Search

ObjectivesThe COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes.DesignMulticenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021).SettingData source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial.PatientsChildren (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS.InterventionsNone.Measurements and main resultsAmong 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic ( p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0-3] vs 0 [0-2]; p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35-2.04] FSS points; p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03-3.46]; p = 0.04).ConclusionsUsing the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors.

The objective of this study was to evaluate patient-specific factors associated with dexmedetomidine dose requirements during continuous infusion. A retrospective cross-sectional analysis of electronic health record-derived data spanning 10 years for patients admitted with a primary respiratory diagnosis at a quaternary children's hospital and who received a dexmedetomidine continuous infusion (n = 346 patients) was conducted. Penalized regression was used to select demographic, clinical, and medication characteristics associated with a median daily dexmedetomidine dose. Identified characteristics were included in multivariable linear regression models and sensitivity analyses. Critically ill children had a median hourly dexmedetomidine dose of 0.5 mcg/kg/h (range: 0.1–1.8), median daily dose of 6.7 mcg/kg/d (range: 0.9–38.4), and median infusion duration of 1.6 days (range: 0.25–5.0). Of 26 variables tested, 15 were selected in the final model with days of dexmedetomidine infusion (β: 1.9; 95% confidence interval [CI]: 1.6, 2.3), median daily morphine milligram equivalents dosing (mg/kg/d) (β: 0.3; 95% CI: 0.1, 0.5), median daily ketamine dosing (mg/kg/d) (β: 0.2; 95% CI: 0.1, 0.3), male sex (β: −1.1; 95% CI: −2.0, −0.2), and non-Black reported race (β: −1.2; 95% CI: −2.3, −0.08) significantly associated with median daily dexmedetomidine dose. Approximately 56% of dose variability was explained by the model. Readily obtainable information such as demographics, concomitant medications, and duration of infusion accounts for over half the variability in dexmedetomidine dosing. Identified factors, as well as additional environmental and genetic factors, warrant investigation in future studies to inform precision dosing strategies.

Purpose To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). Methods Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. Results We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (– 1 to 15), 0 (– 1 to 9) and—1 (– 1 to 7), respectively, compared to 6 (– 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). Conclusion Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06448-5.

Objective: The purpose of this report is to provide insight from pediatric stakeholders with a shared desire to facilitate a revision of the current United States regulatory pathways for the development of pediatric healthcare devices. Methods: On August 5, 2020, a group of innovators, engineers, professors and clinicians met to discuss challenges and opportunities for the development of new medical devices for pediatric health and the importance of creating a regulatory environment that encourages and accelerates the research and development of such devices. On January 6, 2021, this group joined regulatory experts at a follow-up meeting. Results: One of the primary issues identified was the need to present decision-makers with opportunities that change the return-on-investment balance between adult and pediatric devices to promote investment in pediatric devices. Discussion/Conclusion: Several proposed strategies were discussed, and these strategies can be divided into two broad categories: 1. Removal of real and perceived barriers to pediatric device innovation; 2. Increasing incentives for pediatric device innovation.

Background A variety of approaches to defining sepsis using administrative datasets have been previously reported. We aimed to compare estimates, demographics, treatment factors, outcomes and longitudinal trends of patients identified with sepsis in United States emergency departments (EDs) using differing sets of sepsis criteria. Methods We performed a cross-sectional study using the National Healthcare Ambulatory Medical Care Survey, a complex survey of nonfederal US ED encounters between 2002 to 2018. We obtained survey-weighted population-adjusted encounters of sepsis using the following criteria: explicit sepsis, severe sepsis, and quick Sequential Organ Failure Assessment (qSOFA) score combined with the presence of infection. Results Age-adjusted for US adults, 18.6, 16.1 and 8.9 encounters per 10 000 population were identified when using the explicit, severe sepsis and qSOFA definitions, respectively. A higher proportion of the explicit cohort was hospitalized and had blood cultures performed, compared to cohorts ascertained using severe sepsis and qSOFA criteria, though confidence intervals overlapped. Antibiotic use was highest in encounters meeting qSOFA criteria. When inspecting unweighted encounters meeting each set of criteria, there was minimal overlap, with only 3% meeting all three. Encounters meeting the explicit and severe sepsis criteria were increasing over time. Conclusion The explicit, severe sepsis and qSOFA criteria generated similar annual rates of presentation when applied to US ED encounters, with some evidence of the explicit sepsis cohort being higher acuity. There was minimal overlap of cases and instability in estimates when assessed longitudinally. Our findings inform research efforts to accurately identify sepsis among ED encounters using administrative data.

