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Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks.A prospective, observational cohort study.Children with sepsis and organ failure in nine pediatric intensive care units in the United States.Two hundred and fifty-five children were enrolled. Five distinct clinical multi-trajectory groups were identified. Plasma CRP (mg/dL), ferritin (ng/mL), and 31 cytokine levels were measured at two timepoints during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin.Group 1 had normal CRP and ferritin levels ( n = 8; 0% mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout ( n = 80; 5% mortality); Group 3 had high ferritin levels alone ( n = 16; 6% mortality); Group 4 had very high CRP levels, and high ferritin levels ( n = 121; 11% mortality); and Group 5 had very high CRP and very high ferritin levels ( n = 30; 40% mortality). Cytokine responses differed across the five groups, with ferritin levels correlated with macrophage inflammatory protein 1α levels and CRP levels reflective of many cytokines.Bedside CRP and ferritin levels can be used together to distinguish groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks. These data suggest future potential value in personalized clinical trials with specific targets for anti-inflammatory therapies.

To evaluate associations between sodium bicarbonate use and outcomes during pediatric in-hospital cardiac arrest (p-IHCA).Prespecified secondary analysis of a prospective, multicenter cluster randomized interventional trial.Eighteen participating ICUs of the ICU-RESUScitation Project (NCT02837497).Children less than or equal to 18 years old and greater than or equal to 37 weeks post conceptual age who received chest compressions of any duration from October 2016 to March 2021.None.Child and event characteristics, prearrest laboratory values (2-6 hr prior to p-IHCA), pre- and intraarrest hemodynamics, and outcomes were collected. In a propensity score weighted cohort, the relationships between sodium bicarbonate use and outcomes were assessed. The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Of 1,100 index cardiopulmonary resuscitation events, median age was 0.63 years (interquartile range, 0.19-3.81 yr); 528 (48.0%) received sodium bicarbonate; 773 (70.3%) achieved ROSC; 642 (58.4%) survived to hospital discharge; and 596 (54.2%) survived to hospital discharge with favorable neurologic outcome. Among the weighted cohort, sodium bicarbonate use was associated with lower survival to hospital discharge rate (adjusted odds ratio [aOR], 0.7; 95% CI, 0.54-0.92; p = 0.01) and lower survival to hospital discharge with favorable neurologic outcome rate (aOR, 0.69; 95% CI, 0.53-0.91; p = 0.007). Sodium bicarbonate use was not associated with ROSC (aOR, 0.91; 95% CI, 0.62-1.34; p = 0.621).In this propensity weighted multicenter cohort study of p-IHCA, sodium bicarbonate use was common and associated with lower rates of survival to hospital discharge.

Following initial stabilization, critically ill children often require transfer to a specialized pediatric hospital. While the use of specialized pediatric transport teams has been associated with improved outcomes for these patients, the additional influence of transfer mode (helicopter or ground ambulance) on clinical outcomes remains unknown.We investigated the association between transport mode and outcomes among critically ill children transferred to a single pediatric hospital via a specialized pediatric transport team. We designed a retrospective cohort study to reduce indication bias by limiting analysis to patients for whom a helicopter transport was initially requested. We compared outcomes for those who ultimately traveled via helicopter, and for those who ultimately traveled via ground ambulance due to non-clinical factors.We compared transport times, in-hospital mortality, and hospital length of stay by transport mode. Transport time in minutes was shorter for helicopter transports (median = 143, interquartile range [IQR]: 118-184) compared to ground ambulance transports (median = 289, IQR: 213-258; difference in medians = 146, 95% CI: 12 to 168, p0.001). In unadjusted analysis, helicopter transport was not associated with a difference in in-hospital mortality (helicopter = 6.0%, ground ambulance = 7.0%; 95% CI for difference: -6.6% to 3.3%; p = 0.64) but was associated with a statistically significant reduction in median hospital days (helicopter = 4, ground ambulance = 5; 95% CI -3 to 0; p = 0.04). In adjusted analyses, there were no statistically significant associations. These results were consistent across sensitivity analyses.Among critically ill pediatric patients without traumatic injuries transported by a specialty team, those patients who would have been transferred by helicopter if available but were instead transferred by ground ambulance reached their site of definitive care approximately 2.5 h later. Helicopter transport for these patients was not associated with in-hospital mortality, but was potentially associated with reduced hospital length of stay.

Arterial diastolic blood pressure (DBP) greater than 25 mm Hg in infants and greater than 30 mm Hg in children greater than 1 year old during cardiopulmonary resuscitation (CPR) was associated with survival to hospital discharge in one prospective study. We sought to validate these potential hemodynamic targets in a larger multicenter cohort.Prospective observational study.Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020.Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR.None.Invasive BP waveform data and Utstein-style CPR data were collected, including prearrest patient characteristics, intra-arrest interventions, and outcomes. Primary outcome was survival to hospital discharge, and secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Multivariable Poisson regression models with robust error estimates evaluated the association of DBP greater than 25 mm Hg in infants and greater than 30 mm Hg in older children with these outcomes. Among 1,129 children with inhospital cardiac arrests, 413 had evaluable DBP data. Overall, 85.5% of the patients attained thresholds of mean DBP greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in older children. Initial return of circulation occurred in 91.5% and 25% by placement on extracorporeal membrane oxygenator. Survival to hospital discharge occurred in 58.6%, and survival with favorable neurologic outcome in 55.4% (i.e. 94.6% of survivors had favorable neurologic outcomes). Mean DBP greater than 25 mm Hg for infants and greater than 30 mm Hg for older children was significantly associated with survival to discharge (adjusted relative risk [aRR], 1.32; 1.01-1.74; p = 0.03) and ROSC (aRR, 1.49; 1.12-1.97; p = 0.002) but did not reach significance for survival to hospital discharge with favorable neurologic outcome (aRR, 1.30; 0.98-1.72; p = 0.051).These validation data demonstrate that achieving mean DBP during CPR greater than 25 mm Hg for infants and greater than 30 mm Hg for older children is associated with higher rates of survival to hospital discharge, providing potential targets for DBP during CPR.

