Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the United States. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 hours of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient reported quality of life measures. Discussion: In-vitro and in-vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration: ClinicalTrials.gov (NCT04217551, 2019-12-30).

The Performance of ChatGPT-4 and Gemini Ultra 1.0 for Quality Assurance Review in Emergency Medical Services Chest Pain Calls.

OBJECTIVES: This study assesses the feasibility, inter-rater reliability, and accuracy of using OpenAI's ChatGPT-4 and Google's Gemini Ultra large language models (LLMs), for Emergency Medical Services (EMS) quality assurance. The implementation of these LLMs for EMS quality assurance has the potential to significantly reduce the workload on medical directors and quality assurance staff by automating aspects of the processing and review of patient care reports. This offers the potential for more efficient and accurate and identification of areas requiring improvement, thereby potentially enhancing patient care outcomesMETHODS: Two expert human reviewers, ChatGPT GPT-4, and Gemini Ultra assessed and rated 150 consecutively sampled and anonymized prehospital records from 2 large urban EMS agencies for adherence to 2020 National Association of State EMS metrics for cardiac care. We evaluated the accuracy of scoring, inter-rater reliability, and review efficiency. The inter-rater reliability for the dichotomous outcome of each EMS metric was measured using the kappa statistic.RESULTS: Human reviewers showed high interrater reliability, with 91.2% agreement and a kappa coefficient, 0.782 (0.654-0.910). ChatGPT-4 achieved substantial agreement with human reviewers in EKG documentation and aspirin administration (76.2% agreement, kappa coefficient, 0.401 (0.334-0.468), but performance varied across other metrics. Gemini Ultra's evaluation was discontinued due to poor performance. No significant differences were observed in median review times: 01:28 minutes (IQR 1:12 - 1:51 min) per human chart review, 01:24 minutes (IQR 01:09 - 01:53 min) per ChatGPT-4 chart review (p = 0.46), and 01:50 minutes (IQR 01:10-03:34 min) per Gemini Ultra review (p = 0.06).CONCLUSIONS: Large language models demonstrate potential in supporting quality assurance by effectively and objectively extracting data elements. However, their accuracy in interpreting non-standardized and time-sensitive details remains inferior to human evaluators. Our findings suggest that current LLMs may best offer supplemental support to the human review processes, but their value remains limited. Enhancements in LLM training and integration are recommended for improved and more reliable performance in the quality assurance processes.

Early intramuscular adrenaline administration is associated with improved survival from out-of-hospital cardiac arrest.

BACKGROUND: Early administration of adrenaline is associated with improved survival after out-of-hospital cardiac arrest (OHCA). Delays in vascular access may impact the timely delivery of adrenaline. Novel methods for administering adrenaline before vascular access may enhance survival. The objective of this study was to determine whether an initial intramuscular (IM) adrenaline dose followed by standard IV/IO adrenaline is associated with improved survival after OHCA. METHODS STUDY DESIGN: We conducted a before-and-after study of the implementation of an early, first-dose IM adrenaline EMS protocol for adult OHCAs. The pre-intervention period took place between January 2010 and October 2019. The post-intervention period was between November 2019 and May 2024. SETTING: Single-center urban, two-tiered EMS agency. PARTICIPANTS: Adult, nontraumatic OHCA meeting criteria for adrenaline use. INTERVENTION: Single dose (5 mg) IM adrenaline. All other care, including subsequent IV or IO adrenaline, followed international guidelines. MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge. Secondary outcomes were time from EMS arrival to the first dose of adrenaline, survival to hospital admission, and favorable neurologic function at discharge. RESULTS: Among 1450 OHCAs, 372 (29.9%) received IM adrenaline and 985 (70.1%) received usual care. Fifty-two patients received the first dose of adrenaline through the IV or IO route within the post-intervention period and were included in the standard care group analysis. Age was younger and bystander CPR was higher in the IM adrenaline group. All other characteristics were similar between IM and standard care cohorts. Time to adrenaline administration was faster for the IM cohort [(median 4.3 min (IQR 3.0-6.0) vs. 7.8 min (IQR 5.8-10.4)]. Compared with standard care, IM adrenaline was associated with improved survival to hospital admission (37.1% vs. 31.6%; aOR 1.37, 95% CI 1.06-1.77), hospital survival (11.0% vs 7.0%; aOR 1.73, 95% CI 1.10-2.71) and favorable neurologic status at hospital discharge (9.8% vs 6.2%; aOR 1.72, 95% CI 1.07-2.76). CONCLUSION: In this single-center before-and-after implementation study, an initial IM dose of adrenaline as an adjunct to standard care was associated with improved survival to hospital admission, survival to hospital discharge, and functional survival. A randomized controlled trial is needed to fully assess the potential benefit of IM adrenaline delivery in OHCA.