New neuroprotective therapies for severe traumatic brain injury (TBI) have not translated from pre-clinical to clinical success. Numerous explanations have been suggested in both the pre-clinical and clinical arenas. Coverage of TBI in the lay press has reinvigorated interest, creating a golden age of TBI research with innovative strategies to circumvent roadblocks. We discuss the need for more robust therapies. We present concepts for traditional and novel approaches to defining therapeutic targets. We review lessons learned from the ongoing work of the pre-clinical drug and biomarker screening consortium Operation Brain Trauma Therapy and suggest ways to further enhance pre-clinical consortia. Biomarkers have emerged that empower choice and assessment of target engagement by candidate therapies. Drug combinations may be needed, and it may require moving beyond conventional drug therapies. Precision medicine may also link the right therapy to the right patient, including new approaches to TBI classification beyond the Glasgow Coma Scale or anatomical phenotyping-incorporating new genetic and physiologic approaches. Therapeutic breakthroughs may also come from alternative approaches in clinical investigation (comparative effectiveness, adaptive trial design, use of the electronic medical record, and big data). The full continuum of care must also be represented in translational studies, given the important clinical role of pre-hospital events, extracerebral insults in the intensive care unit, and rehabilitation. TBI research from concussion to coma can cross-pollinate and further advancement of new therapies. Misconceptions can stifle/misdirect TBI research and deserve special attention. Finally, we synthesize an approach to deliver therapeutic breakthroughs in this golden age of TBI research.

Background and Aims Intracranial compliance refers to the relationship between a change in intracranial volume and the resultant change in intracranial pressure (ICP). Measurement of compliance is useful in managing cardiovascular and respiratory failure; however, there are no contemporary means to assess intracranial compliance. Knowledge of intracranial compliance could complement ICP and cerebral perfusion pressure (CPP) monitoring in patients with severe traumatic brain injury (TBI) and may enable a proactive approach to ICP management. In this proof-of-concept study, we aimed to capitalize on the physiologic principles of intracranial compliance and vascular reactivity to CO2, and standard-of-care neurocritical care monitoring, to develop a method to assess dynamic intracranial compliance. Methods Continuous ICP and end-tidal CO2 (ETCO2) data from children with severe TBI were collected after obtaining informed consent in this Institutional Review Board-approved study. An intracranial pressure-PCO2 Compliance Index (PCI) was derived by calculating the moment-to-moment correlation between change in ICP and change in ETCO2. As such, “good” compliance may be reflected by a lack of correlation between time-synched changes in ICP in response to changes in ETCO2, and “poor” compliance may be reflected by a positive correlation between changes in ICP in response to changes in ETCO2. Results A total of 978 h of ICP and ETCO2 data were collected and analyzed from eight patients with severe TBI. Demographic and clinical characteristics included patient age 7.1 ± 5.8 years (mean ± SD); 6/8 male; initial Glasgow Coma Scale score 3 [3–7] (median [IQR]); 6/8 had decompressive surgery; 7.1 ± 1.4 ICP monitor days; ICU length of stay (LOS) 16.1 ± 6.8 days; hospital LOS 25.9 ± 8.4 days; and survival 100%. The mean PCI for all patients throughout the monitoring period was 0.18 ± 0.04, where mean ICP was 13.7 ± 2.1 mmHg. In this cohort, PCI was observed to be consistently above 0.18 by 12 h after monitor placement. Percent time spent with PCI thresholds > 0.1, 0.2, and 0.3 were 62% [24], 38% [14], and 23% [15], respectively. The percentage of time spent with an ICP threshold > 20 mmHg was 5.1% [14.6]. Conclusions Indirect assessment of dynamic intracranial compliance in TBI patients using standard-of-care monitoring appears feasible and suggests a prolonged period of derangement out to 5 days post-injury. Further study is ongoing to determine if the PCI—a new physiologic index, complements utility of ICP and/or CPP in guiding management of patients with severe TBI. Electronic supplementary material The online version of this article (10.1007/s12028-020-01004-3) contains supplementary material, which is available to authorized users.

