Pediatric Hematology and Oncology Patients on Extracorporeal Membrane Oxygenation: Outcomes in a Multicenter, Retrospective Cohort 2009-2021.

OBJECTIVE: To describe characteristics associated with survival for pediatric patients with an oncologic diagnosis or hematopoietic cell transplant (HCT) supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Multicenter, retrospective study. SETTING: Sixteen PICUs in the United States and Israel. PATIENTS: We included patients aged younger than 19 years with an oncologic diagnosis or HCT who required ECMO support between 2009 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 149 patients were included in the study cohort. There were 118 patients with an oncologic diagnosis and 31 that received HCT. The indications for ECMO were respiratory failure (46%), combined respiratory and cardiac failure (28%), and cardiac failure (25%). Venovenous (V-V) ECMO was used in 45% of patients, with 53% of patients being placed on venoarterial (V-A) ECMO. For oncologic and HCT groups, survival to ECMO decannulation was 52% (62/118) and 64% (20/31), and survival to hospital discharge was 36% (43/118) and 42% (13/31), respectively. After adjusting for other factors, requiring cardiopulmonary resuscitation was associated with greater odds ratio of mortality (3.0 [95% CI, 1.2-7.7]). CONCLUSIONS: Survival to ECMO decannulation of pediatric oncologic and HCT patients in this study was 52-64%, depending upon diagnosis. However, survival to hospital discharge remains poor. Future research should prioritize understanding factors contributing to this survival gap within these patient populations.

Case Report: Congenital tuberculosis in a premature infant requiring extracorporeal membrane oxygenation.

Congenital tuberculosis is a rare infectious disease with less than 500 cases documented worldwide. Mortality is significant, ranging from 34 to 53%, and death without treatment is inevitable. Patients exhibit nonspecific symptoms such as fever, cough, respiratory distress, feeding intolerance, and irritability which can make appropriate diagnosis challenging in Peng et al. (2011) Pediatr Pulmonol 46(12), 1215-1224. Tuberculosis prevalence is particularly high in developing countries where access to resources can be limited in World Health Organization (2019) Global tuberculosis report 2019, Geneva. We present a 2.4-kg premature male infant with acute respiratory distress syndrome secondary to congenital tuberculosis caused by Mycobacterium bovis and tuberculosis-immune reconstitution inflammatory syndrome who was successfully supported with veno-arterial extracorporeal membrane oxygenation.

2021 Year in Review: Pediatric Mechanical Ventilation.

Mechanical ventilation is commonly used in the pediatric intensive care unit. This paper reviews studies of pediatric mechanical ventilation published in 2021. Topics include physiology, ventilator modes, alarms, disease states, airway suctioning, ventilator liberation, prolonged ventilation, and others.

Anonymous Reporting Systems for School-Based Violence Prevention: A Systematic Review.

IMPACT STATEMENT: Anonymous reporting systems (ARS) have been used as a violence prevention strategy in schools by providing a means for individuals within a school community to safely and securely report information about potential violence or concerns about mental health, for example, through an anonymous hotline or reporting app. Despite widespread implementation of ARS in schools, as well as mandates for reporting systems in schools in 21 states, there is limited evidence on the effectiveness of ARS for school violence prevention, and information about best practices for ARS implementation is lacking. This systematic review aims to summarize the current research on the effectiveness of ARS as a school safety and violence prevention strategy, which is an important step in building an evidence-base to guide schools and policymakers about best practices.

The Protective Effects of Social Support on Hypertension Among African American Adolescents Exposed to Violence.

African Americans develop hypertension earlier in life than Whites and the racial/ethnic disparities in blood pressure level can appear as early as adolescence. Violence victimization, a prevalent environmental stressor among inner-city youth, may play a role in such disparities. In a sample of inner-city youth in the United States, the current study examines the relationship between violence victimization and hypertension while investigating the role of social support in moderating that relationship. We analyzed eight waves of data from a longitudinal study of African American youth (n = 353, 56.7% female) from mid-adolescence (9th grade, mean age = 14.9 years old) to emerging adulthood (mean age = 23.1 years old) using probit regression. Higher levels of self-reported violence victimization during ages 14-18 was associated with more reports of hypertension during ages 20-23, after adjusting for sex, socioeconomic status, substance use, and mental distress. The relationship of violence victimization with hypertension was moderated by friends' support, but not parental support. The association between victimization and hypertension was weaker and non-significant among individuals with more peer support compared to those with less support. Researchers have reported many instances of associations of early violence exposure to later risk for hypertension; however, most have focused on childhood maltreatment or intimate partner violence. We extend these findings to violence victimization in an African American sample of youth from adolescence to early adulthood, while examining social support modifiers. The disparity in African American hypertension rates relative to Whites may partly be explained by differential exposure to violence. Our findings also suggest that having supportive friends when faced with violence can be beneficial for young adulthood health outcomes.

