Safety, Pharmacokinetics, and Efficacy Signals of Larsucosterol (DUR-928) in Alcohol-Associated Hepatitis.

INTRODUCTION: This study is to evaluate the safety and pharmacokinetics (PK) of larsucosterol (DUR-928 or 25HC3S) in subjects with alcohol-associated hepatitis (AH), a devastating acute illness without US Food and Drug Administration-approved therapies. METHODS: This phase 2a, multicenter, open-label, dose escalation study evaluated the safety, PK, and efficacy signals of larsucosterol in 19 clinically diagnosed subjects with AH. Based on the model for end-stage liver disease (MELD) score, 7 subjects were considered to have moderate AH and 12 to have severe AH. All subjects received 1 or 2 intravenous infusions (72 hours apart) of larsucosterol at a dose of 30, 90, or 150 mg and were followed up for 28 days. Efficacy signals from a subgroup of subjects with severe AH were compared with those from 2 matched arms of those with severe AH treated with standard of care (SOC), including corticosteroids, from a contemporaneous study. RESULTS: All 19 larsucosterol-treated subjects survived the 28-day study. Fourteen (74%) of all subjects including 8 (67%) of the subjects with severe AH were discharged ≤72 hours after receiving a single infusion. There were no drug-related serious adverse events nor early terminations due to the treatment. PK profiles were not affected by disease severity. Biochemical parameters improved in most subjects. Serum bilirubin levels declined notably from baseline to day 7 and day 28, and MELD scores were reduced at day 28. The efficacy signals compared favorably with those from 2 matched groups treated with SOC. Lille scores at day 7 were <0.45 in 16 of the 18 (89%) subjects with day 7 samples. Lille scores from 8 subjects with severe AH who received 30 or 90 mg larsucosterol (doses used in phase 2b trial) were statistically significantly lower ( P < 0.01) than those from subjects with severe AH treated with SOC from the contemporaneous study. DISCUSSION: Larsucosterol was well tolerated at all 3 doses in subjects with AH without safety concerns. Data from this pilot study showed promising efficacy signals in subjects with AH. Larsucosterol is being evaluated in a phase 2b multicenter, randomized, double-blinded, placebo-controlled (AHFIRM) trial.

A Novel Technique for Temporally Securing a Chest Tube in a Resource-Limited Environment.

In the prehospital, transport, and resource-limited setting, patients with traumatic hemothorax, pneumothorax, or cardiac arrest require emergency tube thoracostomy for stabilization and transport. With the possibility of multiple patients, limited providers, and inability to commit a 1:1 provider-to-patient ratio for safe tubeless thoracostomies, a chest tube is often the safest option. Mercy Health Life Flight Air Medical program has developed practice over decades using towel clamps and tape to achieve securement rapidly and reliably. We report on this subject as an option for temporarily securing a chest tube in the disaster, resource-poor, prehospital, or critical care transport setting.

Does the Location of Endotracheal Intubation Affect the Success of Airway Management in a Helicopter Air Ambulance Service? A Simulation Study.

OBJECTIVE: Airway management is a cornerstone of helicopter air ambulance patient management. The purpose of this study was to evaluate the overall quality of airway management of critical care crews in 3 common locations for intubation. METHODS: This was a prospective observational simulation study assessing the overall airway management of critical care providers managing simulated patients in an emergency department, helicopter, and ambulance. Composite scores were obtained and compared with respect to physical environment and provider certification level. RESULTS: Fifty-four participants completed the simulations. The median score for the emergency department was 100; for ambulance, it was 80; and for helicopter, it was 80. Ambulance scores were significantly lower than emergency department scores (median difference = -5 points, P = .002) as were helicopter scores (median difference = -10 points, P < .001). The small sample size limited the statistical power to detect differences in provider type, and no statistically significant differences were found in these groups. CONCLUSION: In this study, the physical location of airway management negatively impacted the overall airway management success as determined by a standardized composite score. This suggests that airway management may have the highest rate of success in an emergency department as opposed to ground ambulance or helicopter air ambulance settings.

Prevalence, co-morbidities, and in-hospital mortality of patients hospitalized with alcohol-associated hepatitis in the United States from 2015 to 2019.

