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The United States Southern Ocean Joint Global Ocean Flux Study (JGOFS), also known as AESOPS (Antarctic Environment and Southern Ocean Process Study), focused on two distinct regions. The first was the Ross-Sea continental shelf, where a series of six cruises collected a variety of data from October 1996 through February 1998. The second area was the southwest Pacific sector of the Southern Ocean, spanning the Antarctic Circumpolar Current (ACC) at ∼ 170°W. Data were collected within this region during five cruises from September 1996 through March 1998, as well as during selected transits between New Zealand and the Ross Sea. The first results of these cruises are described in this issue. The Ross-Sea investigation extensively sampled the area along 76°30′S to elucidate the temporal patterns and processes that contribute to making this one of the Antarctic's most productive seas. Hydrographic distributions confirm that stratification is initiated early in October within the polynya, generating an environment that is favorable for phytoplankton growth. Significant spatial variations in mixed-layer depths, the timing of the onset of stratification, and the strength of the stratification existed throughout the growing season. Nutrient concentrations reflected phytoplankton uptake, and reached their seasonal minimal in early February. Chlorophyll concentrations were maximal in early January, whereas productivity was maximal in late November, which reflects the temporal uncoupling between growth and biomass accumulation in the region. Independent estimates of biogenic export suggest that majority of the flux occurred in late summer and was strongly uncoupled from phytoplankton growth. The ACC region exhibited seasonal changes that in some cases were greater than those observed in the Ross Sea.

Rationale: Both insulin-like growth factor (IGF)-1 and bacterial clearance by Kupffer cells are significantly reduced in severe sepsis. Kupffer cell apoptosis is triggered by tumor necrosis factor (TNF)-alpha and activation of the PI-3 kinase pathway prevents TNF-induced Kupffer cell death.Objectives: We evaluated if the marked decline in IGF-1 is related to bacterial clearance in sepsis.Methods: Sepsis was induced in C57BL/6 mice by intratracheal inoculation with Pseudomonas aeruginosa (strain PA103). Some mice received IGF-1 24 mg/kg either before infection or 12 hours after infection. In vitro studies were performed using the clonal Kupffer cell line KC13-2.Measurements and Main Results: Sepsis resulted in decreased levels of IGF-1. In vitro studies with KC13-2 cells demonstrated that IGF-1 protected Kupffer cells against TNF-alpha-induced apoptosis by activating the PI-3 kinase pathway and stabilizing the inhibitor of apoptosis protein, XIAP. In the animal model, pretreatment with IGF-1 decreased hepatic TNF-alpha and IL-6, improved hepatic bacterial clearance as demonstrated by real-time polymerase chain reaction with primers specific for P. aeruginosa, and improved survival in severe sepsis. Moreover, we rescued mice from severe sepsis by IGF-1 treatment 12 hours after infection.Conclusions: These studies show that the decline in IGF-1 levels in sepsis is related to bacterial clearance and that replacement of IGF-1 in a murine model of sepsis improves overall survival. [ABSTRACT FROM AUTHOR]

Background: Corticosteroids and antiviral agents are widely used to treat the early stages of idiopathic facial paralysis (i.e., Bell's palsy), but their effectiveness is uncertain.Methods: We conducted a double-blind, placebo-controlled, randomized, factorial trial involving patients with Bell's palsy who were recruited within 72 hours after the onset of symptoms. Patients were randomly assigned to receive 10 days of treatment with prednisolone, acyclovir, both agents, or placebo. The primary outcome was recovery of facial function, as rated on the House-Brackmann scale. Secondary outcomes included quality of life, appearance, and pain.Results: Final outcomes were assessed for 496 of 551 patients who underwent randomization. At 3 months, the proportions of patients who had recovered facial function were 83.0% in the prednisolone group as compared with 63.6% among patients who did not receive prednisolone (P<0.001) and 71.2% in the acyclovir group as compared with 75.7% among patients who did not receive acyclovir (adjusted P=0.50). After 9 months, these proportions were 94.4% for prednisolone and 81.6% for no prednisolone (P<0.001) and 85.4% for acyclovir and 90.8% for no acyclovir (adjusted P=0.10). For patients treated with both drugs, the proportions were 79.7% at 3 months (P<0.001) and 92.7% at 9 months (P<0.001). There were no clinically significant differences between the treatment groups in secondary outcomes. There were no serious adverse events in any group.Conclusions: In patients with Bell's palsy, early treatment with prednisolone significantly improves the chances of complete recovery at 3 and 9 months. There is no evidence of a benefit of acyclovir given alone or an additional benefit of acyclovir in combination with prednisolone. (Current Controlled Trials number, ISRCTN71548196 [controlled-trials.com].). [ABSTRACT FROM AUTHOR]