A narrative review of advanced ventilator modes in the pediatric intensive care unit.

Respiratory failure is a common reason for pediatric intensive care unit admission. The vast majority of children requiring mechanical ventilation can be supported with conventional mechanical ventilation (CMV) but certain cases with refractory hypoxemia or hypercapnia may require more advanced modes of ventilation. This paper discusses what we have learned about the use of advanced ventilator modes [e.g., high-frequency oscillatory ventilation (HFOV), high-frequency percussive ventilation (HFPV), high-frequency jet ventilation (HFJV) airway pressure release ventilation (APRV), and neurally adjusted ventilatory assist (NAVA)] from clinical, animal, and bench studies. The evidence supporting advanced ventilator modes is weak and consists of largely of single center case series, although a few RCTs have been performed. Animal and bench models illustrate the complexities of different modes and the challenges of applying these clinically. Some modes are proprietary to certain ventilators, are expensive, or may only be available at well-resourced centers. Future efforts should include large, multicenter observational, interventional, or adaptive design trials of different rescue modes (e.g., PROSpect trial), evaluate their use during ECMO, and should incorporate assessments through volumetric capnography, electric impedance tomography, and transpulmonary pressure measurements, along with precise reporting of ventilator parameters and physiologic variables.

High-Frequency Jet Ventilation in Infants With Congenital Heart Disease.

BACKGROUND: High-frequency jet ventilation (HFJV) is primarily used in neonates but may also have a role in the treatment of infants with congenital heart disease and severe respiratory failure. We hypothesized that HFJV would result in improved gas exchange in these infants. METHODS: We retrospectively reviewed the records of all pediatric patients with complex congenital heart disease treated HFJV in our pediatric cardiac ICU between 2014 and 2018. Patients in whom HFJV was started while on extracorporeal membrane oxygenation (ECMO) were excluded. We extracted data on demographics, pulmonary mechanics, gas exchange, the subsequent need for ECMO, use of inhaled nitric oxide, and outcomes. RESULTS: We included 27 subjects (median [interquartile range {IQR}] weight 4.4 [3.3-5.4] kg; median [IQR] age 2.5 [0.3-5.4] months), 22 (82%) of whom had cyanotic heart disease. Thirteen subjects (48%) survived and 6 (22%) required ECMO. HFJV was started after a median (IQR) of 8.4 (2.1-26.3) d of conventional mechanical ventilation. The subjects spent a median (IQR) of 1.2 (0.5-2.8) d on HFJV. The median (IQR) pre-HFJV blood gas results (n = 25) were pH 7.22 (7.17-7.31), [Formula: see text] 69 (51-77) mm Hg, and [Formula: see text] 51 (41-76) mm Hg. Median (IQR) initial HFJV settings were peak inspiratory pressure of 45 (36-50) cm H2O, breathing frequency of 360 (360-380) breaths/min, and inspiratory time of 0.02 (0.02-0.03) s. Compared with conventional mechanical ventilation, at 4-6 h after HFJV initiation, there were significant improvements in the median pH (7.22 vs 7.34; P = .001) and [Formula: see text] (69 vs 50 mm Hg; P = .001), respectively, but no difference in median [Formula: see text] (51 vs 53 mm Hg; P = .97). CONCLUSIONS: HFJV was associated with a decrease in [Formula: see text] and an increase in pH in infants with congenital heart disease who remained on HFJV 4 to 6 h after initiation.

Extracorporeal membrane oxygenation in critically ill neonatal and pediatric patients with acute respiratory failure: a guide for the clinician.