AIM: The mathematical method used to calculate chest compression (CC) rate during cardiopulmonary resuscitation varies in the literature and across device manufacturers. The objective of this study was to determine the variability in calculated CC rates by applying four published methods to the same dataset. METHODS: This study was a secondary investigation of the first 200 pediatric cardiac arrest events with invasive arterial line waveform data in the ICU-RESUScitation Project (NCT02837497). Instantaneous CC rates were calculated during periods of uninterrupted CCs. The defined minimum interruption length affects rate calculation (e.g., if an interruption is defined as a break in CCs ≥ 2 seconds, the lowest possible calculated rate is 30 CCs/min). Average rates were calculated by four methods: 1) rate with an interruption defined as ≥ 1 second; 2) interruption ≥ 2 seconds; 3) interruption ≥ 3 seconds; 4) method #3 excluding top and bottom quartiles of calculated rates. American Heart Association Guideline-compliant rate was defined as 100–120 CCs/min. A clinically important change was defined as ± 5 CCs/min. The percentage of events and epochs (30 second periods) that changed Guideline-compliant status was calculated. RESULTS: Across calculation methods, mean CC rates (118.7 – 119.5/min) were similar. Comparing all methods, 14 events (7%) and 114 epochs (6%) changed Guideline-compliant status. CONCLUSION: Using four published methods for calculating CC rate, average rates were similar, but 7% of events changed Guideline-compliant status. These data suggest that a uniform calculation method (interruption ≥ 1 second) should be adopted to decrease variability in resuscitation science.

OBJECTIVE: To identify whether a high Pao(2) (hyperoxemia) at the time of presentation to the PICU is associated with in-hospital mortality. DESIGN: Single-center observational study. SETTING: Quaternary-care PICU. PATIENTS: Encounters admitted between January 1, 2009, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Encounters with a measured Pao(2) were included. To account for severity of illness upon presentation, we calculated a modified Pediatric Risk of Mortality IV score excluding Pao(2) for each encounter, calibrated for institutional data. Logistic regression was used to determine whether hyperoxemia (Pao(2) ≥ 300 torr [39.99 kPa]) in the 12 hours surrounding PICU admission was associated with in-hospital mortality. We reperformed our analysis using a cutoff for hyperoxemia obtained by comparisons of observed versus predicted mortality when encounters were classified by highest Pao(2) in 50 torr (6.67 kPa) bins. Results are reported as adjusted odds ratios with 95% CIs. Of 23,719 encounters, 4,093 had a Pao(2) recorded in the period −6 to +6 hours after admission. Two hundred seventy-four of 4,093 (6.7%) had in-hospital mortality. The prevalence of hyperoxemia increased with rising modified Pediatric Risk of Mortality IV and was not associated with mortality in multivariable models (adjusted odds ratio, 1.38; 95% CI, 0.98–1.93). When using a higher cutoff of hyperoxemia derived from comparison of observed versus predicted rates of mortality of greater than or equal to 550 torr (73.32 kPa), hyperoxemia was associated with mortality (adjusted odds ratio, 2.78; 95% CI, 2.54–3.05). CONCLUSIONS: A conventional threshold for hyperoxemia at presentation to the PICU was not associated with in-hospital mortality in a model using a calibrated acuity score. Extreme states of hyperoxemia (≥ 73.32 kPa) were significantly associated with in-hospital mortality. Prospective research is required to identify if hyperoxemia before and/or after PICU admission contributes to poor outcomes.