Background/Objectives : Prior studies suggest that blood transfusion may adversely affect the survival of patients with cancer via transfusion-related immunomodulation. The objective of our study is to investigate the association between transfusion during neoadjuvant chemotherapy and survival in children, adolescent, and young adult (CAYA, 39 years old or younger) patients with osteosarcoma. Methods : This is a multicenter retrospective cohort study of patients between 2007 and 2022. Our primary exposure was receipt of any blood product in the neoadjuvant period (i.e., neoadjuvant transfusion). The primary outcome of interest was 3-year event-free survival (EFS) calculated using the Kaplan-Meier method, while secondary outcomes of interest included 5-year EFS and 3- and 5-year overall survival (OS). Firth multivariable logistic regression models were constructed to evaluate the adjusted association between transfusion status and 3- and 5-year EFS and OS. Results : In total, 73 patients were included in the analytic sample; among them, 34 received neoadjuvant transfusion. There was no significant difference between transfused and non-transfused groups in race, ethnicity, tumor location, stage at diagnosis, histologic response to neoadjuvant chemotherapy, and receipt of ifosfamide or radiation during initial treatment. The transfusion group included more females ( p = 0.02) and lower median hemoglobin at diagnosis ( p = 0.002) than the non-transfusion group. EFS and OS did not significantly vary by transfusion status or type. Conclusions : We did not observe an adjusted association between neoadjuvant transfusion and survival in CAYA patients with osteosarcoma.

Valence bond theory (VB) was used to determine the extent and driving forces for covalent vs. dative bonding in 10-valence-electron diatomic molecules N 2 , CO, NO + , CN - , P 2 , SiS, PS + , and SiP - . VBSCF calculations were performed at the CCSD(T)/cc-pVDZ optimized geometries. The full triply bonded system included 20 VB structures. A separation of the σ and π space allowed for a subdivision of the full 20 structure set into sets of 8 and 3 for the π and σ systems, respectively. The smaller structure sets allowed for a more focused look at each type of bond. In situ bond energies for σ bonds, individual π bonds, the π system, and triple bonds follow expected trends. Our data shows that N 2 and P 2 have three covalent bonds whereas CO and SiS contain two covalent and one dative bond, and charged species NO + , CN - , PS + , and SiP - are a mixture of N 2 and CO type electronic arrangements, resulting in a nearly equal charge distribution. Dative bonds prefer to be in the π position due to enhanced σ covalency and π resonance. Both σ and π resonance energies depend on a balance of ionic strength, orbital compactness, σ constraints, and bond directionality. Resonance energy is a major contributor to bond strength, making up more than 50% of the π bonds in SiS and PS + (charge-shift bonds), and is greater than charge transfer in dative bonds.

Objective: To characterize factors that influence the decision to treat suspected pediatric bacterial tracheostomy-associated respiratory infections (bTRAINs; e.g., pneumonia, tracheitis)., Methods: We conducted a multicenter, prospective cohort study of children with pre-existing tracheostomy hospitalized at six children's hospitals for a suspected bTRAIN (receipt of respiratory culture plus ≥1 doses of an antibiotic within 48 h). The primary predictor was respiratory culture growth categorized as Pseudomonas aeruginosa, P. aeruginosa + ≥1 other bacterium, other bacteria alone, or normal flora/no growth. Our primary outcome was bTRAIN treatment with a complete course of antibiotics as documented by the discharge team. We used logistic regression with generalized estimating equations to identify the association between our primary predictor and outcome and to identify demographic, clinical, and diagnostic testing factors associated with treatment., Results: Of the 440 admissions among 289 patients meeting inclusion criteria, 307 (69.8%) had positive respiratory culture growth. Overall, 237 (53.9%) of admissions resulted in bTRAIN treatment. Relative to a negative culture, a culture positive for P. aeruginosa plus ≥1 other organism (adjusted odds ratio [aOR] 2.3; 95% confidence interval [CI] 1.02-5.0)] or ≥1 other organism alone (aOR: 2.8; 95% CI: 1.4-5.6)] was associated with treatment. Several clinical and diagnostic testing (respiratory Gram-stain and chest radiograph) findings were also associated with treatment. Positive respiratory viral testing was associated with reduced odds of treatment (aOR: 0.5; 95% CI: 0.2-0.9)., Conclusions: Positive respiratory cultures as well as clinical indicators of acute illness and nonculture test results were associated with bTRAIN treatment. Clinicians may be more comfortable withholding antibiotics when a virus is identified during testing., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Noninvasive respiratory support (NRS) for pediatric critical asthma includes CPAP; bi-level positive airway pressure (BPAP); and heated, humidified, high-flow nasal cannula (HFNC). We used the Virtual Pediatric System database to estimate NRS by prescribing rates for pediatric critical asthma and characterize patient clinical features and in-patient outcomes by the initial NRS device applied., Methods: We performed a retrospective cohort study from 125 participating pediatric ICUs among children 2-17 years of age hospitalized for critical asthma and prescribed NRS from 2017 through 2021. The primary outcomes were NRS modality prescribing rates and trends. Secondary outcomes were descriptive and included demographics, comorbidities, severity of illness indices, and NRS failure rates (defined as escalation from the initial NRS modality to invasive ventilation, HFNC to BPAP or CPAP, or CPAP to BPAP)., Results: Of the 10,083 encounters studied, the initial NRS modalities prescribed varied widely by hospital center (HFNC: 69.7 ± 29.6%; BPAP: 27.2 ± 7.1%; CPAP: 3.1 ± 5.9%). The mean rates of HFNC use increased from 59.7% in 2017 to 71.9% in 2021 (+2.5%/y). In contrast, BPAP (-1.6%/y) and CPAP (-0.8%/y) utilization declined throughout the study period. Older children who were obese and with a higher Pediatric Risk of Mortality III-Probability of Mortality score were more frequently prescribed BPAP and CPAP compared with HFNC. Those children on HFNC experienced higher noninvasive respiratory support failure rates versus BPAP (7.3% vs 2.4%; P < .001) but a lower subsequent invasive ventilation rate versus BPAP (0.8% vs 2.4%; P < .001)., Conclusions: In this multi-center cohort study, we observed that children with critical asthma are increasingly exposed to HFNC compared with BPAP and CPAP. Rates of HFNC failure were greater than those of BPAP failure, but a majority were transitioned to BPAP without subsequent invasive ventilation. The next steps include prospective trials, including practical end points such as patient comfort and optimal delivery of nebulized treatments to distinguish device superiority and suitable NRS utilization., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Objectives: Children with certain congenital anomalies of the kidney and urinary tract and neurogenic bladder (CAKUT/NGB) are at higher risk of treatment failure for urinary tract infections (UTIs) than children with normal genitourinary anatomy, but the literature describing treatment and outcomes is limited. The objectives of this study were to describe the rate of treatment failure in children with CAKUT/NGB and compare duration of antibiotics between those with and without treatment failure., Methods: Multicenter retrospective cohort of children 0 to 17 years old with CAKUT/NGB who presented to the emergency department with fever or hypothermia and were diagnosed with UTI between 2017 and 2018. The outcome of interest was treatment failure, defined as subsequent emergency department visit or hospitalization for UTI because of the same pathogen within 30 days of the index encounter. Descriptive statistics and univariates analyses were used to compare covariates between groups., Results: Of the 2014 patient encounters identified, 482 were included. Twenty-nine (6.0%) of the 482 included encounters had treatment failure. There was no difference in the mean duration of intravenous antibiotics (3.4 ± 2.5 days, 3.5 ± 2.8 days, P = .87) or total antibiotics between children with and without treatment failure (10.2 ± 3.8 days, 10.8 ± 4.0 days, P = .39) Of note, there was a higher rate of bacteremia in children with treatment failure (P = .04)., Conclusions: In children with CAKUT/NGB and UTI, 6.0% of encounters had treatment failure. Duration of antibiotics was not associated with treatment failure. Larger studies are needed to assess whether bacteremia modifies the risk of treatment failure., (Copyright © 2024 by the American Academy of Pediatrics.)

