Retrospective Validation of a Computerized Physiologic Equation to Predict Minute Ventilation Needs in Critically Ill Children.

OBJECTIVES: Mechanical ventilation (MV) is pervasive among critically ill children. We sought to validate a computerized physiologic equation to predict minute ventilation requirements in children and test its performance against clinician actions in an in silico trial. DESIGN: Retrospective, electronic medical record linkage, cohort study. SETTING: Quaternary PICU. PATIENTS: Patients undergoing invasive MV, serial arterial blood gas (ABG) analysis within 1-6 hours, and pharmacologic neuromuscular blockade (NMB). MEASUREMENTS AND MAIN RESULTS: ABG values were filtered to those occurring during periods of NMB. Simultaneous ABG and minute ventilation data were linked to predict serial Pa co2 and pH values using previously published physiologic equations. There were 15,121 included ABGs across 500 encounters among 484 patients, with a median (interquartile range [IQR]) of 20 (10-43) ABGs per encounter at a duration of 3.6 (2.1-4.2) hours. The median (IQR) Pa co2 prediction error was 0.00 (-3.07 to 3.00) mm Hg. In Bland-Altman analysis, the mean error was -0.10 mm Hg (95% CI, -0.21 to 0.01 mm Hg). A nested, in silico trial of ABGs meeting criteria for weaning (respiratory alkalosis) or escalation (respiratory acidosis), compared the performance of recommended ventilator changes versus clinician decisions. There were 1,499 of 15,121 ABGs (9.9%) among 278 of 644 (43.2%) encounters included in the trial. Calculated predictions were favorable to clinician actions in 1124 of 1499 ABGs (75.0%), equivalent to clinician choices in 26 of 1499 ABGs (1.7%), and worse than clinician decisions in 349 of 1499 ABGs (23.3%). Calculated recommendations were favorable to clinician decisions in sensitivity analyses limiting respiratory rate, analyzing only when clinicians made changes, excluding asthma, and excluding acute respiratory distress syndrome. CONCLUSIONS: A computerized equation to predict minute ventilation requirements outperformed clinicians' ventilator adjustments in 75% of ABGs from critically ill children in this retrospective analysis. Prospective validation studies are needed.

Temporal Patterns in Brain Tissue and Systemic Oxygenation Associated with Mortality After Severe Traumatic Brain Injury in Children.

BACKGROUND: Brain tissue hypoxia is an independent risk factor for unfavorable outcomes in traumatic brain injury (TBI); however, systemic hyperoxemia encountered in the prevention and/or response to brain tissue hypoxia may also impact risk of mortality. We aimed to identify temporal patterns of partial pressure of oxygen in brain tissue (PbtO2), partial pressure of arterial oxygen (PaO2), and PbtO2/PaO2 ratio associated with mortality in children with severe TBI. METHODS: Data were extracted from the electronic medical record of a quaternary care children's hospital with a level I trauma center for patients ≤ 18 years old with severe TBI and the presence of PbtO2 and/or intracranial pressure monitors. Temporal analyses were performed for the first 5 days of hospitalization by using locally estimated scatterplot smoothing for less than 1,000 observations and generalized additive models with integrated smoothness estimation for more than 1,000 observations. RESULTS: A total of 138 intracranial pressure-monitored patients with TBI (median 5.0 [1.9-12.8] years; 65% boys; admission Glasgow Coma Scale score 4 [3-7]; mortality 18%), 71 with PbtO2 monitors and 67 without PbtO2 monitors were included. Distinct patterns in PbtO2, PaO2, and PbtO2/PaO2 were evident between survivors and nonsurvivors over the first 5 days of hospitalization. Time-series analyses showed lower PbtO2 values on day 1 and days 3-5 and lower PbtO2/PaO2 ratios on days 1, 2, and 5 among patients who died. Analysis of receiver operating characteristics curves using Youden's index identified a PbtO2 of 30 mm Hg and a PbtO2/PaO2 ratio of 0.12 as the cut points for discriminating between survivors and nonsurvivors. Univariate logistic regression identified PbtO2 < 30 mm Hg, hyperoxemia (PaO2 ≥ 300 mm Hg), and PbtO2/PaO2 ratio < 0.12 to be independently associated with mortality. CONCLUSIONS: Lower PbtO2, higher PaO2, and lower PbtO2/PaO2 ratio, consistent with impaired oxygen diffusion into brain tissue, were associated with mortality in this cohort of children with severe TBI. These results corroborate our prior work that suggests targeting a higher PbtO2 threshold than recommended in current guidelines and highlight the potential use of the PbtO2/PaO2 ratio in the management of severe pediatric TBI.

