feature importance for the gradient boosted model found that the top 5 features were the most recent serum total bilirubin, the travel distance from the transplant center, the patient body mass index, the deceased donor terminal Serum glutamic pyruvic transaminase/Alanine transaminase (SGPT/ALT), and the donor PCO2. CONCLUSIONS: Combination of machine learning and expert-based methodology of selecting predictors of survival for pediatric heart transplantation provides a reasonable prediction of 1- and 3-year survival outcomes. SHapley Additive exPlanations can be an effective tool for modeling and visualizing nonlinear interactions.

Evaluation of venous thromboembolism risk factors reveals subtype heterogenicity in children with central venous catheters: a multicenter study from the Children's Hospital Acquired Thrombosis consortium.

BACKGROUND: Acutely ill and medically complex children frequently rely on central venous catheters (CVCs) to provide life-sustaining treatment. Unfortunately, catheter-related thrombosis (CRT) is a serious and common complication. Little is known why some with a CVC develop CRT and others develop venous thromboembolism unrelated to the CVC (non-CRT). OBJECTIVES: The aim of this study was to identify factors associated with CRT in children with hospital-acquired venous thromboembolism (HA-VTE). METHODS: This case-case study included participants in the Children's Hospital Acquired Thrombosis Registry with HA-VTE and CVC aged 0 to 21 years from 8 US children's hospitals. Participants were excluded if they developed HA-VTE prior to CVC insertion or if the CVC insertion date was unknown. Logistic regression models were used to assess associations between clinical factors and CRT status. RESULTS: There were 1144 participants with HA-VTE who had a CVC. CRT developed in 833 participants, and 311 developed non-CRT. Multivariable analysis showed increased odds of CRT (compared with non-CRT) in participants with peripherally inserted central catheters (odds ratio [OR], 3.80; 95% CI, 2.04-7.10; p < .001), CVCs inserted in the femoral vein (OR, 4.45; 95% CI, 1.70-11.65; p = .002), multiple CVCs (OR, 1.42; 95% CI, 1.18-1.71; p < .001), and CVC malfunction (OR, 3.30; 95% CI, 1.80-6.03; p < .001). CONCLUSION: The findings of this study provide new insights on risk factor differences between CRT and non-CRT. Prevention efforts should be directed at modifying the type of CVC, insertion location, and/or number of CVCs placed, if possible, to decrease the incidence of CRT.

Updated guidance for efficacy and safety outcomes for clinical trials in venous thromboembolism in children: communication from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis.

Despite the growing number of pediatric antithrombotic clinical trials, standardized safety and efficacy outcome definitions for pediatric venous thromboembolism (VTE) clinical trials have not been updated since 2011. Many recent trials have adapted the recommended definitions, leading to heterogeneity in outcomes and limiting our ability to compare studies. The International Society on Thrombosis and Haemostasis Scientific and Standardization Subcommittee (SSC) on Pediatric and Neonatal Thrombosis and Hemostasis organized a Task Force to update the efficacy and safety outcome definitions for pediatric VTE clinical trials. The outcome definitions used in the recent pediatric antithrombotic trials, definitions recommended for adult studies, and regulatory guidelines were summarized and reviewed by the Task Force as the basis for this updated guidance. Major updates to the efficacy outcomes include the removal of VTE-related mortality as a part of a composite primary outcome and explicit inclusion of all deep venous anatomic sites. Safety outcomes were updated to include a new bleeding severity category: patient important bleeding, no intervention, which encompasses bleeding for which a patient seeks care but there is no change in management. Menstrual bleeding can now be included in any bleeding category when the criteria are met. We hope that these updated outcome definitions will allow the investigators to focus on clinically relevant and patient-important outcomes and provide standardization to facilitate continued high-quality evidence for the use of antithrombotic therapies in children.

Optimal Donor Allograft Function: The Search for the Lowest Acceptable Donor Left Ventricular Ejection Fraction in Pediatric Heart Transplantation.