A novel method for the determination of per- and polyfluoroalkyl substances (PFAS) in groundwater is presented using a subsample, matrix-matched calibrators, 96-well plate solid phase extraction (SPE), and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Accuracy, precision, measurement of uncertainty (MOU), method detection limit (MDL), method quantitation limit (MQL), analytical measurement range, interferences/ion suppression, and analyte stability were determined as part of the in-house method validation. The method quantitates 42 PFAS compounds from nine different compound classes. Accuracy for the reference material (RM) and matrix spike (MS) ranged from 52.3 to 117.8 %, and precision for the MS and matrix spike duplicate (MSD) had a coefficient of variation (CV) from 2.0 % to 23.3 %. MDLs spanned from 0.07 to 1.97 ng L -1 , with MQLs ranging from 0.20 to 5.90 ng L -1 . Suppression studies determined that iron and manganese have effects on analytes that do not have paired isotopically labeled standards. The results from the in-house validation indicated that this Michigan Department of Health and Human Services laboratory developed test meets the necessary accuracy, precision, MDL, MQL and reporting limits requirement established by the laboratory's quality system essentials (QSEs) and select criteria from the Department of Defense (DoD) Quality Systems Manual for Environmental Laboratories and American Industrial Hygiene Association Laboratory Accreditation Program, LLC (AIHA LAP, LLC) accrediting International Standard Organization (ISO/IEC 17025:2017) check list., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Virtual rounds enable remote participation in bedside clinical encounters. Their effects on education remain poorly characterized and limited by lack of foundational evidence establishing that this approach is welcomed among learners and educators. We assessed technical feasibility and acceptability of incorporating video conferencing into daily work rounds of pediatric residents and attending physicians., Methods: We conducted a cross-sectional survey-based study of attending observers and pediatric residents participating in rounds both at the bedside and via video teleconferencing from September to December 2020. Participant experiences were assessed and summarized using parametric Likert-type questions regarding technical issues, efficiency, educational experience, and engagement. Associations between technical aspects and individual perceptions of virtual rounds and self-reported engagement were also measured., Results: Of 75 encounters, 29% experienced technical issues, 45% of which were attributable to a low-quality tablet stand. Negative impacts of virtual rounding on efficiency were reported in 6% of responses. Virtual participants were engaged (70%) and reported educational value for 65% of encounters. Comfort with virtually asking questions (odds ratio 3.3; 95% confidence interval 2.0-5.7) and performing clinical tasks for other patients (odds ratio 0.42; 95% confidence interval 0.2-0.9) were associated with engagement (P <.05)., Conclusions: Virtual participation in rounds was technically feasible and maintained educational value and engagement for residents in the majority of encounters, without sacrificing efficiency. Even as restrictions from the coronavirus disease 2019 pandemic are lifted, this rounding model has many important applications, including increasing educational opportunities for remote learners and making multidisciplinary rounds more accessible., (Copyright © 2022 by the American Academy of Pediatrics.)