BACKGROUND: The goals of our study are to determine the most recent trends in hospitalization, mortality, and healthcare utilization among hospitalized patients with alcohol-associated hepatitis (AH) in the United States. METHODS: We examined the recent prevalence, co-morbidities, and mortality in hospitalized AH patients in the United States based on the available National Inpatient Sample (NIS) data (2015 to 2019) using appropriate International Classification of Diseases (ICD) codes. We reported our data as national estimates based on the discharge weighting variable (DISCWT). Logistic regression analyses were used to determine factors associated with mortality. RESULTS: We observed an increase in the total number of hospitalized AH patients from 110,135 in 2015 to 136,620 in 2019, which represented 386 per 100,000 total hospitalizations or 42 per 100,000 US population, which in 2019 was 328 million. Patients were a mean of 48 years old and the majority were White and male. The average length of stay was around 6 days with an overall in-hospital mortality that decreased from 4.19% in 2015 to 3.86% in 2019 (p-value for trend = <0.0001). During the 5-year study period, a total of 24,795 hospitalized AH patients died and 592,885 survived the hospital stay. Those who died were older, had a longer length of stay, and higher hospital charges during the stay. Mortality was significantly greater in patients who presented with complications from portal hypertension, those with acute renal failure, underlying cirrhosis, and sepsis. CONCLUSIONS: Our study documented the increasing prevalence of hospitalized AH patients and their significant associated healthcare costs and utilization. Our results underscore a continuing unmet and urgent need to identify effective therapies for hospitalized AH patients.

Helicopter Emergency Medical Services Ultrasound Use in the Diagnosis of Pericardial Effusion Due to Aortic Dissection.

Ultrasound has historically been limited to in-hospital use for the diagnosis and management of various conditions. However, with the advent of smaller and more portable devices, this technology can be used outside the hospital. This report describes a patient with chest pain and hypotension for whom a point-of-care cardiac ultrasound (POCUS) was performed to diagnose cardiac tamponade during critical care transport. She was subsequently found to have an acute type A aortic dissection, and her care was expedited to the operating room. Cardiac tamponade in the setting of acute type A aortic dissection requires urgent surgical repair; therefore, early diagnosis is crucial to survival. In this case, prehospital ultrasound facilitated rapid care for the patient. Further study is needed to define its role in the prehospital setting.

Effects of a Labor Dispute on a Hospital-Based Helicopter Air Ambulance Service's Volume and Destinations.

OBJECTIVE: In the United States, there are few unionized hospitals with air medical transport agencies. When labor disputes and strikes occur, information about the effect on helicopter air ambulances and critical care ground transport services is limited. For this study, a helicopter air ambulance and critical care ground transport agency's volume of transports was examined before, during, and after a strike and compared with volumes from the prior year. METHODS: This was a retrospective, descriptive comparative review of a unionized hospital's air ambulance and critical care mobile ground transport service records from March 28 to July 22, 2018 (control year, 872 transports) and March 28 to July 22, 2019 (strike year, 863 transports). RESULTS: Compared with the prior year, during the strike period alone, the volume of flight transports remained stable; however, there was a significant 31% loss in transports for time-critical diseases including trauma, stroke, and myocardial infarction. CONCLUSION: The unionized helicopter air ambulance experienced little change in overall volume, but there was a statistically and financially significant decline in flight transports for patients with time-critical diseases. When preparing for labor disputes, potential declines in the transportation of this population type should be considered, and future studies should look at patient and requesting agency preferences during strikes.

Prehospital Ketamine Use for Rapid Sequence Intubation: Are Higher Doses Associated With Adverse Events?

OBJECTIVE: Ketamine for rapid sequence intubation (RSI) is typically dosed at 1 to 2 mg/kg intravenously. The need to ensure dissociation during RSI led some to administer ketamine at doses greater than 2 mg/kg. This study assessed associations between ketamine dose and adverse events. METHODS: This multisite, retrospective study included adult subjects undergoing RSI with intravenous ketamine. Subjects were categorized into 2 groups: a standard ketamine dose (≤ 2 mg/kg intravenously) or a high dose (> 2 mg/kg intravenously). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for adverse events. RESULTS: Eighty subjects received standard-dose ketamine, and 50 received high-dose ketamine. The high-dose group had a significantly (P < .05) higher proportion of trauma patients, were younger, and had higher predose blood pressure compared with the standard-dose group. High-dose ketamine was associated with greater odds of adverse events including hypotension (OR = 7.0; 95% CI, 3.0-16.6), laryngospasm (OR = 10.8; 95% CI, 1.3-93.4), bradycardia (OR = 7.5; 95% CI, 1.5-36.6), repeat medications (OR = 12.9; 95% CI, 1.5-107.9), oxygen desaturation (OR = 6.0; 95% CI, 1.8-19.9), multiple attempts (OR = 3.2; 95% CI, 1.5-6.8%), and failed airway (OR = 3.6; 95% CI, 1.0-12.7). CONCLUSION: Ketamine at higher doses was associated with increased odds of adverse events. Studies assessing adverse events of ketamine at lower than standard doses in shock patients are needed.