From an educational point of view, the design of digital games, especially the so-called serious games, is a powerful tool that can improve engagement and motivation, help students develop digital literacy skills, and deepen their understanding of the domain, which could eventually have a positive impact on the overall learning process. For this reason, game development is increasingly being incorporated into the learning process and more and more educators are using this strategy to improve the quality of their teaching. Given the inherent multidisciplinarity and complexity of such projects, the design of game design-based learning activities, as well as their assessment, is not an easy task. As a result, many approaches have been developed, some of which rely on existing, proven models such as Bloom's Taxonomy, while others incorporate the principles of project-based learning or motivational design processes. This study provides an overview of the different approaches to the design and assessment of game-based learning systems and activities, outlining their main features and characteristics.

Emotions are an omnipresent and important factor in the interaction and communication between people. Since emotions are an indispensable part of human life, it would accelerate the progress of artificial intelligence and other fields of science that require data about emotions if they could be adequately described by computer systems. Today there are many different theories of affect, but few of them are used in affective computing. Other areas of computing also benefit from structured and expressive data models of the affective domain, such as human-computer interaction and brain- computer interfaces. Typical tasks include automated recognition and analysis of emotional states, mental fatigue, individual motivation, vigilance and stress resilience. In this paper four often used models of emotion and cognitive behavior are listed and their properties explained: discrete, dimensional, appraisal and action tendency models. For each model, algorithms are provided for similarity measures that can be used to determine the relatedness between different stimulation and estimation artefacts in their respective emotion spaces. The goal of this article is to help professionals find the optimal emotion model for their research and quickly become familiar with data modelling of affective states.

The Children’s Hospital Association’s Improving Pediatric Sepsis Outcomes (IPSO) collaborative is a multi-center quality improvement (QI) learning collaborative of 61 U.S. children’s hospitals that seeks to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions in pediatric emergency departments, intensive care units, general care units, and hematology/oncology units. Specifically, IPSO’s goals are to decrease sepsis-attributable mortality and prevent hospital-onset sepsis among children. The following 10 abstracts represent a select group of projects undertaken by IPSO participating hospitals that were presented at one of three collaborative events in 2020 and 2021. IPSO’s Research Workgroup reviewed all submitted abstracts and selected the top 10 for inclusion in this Supplement

The Children’s Hospital Association’s Improving Pediatric Sepsis Outcomes (IPSO) collaborative is a multi-center quality improvement (QI) learning collaborative of 61 U.S. children’s hospitals that seeks to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions in pediatric emergency departments, intensive care units, general care units, and hematology/oncology units. Specifically, IPSO’s goals are to decrease sepsis-attributable mortality and prevent hospital-onset sepsis among children. The following 10 abstracts represent a select group of projects undertaken by IPSO participating hospitals that were presented at one of three collaborative events in 2020 and 2021. IPSO’s Research Workgroup reviewed all submitted abstracts and selected the top 10 for inclusion in this Supplement