Tandem Therapeutic Plasma Exchange Reduces Continuous Renal Replacement Therapy Downtime.

INTRODUCTION: Continuous renal replacement therapy (CRRT) has become a primary treatment of severe acute kidney injury in children admitted to the intensive care unit. CRRT "downtime" (when the circuit is not active) can represent a significant portion of the prescribed treatment time and adversely affects clearance. The objective of this study was to evaluate factors associated with CRRT "downtime" and to determine whether instituting a tandem therapeutic plasma exchange (TPE) protocol could significantly and robustly decrease circuit downtime in patients receiving both therapies. METHODS: This is a retrospective cohort study of 116 patients undergoing CRRT in the pediatric, neonatal, or cardiac ICU at UPMC Children's Hospital of Pittsburgh from January 2014 to July 2020. We performed multivariable logistic regression to determine factors associated with CRRT downtime. We instituted a tandem TPE protocol whereby TPE and CRRT could run in parallel without pausing CRRT in April 2018. We analyzed the effect of the protocol change by plotting downtime for patients undergoing CRRT and TPE on a run chart. The effect of initiating tandem TPE on downtime was assessed by special cause variation. RESULTS: For 108/139 (77.7%) sessions with downtime data available, the median (IQR) percentage of downtime was 6.2% (1.7-12.7%). Multivariable logistic regression showed that TPE was significantly associated with CRRT downtime (p = 0.003), and that age, sex, race, catheter size, and anticoagulation were not. For patients undergoing TPE, the median (IQR) percentage of downtime was 14.7% (10.5-26%) and 3.4% (1.3-4.9%) before and after initiation of tandem TPE, respectively (p < 0.001). The difference in downtime percentage met criteria for special cause variation. CONCLUSIONS: Interruptions for TPE increase CRRT downtime. Tandem TPE significantly reduces CRRT downtime in patients undergoing both procedures concomitantly.

Forecast modeling to identify changes in pediatric emergency department utilization during the COVID-19 pandemic.

OBJECTIVE: To identify trends in pediatric emergency department (ED) utilization following the COVID-19 pandemic. METHODS: We performed a cross-sectional study from 37 geographically diverse US children's hospitals. We included ED encounters between January 1, 2010 and December 31, 2020, transformed into time-series data. We constructed ensemble forecasting models of the most common presenting diagnoses and the most common diagnoses leading to admission, using data from 2010 through 2019. We then compared the most common presenting diagnoses and the most common diagnoses leading to admission in 2020 to the forecasts. RESULTS: 29,787,815 encounters were included, of which 1,913,085 (6.4%) occurred during 2020. ED encounters during 2020 were lower compared to prior years, with a 65.1% decrease in April relative to 2010-2019. In forecasting models, encounters for depression and diabetic ketoacidosis remained within the 95% confidence interval [CI]; fever, bronchiolitis, hyperbilirubinemia, skin/subcutaneous infections and seizures occurred within the 80-95% CI during the portions of 2020, and all other diagnoses (abdominal pain, otitis media, asthma, pneumonia, trauma, upper respiratory tract infections, and urinary tract infections) occurred below the predicted 95% CI. CONCLUSION: Pediatric ED utilization has remained low following the COVID-19 pandemic, and below forecasted utilization for most diagnoses. Nearly all conditions demonstrated substantial declines below forecasted rates from the prior decade and which persisted through the end of the year. Some declines in non-communicable diseases may represent unmet healthcare needs among children. Further study is warranted to understand the impact of policies aimed at curbing pandemic disease on children.