Females and Minority Racial/Ethnic Groups Remain Underrepresented in Emergency Medical Services: A Ten-Year Assessment, 2008-2017.

Background: Workforce diversity can reduce communication barriers and inequalities in healthcare delivery, especially in settings where time pressure and incomplete information may exacerbate the effects of implicit biases. Emergency medical services (EMS) professionals represent a critical entry point into the healthcare system for diverse populations, yet little is known regarding changes in the demographic composition of this workforce. Our primary objective was to describe the gender and racial/ethnic composition of emergency medical technicians (EMTs) and paramedics who earned initial National EMS Certification from 2008 to 2017. Secondarily, we compared demographic characteristics of the 2017 EMT and paramedic cohorts to the U.S. population. Methods: As a proxy for recent graduates likely to enter the workforce, we conducted a serial cross-sectional analysis of all EMTs and paramedics earning initial National EMS Certification from January 1, 2008 to December 31, 2017. Cuzick's non-parametric test of trend was used to assess for changes in the gender and racial/ethnic composition of the EMS cohorts over time. For 2017, we calculated differences the gender and racial/ethnic composition of the EMT and paramedic cohorts to the U.S population, stratifying by Census region. Results: The study population included 588,337 EMTs and 105,356 paramedics. The proportion of females earning initial EMT certification rose from 28% in 2008 to 35% in 2017. Throughout the study period, less than one-fourth of newly certified paramedics were female (range: 20-23%). The proportion of EMS professionals identifying as black remained near 5% among EMTs and 3% among paramedics. The proportion of newly-certified Hispanic EMS professionals rose from 10% to 13% among EMTs and from 6% to 10% among paramedics. Compared to the U.S. population, females and racial/ethnic minorities were underrepresented among EMTs and paramedics earning initial certification and these representation differences varied across geographic regions. Conclusions: The underrepresentation of females and minority racial/ethnic groups observed during this 10-year investigation of EMTs and paramedics earning initial certification suggests that EMS workforce diversity is unlikely to undergo substantial change in the near future. The representation gaps were larger and more stable among paramedics compared to EMTs and suggest an area where concerted efforts are needed to encourage students of diverse backgrounds to pursue EMS.

The Use of Point-of-Care Ultrasound to Accurately Measure Cardiac Output in Flight.

Cardiac point-of-care ultrasound (POCUS) is a quick and accurate tool to assess a patient's cardiovascular and hemodynamic status by measuring the E-point septal separation (EPSS) and left ventricular ejection fraction. The case presented here highlights the potential for increased use of POCUS to guide resuscitation in the prehospital setting and during critical care transport. A 56-year-old male presented to a rural emergency department with chest pain and was found to have an inferior STelevation myocardial infarction (STEMI). Local helicopter air ambulance was called to transport the patient to a facility capable of cardiac catheterization. In route, the flight physician performed a cardiac POCUS exam which revealed decreased cardiac perfusion, a hypokinetic inferior wall, and overall decreased contractility. EPSS was measured at 0.77cm, indicating moderate left ventricular ejection fraction (LVEF) reduction. A cardiac left ventriculogram later confirmed a 40% ejection fraction as well as wall motion abnormalities of the inferior wall. The patient was found to have 100% occlusion of the right coronary artery that was revascularized with balloon angioplasty and a drug-eluting stent. He ultimately did well and was discharged home.

Botulism Outbreak in a Regional Community Hospital: Lessons Learned in Transfer and Transport Considerations.

Botulism is a potentially lethal disease caused by a toxin released by Clostridium botulinum. Outbreaks of botulism from food sources can lead to a Mass Casualty Incident (MCI) involving sometimes hundreds of individuals. We report on a recent outbreak of botulism treated at a regional community hospital with a focus on emergency medical services (EMS) response and transport considerations. Case Presentation: There were 53 patient evaluated for botulism at the sending facility. In total, 11 botulism exposures required intubation at the sending facility. Twenty-four patients were ultimately transported by critical care capable ALS crews with the majority (16) of these transports occurred in the first 24 hours. There was one fatality in the first days of the outbreak and a second death that occurred in a patient who died after long-term acute care (LTAC) placement several months after hospital discharge. Conclusion: Local EMS providers and public safety officers have a critical role in identifying and following up on potentially exposed botulism cases. The organization of transporting agencies and the logistics of transfer turned out to be 2 opportunities for improvement in response to this mass casualty incident.

Prehospital Stroke Assessment for Large Vessel Occlusions: A Systematic Review.