The coal mine is located in the town of Labin, Istria peninsula, Croatia. Restoration of the tower is a part of the project that includes thorough restoration and re-use of the Labin mining complex for cultural, tourist and educational purposes. The tower was built in 1938 by Italian authorities as part of the pre-war campaign. It is a 32.5 m high steel structure that once enveloped the elevator to a 200 m deep mine shaft. The structure is a built up Vierendeel truss with four columns / chords connected with horizontal moment resistant beams. Two large steel inclined struts were resisting elevator rope forces connected to the elevator machine building. The mine was shut down in 1988. The assessment of the tower consisted of geometry measurement, cross-section shape determination, steel quality determination, condition of members and connections (rivets and bolts), protective coating condition and underground supports condition. Two samples were taken to laboratory to determine the steel grade with tensile yield test. Structural model with existing members has also been analysed. Different loads were considered comparing the original purpose of the tower and the planned representational purpose. In addition, structural member verification according to Eurocode standards has been done. Load bearing steel structure is geometrically sound, mostly with no visible deformations, deflections or drifts. Foundations are crack free and with no visible subsiding. Lack of maintenance of the anticorrosive coating from 1988 until today caused most of the damage. Due to the significantly aggressive environment, anchoring part of the structure was severely ruined. Lower part of the above ground structure was in the similar condition. Water retention and salt carried from the lower part of the shaft caused significant damage to the steel structure in these areas. Replaced members were built in with original riveting technique. Anchoring structure replacement called for a temporary support structure, which represented the most demanding operation in the whole restoration process. The temporary support structure was a steel truss structure in pyramidal form that allowed complete removal of the lowest segment and reconstruction of the anchoring elements and concrete foundation. According to the evaluation, existing galleries that surrounded the tower had to be completely removed and redesigned with new loads. Future use of the tower with its galleries is primarily of representational purpose. Moreover, a new elevator with its own structure inside the existing tower is considered and it has no influence on the existing structure. Since the tower is registered as an architectural heritage by the Croatian Ministry of Culture, specific demands regarding structural restoration were issued. The principles of structural analysis and restoration together with multidisciplinary approach have been applied in this project.

Key Points Question What factors are associated with increasing hospital costs for patients with bronchiolitis? Findings In this cross-sectional study of 385 883 bronchiolitis hospitalizations, children hospitalized in later years received more costly and intensive care without objective evidence of increasing severity of illness. Substantial changes in coding practices were observed, with an increasing proportion of patients diagnosed with respiratory failure between 2010 and 2019. Meaning This study suggests that future research on trends in bronchiolitis should account for changes in the patterns of diagnostic coding., Importance Increasing hospital costs for bronchiolitis have been associated with increasing patient complexity and mechanical ventilation. However, the associations of illness severity and diagnostic coding practices with bronchiolitis hospitalization costs have not been examined. Objective To investigate the association of patient complexity, illness severity, and diagnostic coding practices with bronchiolitis hospitalization costs. Design, Setting, and Participants This retrospective cross-sectional study included 385 883 infants aged 24 months or younger who were hospitalized with bronchiolitis at 39 hospitals in the Pediatric Health Information System database from January 1, 2010, to December 31, 2019. Exposure Hospitalization for bronchiolitis. Main Outcomes and Measures Inflation-adjusted standardized unit cost (expressed in dollar units) per hospitalization over time. A nested subgroup analysis was performed to further examine factors associated with changes in cost. Results A total of 385 883 bronchiolitis hospitalizations were studied; the patients had a mean (SD) age of 7.5 (6.4) months and included 227 309 of 385 883 boys (58.9%) and 253 870 of 385 883 publicly insured patients (65.8%). Among patients hospitalized with bronchiolitis, the median standardized unit cost per hospitalization increased significantly during the study period (from $5636 [95% CI, $5558-$5714] in 2010 to $6973 [95% CI, $6915-$7030] in 2019; P, This cross-sectional study of more than 385 000 children hospitalized with bronchiolitis investigates the association of the complexity of a patient’s condition, illness severity, and diagnostic coding practices with bronchiolitis hospitalization costs.