Correction to: Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings : A Midwest Pediatric Nephrology Consortium (MWPNC) study.

The original version of this article unfortunately contained a mistake. The subtitle "A Midwest Pediatric Nephrology Consortium (MWPNC) study" was missing. The correct title including subtitle is given above.

Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings.

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence. METHODS: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. RESULTS: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3-23.7) compared to FSGS predicted disease recurrence. CONCLUSIONS: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.

The Use of Echocardiography for Pediatric Patients Presenting with Syncope.

OBJECTIVES: To assess the frequency, yield, and cost of echocardiograms meeting "rarely appropriate" criteria. STUDY DESIGN: Retrospective, single-center study of pediatric patients presenting with syncope. Patients were categorized according to the appropriate use criteria and based upon location of care (emergency department only, primary care setting only, or referred to a pediatric cardiologist). Multivariable regression was used to determine factors associated with performance of a "rarely appropriate" echocardiogram. Costs were calculated using fair market values from the Healthcare Bluebook. RESULTS: The cohort included 637 patients presenting with syncope during the 1-year study. Echocardiograms were ordered for 127 of 637 (20.1%) including 0 of 328 emergency department patients, 1 of 66 (1.5%) primary care setting patients, and 127 of 243 (52.3%) patients evaluated by a pediatric cardiologist. Use of echocardiography by pediatric cardiologists was categorized as "appropriate" in 92 of 127 (72.4%), "maybe appropriate" in 6 of 127 (4.7%), and "rarely appropriate" in 29 of 127 (22.8%). Abnormal findings were seen in 6 of 127 (4.7%) echocardiograms but in none of the "rarely appropriate" studies. In multivariable analysis, female sex and younger age were the only factors associated with performance of a "rarely appropriate" echocardiogram. "Rarely appropriate" echocardiograms cost an estimated $16 704.00 ($576.00 per patient) in the 1-year study. CONCLUSIONS: "Rarely appropriate" echocardiograms performed for syncope do not contribute management changing diagnostic information. However, they burden patients with additional cost and perhaps contribute to increased need for follow-up.

Neutropenic enterocolitis (typhlitis) in a pediatric renal transplant patient. A case report and review of the literature.

NE (typhlitis) is a potentially life-threatening disease process characterized by bowel wall edema, ulceration, and hemorrhage in an immunosuppressed patient. We report a 15-year-old boy status post deceased donor renal transplantation who presented with fever, abdominal pain, and diarrhea. Laboratory studies revealed neutropenia 5 days prior to admission, and abdominal computed tomography revealed bowel wall thickening in the cecum consistent with NE. He was treated with piperacillin-tazobactam and gentamicin and recovered. To our knowledge, this is the first report of a case of NE in a pediatric kidney transplant recipient.

Arsenic inhibits mast cell degranulation via suppression of early tyrosine phosphorylation events.