Examining the association between ethnicity and out-of-hospital cardiac arrest interventions in Salt Lake City, Utah.

Aims: Previous research has reported racial disparities in out-of-hospital cardiac arrest (OHCA) interventions, including bystander CPR and AED use. However, studies on other prehospital interventions are limited. The primary objective of this study was to investigate race/ethnic disparities in out-of-hospital cardiac arrest (OHCA) interventions: EMS response times, medication administration, and decisions for intra-arrest transport. The secondary objective was to evaluate differences in the provision of Bystander CPR (CPR) and application of AED. Methods: We retrospectively analyzed data from the Salt Lake City Fire Department (2010-2023). We included adults 18 years or older with EMS-treated OHCA. Race/ethnicity was categorized as White people, Asian people, Black people, Hispanic people, and others. We employed multivariable regression analysis to evaluate the association between race/ethnicity and the outcomes of interest. Results: Unadjusted analyses revealed no significant differences across ethnic groups in EMS response, medication administration, bystander CPR, or intra-arrest transport decisions. However, significant ethnic disparities were observed in Automated External Defibrillator (AED) utilization, Black people having the lowest rate (6.5%) and Asian people the highest (21.8%). The adjusted analysis found no significant association between race/ethnicity and all OHCA intervention measures, nor between race/ethnicity and survival outcomes. Conclusions: Our multivariable analysis found no statistically significant association between race/ethnicity and EMS response time, epinephrine administration, antiarrhythmic medication use, bystander CPR, AED intervention, or intra-arrest transport. These results imply regional variations in ethnic disparities in OHCA may not be consistent across all areas, warranting further research into disparities in other regions and additional influential factors like neighborhood conditions and socioeconomic status.

The impact of time to defibrillation on return of spontaneous circulation in out-of-hospital cardiac arrest patients with recurrent shockable rhythms.

OBJECTIVE: Optimal timing for subsequent defibrillation attempts for Out-of-hospital cardiac arrest (OHCA) patients with recurrent VF/pVT is uncertain. We investigated the relationship between VF/pVT duration and return of spontaneous circulation (ROSC) in OHCA patients with recurrent shockable rhythms. METHODS: We analyzed data from the Salt Lake City Fire Department (SLCFD) spanning from 2012 to 2023. The implementation of rhythm-filtering technology since 2011 enabled real-time rhythm interpretation during CPR, with local protocols allowing early defibrillation for recurrent/refractory VF/pVT cases. We included patients experiencing four or five episodes of VF and pVT rhythms and employed generalized estimating equation (GEE) regression analysis to examine the association between VF/pVT durations preceding recurrent defibrillation and return of spontaneous circulation (ROSC). RESULTS: Analysis of 622 appropriate shocks showed that patients achieving ROSC had significantly shorter median VF/pVT duration than those who did not achieve ROSC (0.83 minutes vs. 1.2 minutes, p = 0.004). Adjusted analysis of those with 4 VF/pVT episodes (N = 142) revealed that longer VF/pVT durations were associated with lower odds of achieving ROSC (odds ratio: 0.81, 95% CI: 0.72-0.93, p = 0.005). Every one-minute delay in intra-arrest defibrillation is predicted to decrease the likelihood of achieving ROSC by 19%. CONCLUSION: Every one-minute increase in intra-arrest VF/pVT duration was associated with a statistically significant 19% decrease in the chance of achieving ROSC. This highlights the importance of reducing time to shock in managing recurrent VF/pVT. The findings suggest reevaluating the current recommendations of two minutes intervals for rhythm check and shock delivery.

