Design and implementation of the hospital airway resuscitation trial.

Guidelines for the management of in-hospital cardiac arrest resuscitation are often drawn from evidence generated in out-of-hospital cardiac arrest populations and applied to the in-hospital setting. Approach to airway management during resuscitation is one example of this phenomenon, with the recommendation to place either a supraglottic airway or endotracheal tube when performing advanced airway management during in-hospital cardiac arrest based mainly in clinical trials conducted in the out-of-hospital setting. The Hospital Airway Resuscitation Trial (HART) is a pragmatic cluster-randomized superiority trial comparing a strategy of first choice supraglottic airway to a strategy of first choice endotracheal intubation during resuscitation from in-hospital cardiac arrest. The design includes a number of innovative elements such as a highly pragmatic design drawing from electronic health records and a novel primary outcome measure for cardiac arrest trials-alive-and-ventilator free days. Many of the topics explored in the design of HART have wide relevance to other trials in in-hospital cardiac arrest populations.

Decreased Utilization of Low Tidal Volume Ventilation Outside of the Intensive Care Unit as Compared to Inside.

Background: Investigations into the use of low tidal volume ventilation (LTVV) have been performed for patients in emergency departments (EDs) or intensive care units (ICUs). Practice differences between the ICU and non-ICU care areas have not been described. We hypothesized that the initial implementation of LTVV would be better inside ICUs than outside. Methods: This is a retrospective observational study of patients initiated on invasive mechanical ventilation (IMV) between January 1, 2016, and July 17, 2019. Initial recorded tidal volumes after intubation were used to compare the use of LTVV between care areas. Low tidal volume was considered 6.5 cc/kg of ideal body weight (IBW) or less. The primary outcome was the initiation of low tidal volume. Sensitivity analyses used a tidal volume of 8 cc/kg of IBW or less, and direct comparisons were performed between the ICU, ED, and wards. Results: There were 6392 initiations of IMV: 2217 (34.7%) in the ICU and 4175 (65.3%) outside. LTVV was more likely to be initiated in the ICU than outside (46.5% vs 34.2%; adjusted odds ratio [aOR] 0.62, 95% confidence interval [CI] 0.56-0.71, P < .01). The ICU also had more implementation when PaO2/FiO2 ratio was less than 300, (48.0% vs 34.6%; aOR 0.59, 95% CI 0.48-0.71, P < .01). When comparing individual locations, wards had lower odds of LTVV than the ICU (aOR 0.82, 95% CI 0.70-0.96, P = .02), the ED had lower odds than the ICU (aOR 0.55, 95% CI 0.48-0.63, P < .01), and the ED had lower odds than the wards (aOR 0.66, 95% CI 0.56-0.77, P < .01). Interpretation: Initial low tidal volumes were more likely to be initiated in the ICU than outside. This finding remained when examining only patients with a PaO2/FiO2 ratio less than 300. Care areas outside of the ICU do not employ LTVV as often as ICUs and are, therefore, a possible target for process improvement.

Applicability of the surgical risk calculator by the American College of Surgeons in the setting of German patients undergoing complete pancreatectomy: multicentre study using data from the StuDoQ|Pancreas registry.

INTRODUCTION: Surgical risk calculators can estimate risk probabilities for postoperative outcomes utilizing patient-specific risk factors. They provide meaningful information for obtaining informed consent. The aim of the present paper was to evaluate the predictive value of the surgical risk calculators by the American College of Surgeons in German patients undergoing total pancreatectomy. METHODS: Data for patients who underwent total pancreatectomy between 2014 and 2018 were acquired from the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery. Risk factors were entered manually into the surgical risk calculators and calculated risks were compared with actual outcomes. RESULTS: Of the 408 patients analysed, predicted risk was higher in patients with complications except for the prediction of re-admission (P = 0.127), delayed gastric emptying (P = 0.243), and thrombosis (P = 0.256). In contrast, classification of patients into below, above, or average risk by the surgical risk calculators only produced meaningful results for discharge to nursing facility (P < 0.001), renal failure (P = 0.003), pneumonia (P = 0.001), serious complications, and overall morbidity (both P < 0.001). Assessment of discrimination and calibration showed poor results (scaled Brier scores 8.46 per cent or less). CONCLUSION: Overall surgical risk calculator performance was poor. This finding promotes the development of a specific surgical risk calculator applicable to the German healthcare system.

Obesity is Unlikely to be an Impediment to First-Pass Success During the Intubation of Critically Ill Patients.