Exposure to arsenic is a global health concern. We previously documented an inhibitory effect of inorganic Arsenite on IgE-mediated degranulation of RBL-2H3 mast cells (Hutchinson et al., 2011; J. Appl. Toxicol. 31: 231-241). Mast cells are tissue-resident cells that are positioned at the host-environment interface, thereby serving vital roles in many physiological processes and disease states, in addition to their well-known roles in allergy and asthma. Upon activation, mast cells secrete several mediators from cytoplasmic granules, in degranulation. The present study is an investigation of Arsenite's molecular target(s) in the degranulation pathway. Here, we report that arsenic does not affect degranulation stimulated by either the Ca(2) (+) ionophore A23187 or thapsigargin, which both bypass early signaling events. Arsenic also does not alter degranulation initiated by another non-IgE-mediated mast cell stimulant, the G-protein activator compound 48/80. However, arsenic inhibits Ca(2) (+) influx into antigen-activated mast cells. These results indicate that the target of arsenic in the degranulation pathway is upstream of the Ca(2) (+) influx. Phospho-Syk and phospho-p85 phosphoinositide 3-kinase enzyme-linked immunosorbent assays data show that arsenic inhibits early phosphorylation events. Taken together, this evidence indicates that the mechanism underlying arsenic inhibition of mast cell degranulation occurs at the early tyrosine phosphorylation steps in the degranulation pathway. Copyright © 2016 John Wiley & Sons, Ltd.

A systematic review of smoking cessation interventions in the emergency setting.

STUDY OBJECTIVE: Cigarette smoking remains the leading cause of preventable death in the United States, and tobacco use rates are known to be higher among emergency department (ED) patients than in the general population. Despite recommendations from the Society for Academic Emergency Medicine and the American College of Emergency Physicians, many emergency clinicians remain uncertain about the benefits of providing ED-based smoking cessation interventions. To address this gap in knowledge, we performed a systematic review of cessation interventions initiated in the adult or pediatric ED setting. METHODS: We conducted an electronic search of the MEDLINE and CINAHL databases through February 2014 and hand searched references from potentially relevant articles. We identified eligible studies, evaluated bias and validity, and extracted data and synthesized findings. RESULTS: Seventeen studies underwent critical appraisal, with 13 included in qualitative synthesis. The majority (11/13, 85%) of investigations did not report significant differences in tobacco abstinence between cessation intervention groups. The 2 studies reporting significant differences in cessation both used motivational interviewing-based interventions. Two studies evaluated patient satisfaction with ED-based tobacco cessation interventions, and both reported greater than 90% satisfaction. CONCLUSIONS: Findings indicate that ED visits in combination with ED-initiated tobacco cessation interventions are correlated with higher cessation rates than those reported in the National Health Interview Survey. Clear data supporting the superiority of one intervention type were not identified. Lack of a standardized control group prevented quantitative evaluation of pooled data, and future research is indicated to definitively evaluate intervention efficacy.

Short stay unit led by pediatric hospital medicine advanced practice providers.

BACKGROUND: In response to a critical pediatric bed shortage in 2022, an urgent process change was required to provide safe and timely medical care. We proposed a pilot for an advanced practice provider (APP)-run short stay unit (SSU) for select pediatric hospital medicine (PHM) patients. OBJECTIVE: To compare length of stay (LOS) and cost before and after implementation of a PHM APP-led SSU pilot at a tertiary pediatric hospital. DESIGNS, SETTINGS, AND PARTICIPANTS: Single-center prospective pilot observational cohort study with historical control. Observation encounters for patients with asthma, bronchiolitis, croup, and dehydration were included. INTERVENTION: An independent-practice model SSU staffed by APPs on the PHM service. MAIN OUTCOME AND MEASURES: SSU encounters (September 1, 2022-December 1, 2022) were compared against pre-SSU encounters (September 1, 2021-August 31, 2022). Cohorts were described with summary statistics. SSU encounters were matched against pre-SSU encounters based on demographics and diagnosis, and the average effect of treatment was calculated. LOS was abstracted from the enterprise data warehouse and standardized unit cost from the Pediatric Health Information Systems database. RESULTS: There were 1110 encounters included, 155 in the SSU cohort and 955 in the pre-SSU cohort: 24.2% asthma, 30.8% bronchiolitis, 8.3% croup, and 36.7% dehydration. Median (interquartile range) unit LOS decreased from 21 (16-26) to 18 (10-22) h, p < .001. Cost decreased from $3593 ($3031-$4560) to $2958 ($2278-$3856), p < .001. After matching, the average treatment effect was reduction of 3.88 h (95% confidence interval [CI] 1.91-5.85) and $593 (95% CI $348-$839). There were no significant differences in 7-day ED revisit rates.