Numerical Cincinnati Stroke Scale versus Stroke Severity Screening Tools for the Prehospital Determination of LVO.

Background: Previous research demonstrated that the numerical Cincinnati Prehospital Stroke Scale (CPSS) identifies large vessel occlusion (LVO) at similar rates compared to a limited number of stroke severity screening tools. We aimed to compare numerical CPSS to additional stroke scales using a national EMS database. Methods: Using the ESO Data Collaborative, the largest EMS database with hospital linked data, we retrospectively analyzed prehospital patient records for the year 2022. Stroke and LVO diagnoses were determined by ICD-10 codes from linked hospital discharge and emergency department records. Prehospital CPSS was compared to the Cincinnati Stroke Triage Assessment Tool (C-STAT), the Field Assessment Stroke Triage for Emergency Destination (FAST-ED), and the Balance Eyes Face Arm Speech Time (BE-FAST). The optimal prediction cut-points for LVO screening were determined by intersecting the sensitivity and specificity curves for each scale. To compare the discriminative abilities of each scale among those diagnosed with LVO, we used the area under the receiver operating curve (AUROC). Results: We identified 17,442 prehospital records from 754 EMS agencies with ≥ 1 documented stroke scale of interest: 30.3% (n=5,278) had a hospital diagnosis of stroke, of which 71.6% (n=3,781) were ischemic; of those, 21.6% (n=817) were diagnosed with LVO. CPSS score ≥ 2 was found to be predictive of LVO with 76.9% sensitivity, 68.0% specificity, and AUROC 0.787 (95% CI 0.722-0.801). All other tools had similar predictive abilities, with sensitivity / specificity / AUROC of: C-STAT 62.5% / 76.5% / 0.727 (0.555-0.899); FAST-ED 61.4% / 76.1%/ 0.780 (0.725-0.836); BE-FAST 70.4% / 67.1% / 0.739 (0.697-0.788). Conclusion: The less complex CPSS exhibited comparable performance to three frequently employed LVO detection tools. EMS agency leadership, medical directors, stroke system directors, and other stroke leaders may consider the complexity of stroke severity instruments and challenges with ensuring accurate recall and consistent application when selecting which instrument to implement. Use of the simpler CPSS may enhance compliance with the utilization of LVO screening instruments while maintaining the accuracy of prehospital LVO determination.

Epidemiology and outcome of out-of-hospital cardiac arrest in Salt Lake City: Sex-based investigations.

Objectives: Prior research indicates sex disparities in the incidence and outcomes of out-of-hospital cardiac arrest (OHCA). This study investigates the presence of such differences in Salt Lake City, Utah. Methods: We analyzed data from the Salt Lake City Fire Department (2008‒2023). We included adults with non-traumatic OHCA. We calculated the annual incidence of OHCA and examined sex-specific survival outcomes using multivariable logistic regression, adjusting for OHCA characteristics known to be associated with survival. Results: The annual incidence of OHCA was 76 per 100,000 person-years. Among the 894 OHCA cases included in the analysis, 67.5% were males, 37.3% achieved return of spontaneous circulation (ROSC), and 13.6% survived hospital discharge. Unadjusted analysis revealed that males had significantly higher OHCA in public locations (43.9% vs. 28.6%), witnessed arrests (54.5% vs. 47.8%), and shockable rhythms (33.3% vs. 22.9%). Males also showed higher rates of ROSC (37.5% vs. 36.9%), hospital discharge survival (14.5% vs. 11.7%), and neurologically intact survival. After adjusting for the OHCA characteristics, there was no significant differences between males and females in ROSC, survival to hospital discharge, and favorable neurological function with adjusted odds ratios (male vs. female) of 0.92 (95% confidence interval [CI] 0.73‒1.16), 0.85 (95% CI 0.59‒1.22), and 0.92 (95% CI 0.62‒1.40), respectively. Conclusion: Approximately, 128 adults suffer OHCA in Salt Lake City annually. Males initially showed higher crude survival rates, but after adjusting for OHCA characteristics, no significant sex differences in survival outcomes were found. Enhancing OHCA characteristics could benefit both sexes. Investigations into the relationship between sex- and region-specific factors influencing OHCA outcomes are needed.

