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Protein synthesis supports robust immune responses. Nutrient competition and global cell stressors in the tumor microenvironment (TME) may impact protein translation in T cells and antitumor immunity. Using human and mouse tumors, we demonstrated here that protein translation in T cells is repressed in solid tumors. Reduced glucose availability to T cells in the TME led to activation of the unfolded protein response (UPR) element eIF2α (eukaryotic translation initiation factor 2 alpha). Genetic mouse models revealed that translation attenuation mediated by activated p-eIF2α undermines the ability of T cells to suppress tumor growth. Reprograming T-cell metabolism was able to alleviate p-eIF2α accumulation and translational attenuation in the TME, allowing for sustained protein translation. Metabolic and pharmacological approaches showed that proteasome activity mitigates induction of p-eIF2α to support optimal antitumor T-cell function, protecting from translation attenuation and enabling prolonged cytokine synthesis in solid tumors. Together, these data identify a new therapeutic avenue to fuel the efficacy of tumor immunotherapy. Significance: Proteasome function is a necessary cellular component for endowing T cells with tumor killing capacity by mitigating translation attenuation resulting from the unfolded protein response induced by stress in the tumor microenvironment.

Background: For hospitalized children admitted outside of a critical care unit, the location, mode of death, "do-not-resuscitate" order (DNR) use, and involvement of palliative care teams have not been described across high-income countries. Objective: To describe location of death, patient and terminal care plan characteristics of pediatric inpatient deaths inside and outside the pediatric intensive care unit (PICU). Design: Secondary analysis of inpatient deaths in the Evaluating Processes of Care and Outcomes of Children in Hospital (EPOCH) randomized controlled trial. Setting/Subjects: Twenty-one centers from Canada, Belgium, the United Kingdom, Ireland, Italy, the Netherlands, and New Zealand. Measurement: Descriptive statistics were used to compare patient and terminal care plan characteristics. A multivariable generalized estimating equation examined if palliative care consult during hospital admission was associated with location of death. Results: A total of 365 of 144,539 patients enrolled in EPOCH died; 219 (60%) died in PICU and 143 (40%) died on another inpatient unit. Compared with other inpatient wards, patients who died in PICU were less likely to be expected to die, have a DNR or palliative care consult. Hospital palliative care consultation was more common in older children and independently associated with a lower adjusted odds (95% confidence interval) of dying in PICU [0.59 (0.52-0.68)]. Conclusion: Most pediatric inpatient deaths occur in PICU where patients were less likely to have a DNR or palliative care consult. Palliative care consultation could be better integrated into end-of-life care for younger children and those dying in PICU.

Supplemental Figures S1-S11

Mixed linear modeling results for tumor curves

Protein synthesis supports robust immune responses. Nutrient competition and global cell stressors in the tumor microenvironment (TME) may impact protein translation in T cells and antitumor immunity. Using human and mouse tumors, we demonstrated here that protein translation in T cells is repressed in solid tumors. Reduced glucose availability to T cells in the TME led to activation of the unfolded protein response (UPR) element eIF2α (eukaryotic translation initiation factor 2 alpha). Genetic mouse models revealed that translation attenuation mediated by activated p-eIF2α undermines the ability of T cells to suppress tumor growth. Reprograming T-cell metabolism was able to alleviate p-eIF2α accumulation and translational attenuation in the TME, allowing for sustained protein translation. Metabolic and pharmacological approaches showed that proteasome activity mitigates induction of p-eIF2α to support optimal antitumor T-cell function, protecting from translation attenuation and enabling prolonged cytokine synthesis in solid tumors. Together, these data identify a new therapeutic avenue to fuel the efficacy of tumor immunotherapy.Significance:Proteasome function is a necessary cellular component for endowing T cells with tumor killing capacity by mitigating translation attenuation resulting from the unfolded protein response induced by stress in the tumor microenvironment.

Families and clinicians have limited validated tools available to assist in estimating long-term outcomes early after pediatric cardiac arrest. Blood-based brain-specific biomarkers may be helpful tools to aid in outcome assessment.To analyze the association of blood-based brain injury biomarker concentrations with outcomes 1 year after pediatric cardiac arrest.The Personalizing Outcomes After Child Cardiac Arrest multicenter prospective cohort study was conducted in pediatric intensive care units at 14 academic referral centers in the US between May 16, 2017, and August 19, 2020, with the primary investigators blinded to 1-year outcomes. The study included 120 children aged 48 hours to 17 years who were resuscitated after cardiac arrest, had pre-cardiac arrest Pediatric Cerebral Performance Category scores of 1 to 3 points, and were admitted to an intensive care unit after cardiac arrest.Cardiac arrest.The primary outcome was an unfavorable outcome (death or survival with a Vineland Adaptive Behavior Scales, third edition, score of70 points) at 1 year after cardiac arrest. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCH-L1), neurofilament light (NfL), and tau concentrations were measured in blood samples from days 1 to 3 after cardiac arrest. Multivariate logistic regression and area under the receiver operating characteristic curve (AUROC) analyses were performed to examine the association of each biomarker with outcomes on days 1 to 3.Among 120 children with primary outcome data available, the median (IQR) age was 1.0 (0-8.5) year; 71 children (59.2%) were male. A total of 5 children (4.2%) were Asian, 19 (15.8%) were Black, 81 (67.5%) were White, and 15 (12.5%) were of unknown race; among 110 children with data on ethnicity, 11 (10.0%) were Hispanic, and 99 (90.0%) were non-Hispanic. Overall, 70 children (58.3%) had a favorable outcome, and 50 children (41.7%) had an unfavorable outcome, including 43 deaths. On days 1 to 3 after cardiac arrest, concentrations of all 4 measured biomarkers were higher in children with an unfavorable vs a favorable outcome at 1 year. After covariate adjustment, NfL concentrations on day 1 (adjusted odds ratio [aOR], 5.91; 95% CI, 1.82-19.19), day 2 (aOR, 11.88; 95% CI, 3.82-36.92), and day 3 (aOR, 10.22; 95% CI, 3.14-33.33); UCH-L1 concentrations on day 2 (aOR, 11.27; 95% CI, 3.00-42.36) and day 3 (aOR, 7.56; 95% CI, 2.11-27.09); GFAP concentrations on day 2 (aOR, 2.31; 95% CI, 1.19-4.48) and day 3 (aOR, 2.19; 95% CI, 1.19-4.03); and tau concentrations on day 1 (aOR, 2.44; 95% CI, 1.14-5.25), day 2 (aOR, 2.28; 95% CI, 1.31-3.97), and day 3 (aOR, 2.04; 95% CI, 1.16-3.57) were associated with an unfavorable outcome. The AUROC models were significantly higher with vs without the addition of NfL on day 2 (AUROC, 0.932 [95% CI, 0.877-0.987] vs 0.871 [95% CI, 0.793-0.949]; P = .02) and day 3 (AUROC, 0.921 [95% CI, 0.857-0.986] vs 0.870 [95% CI, 0.786-0.953]; P = .03).In this cohort study, blood-based brain injury biomarkers, especially NfL, were associated with an unfavorable outcome at 1 year after pediatric cardiac arrest. Additional evaluation of the accuracy of the association between biomarkers and neurodevelopmental outcomes beyond 1 year is needed.

