Acetyl-CoA carboxylase obstructs CD8+ T cell lipid utilization in the tumor microenvironment.

The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors. We reveal that the solid TME imposes perpetual acetyl-coenzyme A (CoA) carboxylase (ACC) activity, invoking lipid biogenesis and storage in TILs that opposes FAO. Using metabolic, lipidomic, and confocal imaging strategies, we find that restricting ACC rewires T cell metabolism, enabling energy maintenance in TME stress. Limiting ACC activity potentiates a gene and phenotypic program indicative of T cell longevity, engendering T cells with increased survival and polyfunctionality, which sustains cancer control.

Using rapid response system trigger clusters to characterize patterns of clinical deterioration among hospitalized adult patients.

BACKGROUND: Many rapid response system (RRS) events are activated using multiple triggers. However, the patterns in which multiple RRS triggers occur together to activate RRS events are unknown. The purpose of this study was to identify these patterns (RRS trigger clusters) and determine their association with outcomes among hospitalized adult patients. METHODS: RRS events among adult patients from January 2015 to December 2019 in the Get With The Guidelines- Resuscitation registry's MET module were examined (n = 134,406). Cluster analysis methods were performed to identify RRS trigger clusters. Pearson's chi-squared and ANOVA tests were used to examine differences in patient characteristics across RRS trigger clusters. Multilevel logistic regressions were used to examine the associations between RRS trigger clusters and outcomes. RESULTS: Six RRS trigger clusters were identified. Predominant RRS triggers for each cluster were: tachypnea, new onset difficulty in breathing, decreased oxygen saturation (Cluster 1); tachypnea, decreased oxygen saturation, staff concern (Cluster 2); respiratory depression, decreased oxygen saturation, mental status changes (Cluster 3); tachycardia, staff concern (Cluster 4); mental status changes (Cluster 5); hypotension, staff concern (Cluster 6). Significant differences in patient characteristics were observed across clusters. Patients in Clusters 3 and 6 had an increased likelihood of in-hospital cardiac arrest (p < 0.01). All clusters had an increased risk of mortality (p < 0.01). CONCLUSIONS: We discovered six novel RRS trigger clusters with differing relationships to adverse patient outcomes. RRS trigger clusters may prove crucial in clarifying the associations between RRS events and adverse outcomes and aiding in clinician decision-making during RRS events.

The associations between rapid response systems and their components with patient outcomes: A scoping review.

Background: While rapid response systems have been widely implemented, their impact on patient outcomes remains unclear. Further understanding of their components-including medical emergency team triggers, medical emergency team member composition, additional roles in patient care beyond responding to medical emergency team events, and their involvement in "Do-Not-Resuscitate" order placement-may elucidate the relationship between rapid response systems and outcomes. Objective: To explore how recent studies have examined rapid response system components in the context of relevant adverse patient outcomes, such as in-hospital cardiac arrests and hospital mortality. Design: Scoping review. Methods: PubMed, CINAHL, and Embase were searched for articles published between November 2014 and June 2022. Studies mainly focused on rapid response systems and associations with in-hospital cardiac arrests were considered. The following were extracted for analysis: study design, location, sample size, participant characteristics, system characteristics (including medical emergency team member composition, additional system roles outside of medical emergency team events), medical emergency team triggers, in-hospital cardiac arrests, and hospital mortality. Results: Thirty-four studies met inclusion criteria. While most studies described triggers used, few analyzed medical emergency team trigger associations with outcomes. Of those, medical emergency team triggers relating to respiratory abnormalities and use of multiple triggers to activate the medical emergency team were associated with adverse patient outcomes. Many studies described medical emergency team member composition, but the way composition was reported varied across studies. Of the seven studies with dedicated medical emergency team members, six found their systems were associated with decreased incidence of in-hospital cardiac arrests. Six of seven studies that described additional medical emergency team roles in educating staff in rapid response system use found their systems were associated with significant decreases in adverse patient outcomes. Four of five studies that described proactive rounding responsibilities reported found their systems were associated with significant decreases in adverse patient outcomes. Reporting of rapid response system involvement in "Do-Not-Resuscitate" order placement was variable across studies. Conclusions: Inconsistencies in describing rapid response system components and related data and outcomes highlights how these systems are complex to a degree not fully captured in existing literature. Further large-scale examination of these components across institutions is warranted. Development and use of robust and standardized metrics to track data related to rapid response system components and related outcomes are needed to optimize these systems and improve patient outcomes.

Interrelationships and biogeography of the New World pufferfish genus Sphoeroides (Tetraodontiformes: Tetraodontidae) inferred using ultra-conserved DNA elements.