Objectives: To develop an institutional machine-learning (ML) tool that utilizes demographic, socioeconomic, and medical information to stratify risk for 7-day readmission after hospital discharge; assess the validity and reliability of the tool; and demonstrate its discriminatory capacity to predict readmissions., Patients and Methods: We performed a combined single-center, cross-sectional, and prospective study of pediatric hospitalists assessing the face and content validity of the developed readmission ML tool. The cross-sectional analyses used data from questionnaire Likert scale responses regarding face and content validity. Prospectively, we compared the discriminatory capacity of provider readmission risk versus the ML tool to predict 7-day readmissions assessed via area under the receiver operating characteristic curve analyses., Results: Overall, 80% (15 of 20) of hospitalists reported being somewhat to very confident with their ability to accurately predict readmission risk; 53% reported that an ML tool would influence clinical decision-making (face validity). The ML tool variable exhibiting the highest content validity was history of previous 7-day readmission. Prospective provider assessment of risk of 413 discharges showed minimal agreement with the ML tool (κ = 0.104 [95% confidence interval 0.028-0.179]). Both provider gestalt and ML calculations poorly predicted 7-day readmissions (area under the receiver operating characteristic curve: 0.67 vs 0.52; P = .11)., Conclusions: An ML tool for predicting 7-day hospital readmissions after discharge from the general pediatric ward had limited face and content validity among pediatric hospitalists. Both provider and ML-based determinations of readmission risk were of limited discriminatory value. Before incorporating similar tools into real-time discharge planning, model calibration efforts are needed., (Copyright © 2022 by the American Academy of Pediatrics.)

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., (Copyright © 2022 by the American Academy of Pediatrics.)

Venous thromboembolism (VTE) is a leading cause of morbidity and preventable harm among noncritically ill hospitalized children. Several clinical factors relevant to the noncritically ill hospitalized child significantly increase the risk of VTE including the presence of central venous catheters, systemic inflammation, and prolonged immobilization. Although risk mitigation strategies have been described, the diagnosis, treatment, and prevention of VTE require standardization of institutional practices combined with multidisciplinary collaboration among pediatric hospitalists, hematologists, and other care providers. In this narrative review, we summarize the epidemiology of VTE, risk models identifying high-risk conditions associated with VTE, and prevention and treatment strategies. We further describe successful quality improvement efforts implementing institutional VTE risk stratification and thromboprophylaxis procedures. Finally, we highlight unique challenges facing pediatric hospital medicine specialists in the era of the COVID-19 pandemic, including caring for adults admitted to pediatric hospital units, and describe future research opportunities for VTE in the noncritically ill hospitalized child., Competing Interests: N.A.G. reports other from Bayer, outside the submitted work; and N.A.G. receives research support and salary support from the National Institutes of Health, National Heart Lung and Blood Institute for clinical and translational investigation in venous thromboembolism in patients <21 years old. He receives consultancy fees from Daiichi Sankyo Inc., Anthos Therapeutics Inc., and the Academic Research Organization CPC Clinical Research for roles in clinical trial oversight committees (e.g., steering, data and safety monitoring) in pharmaceutical industry-sponsored pediatric clinical trials of antithrombotic agents., (Thieme. All rights reserved.)

Background: In cases of critical asthma (CA), heliox may be applied as an adjunctive rescue therapy to avoid invasive mechanical ventilation (MV), improve deposition of aerosolized medications, and enhance laminar airflow through obstructed airways. Using the Pediatric Health Information System (PHIS) registry, we evaluate heliox prescribing and explored for differences in MV rates and hospital length of stay (LOS) among children with and without heliox exposure., Methods: We performed a retrospective cohort study using PHIS data from 42 pediatric intensive care units among children 5-17 years of age admitted for CA from 2010 through 2019. Primary outcomes were heliox prescribing rates and trends. Secondary outcomes were invasive MV rates and LOS assessed in a subgroup of children receiving ≥ 1 adjunctive intervention(s)., Results: Of the 19,780 studied, heliox was prescribed in 12.5% and linearly declined from 16.1% in 2010 to 5.6% in 2019. The overall MV rate was 12.8% and was lower in subjects receiving heliox alone (4.9%) compared to heliox plus alternative adjunctive therapies [31.2%] or children receiving non-heliox adjunctive therapies [22.1%], P < .01). Accounting for MV, no difference in LOS was observed. In exploratory adjusted models, MV free hospitalization was associated with heliox-only exposure (OR: 0.33, 95% CI: 0.17-0.63, P < .01) and exposure to multiple adjunctive therapies was associated with MV (OR: 2.48, 95% CI: 1.56-3.94, P < .01)., Conclusions: In this multicenter retrospective study from 42 children's hospitals, heliox prescribing for CA declined over the last decade. Subjects receiving multiple adjunctive therapies more commonly required invasive MV perhaps indicating a greater severity of illness. At this time, prospective trials needed to identify the role of heliox for pediatric CA.