Evaluation of esophageal injuries after defibrillation with transesophageal ultrasound probe in the mid-esophagus in pigs.

OBJECTIVE: Transesophageal echocardiography (TEE) is becoming increasingly utilized by emergency medicine providers during cardiac arrest. Intra-arrest, TEE confers several benefits including shorter pauses in chest compressions and direct visualization of cardiac compressions. Many ultrasound probe manufacturers recommend against performing defibrillation with the TEE probe in the mid-esophagus for fear of causing esophageal injury or damage to the probe, however no literature exists that has investigated this concern. To assess this, we performed cardiopulmonary resuscitation (CPR) and multiple defibrillations in 8 swine with a TEE probe in place. METHODS: We performed TEE on 8 adult swine during CPR and performed multiple 200 J defibrillations with the TEE probe in the mid-esophagus. Post-mortem, esophagi were dissected and inspected for evidence of injury. RESULTS: On macroscopic inspection of 8 esophagi, no evidence of hematoma, thermal injury, or perforation was noted. CONCLUSION: Our study suggests that performing defibrillation during CPR with a TEE probe in place in the mid-esophagus is likely safe and low risk for significant esophageal injury. This further bolsters the use of TEE in CPR and would enable continuous visualization of cardiac activity without the need to remove the TEE probe for defibrillation.

TEE guided REBOA deflation following ROSC for non-traumatic cardiac arrest.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is most commonly used to manage non-compressible torso hemorrhage. It is also emerging as a promising treatment for non-traumatic refractory cardiac arrest. Aortic occlusion during chest compressions increases cardio-cerebral perfusion, increasing the potential for sustained return of spontaneous circulation (ROSC) or serving as a bridge to extracorporeal cardiopulmonary resuscitation (ECPR). Optimal patient selection and post-ROSC management in such cases is uncertain and not well reported in the literature. We present a case of non-traumatic out-of-hospital cardiac arrest in which REBOA was placed in the emergency department with subsequent ROSC. Transesophageal echocardiography was used to guide post-ROSC REBOA management and balloon deflation.

The Association of Modifiable Postresuscitation Management and Annual Case Volume With Survival After Extracorporeal Cardiopulmonary Resuscitation.