Colonization of the New World by marine taxa has been hypothesized to have occurred through the Tethys Sea or by crossing the East Pacific Barrier. To better understand patterns and timing of diversification, geological events can be coupled with time calibrated phylogenetic hypotheses to infer major drivers of diversification. Phylogenetic relationships among members of Sphoeroides, a genus of four toothed pufferfishes (Tetraodontiformes: Tetraodontidae) which are found nearly exclusively in the New World (eastern Pacific and western Atlantic), were reconstructed using sequences from ultra-conserved DNA elements, nuclear markers with clear homology among many vertebrate taxa. Hypotheses derived from concatenated maximum-likelihood and species tree summary methods support a paraphyletic Sphoeroides, with Colomesus deeply nested within the genus. Analyses also revealed S. pachygaster, a pelagic species with a cosmopolitan distribution, as the sister taxon to the remainder of Sphoeroides and recovered distinct lineages within S. pachygaster, indicating that this cosmopolitan species may represent a species complex. Ancestral range reconstruction may suggest the genus colonized the New World through the eastern Pacific before diversifying in the western Atlantic, though date estimates for these events are uncertain due to the lack of reliable fossil record for the genus.

Assessment of Brain Magnetic Resonance and Spectroscopy Imaging Findings and Outcomes After Pediatric Cardiac Arrest.

Importance: Morbidity and mortality after pediatric cardiac arrest are chiefly due to hypoxic-ischemic brain injury. Brain features seen on magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) after arrest may identify injury and aid in outcome assessments. Objective: To analyze the association of brain lesions seen on T2-weighted MRI and diffusion-weighted imaging and N-acetylaspartate (NAA) and lactate concentrations seen on MRS with 1-year outcomes after pediatric cardiac arrest. Design, Setting, and Participants: This multicenter cohort study took place in pediatric intensive care units at 14 US hospitals between May 16, 2017, and August 19, 2020. Children aged 48 hours to 17 years who were resuscitated from in-hospital or out-of-hospital cardiac arrest and who had a clinical brain MRI or MRS performed within 14 days postarrest were included in the study. Data were analyzed from January 2022 to February 2023. Exposure: Brain MRI or MRS. Main Outcomes and Measures: The primary outcome was an unfavorable outcome (either death or survival with a Vineland Adaptive Behavior Scales, Third Edition, score of <70) at 1 year after cardiac arrest. MRI brain lesions were scored according to region and severity (0 = none, 1 = mild, 2 = moderate, 3 = severe) by 2 blinded pediatric neuroradiologists. MRI Injury Score was a sum of T2-weighted and diffusion-weighted imaging lesions in gray and white matter (maximum score, 34). MRS lactate and NAA concentrations in the basal ganglia, thalamus, and occipital-parietal white and gray matter were quantified. Logistic regression was performed to determine the association of MRI and MRS features with patient outcomes. Results: A total of 98 children, including 66 children who underwent brain MRI (median [IQR] age, 1.0 [0.0-3.0] years; 28 girls [42.4%]; 46 White children [69.7%]) and 32 children who underwent brain MRS (median [IQR] age, 1.0 [0.0-9.5] years; 13 girls [40.6%]; 21 White children [65.6%]) were included in the study. In the MRI group, 23 children (34.8%) had an unfavorable outcome, and in the MRS group, 12 children (37.5%) had an unfavorable outcome. MRI Injury Scores were higher among children with an unfavorable outcome (median [IQR] score, 22 [7-32]) than children with a favorable outcome (median [IQR] score, 1 [0-8]). Increased lactate and decreased NAA in all 4 regions of interest were associated with an unfavorable outcome. In a multivariable logistic regression adjusted for clinical characteristics, increased MRI Injury Score (odds ratio, 1.12; 95% CI, 1.04-1.20) was associated with an unfavorable outcome. Conclusions and Relevance: In this cohort study of children with cardiac arrest, brain features seen on MRI and MRS performed within 2 weeks after arrest were associated with 1-year outcomes, suggesting the utility of these imaging modalities to identify injury and assess outcomes.

Using rapid response system trigger clusters to characterize patterns of clinical deterioration among hospitalized adult patients.