Background: Children with tracheostomy are frequently admitted to the hospital for tracheostomy-associated respiratory infections (TRAINs). However, there remains a paucity of evidence to direct the diagnosis, treatment, and prevention of TRAINs. An important first step to addressing this knowledge gap is to synthesize existing data regarding TRAINs to inform current practice and facilitate innovation., Data Sources: We searched PubMed, Embase, Cochrane Library, CINAHL, and Web of Science from inception to October 2020. Original research articles and published abstracts including children and young adults 0-21 years of age with tracheostomy were included. Included studies assessed the clinical definitions of and risk factors for TRAINs, microbiologic epidemiology and colonization of tracheostomies, and treatment and outcomes of TRAINs., Data Synthesis: Out of 5755 studies identified in the search, 78 full-text studies were included in the final review. A substantial number of studies focused on the detection of specific pathogens in respiratory cultures including Pseudomonas aeruginosa. Several different definitions of TRAIN including clinical, microbiologic, and laboratory testing results were utilized; however, no uniform set of criteria were identified. The few studies focused on treatment and prevention of TRAIN emphasized the role of empiric antimicrobial therapy and the use of inhaled antibiotics., Conclusions: Despite a growing number of research articles studying TRAINs, there is a paucity of prospective interventional trials to guide the diagnosis, treatment, and prevention of respiratory disease in this vulnerable population. Future research should include studies of interventions designed to improve short- and long-term respiratory-related outcomes of children with tracheostomy., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Children with asthma exacerbations requiring pediatric ICU (PICU) admission, known as critical asthma (CA), are prescribed a variety of therapeutic interventions including heliox. Delivered invasively and noninvasively, heliox is employed to enhance deposition of aerosolized medications, improve obstructive pulmonary pathophysiology, and avoid complications associated with invasive mechanical ventilation. We used the Virtual Pediatric Systems database to update estimates of heliox prescription and explore for relationships between heliox and mechanical ventilation frequency and duration., Methods: We performed a retrospective cohort study using data from 97 PICUs among children 3-17 y of age admitted for CA from 2013-2019. The primary outcome was heliox prescribing rates and trends. Subgroup analyses assessed mechanical ventilation rates and duration by heliox exposure., Results: Of 43,238 subjects studied, 1,070 (2.5%) were prescribed heliox. Mean heliox prescribing rates fell from 4.11% in 2013 to 2.37% in 2019. Heliox use was greater from centers in the South (2.6%) and Midwest (3.3%) as compared to the West (1.6%) and Northeast United States (1.6%, P < .001). In the subgroup assessing mechanical ventilation frequency, mechanical ventilation rates were 273/39,739 (0.7%) and greater for those provided heliox (1.9% vs 0.7%, P < .001). In the subgroup assessing mechanical ventilation duration, no differences in median mechanical ventilation duration were observed (4.94 [interquartile range [IQR] 3.04-6.36] vs 4.63 [IQR 3.11-7.30] d; P = .35) for those with and without heliox. In exploratory adjusted models, noninvasive heliox was not associated with mechanical ventilation. Mortality was rare (206/43,238 [0.47%]) and predominantly among subjects intubated prehospitalization (188/206 [91.3%])., Conclusions: Heliox as adjunctive therapy for children with CA is uncommon (2.5%) and not associated with mechanical ventilation or decreased mechanical ventilation duration in adjusted models. Updated estimates provided herein inform prospective controlled trial development to better define the role of heliox for CA., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

Introduction: We aimed to describe patient characteristics and clinical outcomes for children hospitalized for status asthmaticus (SA) receiving high-flow nasal cannula (HFNC) or bilevel positive airway pressure (BiPAP)., Methods: We performed a single center, retrospective cohort study among 39 children admitted for SA aged 5-17 years from January 2016 to May 2019 to a quaternary pediatric intensive care unit (PICU). Cohorts were defined by BiPAP versus HFNC exposure and assessed to determine if differences existed in demographics, anthropometrics, comorbidities, asthma severity indices, historical factors, duration of noninvasive ventilation, and asthma-related clinical outcomes (i.e. length of stay, mechanical ventilation rates, exposure to concurrent sedatives/anxiolysis, and rate of adjunctive therapy exposure)., Results: Thirty-three percent ( n  = 13) received HFNC (33%) and 67% ( n  = 26) BiPAP. Children receiving BiPAP had greater age (10.9 ± 3.7 vs. 6.8 ± 2.2 years, P  < 0.01), asthma severity (proportion with severe NHLBI classification: 38% vs. 0%, P  < 0.01; median pediatric asthma severity score: 13[12,14] vs. 10[9,12], P  < 0.01), previous PICU admissions (62% vs. 15%, P  = 0.01), frequency of prescribed anxiolysis/sedation (42% vs. 8%, P  = 0.02), and median duration of continuous albuterol (1.7[1,3.1] vs. 0.9[0.7,1.6] days, P  = 0.03) compared to those on HFNC. Those on HFNC more commonly were treated comorbid bacterial pneumonia (69% vs. 19%, P  < 0.01). No differences in NIV duration, mortality, mechanical ventilation rates, or LOS were observed., Conclusions: Our data suggest a trial of BiPAP or HFNC appears well tolerated in children with SA. Prospective trials are needed to establish modality superiority and identify patient or clinical characteristics that prompt use of HFNC over BiPAP.