It is not know if hospital-level extracorporeal cardiopulmonary resuscitation (ECPR) case volume, or postcannulation clinical management associate with survival outcomes. OBJECTIVES: To describe variation in postresuscitation management practices, and annual hospital-level case volume, for patients who receive ECPR and to determine associations between these management practices and hospital survival. DESIGN: Observational cohort study using case-mix adjusted survival analysis. SETTING AND PARTICIPANTS: Adult patients greater than or equal to 18 years old who received ECPR from the Extracorporeal Life Support Organization Registry from 2008 to 2019. MAIN OUTCOMES AND MEASURES: Generalized estimating equation logistic regression was used to determine factors associated with hospital survival, accounting for clustering by center. Factors analyzed included specific clinical management interventions after starting extracorporeal membrane oxygenation (ECMO) including coronary angiography, mechanical unloading of the left ventricle on ECMO (with additional placement of a peripheral ventricular assist device, intra-aortic balloon pump, or surgical vent), placement of an arterial perfusion catheter distal to the arterial return cannula (to mitigate leg ischemia); potentially modifiable on-ECMO hemodynamics (arterial pulsatility, mean arterial pressure, ECMO flow); plus hospital-level annual case volume for adult ECPR. RESULTS: Case-mix adjusted patient-level management practices varied widely across individual hospitals. We analyzed 7,488 adults (29% survival); median age 55 (interquartile range, 44-64), 68% of whom were male. Adjusted hospital survival on ECMO was associated with mechanical unloading of the left ventricle (odds ratio [OR], 1.3; 95% CI, 1.08-1.55; p = 0.005), performance of coronary angiography (OR, 1.34; 95% CI, 1.11- 1.61; p = 0.002), and placement of an arterial perfusion catheter distal to the return cannula (OR, 1.39; 95% CI, 1.05-1.84; p = 0.022). Survival varied by 44% across hospitals after case-mix adjustment and was higher at centers that perform more than 12 ECPR cases/yr (OR, 1.23; 95% CI, 1.04-1.45; p = 0.015) versus medium- and low-volume centers. CONCLUSIONS AND RELEVANCE: Modifiable ECMO management strategies and annual case volume vary across hospitals, appear to be associated with survival and should be the focus of future research to test if these hypothesis-generating associations are causal in nature.

Automated aortic endovascular balloon volume titration prevents re-arrest immediately after return of spontaneous circulation in a swine model of nontraumatic cardiac arrest.

Objectives: Endovascular aortic occlusion as an adjunct to cardiopulmonary resuscitation (CPR) for non-traumatic cardiac arrest is gaining interest. In a recent clinical trial, return of spontaneous circulation (ROSC) was achieved despite prolonged no-flow times. However, 66% of patients re-arrested upon balloon deflation. We aimed to determine if automated titration of endovascular balloon volume following ROSC can augment diastolic blood pressure (DBP) to prevent re-arrest. Methods: Twenty swine were anesthetized and placed into ventricular fibrillation (VF). Following 7 minutes of no-flow VF and 5 minutes of mechanical CPR, animals were subjected to complete aortic occlusion to adjunct CPR. Upon ROSC, the balloon was either deflated steadily over 5 minutes (control) or underwent automated, dynamic adjustments to maintain a DBP of 60 mmHg (Endovascular Variable Aortic Control, EVAC). Results: ROSC was obtained in ten animals (5 EVAC, 5 REBOA). Sixty percent (3/5) of control animals rearrested while none of the EVAC animals rearrested (p = 0.038). Animals in the EVAC group spent a significantly higher proportion of the post-ROSC period with a DBP > 60 mmHg [median (IQR)] [control 79.7 (72.5-86.0)%; EVAC 97.7 (90.8-99.7)%, p = 0.047]. The EVAC group had a statistically significant reduction in arterial lactate concentration [7.98 (7.4-8.16) mmol/L] compared to control [9.93 (8.86-10.45) mmol/L, p = 0.047]. There were no statistical differences between the two groups in the amount of adrenaline (epinephrine) required. Conclusion: In our swine model of cardiac arrest, automated aortic endovascular balloon titration improved DBP and prevented re-arrest in the first 20 minutes after ROSC.

Establishing a multicenter, preclinical consortium in resuscitation: A pilot experimental trial evaluating epinephrine in cardiac arrest.

BACKGROUND: Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results. METHODS: Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy. RESULTS: There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004). CONCLUSION: This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

The association of modifiable mechanical ventilation settings, blood gas changes and survival on extracorporeal membrane oxygenation for cardiac arrest.