Background: Obesity has been described as a potential risk factor for difficult intubation among critically ill patients. Our primary aim was to further elucidate the association between obesity and first-pass success. Our secondary aim was to determine whether the use of hyper-angulated video laryngoscopy improves first-pass success compared to direct laryngoscopy when utilized for the intubation of critically ill obese patients. Study Design and Methods: A retrospective cohort study of adult patients undergoing endotracheal intubation outside of the operating room or emergency department between January 30, 2016 and May 1, 2020 at 3 campuses of an academic hospital system in the Bronx, NY. Our primary outcome was first-pass success of intubation. A multivariate logistic analysis was utilized to compare obesity status with first-pass success. Results: We identified 3791 critically ill patients who underwent endotracheal intubation of which 1417 were obese (body mass index [BMI] ≥ 30). The incidence of hyper-angulated video laryngoscopy increased over the study period. A total of 46.6% of obese patients underwent intubation with hyper-angulated video laryngoscopy as compared to 35.1% of the nonobese group. First-pass success was 79.2% among the entire cohort. Obesity status did not appear to be associated with first-pass success (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI]: 090-1.27; P = .47). Hyper-angulated video laryngoscopy did not seem to improve first-pass success among obese patients as compared to nonobese patients (adjusted OR 1.21, 95% CI: 0.85-1.71; P = .29). These findings persisted even after redefining the obesity cutoff as BMI ≥ 40 and excluding patients intubated during cardiac arrests. Conclusion: We did not detect an association between obesity and first-pass success. Hyper-angulated video laryngoscopy did not appear offer additional benefit over direct laryngoscopy during the intubation of critically ill obese patients.

Protocol and statistical analysis plan for the PREOXI trial of preoxygenation with noninvasive ventilation vs oxygen mask.

Background: Hypoxemia is a common and life-threatening complication during emergency tracheal intubation of critically ill adults. The administration of supplemental oxygen prior to the procedure ("preoxygenation") decreases the risk of hypoxemia during intubation. Research Question: Whether preoxygenation with noninvasive ventilation prevents hypoxemia during tracheal intubation of critically ill adults, compared to preoxygenation with oxygen mask, remains uncertain. Study Design and Methods: The PRagmatic trial Examining OXygenation prior to Intubation (PREOXI) is a prospective, multicenter, non-blinded randomized comparative effectiveness trial being conducted in 7 emergency departments and 17 intensive care units across the United States. The trial compares preoxygenation with noninvasive ventilation versus oxygen mask among 1300 critically ill adults undergoing emergency tracheal intubation. Eligible patients are randomized in a 1:1 ratio to receive either noninvasive ventilation or an oxygen mask prior to induction. The primary outcome is the incidence of hypoxemia, defined as a peripheral oxygen saturation <85% between induction and 2 minutes after intubation. The secondary outcome is the lowest oxygen saturation between induction and 2 minutes after intubation. Enrollment began on 10 March 2022 and is expected to conclude in 2023. Interpretation: The PREOXI trial will provide important data on the effectiveness of noninvasive ventilation and oxygen mask preoxygenation for the prevention of hypoxemia during emergency tracheal intubation. Specifying the protocol and statistical analysis plan prior to the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial. Clinical trial registration number: NCT05267652.

Virtual Reality as Anxiolysis During Laceration Repair in the Pediatric Emergency Department.

BACKGROUND: Although procedural pain is effectively treated with analgesics, managing anxiety during laceration repair is more challenging. OBJECTIVES: We examined the feasibility of using immersive virtual reality (VR) as anxiolysis during laceration repair in the pediatric emergency department (ED). METHODS: We conducted a non-blinded, observational, pilot study in an urban pediatric ED that enrolled a convenience sample of children aged 5-13 years undergoing sutured repair of non-facial lacerations. Subjects played an immersive VR game while undergoing laceration repair. Parents assessed their child's anxiety on a 100-mm visual analogue scale at enrollment and during laceration repair. The primary outcome measure was the percentage of children whose anxiety score did not increase by ≥ 20 mm from enrollment to the first stitch. RESULTS: Forty patients completed the study. Mean initial anxiety score was 54 mm (standard deviation 33 mm). Thirty-seven of forty patients (93%; 95% confidence interval [CI] 83-99%) had anxiety scores that did not increase by 20 mm or more from enrollment to the first stitch. Eighty percent (95% CI 64-91%) of patients' anxiety scores decreased between enrollment and first stitch. The mean change in anxiety score at first stitch was -39 mm (95% CI -51 mm to -27 mm; p < 0.001). Similar downward trends in anxiety scores were noted throughout the procedure. All laceration repairs were successfully completed without sedation or restraints. There were no adverse events noted, and the main barriers identified with VR use involved easily correctable technical difficulties with the equipment. CONCLUSION: Immersive VR is a safe and effective distractive technique to reduce procedural anxiety during laceration repair in the pediatric ED.

Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma-A 3-D In Vitro Study.

Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.

Guiding Fellows to Independent Practice: Current Trends in Pediatric Emergency Medicine Fellow Supervision.

BACKGROUND: Recent studies highlight the importance of physician readiness to practice beyond graduate training. The Accreditation Council for Graduate Medical Education mandates that pediatric emergency medicine (PEM) fellows be prepared for independent practice by allowing "progressive responsibility for patient care." Prior unpublished surveys of program directors (PDs) indicate variability in approaches to provide opportunities for more independent practice during fellowship training. OBJECTIVES: The aims of the study were to describe practices within PEM fellowship programs allowing fellows to work without direct supervision and to identify any barriers to independent practice in training. DESIGN/METHODS: An anonymous electronic survey of PEM fellowship PDs was performed. Survey items were developed using an iterative modified Delphi process and pilot tested. Close-ended survey responses and demographic variables were summarized with descriptive statistics. Responses to open-ended survey items were reviewed and categorized by theme. RESULTS: Seventy two of 84 PDs (88%) responded to the survey; however, not all surveys were completed. Of the 68 responses to whether fellows could work without direct supervision (as defined by the Accreditation Council for Graduate Medical Education) during some part of their training, 31 (45.6%) reported that fellows did have this opportunity. In most programs, clinical independence was conditional on specific measures including the number of clinical hours completed, milestone achievement, and approval by the clinical competency committee. Reported barriers to fellow practice without direct oversight included both regulatory and economic constraints. CONCLUSIONS: Current training practices that provide PEM fellows with conditional clinical independence are variable. Future work should aim to determine best practices of entrustment, identify ideal transition points, and mitigate barriers to graduated responsibility.

Effectiveness of a Simulation Curriculum on Clinical Application: A Randomized Educational Trial.

INTRODUCTION: The use of simulation to develop clinical reasoning and medical decision-making skills for common events is poorly established. Validated head trauma rules help identify children at low risk for clinically important traumatic brain injury and guide the need for neuroimaging. We predicted that interns trained using a high-fidelity, immersive simulation would understand and apply these rules better than those trained using a case-based discussion. Our primary outcomes were to determine the effectiveness of a single targeted intervention on an intern's ability to learn and apply the rules. METHODS: This was a prospective randomized controlled trial. Interns were randomized to participate in either a manikin-based simulation or a case discussion. Knowledge and application of the Pediatric Emergency Care Applied Research Network Head Trauma tool were assessed both under testing conditions using standardized vignettes and in clinical encounters. In both settings, interns completed a validated assessment tool to test their knowledge and application of the Pediatric Emergency Care Applied Research Network Head Trauma tool when assessing patients with head injury. RESULTS: Under testing conditions, both being in the simulation group and shorter time from training were independently associated with higher score under testing conditions using standardized vignettes (P = 0.038 and P < 0.001), but not with clinical encounters. CONCLUSIONS: Interns exposed to manikin-based simulation training demonstrated performance competencies that are better than those in the case discussion group under testing conditions using standardized vignettes, but not in real clinical encounters. This study suggests that information delivery and comprehension may be improved through a single targeted simulation-based education.

Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNFα-antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure.

BACKGROUND: A feedforward pathological signaling loop generated by TNFα and IFN-γ synergy in the inflamed lung, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define the inflammatory biology of lethal COVID-19 respiratory failure. METHODS: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5 mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥50 compared to baseline and sustained for 48 h. Secondary endpoints included 28-day mortality, dynamic cytokine profiles, secondary infections, duration of supplemental oxygen support, and hospitalization. FINDINGS: Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 years, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953 ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days; 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Three deaths were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 to 483 pg/ml at Day 3 and 146 pg/ml at Day 14/discharge. Significant Day 3 declines in IFN-, TNFα, IL-27, CRP, and ferritin occurred. IP-10 and CXCL-9 declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, P-value 0.0006). INTERPRETATION: Infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19.

Practice, Outcomes, and Complications of Emergent Endotracheal Intubation by Critical Care Practitioners During the COVID-19 Pandemic.