OBJECTIVES Optimal cardiopulmonary resuscitation can improve pediatric outcomes but rarely is cardiopulmonary resuscitation performed perfectly despite numerous iterations of Basic and Pediatric Advanced Life Support. Cardiac arrests resuscitation events are complex, often chaotic environments with significant mental and physical workload for team members, especially team leaders. Our primary objective was to determine the impact of a cardiopulmonary resuscitation coach on cardiopulmonary resuscitation provider workload during simulated pediatric cardiac arrest. DESIGN Multicenter observational study. SETTING Four pediatric simulation centers. SUBJECTS Team leaders, cardiopulmonary resuscitation coach, and team members during an 18-minute pediatric resuscitation scenario. INTERVENTIONS National Aeronautics and Space Administration-Task Load Index. MEASUREMENTS AND MAIN RESULTS Forty-one teams (205 participants) were recruited with one team (five participants) excluded from analysis due to protocol violation. Demographic data revealed no significant differences between the groups in regard to age, experience, distribution of training (nurse, physician, and respiratory therapist). For most workload subscales, there were no significant differences between groups. However, cardiopulmonary resuscitation providers had a higher physical workload (89.3 vs 77.9; mean difference, -11.4; 95% CI, -17.6 to -5.1; p = 0.001) and a lower mental demand (40.6 vs 55.0; mean difference, 14.5; 95% CI, 4.0-24.9; p = 0.007) with a coach (intervention) than without (control). Both the team leader and coach had similarly high mental demand in the intervention group (75.0 vs 73.9; mean difference, 0.10; 95% CI, -0.88 to 1.09; p = 0.827). When comparing the cardiopulmonary resuscitation quality of providers with high workload (average score > 60) and low to medium workload (average score < 60), we found no significant difference between the two groups in percentage of guideline compliant cardiopulmonary resuscitation (42.5% vs 52.7%; mean difference, -10.2; 95% CI, -23.1 to 2.7; p = 0.118). CONCLUSIONS The addition of a cardiopulmonary resuscitation coach increases physical workload and decreases mental workload of cardiopulmonary resuscitation providers. There was no change in team leader workload.

Bystander cardiopulmonary resuscitation (CPR) is critical to increasing survival from out-of-hospital cardiac arrest. However, the percentage of cases in which an individual receives bystander CPR is actually low, at only 35% to 40% globally. Preparing lay responders to recognize the signs of sudden cardiac arrest, call 9-1-1, and perform CPR in public and private locations is crucial to increasing survival from this public health problem. The objective of this scientific statement is to summarize the most recent published evidence about the lay responder experience of training, responding, and dealing with the residual impact of witnessing an out-of-hospital cardiac arrest. The scientific statement focuses on the experience-based literature of actual responders, which includes barriers to responding, experiences of doing CPR, use of an automated external defibrillator, the impact of dispatcher-assisted CPR, and the potential for postevent psychological sequelae. The large body of qualitative and observational studies identifies several gaps in crucial knowledge that, if targeted, could increase the likelihood that those who are trained in CPR will act. We suggest using the experience of actual responders to inform more contextualized training, including the implications of performing CPR on a family member, dispelling myths about harm, training and litigation, and recognition of the potential for psychologic sequelae after the event.

Little is known about cardiopulmonary resuscitation (CPR) quality during pediatric interhospital transport; hence, our aim was to investigate its feasibility.After implementing an institutional education curriculum on pediatric resuscitation during ambulance transport, we conducted a 4-year prospective observational study involving simulation events. Simulated scenarios were (1) interhospital transport of a child retrieved in cardiac arrest (Sim1) and (2) unanticipated cardiac arrest of a child during transport (Sim2). Cardiopulmonary resuscitation data were collected via Zoll RSeries defibrillators. Performance was evaluated using age-appropriate American Heart Association (AHA) Guidelines. Video recordings were reviewed for qualitative thematic analysis.Twenty-six simulations were included: 16 Sim1 [mannequins: Laerdal SimMan 3G (n = 13); Gaumard 5-year-old HAL (n = 3)] and 10 Sim2 [Gaumard 1-year-old HAL (n = 8); Laerdal SimBaby (n = 2)]. Median (IQR) CPR duration was 18 minutes 23 seconds (14-22 minutes), chest compression rate was 112 per minute (106-118), and fraction (CCF) was 1 (0.9-1). Five hundred eight 60-second resuscitation epochs were evaluated (Sim1: 356; Sim2: 152); 73% were AHA compliant for rate and 87.8% for CCF. Twenty-four minutes (4.7%) had pauses more than 10 seconds. One hundred fifty seven Sim1 epochs (44.1%) met criteria for excellent CPR (AHA-compliant for rate, depth, and CCF). Rates of excellent CPR were higher for learner groups with increased simulation and transport experience (59.1% vs. 35.3%, P0.001). Thematic analysis identified performance-enhancing strategies, stemming from anticipating challenges, planning solutions, and ensuring team's shared mental model.High-quality CPR may be achievable during pediatric interhospital transport. Certain transport-specific strategies may enhance resuscitation quality. Learners' performance improved with simulation and transport experience, highlighting ongoing education's role.