Background: Social determinants of health (SDoH) play an important role in pediatric health outcomes. Trainees receive little to no training on how to identify, discuss and counsel families in a clinical setting. The aim of this study was to determine if a simulation-based SDoH training activity would improve pediatric resident comfort with these skills., Methods: We performed a prospective study of a curricular intervention involving simulation cases utilizing standardized patients focused on four social determinants (food insecurity, housing insecurity, barriers to accessing care, and adverse childhood experiences [ACEs]). Residents reported confidence levels with discussing each SDoH and satisfaction with the activity in a retrospective pre-post survey with five-point Likert style questions. Select residents were surveyed again 9-12 months after participation., Results: 85% (33/39) of residents expressed satisfaction with the simulation activity. More residents expressed comfort discussing each SDoH after the activity (Δ% 38-47%; all p < .05), with the greatest effect noted in post-graduate-year-1 (PGY-1) participants. Improvements in comfort were sustained longitudinally during the academic year. More PGY-1 participants reported engaging in ≥ 2 conversations in a clinical setting related to food insecurity (43% vs. 5%; p = .04) and ACEs (71% vs. 20%; p = .02)., Discussion: Simulation led to an increased resident comfort with discussing SDoH in a clinical setting. The greatest benefit from such a curriculum is likely realized early in training. Future efforts should investigate if exposure to the simulations and increased comfort level with each topic correlate with increased likelihood to engage in these conversations in the clinical setting., (© 2021. The Author(s).)

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., (© 2021 John Wiley & Sons Ltd.)

Objectives: Standard treatment of children hospitalized for acute orbital cellulitis includes systemic antibiotics. Recent data from single-center studies suggest the addition of systemic corticosteroids may hasten clinical improvement and reduce hospital length of stay (LOS). We investigate the potential relationship between corticosteroid exposure and duration of hospitalization for pediatric orbital cellulitis., Methods: Using Pediatric Health Information System registry data from 51 children's facilities, we performed a retrospective cohort study of children hospitalized for orbital cellulitis <18 years of age from 2007 to 2018. The primary study outcome was hospital LOS. Secondary outcomes included frequency of surgical interventions, PICU admission, and 30-day related-cause readmission., Results: Of the 5645 children included for study, 1347 (24%) were prescribed corticosteroids within 2 days of admission. Corticosteroid prescription was not associated with LOS in analyses adjusted for age; presence of meningitis, abscess, or vision issues; and operative episode and PICU admission within 2 days ( e β = 1.01, 95% confidence interval [CI]: 0.97-1.06). Corticosteroid exposure was associated with operative episodes after 2 days of hospitalization (odds ratio = 2.05, 95% CI: 1.29-3.27) and 30-day readmission (odds ratio = 2.40, 95% CI: 1.52-3.78) among patients with a primary diagnosis of orbital cellulitis., Conclusions: In this database query, we were not able to detect a reduction in LOS associated with corticosteroid exposure during hospitalization for orbital cellulitis. Corticosteroid prescription was associated with PICU admission and operative episodes after 2 days of hospitalization. Before the adoption of routine corticosteroid use, prospective, randomized control trials are needed., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: To assess face validity, interobserver reliability, and the ability to discriminate escalations of care within 24-h of admission (late rescues) for the bronchiolitis severity score (BSS) for children hospitalized for acute bronchiolitis., Hypotheses: The BSS will yield variable face validity, have clinically relevant interobserver reliability (kappa > 0.7), and distinguish late rescues during hospitalization., Methods: We performed a combined retrospective and prospective, mixed methods study where (1) interobserver agreement was prospectively assessed by overall and subcategory congruence (kappa) calculations, (2) face value were qualitatively assessed from aggregate questionnaire responses, and (3) construct validity for late rescues were assessed using receiver operator characteristic (ROC) curve analyses., Results: Face validity, assessed from 39 questionnaire respondents, were generally positive for BSS utility, reliability, and usability. The BSS exhibited weak interobserver reliability (kappa = 0.22, 95% confidence interval [CI]: 0.11-0.31) calculated from 72 sequential, blinded calculations. Retrospectively, 181 children less than 2 years of age admitted to the general pediatric ward for acute bronchiolitis from November 2017 to April 2019 were identified of which 18 (9.9%) experienced late rescues. Admission BSS values were no different for children with and without late rescues (6[3,6] vs. 4[3,6]; p = .09). An ROC curve analysis revealed an area under the curve of 0.61 (95% CI: 0.48-0.75; threshold ≥6 with sensitivity = 56%, specificity = 69%) for BSS to discriminate late rescues., Conclusion: Although clinicians expressed favorable perceptions of BSS face and content validity, we noted weak interobserver reliability and limited construct validity. Further development and validation are needed to strengthen the BSS before routine use., (© 2021 Wiley Periodicals LLC.)