BACKGROUND: The availability of heart donors is limited by organ shortage. Due to concerns of reduced survival, donors with depressed left ventricular ejection fraction (LVEF <50%) have been cautiously used in pediatric heart transplantation. One strategy to expand the donor pool is to re-evaluate whether lower donor LVEF may be acceptable for transplantation. METHODS: We performed a multicenter retrospective cohort study of patients <18 y receiving heart transplants from April 2007 to September 2021 using the United Network of Organ Sharing dataset. We excluded retransplants and multiorgan transplants. Cut-point analyses of LVEF was performed and Kaplan-Meier method was used to compare 1-y survival for new cut-points and the standard (LVEF >50%). RESULTS: The analytic sample consisted of 5255 patients. Recipients receiving hearts with lower LVEFs were more likely to be on ventilator and extracorporeal membrane oxygenation support. Recipients did not differ in waitlist times or transplant status. Cut-point analysis identified LVEF 45% as a potentially new cutoff. One-year survival of recipients of donors with LVEF ≥45% (92.1%; 95% confidence interval [CI], 91.3%-92.8%) was similar to that of LVEF >50% (92.1%; CI, 91.4%-92.9%). Survival for the LVEF 45%-49% (88.8%; CI, 72.9%-95.7%) cohort was slightly lower than the ≥50% cohort, albeit nonsignificant. CONCLUSIONS: One-year survival among pediatric heart transplants using a donor heart LVEF threshold of 45% or 40% was similar to a threshold of 50%. However, the finding is based on a small number of patients with LVEF <50%, and future larger prospective studies are warranted to confirm the findings of this study before a lower LVEF threshold is considered.

Risk factors for hospital acquired venous thromboembolism in congenital heart disease patients: A report from the children's hospital acquired thrombosis (CHAT) consortium.

INTRODUCTION: The incidence of pediatric hospital-acquired venous thromboembolism (HA-VTE) has increased over time. Congenital heart disease (CHD) as a co-morbidity has been demonstrated to significantly increase HA-VTE risk among hospitalized children. OBJECTIVE: To identify specific risks factors for the development of HA-VTE in hospitalized children with CHD. MATERIALS AND METHODS: This retrospective case-control study included hospitalized participants aged 0-21 years within the Children's Hospital Acquired Thrombosis (CHAT) Consortium Registry with a co-morbidity of CHD. Participants with HA-VTE and non-VTE controls with a past medical history of CHD were selected from the CHAT Registry and data regarding multiple clinical variables were extracted. These variables were then analyzed to assess their association with HA-VTE development. RESULTS: Three hundred and thirty-three participants with a co-morbidity of CHD were identified, comprising 275 HA-VTE cases and 58 controls. Median age for HA-VTE cases was 0.4 (IQR = 0-2.6) years compared to 3.4 (IQR = 0.7-6.5) for controls. Male participants were predominant in both groups (57.5 % HA-VTE cases vs 51.7 % controls). Multivariable analysis identified prior recent hospitalization (OR = 4.12, 95%CI = 1.66-10.24), intensive care unit (ICU) admission (OR = 3.29, 95 % CI = 1.15-9.40), and CVC placement (OR = 9.14, 95 % CI = 3.38-24.72) as significant risk factors for HA-VTE in subjects with CHD. CONCLUSIONS: ICU admission, CVC placement, and prior hospitalization were identified as statistically significant predictors associated with HA-VTE development in hospitalized children with history of CHD. Prospective studies are needed to validate these results and help develop strategies to mitigate HA-VTE development in these patients.

Risk of venous thromboembolism in pediatric hospitalized patients undergoing noncardiac surgery: A report from the Children's Hospital-Acquired Thrombosis consortium.

Background: Surgery is a known risk factor for hospital-acquired venous thromboembolism (HA-VTE) in children. Objectives: To assess whether the odds of HA-VTE differs across six anatomic sites of noncardiac surgery and to identify risk factors for HA-VTE in these children. Methods: This was a multicenter, case-control study. Anatomic sites of surgery and risk factors for HA-VTE were collected on hospitalized pediatric patients who had undergone a single noncardiac surgery and developed HA-VTE (cases), and those who did not develop HA-VTE (controls), via the Children's Hospital-Acquired Thrombosis (CHAT) Registry. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals (CIs) between six anatomic sites of surgery and 16 putative HA-VTE risk factors. Variables with a p value of 0.10 or less in unadjusted analyses were included in adjusted models for further evaluation. The final model used backward selection, with a significance level of 0.05. Results: From January 2012 to March 2020, 163 cases (median age, 5.7 years; interquartile range [IQR], 0.3-14.2) and 208 controls (median age of 7.5 years; IQR, 3.7-12.9) met our criteria. There was no statistically significant increased odds of VTE among the types of noncardiac surgery. In the final adjusted model, central venous catheter (CVC; OR, 14.69; 95% CI, 7.06-30.55), intensive care unit (ICU) stay (OR, 5.31; 95% CI, 2.53-11.16), and hospitalization in the month preceding surgery (OR, 2.75; 95% CI, 1.24-6.13) were each independently significant risk factors for HA-VTE. Conclusion: In children undergoing noncardiac surgery, placement of CVCs, admission/transfer to the ICU, or hospitalization in the month prior to surgery were positively associated with HA-VTE.