BACKGROUND: Acute Kidney Disease (AKD) is defined as impaired kidney function present for < 90 days with or without an acute kidney injury (AKI) event. Adults with AKD have an increased risk for progression to chronic kidney disease (CKD) and mortality. There are no data on the epidemiology of AKD in children after transplant. The aim of this study was to evaluate the incidence and risk factors for AKI, AKD, and CKD in children after transplantation. METHODS: This is a retrospective cohort study of all children undergoing non-kidney solid organ transplant between 2011–2019 at UPMC Children’s Hospital of Pittsburgh. AKI and AKD were defined using the Kidney Disease Improving Global Outcomes criteria. Patients with a new estimated glomerular filtration rate < 60 ml/min/1.73m(2) persisting for > 3 months met criteria for new CKD. Variables associated with AKI, AKD, and CKD were analyzed. RESULTS: Among 338 patients 37.9% met criteria for severe AKI, 13% for AKD, and 8% for a new diagnosis of CKD. Stage 3 AKI was independently associated with AKD (OR: 5.35; 95% CI: 2.23–12.86). Severe AKI was not associated with new onset CKD whereas AKD was associated with new onset CKD (OR: 29.74; CI: 11.22–78.82). CONCLUSION: AKD may be superior to AKI in predicting risk of CKD in children after non-kidney solid organ transplantation.

IntroductionRapid, continuous implementation of credible scientific findings and regulatory approvals is often slow in large, diverse health systems. The COVID-19 pandemic created a new threat to this common “slow to learn and adapt” model in healthcare. We describe how UPMC committed to a rapid learning health system (LHS) model to respond to the COVID-19 pandemic.MethodsAn observational cohort study was conducted among 11,429 hospitalized patients from 22 hospitals (PA, NY) with a primary diagnosis of COVID-19 infection (March 19, 2020 – June 6, 2021). Sociodemographic and clinical data were captured from UPMC electronic medical record (EMR) systems. Patients were grouped into four time-defined patient “waves” based on nadir of daily hospital admissions, with wave 3 (September 20, 2020 – March 10, 2021) split at its zenith due to high volume with steep acceleration and deceleration. Outcomes included changes in clinical practice (e.g., use of corticosteroids, antivirals, and other therapies) in relation to timing of internal system analyses, scientific publications, and regulatory approvals, along with 30-day rate of mortality over time.ResultsMean (SD) daily number of hospital admissions was 26 (28) with a maximum 7-day moving average of 107 patients. System-wide implementation of the use of dexamethasone, remdesivir, and tocilizumab occurred within days of release of corresponding seminal publications and regulatory actions. After adjustment for differences in patient clinical profiles over time, each month of hospital admission was associated with an estimated 5% lower odds of 30-day mortality (adjusted OR = 0.95, 95% confidence interval: 0.92 – 0.97, p < .001).ConclusionsIn our large LHS, near real-time changes in clinical management of COVID-19 patients happened promptly as scientific publications and regulatory approvals occurred throughout the pandemic. Alongside these changes, patients with COVID-19 experienced lower adjusted 30-day mortality following hospital admission over time.

Severe sepsis in immunocompromised children is associated with increased mortality. This paper describes the epidemiology landscape, clinical acuity, and outcomes for severe sepsis in pediatric intestinal (ITx) and multi-visceral (MVTx) transplant recipients requiring admission to the pediatric intensive care unit (PICU). Severe sepsis episodes were retrospectively reviewed in 51 ITx and MVTx patients receiving organs between 2009 and 2015. Twenty-nine (56.8%) patients had at least one sepsis episode (total of 63 episodes) through December 2016. Bacterial etiologies accounted for 66.7% of all episodes (n = 42), occurring a median of 122.5 days following transplant (IQR 59-211.8 days). Multidrug-resistant organisms (MDROs) accounted for 73.8% of bacterial infections; extended spectrum beta-lactamase producers, vancomycin-resistant enterococcus, and highly-resistant Pseudomonas aeruginosa were the most commonly identified. Increased mechanical ventilation and vasoactive requirements were noted in MDRO episodes (OR 3.03, 95% CI 1.09-8.46 and OR 3.07, 95% CI 1.09-8.61, respectively; p