Background: Malnutrition in medical and surgical inpatients is an on-going problem. More-2-Eat (M2E) Phase 1 demonstrated that improved detection and treatment of hospital malnutrition could be embedded into routine practice using an intensive researcher-facilitated implementation process. Yet, spreading and sustaining new practices in diverse hospital cultures with minimal researcher support is unknown., Aims: To demonstrate that a scalable model of implementation can increase three key nutrition practices (admission screening; Subjective Global Assessment (SGA); and medication pass (MedPass) of oral nutritional supplement) in diverse acute care hospitals to detect and treat malnutrition in medical and surgical patients., Methods: Ten hospitals participated in this pretest post-test time series implementation study from across Canada, including 21 medical or surgical units (Phase 1 original units (n = 4), Phase 1 hospital new units (n = 9), Phase 2 new hospitals and units (n = 8)). The scalable implementation model included: training champions on implementation strategies and providing them with education resources for teams; creating a self-directed audit and feedback process; and providing mentorship. Standardized audits of all patients on the study unit on an audit day were completed bi-monthly to track nutrition care activities since admission. Bivariate comparisons were performed by time period (initial, mid-term and final audits). Run-charts depicted the trajectory of change and qualitatively compared to Phase 1., Results: 5158 patient charts were audited over the course of 18-months. Admission nutrition screening rates increased from 50% to 84% (p < 0.0001). New Phase 1 units more readily implemented screening than Phase 2 sites, and the original Phase 1 units generally sustained screening practices from Phase 1. SGA was a sustained practice at Phase 1 hospitals including in new Phase 1 units. The new Phase 2 units improved completion of SGA but did not reach the levels of Phase 1 units (original or new). MedPass almost doubled over the time periods (7%-13% of all patients p < 0.007). Other care practices significantly increased (e.g. volunteer mealtime assistance)., Conclusion: Nutrition-care activities significantly increased in diverse hospital units with this scalable model. This heralds the transition from implementation research to sustained changes in routine practice. Screening, SGA, and MedPass can all be implemented, improve nutrition care for all patients, spread within an organization, and for the most part, sustained (and in the case of original Phase 1 units, for over 3 years) with champion leadership., Competing Interests: Conflict of interest The authors declare that funding was provided by Abbott Laboratories Canada, as required matching funding by the primary funder, The Canadian Frailty Network. Funds were used to develop the INPAC registry and feedback reports used by sites., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: In children hospitalized for bronchiolitis, enteral nutrition (EN) practices during noninvasive ventilation (NIV) vary widely. We sought to assess the potential impact of EN by observing changes in physiometric indices (heart rate [HR] and respiratory rate [RR]) before and after EN initiation., Methods: We performed a retrospective cohort study in children <2 years of age hospitalized for bronchiolitis receiving NIV from 2017 to 2019 in a quaternary ICU. The primary outcome was patient HR and RR before and after EN initiation. Descriptive data included demographics, anthropometrics, comorbidities, NIV parameters, EN characteristics, and general hospital outcomes. Analyses included paired comparative and descriptive statistics., Results: Of the 124 children studied, 85 (69%) were permitted EN at a median of 12 (interquartile range [IQR]: 7 to 29) hours. The route was oral (76.5%), nasogastric (15.3%), or postpyloric (8.2%) and was predominantly started during high-flow nasal cannula (71%) at flow rates of 1 (IQR: 0.7 to 1.4) L/kg per minute. After EN initiation, reductions in the median RR (percentage change: -11 [IQR: -23 to 3]; P < .01) and HR (percentage change: -5 [IQR: -12 to 1]; P < .01) were noted. Those permitted EN were younger (5 [IQR: 2 to 11] vs 11 [IQR: 3 to 17] months; P < .01) and more likely to have bronchopulmonary dysplasia (19% vs 5%; P = .04). Malnutrition rates, comorbidities, admission timing, flow rates, length of stay, and NIV duration did not differ for those provided or not provided EN. No aspiration events were observed., Conclusions: Reductions between pre- and postprandial RR after EN initiation among children hospitalized for bronchiolitis on NIV were observed without clinically significant aspiration. These findings support existing data that suggest that EN is safe during NIV and may lessen distress in some patients., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: To describe the rate of high-flow nasal cannula (HFNC) nonresponse and paired physiometric responses (changes [∆] in heart rate [HR] and respiratory rate [RR]) before and after HFNC initiation in hospitalized children with bronchiolitis., Methods: We performed a single-center, prospective descriptive study in a PICU within a quaternary referral center, assessing children aged ≤2 years admitted for bronchiolitis on HFNC from November 2017 to March 2020. We excluded for cystic fibrosis, airway anomalies, pulmonary hypertension, tracheostomy, neuromuscular disease, congenital heart disease, or preadmission intubation. Primary outcomes were paired ∆ and %∆ in HR and RR before and after HFNC initiation. Secondary outcomes were HFNC nonresponse rate (ie, intubation or transition to noninvasive positive pressure ventilation). Analyses included χ 2 , Student's t , Wilcoxon rank, and paired testing., Results: Of the 172 children studied, 56 (32.6%) experienced HFNC nonresponse at a median of 14.4 (interquartile range: 4.8-36) hours and 11 (6.4%) were intubated. Nonresponders had a greater frequency of bacterial pneumonia, but otherwise no major differences in demographics, comorbidities, or viral pathogens were noted. Responders experienced reductions in both %ΔRR (-17.1% ± 15.8% vs +5.3% ± 22.3%) and %ΔHR (-6.5% ± 10.5% vs 0% ± 10.9%) compared with nonresponders., Conclusions: In this prospective, observational cohort study, we provide baseline data describing expected physiologic changes after initiation of HFNC for children admitted to the PICU for bronchiolitis. In our descriptive analysis, patients with comorbid bacterial pneumonia appear to be at additional risk for subsequent HFNC nonresponse., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Nakagawa received royalties from Wolters Kluwer, UpToDate and was a consultant for Fresenius Kabi; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: When grown in human serum, laboratory isolates of Pseudomonas aeruginosa exhibit tolerance to antibiotics at inhibitory concentrations. This phenomenon, known as serum-associated antibiotic tolerance (SAT), could lead to clinical treatment failure of pseudomonal infections. Our purpose in this study was to determine the prevalence and clinical impact of SAT in Pseudomonas isolates in hospitalized children., Methods: The SAT phenotype was assessed in patients aged <18 years admitted with respiratory or blood cultures positive for P. aeruginosa. The SAT phenotype was a priori defined as a ≥2-log increase in colony-forming units when grown in human serum compared with Luria-Bertani medium in the presence of minocycline or tobramycin., Results: SAT was detected in 29 (64%) patients. Fourteen patients each (34%) had cystic fibrosis (CF) and tracheostomies. Patient demographics and comorbidities did not differ by SAT status. Among CF patients, SAT was associated with longer duration of intravenous antibiotics (10 days vs 5 days; P < .01)., Conclusions: This study establishes that SAT exists in P. aeruginosa from human serum and may be a novel factor that contributes to differences in clinical outcomes. Future research should investigate the mechanisms that contribute to SAT in order to identify novel targets for adjunctive antimicrobial therapies., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: Drs First and Kemper are editors of the journal Pediatrics; and Dr Morrison has indicated he has no potential conflicts of interest to disclose.