Comparison of general endotracheal anesthesia versus sedation without endotracheal intubation during initial percutaneous endoscopic gastrostomy insertion for infants: A retrospective cohort study.

BACKGROUND: Critical airway incidents are a major cause of morbidity and mortality during anesthesia. Delayed management of airway obstruction quickly leads to severe complications due to the reduced apnea tolerance in infants and neonates. The decision of whether to intubate the trachea during anesthesia is therefore of great importance, particularly as an increasing number of procedures are performed outside of the operating room. AIM: In this retrospective cohort study, we evaluated airway management for infants below 6 months of age undergoing percutaneous endoscopic gastrostomy insertion. We compared demographic, procedural, and health outcome-related data for infants undergoing percutaneous endoscopic gastrostomy insertion under general endotracheal anesthesia (n = 105) to those receiving monitored anesthesia care (n = 44) without endotracheal intubation. METHODS: A retrospective chart review was completed for all infants <6 months of age who underwent percutaneous endoscopic gastrostomy insertion in our institution's endoscopy suite between January 2002 and January 2017. Descriptive statistics summarized numeric variables using medians and corresponding ranges (minimum-maximum), and categorical variables using frequencies and percentages. Differences in study outcomes between patients undergoing general anesthesia or monitored anesthesia care were evaluated with univariate quantile or Firth logistic regression for numerical and categorical outcomes, respectively. Results are presented as ß [95% confidence interval] or odds ratio [95% confidence interval] along with corresponding p-values. RESULTS: Both groups were similar in distribution of age, race, and gender. However, patients selected for general anesthesia had lower median body weights (3.9 kg [range: 2.0-6.7] vs. 4.4 kg [range: 2.6-6.9]), higher percentages of cardiac (95.2% vs. 84.1%), and/or neurologic comorbidities (74.3% vs. 56.8%) and were more frequently given American Society of Anesthesiologists level IV classifications (41.9% vs. 29.6%) indicating that these infants may have had more severe disease than patients selected for monitored anesthesia care. Three monitored-anesthesia-care patients required intraoperative conversion to general anesthesia. General anesthesia patients experienced greater odds of intraoperative hypoxemia (45.2% vs. 29.0%; odds ratio: 2.0 [0.9-4.3], p-value: .09) and required postoperative airway intervention more frequently than monitored-anesthesia-care patients (13.03% vs. 2.3%; odds ratio: 4.6 [0.8-25.6], p-value: .08). Procedure times were identical in both groups (6 min), but general anesthesia resulted in longer median anesthesia times (44 min [range: 22-292] vs. 12 min [range:19-136]; ß:13 [95% 6.9-19.1], p-value: < .001). CONCLUSION: Study results suggest that providers selected general anesthesia over monitored anesthesia care for infants and neonates with low body weights, cardiac comorbidities, and neurologic comorbidities. Increased rates of airway intervention, and increased length of stay may be at least partially related to more severe patient comorbidity, as indicated by higher American Society of Anesthesiologists classifications. However, due to the exploratory nature of these analyses, further confirmatory studies are needed to evaluate the impact of airway selection during PEG on postoperative patient outcomes.

Assessing Preseason Baseline Cognitive Functioning in High School Student Athletes: A "Hybrid" Approach.