Background: Many rapid response system (RRS) events are activated using multiple triggers. However, the patterns in which RRS triggers co-occur to activate the medical emergency team (MET) to respond to RRS events is unknown. The purpose of this study was to identify and describe the patterns (RRS trigger clusters) in which RRS triggers co-occur when used to activate the MET and determine the association of these clusters with outcomes using a sample of hospitalized adult patients. Methods: RRS events among adult patients from January 2015 to December 2019 in the Get With The Guidelines- Resuscitation registry's MET module were examined (n=134,406). A combination of cluster analyses methods was performed to group patients into RRS trigger clusters based on the triggers used to activate their RRS events. Pearson's chi-squared and ANOVA tests were used to examine differences in patient characteristics across RRS trigger clusters. Multilevel logistic regression was used to examine the associations between RRS trigger clusters and outcomes following RRS events. Results: Six RRS trigger clusters were identified in the study sample. The RRS triggers that predominantly identified each cluster were as follows: tachypnea, new onset difficulty in breathing, and decreased oxygen saturation (Cluster 1); tachypnea, decreased oxygen saturation, and staff concern (Cluster 2); respiratory depression, decreased oxygen saturation, and mental status changes (Cluster 3); tachycardia and staff concern (Cluster 4); mental status changes (Cluster 5); hypotension and staff concern (Cluster 6). Significant differences in patient characteristics were observed across RRS trigger clusters. Patients in Clusters 3 and 6 were associated with an increased likelihood of in-hospital cardiac arrest (IHCA [p<0.01]), while Cluster 4 was associated with a decreased likelihood of IHCA (p<0.01). All clusters were associated with an increased risk of mortality (p<0.01). Conclusions: We discovered six novel RRS trigger clusters with differing relationships to adverse patient outcomes following RRS events. RRS trigger clusters may prove crucial in clarifying the associations between RRS events and adverse outcomes and may aid in clinician decision-making during RRS events.

Cardiopulmonary Resuscitation During Simulated Pediatric Interhospital Transport: Lessons Learned From Implementation of an Institutional Curriculum.

INTRODUCTION: Little is known about cardiopulmonary resuscitation (CPR) quality during pediatric interhospital transport; hence, our aim was to investigate its feasibility. METHODS: 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. RESULTS: 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%, P < 0.001). Thematic analysis identified performance-enhancing strategies, stemming from anticipating challenges, planning solutions, and ensuring team's shared mental model. CONCLUSIONS: 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.

Delusions of parasitosis and delusions of parasitosis by proxy in a mother and her children.

Delusions of parasitosis by proxy is an uncommon entity wherein an individual projects a delusional belief onto another person who lacks capacity to hold the same belief. We report a case of delusions of parasitosis by proxy in a mother who believed that she was infested with scabies and projected her fixed, delusional belief of scabies infestation onto her children. She subjected her children to numerous home remedies and medical treatments as well as removing them from school in an effort to cure them of the supposed infestation. Child maltreatment can be a concern in such cases with a low threshold for involving child protective services if harm to the children is suspected.

Association of Blood-Based Brain Injury Biomarker Concentrations With Outcomes After Pediatric Cardiac Arrest.

Importance: 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. Objective: To analyze the association of blood-based brain injury biomarker concentrations with outcomes 1 year after pediatric cardiac arrest. Design, Setting, and Participants: 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. Exposure: Cardiac arrest. Main Outcomes and Measures: The primary outcome was an unfavorable outcome (death or survival with a Vineland Adaptive Behavior Scales, third edition, score of <70 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. Results: 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). Conclusions and Relevance: 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.

Stress-Mediated Attenuation of Translation Undermines T-cell Activity in Cancer.

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.

The ER-Mitochondria Interface as a Dynamic Hub for T Cell Efficacy in Solid Tumors.

The endoplasmic reticulum (ER) is a large continuous membranous organelle that plays a central role as the hub of protein and lipid synthesis while the mitochondria is the principal location for energy production. T cells are an immune subset exhibiting robust dependence on ER and mitochondrial function based on the need for protein synthesis and secretion and metabolic dexterity associated with foreign antigen recognition and cytotoxic effector response. Intimate connections exist at mitochondrial-ER contact sites (MERCs) that serve as the structural and biochemical platforms for cellular metabolic homeostasis through regulation of fission and fusion as well as glucose, Ca2+, and lipid exchange. Work in the tumor immunotherapy field indicates that the complex interplay of nutrient deprivation and tumor antigen stimulation in the tumor microenvironment places stress on the ER and mitochondria, causing dysfunction in organellar structure and loss of metabolic homeostasis. Here, we assess prior literature that establishes how the structural interface of these two organelles is impacted by the stress of solid tumors along with recent advances in the manipulation of organelle homeostasis at MERCs in T cells. These findings provide strong evidence for increased tumor immunity using unique therapeutic avenues that recharge cellular metabolic homeostasis in T cells.