BACKGROUND: For patients with COVID-19 who undergo emergency endotracheal intubation, data are limited regarding the practice, outcomes, and complications of this procedure. RESEARCH QUESTION: For patients with COVID-19 requiring emergency endotracheal intubation, how do the procedural techniques, the incidence of first-pass success, and the complications associated with the procedure compare with intubations of critically ill patients before the COVID-19 pandemic? STUDY DESIGN AND METHODS: We conducted a retrospective study of adult patients with COVID-19 at Montefiore Medical Center who underwent first-time endotracheal intubation by critical care physicians between July 19, 2019, and May 1, 2020. The first COVID-19 patient was admitted to our institution on March 11, 2020; patients admitted before this date are designated the prepandemic cohort. Descriptive statistics were used to compare groups. A Fisher exact test was used to compare categorical variables. For continuous variables, a two-tailed Student t test was used for parametric variables or a Wilcoxon rank-sum test was used for nonparametric variables. RESULTS: One thousand two hundred sixty intubations met inclusion criteria (782 prepandemic cohort, 478 pandemic cohort). Patients during the pandemic were more likely to be intubated for hypoxemic respiratory failure (72.6% vs 28.1%; P < .01). During the pandemic, operators were more likely to use video laryngoscopy (89.4% vs 53.3%; P < .01) and neuromuscular blocking agents (86.0% vs 46.2%; P < .01). First-pass success was higher during the pandemic period (94.6% vs 82.9%; P < .01). The rate of associated complications was higher during the pandemic (29.5% vs 15.2%; P < .01), a finding driven by a higher rate of hypoxemia during or immediately after the procedure (25.7% vs 8.2%; P < .01). INTERPRETATION: Video laryngoscopy and neuromuscular blockade were used increasingly during the COVID-19 pandemic. Despite a higher rate of first-pass success during the pandemic, the incidence of complications associated with the procedure was higher.

Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNF-α antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure.

BACKGROUND: A feed-forward pathological signaling loop generated by TNFα and IFN-γ in inflamed lung tissue, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define, sustain and amplify the inflammatory biology of lethal COVID-19 respiratory failure. METHODS: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥ 50 compared to baseline and sustained for 48 hours. Secondary endpoints included 28-day mortality, dynamic cytokine profiles (Human Cytokine 48-Plex Discovery Assay, Eve Technologies), secondary infections, duration of supplemental oxygen support and hospitalization. FINDINGS: Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 yrs, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days, 15/18 (83%) recovered from respiratory failure, and 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Deaths among three patients ≥ 65yrs age with pre-existing lung disease or multiple comorbidities were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 pg/ml to 483 pg/ml at Day 3 and further to 146 pg/ml at Day 14/discharge. Significant declines in IFN- γ , TNFα, IL-27, CRP and ferritin were specifically observed at Day 3 whereas other cytokines were unmodified. IL-6 levels declined sharply among patients with baseline levels >10 pg/ml. Among 13 lymphopenic patients, six (46%) had resolution of lymphopenia by day 3, and 11 by day 14. CXCR3-ligand (IP-10 and CXCL-9) declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, p-value: 0.0006). INTERPRETATION: Consistent with a pathophysiological role of TNFα, the clinical and cytokine data indicate that infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19. Randomized studies are required to formally assess mortality outcomes. Funding: National Center for Advancing Translational Sciences.

The ongoing impact of COVID-19 on asthma and pediatric emergency health-seeking behavior in the Bronx, an epicenter.

BACKGROUND: The Bronx has the highest prevalence of asthma in the United States (US), and was also an early COVID-19 epicenter, making it a unique study location. Worldwide reports describe significant declines in pediatric emergency department (PED) visits during COVID-19. The ongoing impact of COVID-19 on all PED presentations, including asthma, at an early epicenter has not been studied beyond the pandemic peak and into the early phases of state re-opening. OBJECTIVES: To compare PED health-seeking behaviors and clinical characteristics during the 2020 pandemic and subsequent initial New York State (NYS) phased re-opening to the same period in 2019. METHODS: Retrospective chart review of children <21 years utilizing the PED at a high-volume quaternary children's hospital in The Bronx, NY from March 15th 2020 - July 6th 2020 (pandemic cohort) and the same interval in 2019 (comparison cohort). Visits were assigned to pre-determined diagnostic categories. Demographic and clinical data were compared. RESULTS: 19,981 visits were included. Visits declined by 66% during 2020. Proportions of asthma visits (2% vs. 7%, p < 0.0001) and minor medical problems (61% vs. 67%, p < 0.0001) had significant declines in the pandemic cohort, while major medical problems (13% vs. 8%, p < 0.0001), appendicitis (1% vs. 0.4%, p < 0.0001) and other surgical complaints (1% vs. 0.5%, p < 0.0001) had proportional increases in the pandemic cohort. No significant proportional changes were noted among psychosocial and trauma groups between the two cohorts. CONCLUSION: The pandemic cohort experienced a substantial decrease in PED volume, but an increase in acuity and admission rates, which was sustained through the NYS phase-II re-opening. Despite being located in an asthma hub, the incidence of asthma-related PED visits declined appreciably in the pandemic cohort. Future studies examining the effects of indoor allergens in isolation on pediatric asthma are warranted.

Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments.

OBJECTIVE: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. STUDY DESIGN: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. RESULTS: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%. CONCLUSIONS: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.