RESEARCH QUESTION: Given the relative independence of ventilator settings from gas exchange and plasticity of blood gas values during extracorporeal cardiopulmonary resuscitation (ECPR), do mechanical ventilation parameters and blood gas values influence survival? METHODS: Observational cohort study of 7488 adult patients with ECPR from the Extracorporeal Life Support Organization (ELSO) Registry. We performed case-mix adjustment for severity of illness and patient type using generalized estimating equation logistic regression to determine factors associated with hospital survival accounting for clustering by center, standardizing variables by 1 standard deviation (SD) of their values. We examined non-linear relationships between ventilatory and blood gas values with hospital survival. RESULTS: Hospital survival was decreased with higher PaO2 on ECMO (OR 0.69, per 1SD increase [95% CI 0.64, 0.74]; p < 0.001) and with any relative changes in PaCO2 (pre-arrest to on-ECMO) in a non-linear fashion. Survival was worsened with any peak inspiratory pressure >20 cmH20 (OR 0.69, per 1SD [0.64, 0.75]; p < 0.001) and above 40% fraction of inspired oxygen (OR 0.75, per 1SD [0.69, 0.82]; p < 0.001), and with higher dynamic driving pressure (OR 0.72, per 1 SD increase [0.65, 0.79]; <0.001). Ventilation settings and blood gas values varied widely across hospitals, but were not associated with annual hospital ECPR case volume. CONCLUSION: Lower ventilatory pressures, avoidance of hyperoxia, and relatively unchanged CO2 (pre- to on-ECMO) were all associated with survival in patients after ECPR, yet varied across hospitals. Our findings represent potential targets for prospective trials for this rapidly growing therapy to test if these associations have causality.

Paramedic rhythm interpretation misclassification is associated with poor survival from out-of-hospital cardiac arrest.

BACKGROUND: Early recognition and rapid defibrillation of shockable rhythms is strongly associated with survival in out of hospital cardiac arrest (OHCA). Little is known about the accuracy of paramedic rhythm interpretation and its impact on survival. We hypothesized that inaccurate paramedic interpretation of initial rhythm would be associated with worse survival. METHODS: This is a retrospective cohort analysis of prospectively collected OHCA data over a nine-year period within a single, urban, fire-based EMS system that utilizes manual defibrillators equipped with rhythm-filtering technology. We compared paramedic-documented initial rhythm with a reference standard of post-event physician interpretation to estimate sensitivity and specificity of paramedic identification of and shock delivery to shockable rhythms. We assessed the association between misclassification of initial rhythm and neurologically intact survival to hospital discharge using multivariable logistic regression. RESULTS: A total of 863 OHCA cases were available for analysis with 1,756 shocks delivered during 542 (63%) resuscitation attempts. Eleven percent of shocks were delivered to pulseless electrical activity (PEA). Sensitivity and specificity for paramedic initial rhythm interpretation were 176/197 (0.89, 95% CI 0.84-0.93) and 463/504 (0.92, 95% CI 0.89-0.94) respectively. No patient survived to hospital discharge when paramedics misclassified the initial rhythm. CONCLUSIONS: Paramedics achieved high sensitivity for shock delivery to shockable rhythms, but with an 11% shock delivery rate to PEA. Misclassification of initial rhythm was associated with poor survival. Technologies that assist in rhythm identification during CPR, rapid shock delivery, and minimal hands-off time may improve outcomes.

Regional Systems of Care in ST Elevation Myocardial Infarction.

ST-segment elevation myocardial infarction is a medical emergency with significant health care delivery challenges to ensure rapid triage and treatment. Several developments over the past decades have led to improved care delivery, decreased time to reperfusion, and decreased mortality. Still, significant challenges remain to further optimize the delivery of care for this patient population.

Extracorporeal Cardiopulmonary Resuscitation in Adults. Interim Guideline Consensus Statement From the Extracorporeal Life Support Organization.

DISCLAIMER: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being deployed for selected patients in cardiac arrest who do not attain a native circulation with conventional CPR (ECPR). This ELSO guideline is intended to be a practical guide to implementing ECPR and the early management following establishment of ECMO support. Where a paucity of high-quality evidence exists, a consensus has been reached amongst the authors to provide guidance to the clinician. This guideline will be updated as further evidence in this field becomes available.