Charge-shift bonds (CSBs) constitute a new class of bonds different than covalent/polar-covalent and ionic bonds. Bonding in CSBs does not arise from either the covalent or the ionic structures of the bond, but rather from the resonance interaction between the structures. This Essay describes the reasons why the CSB family was overlooked by valence-bond pioneers and then demonstrates that the unique status of CSBs is not theory-dependent. Thus, valence bond (VB), molecular orbital (MO), and energy decomposition analysis (EDA), as well as a variety of electron density theories all show the distinction of CSBs vis-à-vis covalent and ionic bonds. Furthermore, the covalent-ionic resonance energy can be quantified from experiment, and hence has the same essential status as resonance energies of organic molecules, e.g., benzene. The Essay ends by arguing that CSBs are a distinct family of bonding, with a potential to bring about a Renaissance in the mental map of the chemical bond, and to contribute to productive chemical diversity., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Academic medical centers and health systems are increasingly challenged with supporting appropriate secondary use of clinical data. Enterprise data warehouses have emerged as central resources for these data, but often require an informatician to extract meaningful information, limiting direct access by end users. To overcome this challenge, we have developed Leaf, a lightweight self-service web application for querying clinical data from heterogeneous data models and sources., Materials and Methods: Leaf utilizes a flexible biomedical concept system to define hierarchical concepts and ontologies. Each Leaf concept contains both textual representations and SQL query building blocks, exposed by a simple drag-and-drop user interface. Leaf generates abstract syntax trees which are compiled into dynamic SQL queries., Results: Leaf is a successful production-supported tool at the University of Washington, which hosts a central Leaf instance querying an enterprise data warehouse with over 300 active users. Through the support of UW Medicine (https://uwmedicine.org), the Institute of Translational Health Sciences (https://www.iths.org), and the National Center for Data to Health (https://ctsa.ncats.nih.gov/cd2h/), Leaf source code has been released into the public domain at https://github.com/uwrit/leaf., Discussion: Leaf allows the querying of single or multiple clinical databases simultaneously, even those of different data models. This enables fast installation without costly extraction or duplication., Conclusions: Leaf differs from existing cohort discovery tools because it does not specify a required data model and is designed to seamlessly leverage existing user authentication systems and clinical databases in situ. We believe Leaf to be useful for health system analytics, clinical research data warehouses, precision medicine biobanks, and clinical studies involving large patient cohorts., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Purpose: To describe the prevalence and characteristics of modified-texture food (MTF) consumers when applying standard diet terminology. Methods: Making the Most of Mealtimes (M3) is a cross-sectional multi-site study including 32 long-term care (LTC) homes located in 4 Canadian provinces. Resident characteristics were collected from health records using a defined protocol and extraction form. Since homes used 67 different terms to describe MTFs, diets were recategorized using the International Dysphagia Diet Standardization Initiative Framework as a basis for classification. Results: MTFs were prescribed to 47% (n = 298) of participants (n = 639) and prevalence significantly differed among provinces ( P  < 0.0001). Various resident characteristics were significantly associated with use of MTFs: dysphagia and malnutrition risk, dementia diagnosis, prescription of oral nutritional supplements; lower body weight and calf circumference; greater need for physical assistance with eating; poor oral health status; and dependence in all activities of daily living. Conclusions: This is the first study that used a diverse sample of LTC residents to determine prevalence of MTF use and described consumers. The prevalence of prescribed MTFs was high and diverse across provinces in Canada. Residents prescribed MTFs were more vulnerable than residents on regular texture diets. These findings add value to our understanding of MTF consumers.