OBJECTIVES: To determine the changes in ICU admissions, ventilatory support, length of stay, and cost for patients with bronchiolitis in the United States. METHODS: Retrospective cross-sectional study of the Pediatric Health Information Systems database. All patients age RESULTS: Of 203 859 admissions for bronchiolitis, 39 442 (19.3%) were admitted to an ICU, 6751 (3.3%) received IMV, and 9983 (4.9%) received NIV. ICU admissions for bronchiolitis doubled from 11.7% in 2010 to 24.5% in 2019 (P < .001 for trend), whereas ICU admissions for all children in Pediatric Health Information Systems CONCLUSIONS: The proportions of children with bronchiolitis admitted to an ICU and receiving NIV have substantially increased, whereas the proportion receiving IMV is unchanged over the past decade. Further study is needed to better understand the factors underlying these temporal patterns.

The objective of this study was to characterize the population pharmacokinetics of fentanyl and identify factors that contribute to exposure variability in critically ill pediatric patients. We conducted a single-center, retrospective cohort study using electronic record data and remnant blood samples in the setting of a mixed medical/surgical intensive care unit (ICU) at a quaternary children’s hospital. Children with a predicted ICU length of stay of at least 3 days and presence of an indwelling central venous or arterial line were included. Serum fentanyl measurements were performed for 278 unique remnant samples from 66 patients. Both one- and two-compartment models were evaluated to describe fentanyl disposition. Covariates were introduced into the model in a forward/backward, stepwise approach and included age, sex, race, weight, cytochrome P450 (CYP) 3A5 genotype, and the presence of CYP3A4 or CYP3A5 inducers or inhibitors. Simulations were performed using the successful model to depict the influence of inducers on fentanyl concentrations. A two-compartment base model best described the data. There was good agreement between observed and predicted concentrations in the final model. The typical fentanyl clearance for 70 kg (reference weight) and 20.1 kg (median weight) patients were 34.6 and 13.6 L/h, respectively. The magnitude of the unexplained random inter-individual variability was high for both clearance (60.7%) and apparent volume of the central compartment (V1) (107.2%). Coadministration of the known CYP3A4/5 inducers fosphenytoin and/or phenobarbital was associated with significantly increased fentanyl clearance. Simulations demonstrate that the effect of inducer administration was most pronounced following discontinuation of a fentanyl infusion. In this study we show the feasibility and utility of using electronic record data and remnant blood samples to successfully construct population pharmacokinetic models for a heterogeneous cohort of critically ill children. A clinically relevant effect of concomitant CYP3A4/5 inducers was identified. Scaling this population pharmacokinetic approach is necessary to craft precision approaches to fentanyl administration for critically ill children.

Objective: Legitimate opioid prescriptions have been identified as a risk factor for opioid misuse in pediatric patients. In 2014, Pennsylvania legislation expanded a prescription drug monitoring program (PDMP) to curb inappropriate controlled substance prescriptions. The authors’ objective was to describe recent opioid prescribing trends at a large, pediatric health system situated in a region with one of the highest opioid-related death rates in the United States and examine the impact of the PDMP on prescribing trends. Design: Quasi-experimental assessment of trends of opioid e-prescriptions, from 2012 to 2017. Multivariable Poisson segmented regression examined the effect of the PDMP. Period prevalence comparison of opioid e-prescriptions across the care continuum in 2016. Results: There were 62,661 opioid e-prescriptions identified during the study period. Combination opioid/non-opioid prescriptions decreased, while oxycodone prescriptions increased. Seasonal variation was evident. Of 110,884 inpatient encounters, multivariable regression demonstrated lower odds of an opioid being prescribed at discharge per month of the study period (p < 0.001) and a significant interaction between passage of the PDMP legislation and time (p = 0.03). Black patients had lower odds of receiving an opioid at discharge compared to white patients. Inpatients had significantly greater odds of receiving an opioid compared to emergency department (Prevalence Odds Ratio 7.1 [95% confidence interval: 6.9-7.3]; p < 0.001) and outpatient (398.9 [355.5-447.5]; p < 0.001) encounters. Conclusion: In a large pediatric health system, oxycodone has emerged as the most commonly prescribed opioid in recent years. Early evidence indicates that a state-run drug monitoring program is associated with reduced opioid prescribing. Additional study is necessary to examine the relationship between opioid prescriptions and race.