OBJECTIVE: International consensus statements highlight the value of neuropsychological testing for sport-related concussion. Computerized measures are the most frequently administered assessments of pre-injury baseline and post-injury cognitive functioning, despite known measurement limitations. To our knowledge, no studies have explored the convergent validity of computerized Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and traditional, well-validated paper and pencil (P&P) neuropsychological tests in high school student athletes. This study aimed to assess a "hybrid" adolescent test battery composed of ImPACT and P&P measures to determine the extent of shared variance among ImPACT and P&P tests to inform comprehensive yet streamlined assessment. METHOD: Participants included male and female high school student athletes in the Southeastern United States participating in American football, hockey, and soccer who completed a battery of ImPACT and P&P tests (N = 69). RESULTS: We performed principal component analysis with ProMax rotation to determine components of the hybrid battery that maximally accounted for observed variance of the data (Kaiser-Meyer-Olkin factor adequacy = 0.71). Our analysis revealed four independent factors (Verbal Learning and Memory, ImPACT Memory and Speed, Verbal Processing Speed/Executive Functions, and Nonverbal Processing Speed/Executive Functions) explaining 75% of the variance. CONCLUSIONS: Findings of this study in adolescent student athletes support those from the adult literature demonstrating the independence of ImPACT and P&P tests. Providers should be aware of limitations in using standalone ImPACT or P&P measures to evaluate cognitive functioning after concussion. If confirmed in a larger, clinical sample, our findings suggest that a hybrid battery of computerized and P&P measures provides a broad scope of adolescent cognitive functioning to better inform recovery decisions, including return to play after concussion.

Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial.

BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

Defining the Healthy Infant Metabolome: Liquid Chromatography Tandem-Mass Spectrometry Analysis of Dried Blood Spot Extracts from the Prospective Research on Early Determinants of Illness and Children's Health Trajectories Birth Cohort Study.

Newborn screening using dried plasma spots offers preanalytical advantages over conventional cards for plasma-associated targets of interest. Herein we present dried plasma spot-based methods for measuring metabolites using a 250+ compound liquid chromatography tandem mass spectrometry library. Quality assurance reduced this library to 134, and from these, 30 compounds determined the normal newborn reference ranges.

A New Risk Assessment Model for Hospital-Acquired Venous Thromboembolism in Critically Ill Children: A Report From the Children's Hospital-Acquired Thrombosis Consortium.

OBJECTIVES: To create a risk model for hospital-acquired venous thromboembolism in critically ill children upon admission to an ICU. DESIGN: Case-control study. SETTING: ICUs from eight children's hospitals throughout the United States. SUBJECTS: Critically ill children with hospital-acquired venous thromboembolism (cases) 0-21 years old and similar children without hospital-acquired venous thromboembolism (controls) from January 2012 to December 2016. Children with a recent cardiac surgery, asymptomatic venous thromboembolism, or a venous thromboembolism diagnosed before ICU admission were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The multi-institutional Children's Hospital-Acquired Thrombosis registry was used to identify cases and controls. Multivariable logistic regression was used to determine the association between hospital-acquired venous thromboembolism and putative risk factors present at or within 24 hours of ICU admission to develop the final model. A total of 548 hospital-acquired venous thromboembolism cases (median age, 0.8 yr; interquartile range, 0.1-10.2) and 187 controls (median age, 2.4 yr; interquartile range, 0.2-8.3) were analyzed. In the multivariable model, recent central venous catheter placement (odds ratio, 4.4; 95% CI, 2.7-7.1), immobility (odds ratio 3.6, 95% CI, 2.1-6.2), congenital heart disease (odds ratio 2.9, 95% CI, 1.7-4.7), length of hospital stay prior to ICU admission greater than or equal to 3 days (odds ratio, 2.5; 95% CI, 1.1-5.6), and history of autoimmune/inflammatory condition or current infection (odds ratio, 2.1; 95% CI, 1.2-3.4) were each independently associated with hospital-acquired venous thromboembolism. The risk model had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.73-0.84). CONCLUSIONS: Using the multicenter Children's Hospital-Acquired Thrombosis registry, we identified five independent risk factors for hospital-acquired venous thromboembolism in critically ill children, deriving a new hospital-acquired venous thromboembolism risk assessment model. A prospective validation study is underway to define a high-risk group for risk-stratified interventional trials investigating the efficacy and safety of prophylactic anticoagulation in critically ill children.

Impact of Coronavirus-2019 On Pediatric and Adult Heart Transplantation Waitlist Activity and Mortality in The United States: A Descriptive Approach.