Association Between the COI and Excess Health Care Utilization and Costs for ACSC.

BACKGROUND AND OBJECTIVES: The authors of previous work have associated the Childhood Opportunity Index (COI) with increased hospitalizations for ambulatory care sensitive conditions (ACSC). The burden of this inequity on the health care system is unknown. We sought to understand health care resource expenditure in terms of excess hospitalizations, hospital days, and cost. METHODS: We performed a retrospective cross-sectional study of the Pediatric Health Information Systems database, including inpatient hospitalizations between January 1, 2016 and December 31, 2022 for children <18 years of age. We compared ACSC hospitalizations, mortality, and cost across COI strata. RESULTS: We identified 2 870 121 hospitalizations among 1 969 934 children, of which 44.5% (1 277 568/2 870 121) were for ACSCs. A total of 49.1% (331 083/674 548) of hospitalizations in the very low stratum were potentially preventable, compared with 39.7% (222 037/559 003) in the very high stratum (P < .001). After adjustment, lower COI was associated with higher odds of potentially preventable hospitalization (odds ratio 1.18, 95% confidence interval [CI] 1.17-1.19). Compared with the very high COI stratum, there were a total of 137 550 (95% CI 134 582-140 517) excess hospitalizations across all other strata, resulting in an excess cost of $1.3 billion (95% CI $1.28-1.35 billion). Compared with the very high COI stratum, there were 813 (95% CI 758-871) excess deaths, with >95% from the very low and low COI strata. CONCLUSIONS: Children with lower neighborhood opportunity have increased risk of ACSC hospitalizations. The COI may identify communities in which targeted intervention could reduce health care utilization and costs.

Respiratory Support Practices for Bronchiolitis in the Pediatric Intensive Care Unit.

Importance: Admissions to the pediatric intensive care unit (PICU) due to bronchiolitis are increasing. Whether this increase is associated with changes in noninvasive respiratory support practices is unknown. Objective: To assess whether the number of PICU admissions for bronchiolitis between 2013 and 2022 was associated with changes in the use of high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) and to identify factors associated with HFNC and NIV success and failure. Design, Setting, and Participants: This cross-sectional study examined encounter data from the Virtual Pediatric Systems database on annual PICU admissions for bronchiolitis and ventilation practices among patients aged younger than 2 years admitted to 27 PICUs between January 1, 2013, and December 31, 2022. Use of HFNC and NIV was defined as successful if patients were weaned to less invasive support (room air or low-flow nasal cannula for HFNC; room air, low-flow nasal cannula, or HFNC for NIV). Main Outcomes and Measures: The main outcome was the number of PICU admissions for bronchiolitis requiring the use of HFNC, NIV, or IMV. Linear regression was used to analyze the association between admission year and absolute numbers of encounters stratified by the maximum level of respiratory support required. Multivariable logistic regression was used to analyze factors associated with HFNC and NIV success and failure (defined as not meeting the criteria for success). Results: Included in the analysis were 33 816 encounters for patients with bronchiolitis (20 186 males [59.7%]; 1910 patients [5.6%] aged ≤28 days and 31 906 patients [94.4%] aged 29 days to <2 years) treated at 27 PICUs from 2013 to 2022. A total of 7615 of 15 518 patients (49.1%) had respiratory syncytial virus infection and 1522 of 33 816 (4.5%) had preexisting cardiac disease. Admissions to the PICU increased by 350 (95% CI, 170-531) encounters annually. When data were grouped by the maximum level of respiratory support required, HFNC use increased by 242 (95% CI, 139-345) encounters per year and NIV use increased by 126 (95% CI, 64-189) encounters per year. The use of IMV did not significantly change (10 [95% CI, -11 to 31] encounters per year). In all, 22 381 patients (81.8%) were successfully weaned from HFNC to low-flow oxygen therapy or room air, 431 (1.6%) were restarted on HFNC, 3057 (11.2%) were escalated to NIV, and 1476 (5.4%) were escalated to IMV or extracorporeal membrane oxygenation (ECMO). Successful use of HFNC increased from 820 of 1027 encounters (79.8%) in 2013 to 3693 of 4399 encounters (84.0%) in 2022 (P = .002). In all, 8476 patients (81.5%) were successfully weaned from NIV, 787 (7.6%) were restarted on NIV, and 1135 (10.9%) were escalated to IMV or ECMO. Success with NIV increased from 224 of 306 encounters (73.2%) in 2013 to 1335 of 1589 encounters (84.0%) in 2022 (P < .001). In multivariable logistic regression, lower weight, higher Pediatric Risk of Mortality III score, cardiac disease, and PICU admission from outside the emergency department were associated with greater odds of HFNC and NIV failure. Conclusions and Relevance: Findings of this cross-sectional study of patients aged younger than 2 years admitted for bronchiolitis suggest there was a 3-fold increase in PICU admissions between 2013 and 2022 associated with a 4.8-fold increase in HFNC use and a 5.8-fold increase in NIV use. Further research is needed to standardize approaches to HFNC and NIV support in bronchiolitis to reduce resource strain.