Protein synthesis enables cell growth and survival, but the molecular mechanisms through which T cells suppress or maintain protein translation in the stress of solid tumors are unknown. Using mouse models and human tumors we demonstrate that protein translation in T cells is repressed by the solid tumor microenvironment (TME) due to activation of the unfolded protein response (UPR) via phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (p-eIF2α). Given that acute glucose deprivation in T cells exacerbated p-eIF2α, we show that metabolic reprogramming toward glycolytic independence allays the UPR and p-eIF2α, enabling sustained protein translation in T cells in TME stress. UPR mitigation was associated with enhanced degradation of proteins in antitumor T cells, as proteasome inhibition resulted in eIF2α phosphorylation, attenuation of translation, and loss of antitumor efficacy. In contrast, proteasome stimulation relieved translation inhibition, inducing robust T cell tumor control, offering a new therapeutic avenue to fuel the efficacy of tumor immunotherapy.

Aim: To evaluate an algorithm that uses an end-tidal carbon dioxide (ETCO2) target of ≥ 30 torr to guide specific changes in chest compression rate and epinephrine administration during cardiopulmonary resuscitation (CPR) in paediatric swine. Methods: Swine underwent asphyxial cardiac arrest followed by resuscitation with either standard or ETCO2-guided algorithm CPR. The standard group received chest compressions at a rate of 100/min and epinephrine every 4 min during advanced life support consistent with the American Heart Association paediatric resuscitation guidelines. In the ETCO2-guided algorithm group, chest compression rate was increased by 10 compressions/min for every minute that the ETCO2 was < 30 torr, and the epinephrine administration interval was decreased to every 2 min if the ETCO2 remained < 30 torr. Short-term survival and physiologic data during active resuscitation were compared. Results: Short-term survival was significantly greater in the ETCO2-guided algorithm CPR group than in the standard CPR group (16/28 [57.1%] versus 4/28 [14.3%]; p = 0.002). Additionally, the algorithm group had higher predicted mean ETCO2, chest compression rate, diastolic and mean arterial pressure, and myocardial perfusion pressure throughout resuscitation. Swine in the algorithm group also exhibited significantly greater improvement in diastolic and mean arterial pressure and cerebral perfusion pressure after the first dose of epinephrine than did those in the standard group. Incidence of resuscitation-related injuries was similar in the two groups. Conclusions: Use of a resuscitation algorithm with stepwise guidance for changes in the chest compression rate and epinephrine administration interval based on a goal ETCO2 level improved survival and intra-arrest hemodynamics in this porcine cardiac arrest model.

Phylogenetic relationships among the four currently recognized species in the genus Erimyzon were reconstructed using sequence data obtained from the mitochondrially encoded COI and the nuclear-encoded IRBP2 genes. Maximum likelihood and Bayesian analyses yielded five groups of Erimyzon. Three of the clades corresponded to the species E. oblongus, E. tenuis, and E. claviformis. Individuals identified as E. sucetta were split into two separate clades, with one clade more closely related to E. oblongus than to the other E. sucetta clade in three of four analyses. Two instances of putative hybridization between sympatrically distributed species were also detected, one involving E. oblongus and E. sucetta and the other involving E. claviformis and E. tenuis. The results suggest that the currently recognized E. sucetta comprises two species, with potentially non-overlapping distributions. Further morphological investigation is warranted to provide additional support for recognizing this putative fifth species of Erimyzon.

AIM: To examine the relationship between survival and diastolic blood pressure (DBP) throughout resuscitation from paediatric asphyxial cardiac arrest. METHODS: Retrospective, secondary analysis of 200 swine resuscitations. Swine underwent asphyxial cardiac arrest and were resuscitated with predefined periods of basic and advanced life support (BLS and ALS, respectively). DBP was recorded every 30 s. Survival was defined as 20-min sustained return of spontaneous circulation (ROSC). RESULTS: During BLS, DBP peaked between 1–3 min and was greater in survivors (20.0 [11.3, 33.3] mmHg) than in non-survivors (5.0 [1.0, 10.0] mmHg; p

Statins, widely used to treat hypercholesterolemia, inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme of de novo cholesterol (Chol) synthesis. Statins have been also reported to slow tumor progression. In cancer cells, ATP is generated both by glycolysis and oxidative phosphorylation. Mitochondrial membrane potential (ΔΨ), a readout of mitochondrial metabolism, is sustained by the oxidation of respiratory substrates in the Krebs cycle to generate NADH and flavin adenine dinucleotide, which are further oxidized by the respiratory chain. Here, we studied the short-term effects of statins (3–24 h) on mitochondrial metabolism on cancer cells. Lovastatin (LOV) and simvastatin (SIM) increased ΔΨ in HepG2 and Huh7 human hepatocarcinoma cells and HCC4006 human lung adenocarcinoma cells. Mitochondrial hyperpolarization after LOV and SIM was dose and time dependent. Maximal increase in ΔΨ occurred at 10 µM and 24 h for both statins. The structurally unrelated atorvastatin also hyperpolarized mitochondria in HepG2 cells. Cellular and mitochondrial Chol remained unchanged after SIM. Both LOV and SIM decreased basal respiration, ATP-linked respiration, and ATP production. LOV and SIM did not change the rate of lactic acid production. In summary, statins modulate mitochondrial metabolism in cancer cells independently of the Chol content in cellular membranes without affecting glycolysis.—Christie, C. F., Fang, D., Hunt, E. G., Morris, M. E., Rovini, A., Heslop, K. A., Beeson, G. C., Beeson, C. C., Maldonado, E. N. Statin-dependent modulation of mitochondrial metabolism in cancer cells is independent of cholesterol content.