BACKGROUND: Transplant centers saw a substantial reduction in deceased donor solid organ transplantation since the beginning of the coronavirus 2019 (COVID-19) pandemic in the United States. There is limited data on the impact of COVID-19 on adult and pediatric heart transplant volume and variation in transplant practices. We hypothesized that heart transplant activity decreased during COVID-19 with associated increased waitlist mortality. METHODS: The United Network for Organ Sharing (UNOS) database was used to identify patients at the time of listing for heart transplant from 2017-2020. Patients were categorized as pediatric (<18 years) or adult (≥18 years) and as pre-COVID (2017-2019) or post-COVID (2020). Regional and statewide data were taken from United States Census Bureau. CovidActNow project was used to obtain COVID-19 mortality rates. FINDINGS: Among pediatric patients, average time on the waiting list decreased by 28 days. Even though the average number of pediatric transplants (n=39 per month) did not change significantly during 2020, there was a temporal decline in the first quarter of 2020 followed by a sharp increase. Overall absolute pediatric waitlist mortality decreased from 5•31 to 4•73, however female mortality increased by 2%. Regional differences in pediatric mortality were observed: Northeast, decreased by 7•5%; Midwest, decreased by 9%; West, increased by 3•5%; and South, increased by 13%. North Dakota (0•55), Oklahoma (0•21) and Hawaii (0•33) showed higher mortality than other states per 100,000. In adults, average time on waiting list increased by 40 days and there was an increase in the number of transplants from 242 to 266. Adult waitlist mortality had a larger decrease, 18•44 to 15•70, with an increase in female mortality of 7%. Regional differences in adult mortality were also observed: Northeast, decreased by 3%; Midwest, increased by 5•5%; West, increased by 4•5% and South, decreased by 5%. Iowa (0•37), Wyoming (0•22), Arkansas (0•18) and Vermont (0•19) had the highest mortality per 100,000 compared to the other states. INTERPRETATION: Pediatric heart transplant volume declined in early 2020 followed by a later increase, while adult transplant volume increased all year round. Although, overall pediatric waitlist mortality decreased, female waitlist mortality increased for both adults and pediatrics. Regional differences in waitlist mortality were observed for both pediatrics and adults. Future studies are needed to understand this initial correlation and to determine the impact of COVID-19 on heart transplant recipients. FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Volatile anesthetic agents for life-threatening pediatric asthma: A multicenter retrospective cohort study and narrative review.

BACKGROUND: Volatile anesthetic agents are described as rescue therapy for children invasively ventilated for critical asthma. Yet, data are currently limited to case series. AIMS: Using the Virtual Pediatric Systems database, we assessed children admitted to a pediatric intensive care unit invasively ventilated for life-threatening asthma and hypothesized ventilation duration and mortality rates would be lower for subjects exposed to volatile anesthetics compared with those without exposure. METHODS: We performed a multicenter retrospective cohort study among nine institutions including children 5-17 years of age invasively ventilated for asthma from 2013 to 2019 with and without exposure to volatile anesthetics. Primary outcomes were ventilation duration and mortality. Secondary outcomes included patient characteristics, length of stay, and anesthetic-related adverse events. A subgroup analysis was performed evaluating children intubated ≥2 days. RESULTS: Of 203 children included in study, there were 29 (14.3%) with and 174 (85.7%) without exposure to volatiles. No differences in odds of mortality (1.1, 95% CI: 0.3-3.9, p > .999) were observed. Subjects receiving volatiles experienced greater median difference in length of stay (4.8, 95% CI: 1.9-7.8 days, p < .001), ventilation duration (2.3, 95% CI: 1-3.3 days, p < .001), and odds of extracorporeal life support (9.1, 95% CI: 1.9-43.2, p = .009) than those without volatile exposure. For those ventilated ≥2 days, no differences were detected in mortality, ventilation duration, length of stay, arrhythmias, or acute renal failure. However, the odds of extracorporeal life support remained greater for those receiving volatiles (7.6, 95% CI: 1.3-44.5, p = .027). No children experienced malignant hyperthermia or hepatic failure after volatile exposure. CONCLUSIONS: For intubated children for asthma, no differences in mechanical ventilation duration or mortality between those with and without volatile anesthetic exposure were observed. Although volatiles may represent a viable rescue therapy for severe cases of asthma, definitive, and prospective trials are still needed.

Measuring the Validity and Reliability of the Vascular Access Complication Staging and Treatment Instrument in a Pediatric Population.