Virtual Learning Improves Attendance for Critical Care Education During the COVID-19 Pandemic.

The COVID-19 pandemic has pushed medical educators and learners to adapt to virtual learning (VL) in an expedited manner. The effect of VL for critical care education has not yet been evaluated. In a quantitative analysis of survey data and attendance records, we sought to determine the association of VL with conference attendance and work-life balance. Attending physicians, fellows, and advanced practice providers (APP) at a pediatric critical care department at a quaternary children's hospital participated in the study. Attendance records were obtained before and after the adaption of a VL platform. In addition, an electronic, anonymous survey to evaluate current satisfaction and the strengths and weaknesses of VL as well as its impact on work-life balance was administered. In total, 31 learners (17 attending physicians, 13 fellows, and 1 APP) completed the survey. A total of 83.9% (26/31) of participants were satisfied, and 77.4% (24/31) found VL to be similar or more engaging than non-VL. However, 6.5% (2/31) of learners reported difficulty in using the new platform, 87% (27/31) of participants supported VL as an effective learning tool, and 83.3% (25/30) reported a positive impact on work-life balance. Additionally, median monthly conference attendance increased significantly from 85 to 114 attendees per month ( p < 0.05). Our results suggest that a virtual model has advantages for overall attendance and work-life balance. We anticipate VL will continue to be an integral part of medical education. Future work evaluating the impact of VL on interdepartmental and interinstitutional collaborations is needed.

Admissions for Bronchiolitis at Children's Hospitals Before and During the COVID-19 Pandemic.