Understanding the Importance of the Lay Responder Experience in Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association.

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.

Death and Dying in Hospitalized Pediatric Patients: A Prospective Multicenter, Multinational Study.

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.

Association of end-tidal carbon dioxide levels during cardiopulmonary resuscitation with survival in a large paediatric cohort.

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 < 0.05). When the events were based on patient age, this relationship held in adolescents (ROSC: 18.8 [15.5-22.3] vs. NO ROSC: 9.6 [4.4-15.9] mmHg; p < 0.05), but not in children or infants. Median event ETCO2 was significantly associated with chest compression rate less than 140 (p < 0.0001) and chest compression fraction 90-100 (p < 0.0001). CONCLUSIONS: This represents the largest collection of ETCO2 and chest compression data in paediatric patients to date and unadjusted analyses suggests an association between ETCO2 and ROSC in some paediatric patients.

Use of an end-tidal carbon dioxide-guided algorithm during cardiopulmonary resuscitation improves short-term survival in paediatric swine.

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.

CPR coaching during cardiac arrest improves adherence to PALS guidelines: a prospective, simulation-based trial.

AIM: Recent studies have shown that the integration of a trained cardiopulmonary resuscitation (CPR) Coach during resuscitation enhances the quality of CPR during simulated paediatric cardiac arrest. The objective of our study was to evaluate the effect of a CPR Coach on adherence to Paediatric Advanced Life Support (PALS) guidelines during simulated paediatric cardiac arrest. METHODS: This was a secondary analysis of data collected from a multicentre randomized controlled trial assessing the quality of CPR in teams with and without a CPR Coach. Forty paediatric resuscitation teams were equally randomized into 2 groups (with or without a CPR Coach). The primary outcome was adherence to PALS guidelines during a simulated paediatric cardiac arrest case as measured by the Clinical Performance Tool (CPT). Video recordings were assigned to 2 pairs of expert raters. Raters were trained to independently score performances using the tool. RESULTS: The reliability of the rating was adequate for the Clinical Performance Tool with an intraclass coefficients of 0.67 (95%CI: 0.22 to 0.84). Performance scores of the different teams varied between 51 and 84 points on the Clinical Performance Tool with a mean score of 70. Teams with a CPR Coach demonstrated better adherence to PALS guidelines (i.e. CPT score 73 points) compared to teams without a CPR Coach (68 points, difference 5 points; 95%CI: 1.0-9.3, p = 0.016). CONCLUSION: In addition to improving CPR quality, the presence of a CPR Coach improves adherence to PALS guidelines during simulated paediatric cardiac arrests when compared with teams without a CPR Coach.

Change in Cardiopulmonary Resuscitation Performance Over Time During Simulated Pediatric Cardiac Arrest and the Effect of Just-in-Time Training and Feedback.

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.

Rapid Cycle Deliberate Practice to Facilitate "Nano" In Situ Simulation: An Interprofessional Approach to Just-in-Time Training.

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.

Vertigoheel induced psychosis: A patient case report.

OBJECTIVE: To describe a case of a patient who developed psychosis after ingestion of Vertigoheel for treatment of dizziness. CASE SUMMARY: A 28-year-old male with no psychiatric history presented with 5 days of worsening depression and psychosis. He denied current use of prescription medications, alcohol, or illicit substances. Approximately 2 weeks prior, while visiting family in Germany, he developed dizziness. A provider in Germany prescribed Vertigoheel, 1 tablet to be taken every hour until symptom improvement. This did not improve his dizziness but did cause him to feel as if he were "in a dream." He stopped taking the medication after 2 days but continued to feel amotivated with decreased appetite and insomnia. Several days later, he developed ego-dystonic auditory hallucinations. He returned to the United States; was admitted to an inpatient psychiatric unit for 4 days; and given olanzapine 5 mg at bedtime, lorazepam 1 mg every evening, and melatonin 6 mg every evening. He experienced gradual improvement in symptoms and was discharged with olanzapine 5 mg daily and outpatient follow-up. DISCUSSION: Vertigoheel is a homeopathic preparation containing ambra grisea, Cocculus indicus, Conium maculatum, and petroleum. Psychosis was not reported in any of the randomized controlled trials evaluating the use of Vertigoheel for treatment of vertigo. A literature search revealed no published reports of psychosis as a result of administration of any components of Vertigoheel. CONCLUSION: A possible causal relationship was observed between the homeopathic supplement Vertigoheel and an acute episode of psychosis in a young male patient with no comorbidities.