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.

Importance In early 2020, the United States declared a public health emergency in response to coronavirus disease 2019 (COVID-19) and implemented a variety of social distancing measures. The association between the COVID-19 pandemic and the number of pediatric admissions is unclear. Objective To determine the changes in patterns of pediatric admissions in 2020 compared with the prior decade. Design, Setting, and Participants This cross-sectional study included 49 US hospitals contributing to the Pediatric Health Information Systems database. Inpatient admissions were transformed into time-series data, and ensemble forecasting models were generated to analyze admissions across a range of diagnoses in 2020 compared with previous years. The setting was inpatient admissions. All patients discharged between January 1, 2010, and June 30, 2020, from an inpatient hospital encounter were included. Main Outcomes and Measures Number of hospital admissions by primary diagnosis for each encounter. Results Of 5 424 688 inpatient encounters among 3 372 839 patients (median [interquartile range] age, 5.1 [0.7-13.3] years; 2 823 748 [52.1%] boys; 3 171 224 [58.5%] White individuals) at 49 hospitals, 213 571 (3.9%) were between January 1, 2020, and June 30, 2020. There was a decrease in the number of admissions beginning in March 2020 compared with the period from 2010 to 2019. At the nadir, admissions in April 2020 were reduced 45.4% compared with prior years (23 798 in April 2020 compared with a median [interquartile range] of 43 550 [42 110-43 946] in April 2010-2019). Inflation-adjusted hospital charges decreased 27.7% in the second quarter of 2020 compared with prior years ($4 327 580 511 in 2020 compared with a median [interquartile range] of $5 983 142 102 [$5 762 690 022-$6 324 978 456] in 2010-2019). Seasonal patterns were evident between 2010 and 2019 for a variety of common pediatric conditions, including asthma, atrial septal defects, bronchiolitis, diabetic ketoacidosis, Kawasaki syndrome, mental health admissions, and trauma. Ensemble models were able to discern seasonal patterns in admission diagnoses and accurately predicted admission rates from July 2019 until December 2019 but not from January 2020 to June 2020. All diagnoses except for birth decreased below the model 95% CIs between January 2020 and June 2020. Conclusions and Relevance In this cross-sectional study, pediatric admissions to US hospitals decreased in 2020 across an array of pediatric conditions. Although some conditions may have decreased in incidence, others may represent unmet needs in pediatric care during the COVID-19 pandemic.

This cross-sectional study assesses potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence and estimating the prevalence of potentially actionable prescribing decisions., Key Points Question What is the opportunity for genotype-guided prescribing among pediatric patients in the US? Findings In this serial cross-sectional study of annual prescribing data at 16 health systems representing approximately 2.9 million pediatric patients per year from 2011 to 2017, the annual prevalence of exposure to at least 1 Clinical Pharmacogenetics Implementation Consortium level A drug ranged from 7987 to 10 629 per 100 000 pediatric patients, with increasing prevalence before reaching a plateau in 2014. The medications with the highest potential for actionability were analgesics (oxycodone, codeine, and tramadol), the antiemetic ondansetron, and antidepressants (citalopram, escitalopram, and amitriptyline). Meaning These findings suggest that ample opportunity exists for genotype-guided prescribing among pediatric patients in the US, especially for drugs metabolized by CYP2D6 or CYP2C19., Importance Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. Objective To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. Design, Setting, and Participants This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children’s hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. Exposures Prescription of 38 level A medications based on electronic health records. Main Outcomes and Measures Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. Results Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. Conclusions and Relevance These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants.