Association of diastolic blood pressure with coronary perfusion pressure during resuscitation in pediatric swine.

BACKGROUND: Diastolic blood pressure (DBP) is suggested as a surrogate for coronary perfusion pressure (CPP) during cardiopulmonary resuscitation. We examined the correlation between DBP and CPP and hypothesized that both would be associated with survival in a pediatric swine model of asphyxial cardiac arrest. METHODS: We performed a retrospective, secondary analysis of 102 pediatric swine resuscitations. DBP and CPP were recorded every 30 s during resuscitation. Values were compared between survivors and non-survivors. RESULTS: DBP mirrored CPP in survivors and non-survivors throughout resuscitation and both were associated with survival. Improvements in DBP and CPP after the first epinephrine administration were greater in survivors (DBP: 25.1 ± 3.0 vs. 5.4 ± 0.8 mmHg, p < 0.01; CPP: 24.9 ± 3.2 vs. 4.8 ± 0.9 mmHg, p < 0.01). DBP and CPP after epinephrine administration were highly predictive of survival, with an area under the curve of 0.95 (0.89-1.00) for DBP and 0.90 (0.81-0.99) for CPP. The optimal threshold for DBP was 22.5 mmHg, whereas that for CPP was 14.5 mmHg. CONCLUSIONS: DBP and CPP were associated with survival throughout resuscitation, and the response of both to the first epinephrine administration was highly predictive of survival in this model. Clinically, the availability of DBP makes it useful as a target for physiologic feedback during resuscitation. IMPACT: Diastolic blood pressure (DBP) mirrored coronary perfusion pressure (CPP) throughout prolonged resuscitation in a pediatric model of asphyxial cardiac arrest. Mean DBP and CPP were significantly greater in survivors than in non-survivors both before and after administration of epinephrine. The response of both DBP and CPP to the first dose of epinephrine was highly predictive of return of spontaneous circulation. Given the clinical availability of DBP, these findings support its use as a surrogate for CPP to guide high-quality cardiopulmonary resuscitation in this pediatric swine model.

Trends in Disease Severity Among Critically Ill Children With Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Multicenter Cohort Study in the United States.

OBJECTIVES: To describe trends in critical illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children over the course of the COVID-19 pandemic. We hypothesized that PICU admission rates were higher in the Omicron period compared with the original outbreak but that fewer patients needed endotracheal intubation. DESIGN: Retrospective cohort study. SETTING: This study took place in nine U.S. PICUs over 3 weeks in January 2022 (Omicron period) compared with 3 weeks in March 2020 (original period). PATIENTS: Patients less than or equal to 21 years old who screened positive for SARS-CoV-2 infection by polymerase chain reaction or hospital-based rapid antigen test and were admitted to a PICU or intermediate care unit were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 267 patients (239 Omicron and 28 original) were reviewed. Forty-five patients in the Omicron cohort had incidental SARS-CoV-2 and were excluded from analysis. The Omicron cohort patients were younger compared with the original cohort patients (median [interquartile range], 6 yr [1.3-13.3 yr] vs 14 yr [8.3-17.3 yr]; p = 0.001). The Omicron period, compared with the original period, was associated with an average increase in COVID-19-related PICU admissions of 13 patients per institution (95% CI, 6-36; p = 0.008), which represents a seven-fold increase in the absolute number admissions. We failed to identify an association between cohort period (Omicron vs original) and odds of intubation (odds ratio, 0.7; 95% CI, 0.3-1.7). However, we cannot exclude the possibility of up to 70% reduction in intubation. CONCLUSIONS: COVID-19-related PICU admissions were seven times higher in the Omicron wave compared with the original outbreak. We could not exclude the possibility of up to 70% reduction in use of intubation in the Omicron versus original epoch, which may represent differences in PICU/hospital admission policy in the later period, or pattern of disease, or possibly the impact of vaccination.

Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation.

Alcohol use disorder (AUD) is a chronic debilitating disorder with limited treatment options and poorly defined pathophysiology. There are substantial genetic and epigenetic components; however, the underlying mechanisms contributing to AUD remain largely unknown. We conducted the largest DNA methylation epigenome-wide association study (EWAS) analyses currently available for AUD (total N = 625) and employed a top hit replication (N = 4798) using a cross-tissue/cross-phenotypic approach with the goal of identifying novel epigenetic targets relevant to AUD. Results show that a network of differentially methylated regions in glucocorticoid signaling and inflammation-related genes were associated with alcohol use behaviors. A top probe consistently associated across all cohorts was located in the long non-coding RNA growth arrest specific five gene (GAS5) (p < 10-24). GAS5 has been implicated in regulating transcriptional activity of the glucocorticoid receptor and has multiple functions related to apoptosis, immune function and various cancers. Endophenotypic analyses using peripheral cortisol levels and neuroimaging paradigms showed that methylomic variation in GAS5 network-related probes were associated with stress phenotypes. Postmortem brain analyses documented increased GAS5 expression in the amygdala of individuals with AUD. Our data suggest that alcohol use is associated with differential methylation in the glucocorticoid system that might influence stress and inflammatory reactivity and subsequently risk for AUD.

Closing the Gap: Optimizing Performance to Reduce Interruptions in Cardiopulmonary Resuscitation.

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 < 0.001). 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.

Genetic Association and Expression Analyses of the Phosphatidylinositol-4-Phosphate 5-Kinase (PIP5K1C) Gene in Alcohol Use Disorder-Relevance for Pain Signaling and Alcohol Use.

BACKGROUND: The gene encoding phosphatidylinositol-4-phosphate 5-kinase (PIP5K1C) has been recently implicated in pain regulation. Interestingly, a recent cross-tissue and cross-phenotypic epigenetic analysis identified the same gene in alcohol use disorder (AUD). Given the high comorbidity between AUD and chronic pain, we hypothesized that genetic variation in PIP5K1C might contribute to susceptibility to AUD. METHODS: We conducted a case-control association study of genetic variants in PIP5K1C. Association analyses of 16 common PIP5K1C single nucleotide polymorphisms (SNPs) were conducted in cases and controls of African (427 cases and 137 controls) and European ancestry (488 cases and 324 controls) using standard methods. In addition, given the prominent role of the opioid system in pain signaling, we investigated the effects of acute alcohol exposure on PIP5K1C expression in humanized transgenic mice for the µ-opioid receptor that included the OPRM1 A118G polymorphism, a widely used mouse model to study analgesic response to opioids in pain. PIP5K1C expression was measured in the thalamus and basolateral amygdala (BLA) in mice after short-term administration (single 2 g/kg dose) of alcohol or saline using immunohistochemistry and analyzed by 2-way analysis of variance. RESULTS: In the case-control association study using an NIAAA discovery sample, 8 SNPs in PIP5K1C were significantly associated with AUD in the African ancestry (AA) group (p < 0.05 after correction; rs4807493, rs10405681, rs2074957, rs10432303, rs8109485, rs1476592, rs10419980, and rs4432372). However, a replication analysis using an independent sample (N = 3,801) found no significant associations after correction for multiple testing. In the humanized transgenic mouse model with the OPRM1 polymorphism, PIP5K1C expression was significantly different between alcohol and saline-treated mice, regardless of genotype, in both the thalamus (p < 0.05) and BLA (p < 0.01). CONCLUSIONS: Our discovery sample shows that genetic variants in PIP5K1C are associated with AUD in the AA group, and acute alcohol exposure leads to up-regulation of PIP5K1C, potentially explaining a mechanism underlying the increased risk for chronic pain conditions in individuals with AUD.

Evaluating the Impact of an Adolescent Sexuality Education Workshop on Medical Student Communication in an Objective Structured Clinical Examination.

PURPOSE: Gaps still exist in medical education about the sexual health needs of sexual diverse populations, and little is known about how translatable current learning modules are to patient encounters. Efforts at an academic medical institution have been made to address this need, including a two-hour adolescent sexuality workshop during the Core Clerkship in Pediatrics. This workshop's efficacy was evaluated in an objective structured clinical examination (OSCE) given to rising fourth-year medical students, where the standardized patient case focused on an adolescent cisgender male with dysuria and in a new, same-sex relationship. METHODS: Performance of students who completed the workshop prior to the OSCE (n = 48) were compared to those of students who did not participate in the workshop prior to the OSCE (n = 17). The encounters were recorded and transcribed, and the deidentified transcripts were scored on a rubric focusing on five domains: sexual identity disclosure, behavioral assessment, psychosocial history, counseling and anticipatory guidance, and relationship building. RESULTS: Student's t-test comparison of the scores found significantly higher scores for the psychosocial history domain (p = .04), particularly concerning disclosure of a new boyfriend and recent sexual activity (p = .008), for students who had the workshop before the OSCE. DISCUSSION: Students who took the adolescent sexuality workshop performed better in gathering psychosocial information in an OSCE encounter a sexual minority adolescent. These results affirm prior work that active learning on sexual diverse health in medical school curricula may prepare students for effective engagement with adolescents exploring their sexuality.

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.

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.