AIM To examine the associations between ETCO2, ROSC, and chest compression quality markers in paediatric patients during active resuscitation. METHODS This was a single-centre cohort study of data collected as part of an institutional prospective quality initiative improvement program that included all paediatric patients who received chest compressions of any duration from January 1, 2013, through July 10, 2018, in the Johns Hopkins Children's Center. Data was collected from Zoll R Series® defibrillators. Events were included if Zoll data files contained both chest compression and ETCO2 data. 2,746 minutes corresponding to 143 events were included in the analyses. RESULTS The median event ETCO2 for all 143 events was 16.8 [9.3-26.3] mmHg. There was a significant difference in median event ETCO2 between events that achieved ROSC and those that did not (ROSC: 19.3 [14.4-26.6] vs. NO ROSC: 13.9 [6.6-25.5] mmHg; p

OBJECTIVES Effective cardiopulmonary resuscitation (CPR) is critical to ensure optimal outcomes from cardiac arrest, yet trained health care providers consistently struggle to provide guideline-compliant CPR. Rescuer fatigue can impact chest compression (CC) quality during a cardiac arrest event, although it is unknown if visual feedback or just-in-time training influences change of CC quality over time. In this study, we attempt to describe the changes in CC quality over a 12-minute simulated resuscitation and examine the influence of just-in-time training and visual feedback on CC quality over time. METHODS We conducted secondary analysis of data collected from the CPRCARES study, a multicenter randomized trial in which CPR-certified health care providers from 10 different pediatric tertiary care centers were randomized to receive visual feedback, just-in-time CPR training, or no intervention. They participated in a simulated cardiac arrest scenario with 2 team members providing CCs. We compared the quality of CCs delivered (depth and rate) at the beginning (0-4 minutes), middle (4-8 minutes), and end (8-12 minutes) of the resuscitation. RESULTS There was no significant change in depth over the 3 time intervals in any of the arms. There was a significant increase in rate (128 to 133 CC/min) in the no intervention arm over the scenario duration (P < 0.05). CONCLUSIONS There was no significant drop in CC depth over a 12-minute cardiac arrest scenario with 2 team members providing compressions.

Background Simulation is increasingly used to identify latent threats to patient safety, such as delays in recognition and management of time-sensitive conditions. The Rapid Cycle Deliberate Practice teaching method may facilitate “nano” (brief) in situ simulation training in a critical care setting to improve multidisciplinary team performance of time-sensitive clinical tasks. Objective To determine whether nano–in situ simulation training with Rapid Cycle Deliberate Practice can improve pediatric intensive care unit team proficiency in identifying and managing postoperative shock in a pediatric cardiac patient. Methods A quality improvement educational project was conducted involving nano–in situ simulation sessions in a combined pediatric and pediatric cardiac intensive care unit. The Rapid Cycle Deliberate Practice method was used with an expert-driven checklist for 30-minute simulation scenarios. Results A total of 23 critical care providers participated. The proportion of time-sensitive tasks completed within 5 minutes increased significantly from before to after training (52% [13 of 25] vs 100% [25 of 25]; P ≤ .001). Using a 5-point Likert scale, with higher scores indicating higher levels, the participants reported high degrees of performance confidence (mean, 4.42; SD, 0.20) and satisfaction with the simulation experience (mean, 4.96; SD, 0.12). Conclusion The Rapid Cycle Deliberate Practice method was used to facilitate nano–in situ simulation training and identify areas requiring additional education to improve patient safety. In situ simulation can educate providers in a cost-effective and timely manner.

In this chapter, Jesus’s high priestly prayer, John 17, is analyzed from a historical-grammatical perspective to examine grammatical, semantic, and syntactical patterns and usages in light of understanding the intended meaning of the original author (Osborne, 2006). The text, divided into three sections which focus separately on Jesus, the disciples, and future disciples, provides four important principles for use in succession discourse. Successful execution of succession must: (1) be executed and communicated with clarity; (2) affirm organizational mission and vision; (3) communicate what knowledge and skills followers possess to navigate their roles and task under new leadership; and (4) communicate the need for current and future unity within the organization centered around the mission and vision.

This chapter provides a brief overview of the science of teamwork and team training. We define common terminology review key concepts from the science of teams. We introduce a systems-based framework for the factors influencing team training effectiveness including the management of the curriculum, organizational and training environments, scenarios, performance measurement, feedback, and continuous improvement. We provide a discussion of key tasks that should be completed before, during, and after a team training activity in order to maximize the value of the team training program.

STATEMENT Rapid-cycle deliberate practice (RCDP) is a learner-centered simulation instructional strategy that identifies performance gaps and targets feedback to improve individual or team deficiencies. Learners have multiple opportunities to practice observational, deductive, decision-making, psychomotor, and crisis resource management skills. As its implementation grows, simulationists need to have a shared mental model of RCDP to build high-quality RCDP-based initiatives. To compare and make general inferences from RCDP data, each training needs to follow a similar structure. This article seeks to describe the fundamentals of RCDP, including essential components and potential variants. We also summarize the current published evidence regarding RCDP's effectiveness. This article serves to create a shared understanding of RCDP, provide clear definitions and classifications for RCDP research, and provide options for future RCDP investigation.

Mitochondrial membrane potential (ΔΨm) is a global indicator of mitochondrial function. Previous reports on heterogeneity of ΔΨm were qualitative or semiquantitative. Here, we quantified intercellular differences in ΔΨm in unsynchronized human cancer cells, cells synchronized in G1, S, and G2, and human fibroblasts. We assessed ΔΨm using a two-pronged microscopy approach to measure relative fluorescence of tetramethylrhodamine methyl ester (TMRM) and absolute values of ΔΨm. We showed that ΔΨm is more heterogeneous in cancer cells compared to fibroblasts, and it is maintained throughout the cell cycle. The effect of chemical inhibition of the respiratory chain and ATP synthesis differed between basal, low and high ΔΨm cells. Overall, our results showed that intercellular heterogeneity of ΔΨm is mainly modulated by intramitochondrial factors, it is independent of the ΔΨm indicator and it is not correlated with intercellular heterogeneity of plasma membrane potential or the phases of the cell cycle.

STATEMENT The International Network for Simulation-based Pediatric Innovation, Research, and Education co-hosted a novel research accelerator meeting with the International Pediatric Simulation Society in May of 2019 in Toronto. The purpose of the meeting was to bring together healthcare simulation scientists with resuscitation stakeholders to brainstorm strategies for accelerating progress in the science of saving pediatric lives from cardiac arrest. This was achieved by working in teams to draft targeted requests for proposals calling the research community to action investigating this topic. During the 1-day meeting, groups were divided into 6 teams lead by experts representing specific domains of simulation research. Teams developed a pitch and presented a sample request for proposals to a panel of expert judges, making a case for why their domain was the most important to create a funding opportunity. The winner of the competition had their specific request for proposal turned into an actual funding opportunity, supported by philanthropy that was subsequently disseminated through International Network for Simulation-based Pediatric Innovation, Research, and Education as a competitive award. An inspired donor supported an award for the second-place proposal as well, evidence of early research acceleration catalyzed from this conference. This article is a summary of the meeting rationale, format, and a description of the requests for proposals that emerged from the meeting. Our goal is to inspire other stakeholders to use this document that leverages simulation and resuscitation science expertise, as the framework to create their own funding opportunities, further accelerating pediatric resuscitation research, ultimately saving the lives of more children worldwide.

Acute care pediatric nurse practitioners have become frontline providers in the critical care environment and are expected to provide leadership in acutely critical situations. We describe a 2-day, high-fidelity, simulation-based curriculum focused on training the pediatric nurse practitioners for leadership in critical care scenarios.This prospective pre-post interventional study used simulation-based pedagogy. Knowledge tests, time-to-task, and a follow-up survey were used to determine the effectiveness of the training.Participants (n = 23) improved their knowledge scores by 27% (pretest: 35.2% [standard deviation = 12.1%]; posttest: 62.2% [standard deviation = 13.8%], p.001). In addition, time-to-task for resuscitation variables improved significantly. At 3 months, 100% of the participants who responded either agreed (15.4%) or strongly agreed (84.6%) that the boot camp prepared them to lead in a critical emergency.Simulation-based training is an effective strategy for educating critical care pediatric nurse practitioners and improves their ability to manage pediatric emergencies rapidly, which can be lifesaving.

Objectives The American Heart Association recommends minimizing pauses of chest compressions and defines high performance resuscitation as achieving a chest compression fraction greater than 80%. We hypothesize that interruption times are excessively long, leading to an unnecessarily large impact on chest compression fraction. Design A retrospective study using video review of a convenience sample of clinically realistic in situ simulated pulseless electrical activity cardiopulmonary arrests. Setting Johns Hopkins Children's Center; September 2013 to June 2017. Patients Twenty-two simulated patients. Interventions A framework was developed to characterize interruptions. Two new metrics were defined as follows: interruption time excess (the difference between actual and guideline-indicated allowable duration of interruption from compressions), and chest compression fraction potential (chest compression fraction with all interruption time excess excluded). Measurements and main results Descriptive statistics were generated for interruption-level and event-level variables. Differences between median chest compression fraction and chest compression fraction potential were assessed using Wilcoxon rank-sum test. Comparisons of interruption proportion before and after the first 5 minutes were assessed using the X test statistic. Seven-hundred sixty-six interruptions occurred over 22 events. Median event duration was 463.0 seconds (interquartile range, 397.5-557.8 s), with a mean 34.8 interruptions per event. Auscultation and intubation had the longest median interruption time excess of 13.0 and 7.5 seconds, respectively. Median chest compression fraction was 76.0% (interquartile range, 67.7-80.7 s), and median chest compression fraction potential was 83.4% (interquartile range, 80.4-87.4%). Comparing median chest compression fraction to median chest compression fraction potential found an absolute percent difference of 7.6% (chest compression fraction: 76.0% vs chest compression fraction potential: 83.4%; p Conclusions This lays the groundwork for studying inefficiency during cardiopulmonary resuscitation associated with chest compression interruptions. The framework we created allows for the determination of significant avoidable interruption time. By further elucidating the nature of interruptions, we can design and implement targeted interventions to improve patient outcomes.

AIM: Recommendations for standardised communication to reduce chest compression (CC) pauses are lacking. We aimed to achieve consensus and evaluate feasibility and efficacy using standardised communication during cardiopulmonary resuscitation (CPR) events.METHODS: Modified Delphi consensus process to design standardised communication elements. Feasibility was pilot tested in 16 simulated CPR scenarios (8 scenarios with physician team leaders and 8 with chest compressors) randomized (1:1) to standardised [INTERVENTION] vs. closed-loop communication [CONTROL]. Adherence and efficacy (duration of CC pauses for defibrillation, intubation, rhythm check) was assessed by audiovisual recording. Mental demand and frustration were assessed by NASA task load index subscales.RESULTS: Consensus elements for standardised communication included: 1) team preparation 15-30 s before CC interruption, 2) pre-interruption countdown synchronized with last 5 CCs, 3) specific action words for defibrillation, intubation, and interrupting/resuming CCs. Median (Q1,Q3) adherence to standardised phrases was 98% (80%,100%). Efficacy analysis showed a median [Q1,Q3] peri-shock pause of 5.1 s. [4.4; 5.8] vs. 7.5 s. [6.3; 8.8] seconds, p CONCLUSION: This pilot study demonstrated feasibility of using consensus-based standardised communication that was associated with shorter CC pauses for defibrillation, intubation, and rhythm checks without increasing frustration index or mental demand compared to current best practice, closed loop communication.

While pediatric HeartWare HVAD application has increased, determining candidacy and timing for initiation of pediatric VAD support has remained a challenge. We present our experience with a systematic approach to HVAD implantation as a bridge to pediatric heart transplantation. We performed a retrospective, single center review of pediatric patients (n = 11) who underwent HVAD implantation between September 2014 and January 2018. Primary endpoints evaluated were survival to heart transplantation, need for right ventricular assist device (RVAD) at any point, ongoing HVAD support, or death. Median patient age was 11 years (range: 3-16). Median BSA was 1.25 m2 (range: 0.56-2.1). Heart failure etiologies requiring support were dilated cardiomyopathy (n = 8), myocarditis (n = 1), congenital mitral valve disease (n = 1), and single ventricle heart failure (n = 1). Median time from cardiac ICU admission for heart failure to HVAD placement was 15 days (range 3-55), based on standardized VAD implantation criteria involving imaging assessment and noncardiac organ evaluation. The majority of patients (91%) were INTERMACS Level 2 at time of implant. Three patients (27%) had CentriMag RVAD placement at time of HVAD implantation. Two of these three patients had successful RVAD explanation within 2 weeks. Median length of HVAD support was 60 days (range 6-405 days). Among the 11 patients, survival during HVAD therapy to date is 91% (10/11) with 9 (82%) bridged to heart transplantation and one (9%) continuing to receive support. Posttransplant survival has been 100%, with median follow-up of 573 days (range 152-1126). A systematic approach to HVAD implantation can provide excellent results in pediatric heart failure management for a variety of etiologies and broad BSA range.

To determine if integrating a trained CPR Coach into resuscitation teams can improve CPR quality during simulated pediatric cardiopulmonary arrest (CPA).We conducted a multicenter, prospective, randomized trial. An 18-minute simulated CPA scenario was run for resuscitation teams comprised of CPR-certified professionals from four International Network for Simulation-based Pediatric Innovation, ResearchEducation (INSPIRE) institutions. Forty teams (200 participants) were randomized to having a trained CPR Coach vs. no CPR Coach. CPR Coaches were responsible for providing real-time verbal feedback of CPR performance to compressors. All teams utilized CPR feedback technology. We report the proportion of overall excellent CPR, proportion of chest compressions (CC) with depth 50-60 mm, the proportion of CC with rate 100-120 per minute, CC fraction, and pre-, post-, and peri-shock pause duration.CPR coached teams compared with teams without a CPR Coach resulted in an absolute improvements in overall excellent CPR by 31.8% (95% CI, 17.7, 35.9; p 0.001), mean CC depth compliance by 31.5% (15.7, 47.4; p 0.001), mean CC depth by 4.6 mm (1.6, 7.5; p 0.001), mean CC fraction by 5.4% (0.2, 10.6; p = 0.04), and mean pre-, post- and peri-shock pause duration by -2.7 s (-5.1, -0.4; p = 0.02), -1.0 s (-1.8, -0.2; p = 0.01); and -3.8 (-6.6, -1.0; p = 0.008), respectively. Changes in mean CC rate compliance and mean CC rate were not statistically significant.In the presence of CPR feedback technology, the integration of a trained CPR coach into resuscitation teams enhances CPRquality metrics associated with improved survival outcomes from pediatric cardiac arrest.

Objective A hospital-wide difficult airway response team was developed in 2008 at The Johns Hopkins Hospital with three central pillars: operations, safety monitoring, and education. The objective of this study was to assess the outcomes of the educational pillar of the difficult airway response team program, known as the multidisciplinary difficult airway course (MDAC). Design The comprehensive, full-day MDAC involves trainees and staff from all provider groups who participate in airway management. The MDAC occurs within the Johns Hopkins Medicine Simulation Center approximately four times per year and uses a combination of didactic lectures, hands-on sessions, and high-fidelity simulation training. Participation in MDAC is the main intervention being investigated in this study. Data were collected prospectively using course evaluation survey with quantitative and qualitative components, and prepost course knowledge assessment multiple choice questions (MCQ). Outcomes include course evaluation scores and themes derived from qualitative assessments, and prepost course knowledge assessment MCQ scores. Setting Tertiary care academic hospital center Participants Students, residents, fellows, and practicing physicians from the departments of Surgery, Otolaryngology Head and Neck Surgery, Anesthesiology/Critical Care Medicine, and Emergency Medicine; advanced practice providers (nurse practitioners and physician assistants), nurse anesthetists, nurses, and respiratory therapists. Results Totally, 23 MDACs have been conducted, including 499 participants. Course evaluations were uniformly positive with mean score of 86.9 of 95 points. Qualitative responses suggest major value from high-fidelity simulation, the hands-on skill stations, and teamwork practice. MCQ scores demonstrated significant improvement: median (interquartile range) pre: 69% (60%-81%) vs post: 81% (72%-89%), p Conclusions Implementation of a MDAC successfully disseminated principles and protocols to all airway providers. Demonstrable improvement in prepost course knowledge assessment and overwhelmingly positive course evaluations (quantitative and qualitative) suggest a critical and ongoing role for the MDAC course.

Aims and objectives The aims of this project were to (a) determine barriers to current handover and transport process, (b) develop a new protocol and process for team-to-team handover, and (c) evaluate staff satisfaction with the new process. Background The handover and transport of critically ill patients from the paediatric emergency department to the paediatric intensive care unit is a period of vulnerability associated with adverse events. Design A mixed-methods study using a quasi-experimental design and qualitative approach. Methods Focus groups were conducted to determine the barriers and facilitators of the current handover and transport process. Using these themes, a multidisciplinary team developed and implemented a new process including establishment of eight patient criteria for specialised transport and a standardised, interdisciplinary handover tool for team-to-team handover. Staff satisfaction was examined pre- and postintervention. Results Content analysis of focus groups revealed five categories: need for improved communication, cultural dissonance among units, defects in system and processes, need for standardisation and ambiguity between providers regarding acuity. Staff members reported improvements in their perceptions of satisfaction, safety, communication and role understanding associated with the new process. Conclusions Standardisation through the establishment of severity of illness criteria and communication tools creates shared mental models and decreases risks to safety. A paradigm shift of team-to-team handover and transport is recommended. Relevance to clinical practice This paper suggests the importance of improving communication during the handover and transport process through establishing standardised patient severity of illness criteria, use of standardised tools and team-to-team handover processes.

OBJECTIVES Pediatric in-hospital cardiac arrest cardiopulmonary resuscitation quality metrics have been reported in few children less than 8 years. Our objective was to characterize chest compression fraction, rate, depth, and compliance with 2015 American Heart Association guidelines across multiple pediatric hospitals. DESIGN Retrospective observational study of data from a multicenter resuscitation quality collaborative from October 2015 to April 2017. SETTING Twelve pediatric hospitals across United States, Canada, and Europe. PATIENTS In-hospital cardiac arrest patients (age < 18 yr) with quantitative cardiopulmonary resuscitation data recordings. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS There were 112 events yielding 2,046 evaluable 60-second epochs of cardiopulmonary resuscitation (196,669 chest compression). Event cardiopulmonary resuscitation metric summaries (median [interquartile range]) by age: less than 1 year (38/112): chest compression fraction 0.88 (0.61-0.98), chest compression rate 119/min (110-129), and chest compression depth 2.3 cm (1.9-3.0 cm); for 1 to less than 8 years (42/112): chest compression fraction 0.94 (0.79-1.00), chest compression rate 117/min (110-124), and chest compression depth 3.8 cm (2.9-4.6 cm); for 8 to less than 18 years (32/112): chest compression fraction 0.94 (0.85-1.00), chest compression rate 117/min (110-123), chest compression depth 5.5 cm (4.0-6.5 cm). "Compliance" with guideline targets for 60-second chest compression "epochs" was predefined: chest compression fraction greater than 0.80, chest compression rate 100-120/min, and chest compression depth: greater than or equal to 3.4 cm in less than 1 year, greater than or equal to 4.4 cm in 1 to less than 8 years, and 4.5 to less than 6.6 cm in 8 to less than 18 years. Proportion of less than 1 year, 1 to less than 8 years, and 8 to less than 18 years events with greater than or equal to 60% of 60-second epochs meeting compliance (respectively): chest compression fraction was 53%, 81%, and 78%; chest compression rate was 32%, 50%, and 63%; chest compression depth was 13%, 19%, and 44%. For all events combined, total compliance (meeting all three guideline targets) was 10% (11/112). CONCLUSIONS Across an international pediatric resuscitation collaborative, we characterized the landscape of pediatric in-hospital cardiac arrest chest compression quality metrics and found that they often do not meet 2015 American Heart Association guidelines. Guideline compliance for rate and depth in children less than 18 years is poor, with the greatest difficulty in achieving chest compression depth targets in younger children.

Anaphylaxis is a life-threatening event. Most clinical symptoms of anaphylaxis can be reversed by prompt intramuscular administration of epinephrine using an auto-injector or epinephrine drawn up in a syringe and delays and errors may be fatal. The aim of this scoping review is to identify and compare errors associated with use of epinephrine drawn up in a syringe versus epinephrine auto-injectors in order to assist hospitals as they choose which approach minimizes risk of adverse events for their patients.PubMed, Embase, CINAHL, Web of Science, and the Cochrane Library were searched using terms agreed to a priori.We reviewed human and simulation studies reporting errors associated with the use of epinephrine in anaphylaxis. There were multiple screening stages with evolving feedback.Each study was independently assessed by two reviewers for eligibility. Data were extracted using an instrument modeled from the Zaza et al instrument and grouped into themes.Three main themes were noted: 1) ergonomics, 2) dosing errors, and 3) errors due to route of administration. Significant knowledge gaps in the operation of epinephrine auto-injectors among healthcare providers, patients, and caregivers were identified. For epinephrine in a syringe, there were more frequent reports of incorrect dosing and erroneous IV administration with associated adverse cardiac events. For the epinephrine auto-injector, unintentional administration to the digit was an error reported on multiple occasions.This scoping review highlights knowledge gaps and a diverse set of errors regardless of the approach to epinephrine preparation during management of anaphylaxis. There are more potentially life-threatening errors reported for epinephrine drawn up in a syringe than with the auto-injectors. The impact of these knowledge gaps and potentially fatal errors on patient outcomes, cost, and quality of care is worthy of further investigation.

We used sleep monitoring data from a study that investigated the prevalence, characteristics, risk factors and type of sleep apnea (SA) in 579 patients with paroxysmal atrial fibrillation. Most patients were screened for two nights, resulting in 1,043 sleep recordings that each contained data from one night. SA was diagnosed using the Nox T3 portable sleep monitor. An experienced sleep specialist scored the recordings manually using Noxturnal software. A total of 157 women (27%) and 422 men (73%) were examined; 477 (82.7%) had an apnea–hypopnea index (AHI) ≥ 5/hr, whereas moderate to severe SA (AHI ≥ 15/hr) was diagnosed in 243 patients (42.1%). The AHI derived from automatic and manual scoring showed a good agreement (Pearson's r coefficient of 0.96). The median difference in AHI was very small (i.e., 0.72 [mean difference, 1.06]), but was statistically significant (p < .0001). Automatic scoring classified sleep recordings with more than 90% accuracy into SA categories of mild (AHI ≥ 5/hr), moderate (AHI ≥ 15/hr) and severe (AHI ≥ 30/hr). We found a minor (11%–21%) mis‐estimation of the number of recordings right above and below the boundary separating mild and moderate SA. The accuracy of automatic scoring differed from recording to recording, especially regarding the sensitivity of detecting disrupted breathing events. We found low to moderate agreement for the duration of disrupted breathing events (r = .53), for which the automatic scoring led to a statistically significant overestimation by 5.22 s (p < .0001).

Background: Recommendations for “standardized” communication during cardiopulmonary resuscitation (CPR) events to reduce interruptions in chest compressions (CCs) are lacking. We aimed to achieve consensus on standardized communication during in-hospital CPR, evaluate feasibility and potential to decrease CC pauses, mental task load, and frustration. Methods: Modified Delphi consensus surveys of International Liaison Committee on Resuscitation taskforce members to identify preferred communication for in-hospital cardiac arrest teams. Consensus was reached after-survey teleconference resolution by a team of interdisciplinary experts in communication and CPR. Feasibility was tested in 8 simulated CPR scenarios with physician team leaders randomized (1:1) to ‘standardized’ communication vs. “usual best practice”, closed loop communication. Team leaders watched a 3-min video and received a 10-min training on the assigned intervention before the CPR scenario. NASA task load index questionnaires were used to assess mental task load and frustration (0=lowest to 100=highest). Results: Modified Delphi consensus on standardized communication included: 1) preparing the team 15-30 seconds before interrupting CCs, 2) countdown for interruption synchronized with 5 CCs, 3) action words for stopping and resuming CCs, 4) action words for intubation and defibrillation. Among 8 CPR teams (4 standardized, 4 usual communication), median (Q1; Q3) CC interruption duration for rhythm check was significantly shorter, 5.3 (4.8; 6.8) vs. 9.4 (6.4; 13.0) sec for standardized vs. closed loop communication [p=0.02]. Median (Q1; Q3) scores of mental task load were 63 (33; 70) vs 85 (70; 96), [p=0.10] and frustration 10 (5; 34) vs 40 (26; 50) [p=0.11] for standardized vs. closed loop communication. Trained team leaders adhered to standardized phrases 77% of the time. Conclusion: Expert consensus for standardized communication during in-hospital CPR was achieved. Pilot simulation implementation of standardized communication demonstrated feasibility of team leader adherence, significantly decreased duration of CC interruption during rhythm checks, and a tendency to reduce team leader task load and frustration.