Importance: The COVID-19 pandemic has been associated with a transient decrease in bronchiolitis hospitalizations compared with prepandemic patterns, but current effects remain unknown. Objective: To analyze changes in patterns of bronchiolitis admissions at US children's hospitals during the 2020-2023 bronchiolitis seasons compared with the 2010-2019 seasons. Design, Setting, and Participants: This retrospective cross-sectional study used data from 41 US children's hospitals in the Pediatric Health Information System database. Bronchiolitis has winter-predominant seasonality, so hospitalizations were grouped according to bronchiolitis season (from July through June). This study included all patients aged younger than 2 years admitted with a diagnosis of bronchiolitis between July 1, 2010, and June 30, 2023. Bronchiolitis seasons from July through June between 2010-2011 and 2019-2020 were classified as the prepandemic era, and seasons between 2020-2021 and 2022-2023 were classified as the pandemic era. Data analysis was performed from July 1, 2010, through June 30, 2023. Exposures: Admission date. Main Outcomes and Measures: The primary outcome was number of hospitalizations for bronchiolitis by season and month. Monthly admission counts from the prepandemic era were transformed into time series and used to train seasonal ensemble forecasting models. Forecasts were compared to monthly admissions during the pandemic era. Results: In this study, there were 400 801 bronchiolitis admissions among 349 609 patients between July 1, 2010, and June 30, 2023. The median patient age was 6 (IQR, 2-12) months; 58.7% were boys and 43.7% were White. Hospitalizations increased gradually during the prepandemic era (median, 29 309 [IQR, 26 196-34 157]), decreased 69.2% (n = 9030) in the 2020-2021 season, and increased 75.3% (n = 51 397) in the 2022-2023 season. Patients in the pandemic era were older than those in the prepandemic era (median, 7 [IQR, 3-14] vs 6 [2-12] months; P < .001). Intensive care unit (ICU) admissions increased from 32.2% (96 245 of 298 535) in the prepandemic era to 36.7% (37 516 of 102 266) in the pandemic era (P < .001). The seasonality of bronchiolitis admissions changed during the pandemic era. Admissions peaked in August 2021 (actual 5036 vs 943 [95% CI, 0-2491] forecasted) and November 2022 (actual 10 120 vs 5268 [95% CI, 3425-7419] forecasted). These findings were unchanged in sensitivity analyses excluding children with complex chronic conditions and excluding repeat admissions. In a sensitivity analysis including all viral lower respiratory tract infections in children aged younger than 5 years, there were 66 767 admissions in 2022-2023 vs 35 623 (31 301-41 002) in the prepandemic era, with the largest increase in children aged 24 to 59 months. Conclusions and Relevance: The findings of this cross-sectional study suggest that bronchiolitis hospitalizations decreased transiently and then increased markedly during the COVID-19 pandemic era. Patients admitted during the pandemic era were older and were more likely to be admitted to an ICU. These findings suggest that bronchiolitis seasonality has not yet returned to prepandemic patterns, and US hospitals should prepare for the possibility of atypical timing again in 2023.

Antibacterial agent triclosan suppresses RBL-2H3 mast cell function.

Triclosan is a broad-spectrum antibacterial agent, which has been shown previously to alleviate human allergic skin disease. The purpose of this study was to investigate the hypothesis that the mechanism of this action of triclosan is, in part, due to effects on mast cell function. Mast cells play important roles in allergy, asthma, parasite defense, and carcinogenesis. In response to various stimuli, mast cells degranulate, releasing allergic mediators such as histamine. In order to investigate the potential anti-inflammatory effect of triclosan on mast cells, we monitored the level of degranulation in a mast cell model, rat basophilic leukemia cells, clone 2H3. Having functional homology to human mast cells, as well as a very well defined signaling pathway leading to degranulation, this cell line has been widely used to gain insight into mast-cell driven allergic disorders in humans. Using a fluorescent microplate assay, we determined that triclosan strongly dampened the release of granules from activated rat mast cells starting at 2 µM treatment, with dose-responsive suppression through 30 µM. These concentrations were found to be non-cytotoxic. The inhibition was found to persist when early signaling events (such as IgE receptor aggregation and tyrosine phosphorylation) were bypassed by using calcium ionophore stimulation, indicating that the target for triclosan in this pathway is likely downstream of the calcium signaling event. Triclosan also strongly suppressed F-actin remodeling and cell membrane ruffling, a physiological process that accompanies degranulation. Our finding that triclosan inhibits mast cell function may explain the clinical data mentioned above and supports the use of triclosan or a mechanistically similar compound as a topical treatment for allergic skin disease, such as eczema.

Estrogen mimetic 4-tert-octylphenol enhances IgE-mediated degranulation of RBL-2H3 mast cells.