A multiphase study designed with Delphi and observational components was conducted to establish the preliminary validity and reliability of the 2018 Vascular Access Complication Staging and Treatment Instrument in pediatric and neonatal populations from a single, free-standing academic children's hospital. The instrument uses objective measurement criterion to determine the severity of swelling and tissue damage to inform treatment decisions. The results of the study provided preliminary empirical evidence to support a pediatric and neonatal intravenous complication staging instrument to assess degree of swelling and severity of tissue injury. The study also offered preliminary evidence that the instrument was perceived by the nurses who participated in the study to be efficient and easy to use.

Plasma fibrinolysis, inflammatory markers, and postthrombotic syndrome: preliminary findings from the Kids-DOTT Biobank.

Plasma levels of markers of coagulation and inflammation have been identified as prognostic factors for adult postthrombotic syndrome (PTS). We aimed to determine whether plasma fibrinolytic capacity and cytokine levels during the first 3 months after provoked deep venous thrombosis (DVT) are associated with risk of PTS in young patients. We analyzed plasma biospecimens (6 weeks and 3 months after provoked DVT) and clinical data from a National Heart, Lung, and Blood Institute-sponsored multinational trial of anticoagulation for provoked venous thromboembolism in patients younger than age 21 years (Kids-DOTT). Patients with a provoked extremity DVT who had plasma samples available at both 6-week and 3-month post-DVT time points and PTS assessment at 1 year were included. We measured plasma fibrinolytic capacity using the Clot Formation and Lysis (CloFAL) assay and plasma cytokine levels by multiplex immunoassay. Logistic regression analyses evaluated prognostic associations with PTS. Seventy-nine patients were included (median age, 12.8 years; range, 0.04-20.8 years). PTS developed in 34%. Complete veno-occlusion at 6 weeks after diagnosis of DVT (odds ratio [OR], 3.12; 95% confidence interval [CI], 0.81-11.94; P = .097), low fibrinolytic capacity in plasma at 3 months post-DVT (OR, 2.71; 95% CI, 0.92-7.97; P = .07), and elevated serum amyloid A at 3 months post-DVT (OR, 2.85; 95% CI, 0.98-8.34; P = .055) were identified as putative prognostic factors for development of PTS. In multivariable logistic regression analysis, these factors did not retain a statistically significant independent association with PTS, but these preliminary results warrant further investigation in an independent data set to definitively evaluate these findings and identify additional potential prognostic factors for the development of PTS after a provoked DVT in young patients.

Airway Management for Initial PEG Insertion in the Pediatric Endoscopy Unit: A Retrospective Evaluation of 168 Patients.

PURPOSE: Percutaneous endoscopic gastrostomy (PEG) tube placements are commonly performed pediatric endoscopic procedures. Because of underlying disease, these patients are at increased risk for airway-related complications. This study compares patient characteristics and complications following initial PEG insertion with general endotracheal anesthesia (GETA) vs. anesthesia-directed deep sedation with a natural airway (ADDS). METHODS: All patients 6 months to 18 years undergoing initial PEG insertion within the endoscopy suite were considered for inclusion in this retrospective cohort study. Selection of GETA vs. ADDS was made by the anesthesia attending after discussion with the gastroenterologist. RESULTS: This study included 168 patients (GETA n=38, ADDS n=130). Cohorts had similar characteristics with respect to sex, race, and weight. Compared to ADDS, GETA patients were younger (1.5 years vs. 2.9 years, p=0.04), had higher rates of severe American Society of Anesthesiologists (ASA) disease severity scores (ASA 4-5) (21% vs. 3%, p<0.001), and higher rates of cardiac comorbidities (39.5% vs. 18.5%, p=0.02). Significant associations were not observed between GETA/ADDS status and airway support, 30-day readmission, fever, or pain medication in unadjusted or adjusted models. GETA patients had significantly increased length of stay (eß=1.55, 95% confidence interval [CI]=1.11-2.18) after adjusting for ASA class, room time, anesthesia time, fever, and cardiac diagnosis. GETA patients also had increased room time (eß=1.20, 95% CI=1.08-1.33) and anesthesia time (eß=1.50, 95% CI=1.30-1.74) in adjusted models. CONCLUSION: Study results indicate that younger and higher risk patients are more likely to undergo GETA. Children selected for GETA experienced longer room times, anesthesia times, and hospital length of stay.