Introduction: The American Heart Association (AHA) recommends the use of end-tidal CO 2 (ETCO 2 ) to evaluate the quality of chest compression delivery during CPR. In a pediatric model of asphyxial cardiac arrest, ETCO 2 -guided chest compression delivery improved survival over standard CPR. Since the most common cause of pediatric cardiac arrest is respiratory failure, we investigated whether this observed survival benefit persisted in a model of respiratory failure preceding cardiac arrest. Methods: Prior to a 17-min asphyxial cardiac arrest, peak inspiratory pressures were adjusted to a goal PaCO 2 of 80 torr to mimic pre-arrest respiratory failure. Male swine (3-4 kg) were randomized to receive either ETCO 2 -guided or standard CPR for 10 min of BLS followed by 10 min of ALS. In the ETCO 2 -guided group, chest compression rate and depth were adjusted to obtain a maximal ETCO 2 level. In the standard group, chest compressions were delivered per AHA guidelines. Hemodynamic parameters were recorded every 30 seconds, and resuscitation was continued for 20 min or until ROSC. Results: Twenty swine underwent asphyxial cardiac arrest. After adjustment of ventilation prior to asphyxia, pH and PaCO 2 were 7.15 and 79 torr in the ETCO 2 -guided group and 7.14 and 78 torr in the standard group. Survival was greater in the ETCO 2 -guided group than in the standard group (7/10 versus 1/10; p=0.02). During resuscitation, mean ETCO 2 and chest compression rate were higher in the ETCO 2 -guided group (38.6 ± 1.2 versus 22.9 ± 1.2, p=0.01; 154.4 ± 1.2 versus 100.5 ± 0.1, p2 -guided group ( Figure 1 ) Conclusions: ETCO 2 -guided chest compression delivery improves survival and resuscitation hemodynamics over standard CPR in a pediatric model of respiratory failure and cardiac arrest.

Introduction: There is a paucity of data regarding the association of pediatric patient characteristics with hospital mortality and transfer to higher levels of care following medical emergency team (MET) events. Objective: To explore associations of patient characteristics with hospital mortality and transfer to higher levels of care among pediatric patients who experienced a MET event during an admission. Methods: This retrospective observational study included data from patients aged ≤17 years admitted to an urban, tertiary hospital who experienced a MET event between 2014 and 2017. Data specific to the initial MET event for a patient were included for analysis. Multiple logistic regression models were used to test associations between patient characteristics (age, race, sex, ethnicity, timing of MET event, primary admission diagnosis, receiving care on specialized units) and each outcome separately. Results: Of the 366 patients eligible for inclusion, 11% (41 of 366) experienced hospital mortality, and 59% (216 of 366) were transferred to higher levels of care following MET events. Hospital mortality was lower among those who received emergency department care within 24 hours before the MET event compared to patients who did not (OR=0.17; 95% CI=0.04-0.82). Hospital mortality was higher among those with cardiac-related primary admission diagnoses compared to patients with noncardiac-related diagnoses (OR=3.44; 95% CI=1.04-11.39), and among those of unknown race compared to white patients (OR=3.14; 95% CI=1.17-8.48). No patient characteristics were associated with transfers to higher levels of care. Conclusions: While MET events may cause concern about failures to triage patients to appropriate levels of care upon admission, we observed that patients admitted from the emergency department within 24 hours before their MET event were more likely to survive to discharge. Higher hospital mortality following MET events was observed among patients with cardiac diagnoses and those of unknown race; more research is needed to understand how processes and documentation of care are related to these patients. Further study of how these characteristics and other potential confounding factors are associated with MET events and outcomes is warranted.

Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} Little evidence exists to guide end-tidal carbon dioxide (ETCO 2 ) use during cardiac arrest events in pediatric populations. Despite this, integrating physiologic feedback, including ETCO 2 , into resuscitation optimization is recognized as an important component to precision resuscitation. This was a prospective observational study of ETCO 2 , CPR quality and ROSC. The study population included any pediatric patient who received chest compressions from January 1, 2013 through July 10, 2018 in the Johns Hopkins Children’s Center. During this time, 457 arrest events of any length requiring chest compressions occurred. Of these events, 274 utilized ETCO 2 in some capacity and 198 recorded ETCO 2 on a Zoll R Series® defibrillator. Data files from 145 of these events that contained both chest compression and ETCO 2 data were successfully obtained. These 145 events contained 2200 minutes of ETCO 2 data and 2156 minutes of both chest compression and ETCO 2 data; values are reported as median [IQR]. The average ETCO 2 for all events was 21 mmHg [15-32]. ETCO 2 by age category was (0-1: 12 [0-29]; 1-8: 20 [2-35]; 8+: 10.15 [0-21]). When comparing patients who achieved ROSC > 20 minutes to those who did not, we observed a significant difference in ETCO 2 between those who survived and those who did not (ROSC: 25 [15-30] vs. NO ROSC: 15 [9-22]; p2 and resuscitation data, our findings suggest that a difference may exist in survival associated with an ETCO 2 difference between 15 and 20 mmHg.

This chapter presents an exegetical analysis of the book of Esther, focusing on the characteristics and actions of Esther and Mordecai as they related to navigating the crisis of possible Jewish genocide in Susa. Using narrative analysis, the exegetical analysis shows evidence of specific characteristics and behaviors that support and exemplify resilience in the characters of Esther and Mordecai. In addition, the analysis establishes the importance of relationship and spirituality in supporting resilience and the emergence of team leadership between Esther and Mordecai. In all, the chapter provides evidence the leaders during the crisis may benefit from team leadership that supports both individual and group resilience.