Allergic diseases such as asthma have been on the rise in recent decades. Environmental or occupational exposure to estrogenic synthetic chemicals is suspected to be a contributing factor, and previous experimental studies indicated that estradiol and some xenoestrogens increase allergic signaling responses, such as degranulation, in immune cells. In the current study, data showed that the estrogen mimetic 4-tert-octylphenol (4tOP) enhances immunoglobulin (Ig) E-mediated degranulation of mammalian mast cell line RBL-2H3 (RBL). At the noncytotoxic concentrations 10-20 µM, 4tOP significantly increased degranulation in antigen (Ag)-activated RBLs but exerted no marked effect on spontaneous levels. Our data suggest that the industrial chemical 4tOP has the potential to enhance allergic disease in individuals who are exposed.

Gender, Parenting Status, and the Academic Productivity of Pediatricians During the COVID-19 Pandemic.

BACKGROUND: During the coronavirus disease 2019 pandemic, many women physicians experienced increased caregiver responsibilities, potentially leading to worsened gender inequities. METHODS: We surveyed faculty and trainees at a quaternary-care children's hospital regarding work environment, household obligations, and academic productivity to examine differential effects on productivity by gender and parenting status. We used descriptive statistics for demographics and analyzed Likert-scale responses with χ2 or Fisher's exact tests. We performed multivariable logistic regression to determine factors associated with self-reported academic productivity. We analyzed free-response comments using thematic analysis. RESULTS: The August 2021 survey was completed by 366 respondents (65% women; 46% response rate). Women were significantly more likely to report decreased academic productivity than men (66% [146/222] vs 30% [38/129], P <.001). Nearly one-half (49%) were parents with 80% utilizing childcare. Of these, 61% experienced unreliable childcare during the pandemic. Parents with unreliable childcare reported significantly decreased academic productivity compared with those with reliable childcare (76% [64/84] vs 36% [19/53], P <.001), and, among those with unreliable childcare, women disproportionally reported decreased academic productivity compared with men (88.5% [54/61] vs 43.5% [10/23], P <.001). After multivariable adjustment, women physicians with children were significantly more likely to report decreased academic productivity than men with children (adjusted odds ratio: 10.19, 95% confidence interval: 4.68-22.23). CONCLUSIONS: The coronavirus disease 2019 pandemic has differentially impacted men and women physicians, with women physician parents more likely to report decreased academic productivity than men with children. Unreliable childcare was a significant contributor to this disparity. Institutions must prioritize initiatives to improve gender equity in medicine.

Association between pediatric TBI mortality and median family income in the United States: A retrospective cohort study.

BACKGROUND: There are regional disparities in pediatric traumatic brain injury (TBI) mortality across the United States, but the factors underlying these differences are unclear. METHODS: We performed a retrospective cross-sectional analysis of the Pediatric Health Information System database including inpatient hospital encounters for children less than 18 years old with a primary diagnosis of TBI between 2010-2019. FINDINGS: Lower median family income was associated with pediatric TBI mortality. Encounters from zip-codes with a median family income of <$20,000 had a 3.1% (29/950) mortality, as opposed to 1.3% (29/2,267) mortality for zip-codes with a median family income of >$80,000 (p = 0.00096). In multivariable logistic regression, every $10,000 of income was associated with an odds ratio of mortality of 0.94 (95% confidence interval 0.90 - 0.98). 82.5% (397/481) of ballistic TBI injuries were caused by a firearm. Lower income was associated with a higher proportion of ballistic TBI injuries (2.5% [24/950] for <$20,000 versus 0.3% [7/2,267] for >$80,000, p < 0.0001). In multivariable logistic regression, ballistic TBI injuries were associated with an odds ratio of mortality of 5.19 (95% confidence interval 4.00 - 6.73). United States regional variation in pediatric TBI mortality was linearly associated with the percentage of ballistic TBI (adjusted r-squared 0.59, p = 0.0097). INTERPRETATION: Children from lower income zip-codes are more likely to sustain a ballistic TBI, and more likely to die. Further work is necessary to determine causal factors underlying these associations and to design interventions that prevent these injuries and/or improve outcomes.