Intro: Extracorporeal membrane oxygenation for neonatal and pediatric respiratory failure continues to demonstrate improving outcomes, largely due to advances in technology along with refined management strategies despite mounting patient acuity and complexity. Successful use of ECMO requires thoughtful initiation and candidacy strategies, along with reducing the risk of ventilator induced lung injury and the progression to multiorgan failure.Areas Covered: This review describes current ECMO management strategies for neonatal and pediatric patients with acute refractory respiratory failure and summarizes relevant published literature. ECMO initiation and candidacy, along with ventilator and sedation management, are highlighted. Additionally, rapidly expanding areas of interest such as anticoagulation strategies, transfusion thresholds, rehabilitation on ECMO, and drug pharmacokinetics are described.Expert Opinion: Over the last few decades, published studies supporting ECMO use for acute refractory respiratory failure, along with institutional experience, have resulted in increased utilization although more randomized-controlled trials are needed. Future research should focus on filling the knowledge gaps that remain regarding anticoagulation, transfusion thresholds, ventilator strategies, sedation, and approaches to rehabilitation to subsequently implement into clinical practice. Additionally, efforts should focus on well-designed trials, including population pharmacokinetic studies, to develop dosing recommendations.

Crisis Interventions in Schools: A Systematic Review.

This systematic review synthesizes research on school-based crisis intervention protocols, descriptions, and evaluations. We performed a comprehensive literature search, and 60 studies met the inclusion criteria for this review. We found an overwhelming lack of evaluation studies (n=3), suggesting that interventions are being administered post-crises without evaluation. The most frequently named crisis intervention model was the Prevent/Prepare, Reaffirm, Evaluate, Provide and Respond, and Examine (PREPaRE) model (n=6). All evaluation studies in the sample were observational, and most adopted qualitative methods of evaluation. Future studies are needed to evaluate crisis interventions to measure the fidelity, reliability, and effectiveness of such interventions.

Anticoagulation and Transfusion Management During Neonatal and Pediatric Extracorporeal Membrane Oxygenation: A Survey of Medical Directors in the United States.

OBJECTIVES: To compare current practices within the United States of anticoagulation management and blood transfusion in neonatal and pediatric extracorporeal membrane oxygenation patients with a 2013 international report. DESIGN: Cross-sectional survey distributed between August and December 2019. SETTING: Extracorporeal Life Support Organization-registered neonatal and pediatric extracorporeal membrane oxygenation centers in the United States. PARTICIPANTS: Extracorporeal membrane oxygenation medical directors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-three medical directors at 108 centers responded. After removing four duplicate responses, 79 surveys were analyzed. Seventy-nine percent (n = 62) report a written extracorporeal membrane oxygenation protocol for both anticoagulation and blood product management. Ninety-four percent (n = 74) report unfractionated heparin as their primary anticoagulant; the remaining use the direct thrombin inhibitor, bivalirudin. Ninety percent (n = 71) report measuring antifactor Xa levels. Most centers report using a combination of assays to monitor heparin therapy, either antifactor Xa and activated partial thromboplastin time (54%) or more commonly antifactor Xa and activated clotting time (68%). Forty-one percent use viscoelastic tests to aid management. Goal monitoring levels and interventions generated by out of range values are variable. Fifty-one percent will replace antithrombin. Platelet transfusion thresholds vary by age and center with ranges from 50,000 to 100,000 cells/µL. Eighty-two percent of respondents are willing to participate in a randomized controlled trial comparing anticoagulation strategies for patients receiving extracorporeal membrane oxygenation. CONCLUSIONS: Compared with the 2013 pediatric population, extracorporeal membrane oxygenation center anticoagulation and blood transfusion approaches continue to vary widely. Most report continued use of heparin as their primary anticoagulant and follow a combination of monitoring assays with the majority using the antifactor Xa assay in their practices, a significant shift from prior results. Antithrombin activity levels and viscoelastic tests are followed by a growing number of centers. Platelet transfusion thresholds continue to vary widely. Future research is needed to establish optimal anticoagulation and blood transfusion management.

The Longitudinal Association Between Exposure to Violence and Patterns of Health Risk Behaviors Among African American Youth.

PURPOSE: We investigate whether exposure to violence (ETV) during adolescence and emerging adulthood predicts engagement in chronic disease-related health risk behaviors years later among African Americans. DESIGN: A longitudinal study following youth from mid-adolescence (mean age = 14.8 years) to young adulthood (mean age = 32.0 years). SETTING: Flint, Michigan. SAMPLE: Four hundred forty-two African American (96.2%) and mixed African American and White (3.8%) participants. MEASURES: Outcomes were diet, smoking, drinking, and physical inactivity. Covariates were ETV, sex, mother's educational attainment, and substance use by siblings, peers, and parents. ANALYSIS: Latent profile analysis was conducted to identify distinct patterns of adult health risk behaviors and assess the association of youth ETV and identified patterns. RESULTS: Four latent profiles were identified: high substance use (n = 46; 10.41%), high overall risk (n = 71; 16.06%), low overall risk (n = 140; 31.67%) and inactive (n = 185, 41.86%). Relative to the low overall risk profile, ETV was associated with being in the high overall risk profile (b = 0.37, p = 0.04), but not other profiles. Female gender and higher maternal education were associated with being in the inactive profile compared to the low overall risk profile. Peer alcohol and tobacco use were associated with being in the high substance use profile. CONCLUSION: ETV during adolescence and emerging adulthood increased the risk of engagement in multiple health risk behaviors later in life.