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.

To evaluate associations between calcium administration and outcomes among children with in-hospital cardiac arrest and among specific subgroups in which calcium use is hypothesized to provide clinical benefit.This is a secondary analysis of observational data collected prospectively as part of the ICU-RESUScitation project. Children 37 weeks post-conceptual age to 18 years who received chest compressions in one of 18 intensive care units from October 2016-March 2021 were eligible. Data included child and event characteristics, pre-arrest laboratory values, pre- and intra-arrest haemodynamics, and outcomes. Outcomes included sustained return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with favourable neurologic outcome. A propensity score weighted cohort was used to evaluate associations between calcium use and outcomes. Subgroups included neonates, and children with hyperkalaemia, sepsis, renal insufficiency, cardiac surgery with cardiopulmonary bypass, and calcium-avid cardiac diagnoses.Of 1,100 in-hospital cardiac arrests, median age was 0.63 years (IQR 0.19, 3.81); 450 (41%) received calcium. Among the weighted cohort, calcium use was not associated with sustained ROSC (aOR, 0.87; CI95 0.61-1.24; p=0.445), but was associated with lower rates of both survival to hospital discharge (aOR, 0.68; CI95 0.52-0.89; p=0.005) and survival with favourable neurologic outcome at hospital discharge (aOR, 0.75; CI95 0.57-0.98; p=0.038). Among subgroups, calcium use was associated with lower rates of survival to hospital discharge in children with sepsis and renal insufficiency.Calcium use was common during paediatric in-hospital cardiac arrest and associated with worse outcomes at hospital discharge.

OBJECTIVES Healthcare utilization after bronchiolitis hospitalization is incompletely understood. We aimed to characterize readmissions and outpatient visits within 1 year after hospital discharge. METHODS Retrospective multicenter observational cohort study of children under 24-months old admitted with bronchiolitis between January 1, 2010 and December 12, 2019 to the Pediatric Health Information Systems database. A single-center nested subset using linked electronic health records allowed analysis of outpatient visits. RESULTS There were 308 306 admissions for bronchiolitis among 271 115 patients across 47 hospitals between 2010–2019. The percent of patients readmitted within 30 days after discharge was 6.0% (16 167 of 271 115), and 17.8% (48 332 of 271 115) of patients were readmitted within 1 year. 22.9% (16 919 of 74 001) of patients admitted to an ICU and 26.8% (7865 of 29 378) of patients undergoing mechanical ventilation were readmitted within 1 year. There were 1438 patients with outpatient healthcare data available. There were a median (interquartile range) of 9 (6–13) outpatient visits per patient within 1 year after discharge. Outpatient healthcare use increased for 4 months following bronchiolitis hospitalization compared with previously reported age-matched controls. Higher income, white race, commercial insurance, complex chronic conditions, ICU admission, and mechanical ventilation were associated with higher outpatient utilization. Higher quartiles of outpatient use were associated with readmission for bronchiolitis and all-cause readmissions. CONCLUSIONS Readmissions in the year after bronchiolitis hospitalization are common, and outpatient healthcare use is increased for 4 months following discharge. Prospective study is needed to track long-term outcomes of infants with bronchiolitis.

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.

OBJECTIVES To define the clinical characteristics of hospitalized children with moderate traumatic brain injury and identify factors associated with deterioration to severe traumatic brain injury. DESIGN Retrospective cohort study. SETTING Tertiary Children's Hospital with Level 1 Trauma Center designation. PATIENTS Inpatient children less than 18 years old with an International Classification of Diseases code for traumatic brain injury and an admission Glasgow Coma Scale score of 9-13. MEASUREMENTS AND RESULTS We queried the National Trauma Data Bank for our institutional data and identified 177 patients with moderate traumatic brain injury from 2010 to 2017. These patients were then linked to the electronic health record to obtain baseline and injury characteristics, laboratory data, serial Glasgow Coma Scale scores, CT findings, and neurocritical care interventions. Clinical deterioration was defined as greater than or equal to 2 recorded values of Glasgow Coma Scale scores less than or equal to 8 during the first 48 hours of hospitalization. Thirty-seven patients experienced deterioration. Children who deteriorated were more likely to require intubation (73% vs 26%), have generalized edema, subdural hematoma, or contusion on CT scan (30% vs 8%, 57% vs 37%, 35% vs 16%, respectively), receive hypertonic saline (38% vs 7%), undergo intracranial pressure monitoring (24% vs 0%), were more likely to be transferred to inpatient rehabilitation following hospital discharge (32% vs 5%), and incur greater costs of care ($25,568 vs $10,724) (all p < 0.01). There was no mortality in this cohort. Multivariable regression demonstrated that a higher Injury Severity Score, a higher initial international normalized ratio, and a lower admission Glasgow Coma Scale score were associated with deterioration to severe traumatic brain injury in the first 48 hours (p < 0.05 for all). CONCLUSIONS A substantial subset of children (21%) presenting with moderate traumatic brain injury at a Level 1 pediatric trauma center experienced deterioration in the first 48 hours, requiring additional resource utilization associated with increased cost of care. Deterioration was independently associated with an increased international normalized ratio higher Injury Severity Score, and a lower admission Glasgow Coma Scale score.

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.

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