Rationale and Strategies for Development of an Optimal Bundle of Management for Cardiac Arrest.

OBJECTIVES: To construct a highly detailed yet practical, attainable roadmap for enhancing the likelihood of neurologically intact survival following sudden cardiac arrest. DESIGN SETTING AND PATIENTS: Population-based outcomes following out-of-hospital cardiac arrest were collated for 10 U.S. counties in Alaska, California, Florida, Ohio, Minnesota, Utah, and Washington. The 10 identified emergency medical services systems were those that had recently reported significant improvements in neurologically intact survival after introducing a more comprehensive approach involving citizens, hospitals, and evolving strategies for incorporating technology-based, highly choreographed care and training. Detailed inventories of in-common elements were collated from the ten 9-1-1 agencies and assimilated. For reference, combined averaged outcomes for out-of-hospital cardiac arrest occurring January 1, 2017, to February 28, 2018, were compared with concurrent U.S. outcomes reported by the well-established Cardiac Arrest Registry to Enhance Survival. INTERVENTIONS: Most commonly, interventions and components from the ten 9-1-1 systems consistently included extensive public cardiopulmonary resuscitation training, 9-1-1 system-connected smart phone applications, expedited dispatcher procedures, cardiopulmonary resuscitation quality monitoring, mechanical cardiopulmonary resuscitation, devices for enhancing negative intrathoracic pressure regulation, extracorporeal membrane oxygenation protocols, body temperature management procedures, rapid cardiac angiography, and intensive involvement of medical directors, operational and quality assurance officers, and training staff. MEASUREMENTS AND MAIN RESULTS: Compared with Cardiac Arrest Registry to Enhance Survival (n = 78,704), the cohorts from the 10 emergency medical services agencies examined (n = 2,911) demonstrated significantly increased likelihoods of return of spontaneous circulation (mean 37.4% vs 31.5%; p < 0.001) and neurologically favorable hospital discharge, particularly after witnessed collapses involving bystander cardiopulmonary resuscitation and shockable cardiac rhythms (mean 10.7% vs 8.4%; p < 0.001; and 41.6% vs 29.2%; p < 0.001, respectively). CONCLUSIONS: The likelihood of neurologically favorable survival following out-of-hospital cardiac arrest can improve substantially in communities that conscientiously and meticulously introduce a well-sequenced, highly choreographed, system-wide portfolio of both traditional and nonconventional approaches to training, technologies, and physiologic management. The commonalities found in the analyzed systems create a compelling case that other communities can also improve out-of-hospital cardiac arrest outcomes significantly by conscientiously exploring and adopting similar bundles of system organization and care.

The microfollicle: a model of the human hair follicle for in vitro studies.

Access to complex in vitro models that recapitulate the unique markers and cell-cell interactions of the hair follicle is rather limited. Creation of scalable, affordable, and relevant in vitro systems which can provide predictive screens of cosmetic ingredients and therapeutic actives for hair health would be highly valued. In this study, we explore the features of the microfollicle, a human hair follicle organoid model based on the spatio-temporally defined co-culture of primary cells. The microfollicle provides a 3D differentiation platform for outer root sheath keratinocytes, dermal papilla fibroblasts, and melanocytes, via epidermal-mesenchymal-neuroectodermal cross-talk. For assay applications, microfollicle cultures were adapted to 96-well plates suitable for medium-throughput testing up to 21 days, and characterized for their spatial and lineage markers. The microfollicles showed hair-specific keratin expression in both early and late stages of cultivation. The gene expression profile of microfollicles was also compared with human clinical biopsy samples in response to the benchmark hair-growth compound, minoxidil. The gene expression changes in microfollicles showed up to 75% overlap with the corresponding gene expression signature observed in the clinical study. Based on our results, the cultivation of the microfollicle appears to be a practical tool for generating testable insights for hair follicle development and offers a complex model for pre-clinical substance testing.