Pharmacokinetic, efficacy, and safety considerations for the use of antifungal drugs in the neonatal population.

INTRODUCTION: Invasive fungal infections are an important cause of morbidity and mortality in infants, particularly in extreme prematurity. Successful systemic treatment requires consideration of antifungal efficacy, safety, and pharmacokinetics, including optimization of dosing in this population. AREAS COVERED: This review summarizes published pharmacokinetic data on four classes of antifungal agents used in the neonatal population. Alterations in absorption, distribution, drug metabolism and clearance in infants compared to adult populations are highlighted. Additionally, pharmacodynamics, safety, and therapeutic drug monitoring are discussed. Recent advancements in neonatal antifungal pharmacotherapies are examined, with emphasis on clinical application. EXPERT OPINION: Over the last two decades, published studies have provided increased knowledge on pharmacokinetic considerations in the neonatal population. Future research should focus on filling in the knowledge gaps that remain regarding the benefits and risks of combination antifungal therapy, the rising use of micafungin for invasive candidiasis given its fungicidal activity against polyene and azole-resistant Candida species and its minimal adverse effect profile, and the need for pharmacokinetic and safety data of broad spectrum triazoles, like voriconazole and posaconazole, in infants. Furthermore, efforts should focus on well-designed trials, including population pharmacokinetic studies, to develop dosing recommendations with subsequent implementation into clinical practice.

Histoplasmosis Myocarditis in an Immunocompetent Host After a Recreational Mud Run.

Mud runs are an increasingly popular recreational fitness activity across the United States, combining a running race through an obstacle course with submersion in mud. Recent reports estimate 4 million people have participated in these types of events over the last 5 years. We describe an atypical case of myocarditis and multiorgan failure from disseminated histoplasmosis in a previously healthy pediatric patient, likely acquired during participation in a mud run. Although cases of histoplasmosis-associated endocarditis and pericarditis have been reported in the literature, cases of histoplasmosis myocarditis are rare.

Development of an oral operant nicotine/ethanol co-use model in alcohol-preferring (p) rats.

BACKGROUND: Alcohol abuse is frequently associated with nicotine (Nic) use. The current experiments were conducted to establish an oral operant ethanol + Nic (EtOH + Nic) co-use model and to characterize some aspects of EtOH + Nic co-use. METHODS: Rats were allowed to choose between EtOH alone or EtOH + Nic solutions. Additionally, alcohol-preferring (P) rats were allowed to concurrently self-administer 3 distinct EtOH solutions (10, 20, and 30%) with varying amounts of Nic (0.07, 0.14, or 0.21 mg/ml) under operant conditions. P rats were also allowed to concurrently self-administer 2 distinct amounts of Nic (0.07 and 0.14 mg/ml) added to saccharin (Sacc; 0.025%) solutions. RESULTS: During acquisition, P rats responded for the EtOH + Nic solutions at the same level as for EtOH alone, and responding for EtOH + Nic solutions was present throughout all drinking conditions. P rats also readily maintained stable self-administration behaviors for Nic + Sacc solutions. The results demonstrated that P rats readily acquired and maintained stable self-administration behaviors for EtOH + 0.07 and EtOH + 0.14 mg/ml Nic solutions. Self-administration of EtOH + 0.21 mg/ml Nic was established in only 50% of the subjects. P rats readily expressed seeking behaviors for the EtOH + Nic solutions and reacquired EtOH + Nic self-administration during relapse testing. In addition, tail blood samples indicated that EtOH + Nic co-use resulted in pharmacologically relevant levels of both EtOH and Nic in the blood. CONCLUSIONS: Overall, the results indicate that P rats readily consume EtOH + Nic solutions concurrently in the presence of EtOH alone, express drug-seeking behaviors, and will concurrently consume physiologically relevant levels of both drugs. These results support the idea that this oral operant EtOH + Nic co-use model would be suitable for studying the development of co-abuse and the consequences of long-term chronic co-abuse.