BACKGROUND AND OBJECTIVE: Stroke is the leading cause of disability in the United States and new evidence shows interventional procedures provide better outcomes for large vessel occlusions (LVO). We performed a systematic review of the literature on prehospital stroke scales used to identify LVOs comparing the scales with analysis of the sensitivity, specificity, and predictive values. The goal was to determine if emergency medical services (EMS) are able to accurately identify LVO in the field. METHODS: In this systematic review, multiple databases were searched for articles that addressed our goal. The identified studies were evaluated for their statistical performance of various stroke scales. In addition, we assessed biases that may explain the varying results reported. RESULTS: Eight studies encompassing 6787 patients were included in our systematic review. Of the 8 studies, 6 were retrospective studies, 1 was a prospective cohort, and 1 was a prospective observational study. Sensitivities of the studies ranged from 49% to 91% while specificity of the studies varied from 40% to 94%. CONCLUSION: At this time, further evaluations must be done in the prehospital setting to determine the ease of use and true sensitivity and specificity of these scales in identifying LVOs.

Toxic effects of oil and dispersant on marine microalgae.

To better understand the potential impacts of the deepwater horizon oil spill on lower trophic level food sources, a series of toxicological laboratory experiments were conducted with two microalgae species. The acute toxicity of oil (tar mat and MC252 crude oil), dispersant (Corexit 9500A), and dispersed oil on growth inhibition (IC50) and motility of Isochrysis galbana and Chaetoceros sp. were determined. There was no impact on cell division (growth) for microalgae exposed to both oil types and mean motility of I. galbana never dropped below 79 %. However, the addition of dispersant inhibited cell division and motility within 24 h, with Chaetoceros sp. being more susceptible to sublethal effects than I. galbana. These results highlight microalgae sensitivity to the use of dispersants in bioremediation processes, which may be a concern for long-term impacts on fisheries recruitment.

The turnover of continental planktonic diatoms near the middle/late Miocene boundary and their Cenozoic evolution.

Fossil evidence indicates that modern assemblages of temperate nonmarine planktonic diatoms began near the middle/late Miocene boundary when the genus Actinocyclus, an important constituent of lacustrine planktonic diatom assemblages during the early to middle Miocene, was replaced by genera of the family Stephanodiscaceae. This floral turnover has been confirmed in many regions of the world, except eastern Asia where taxonomic data about early and middle Miocene planktonic diatom assemblages have until recently been scarce. Our analysis of Lower and Middle Miocene lacustrine diatomaceous rocks in Japan confirms that species of nonmarine Actinocyclus were important constituents of lake phytoplankton there as well. The appearance of nonmarine Actinocyclus species near the beginning of the Miocene may have resulted from the introduction of euryhaline species into lacustrine environments during a highstand of sea level at that time. Similarly, it is possible that species of Stephanodiscaceae evolved from marine thalassiosiroid ancestors that invaded high latitude lacustrine environments during multiple Paleogene highstands, resulting in a polyphyletic origin of the family. The turnover from nonmarine Actinocyclus to Stephanodiscaceae genera near the middle/late Miocene boundary may be linked to a contemporaneous increase in silica concentrations in lakes caused by active volcanism, increased weathering of silicate rocks due to orogeny, and the expansion of C4 grasslands. This turnover may also have been influenced by enhanced seasonal environmental changes in the euphotic zone caused by the initiation of monsoon conditions and a worldwide increase in meridional temperature gradients during the late Miocene. Morphological characteristics of Stephanodiscaceae genera, such as strutted processes and small size, suggest their species were better adapted to seasonal environmental changes than nonmarine species of Actinocyclus because of their superiority in floating and drifting capabilities and possibly metabolism, intrinsic growth rate, and reproductivity. As climates deteriorated during the late Miocene, Stephanodiscaceae species may have spread from high latitudes to temperate lakes where they diversified, ultimately displacing Actinocyclus.

A Longitudinal Emergency Medical Services Track in Emergency Medicine Residency.

Emergency medicine residency programs offer Emergency Medical Services (EMS) curricula to address Accreditation Council for Graduate Medical Education (ACGME) milestones. While some programs offer advanced clinical tracks in EMS, no standard curriculum exists. We sought to establish a well-defined EMS curriculum to allow interested residents to develop advanced clinical skills and scholarship within this subspecialty. Core EMS fellowship trained faculty were recruited to help develop the curriculum. Building on ACGME graduation requirements and milestones, important elements of EMS fellowship training were incorporated into the curriculum to develop the final document. The final curriculum focuses on scholarly activities relating to the four core areas of EMS identified by The American Board of Emergency Medicine and serves as an intermediary between ACGME graduation requirements for education in EMS and fellowship level training. Standardization of the EMS scholarly track can provide residents with the potential to obtain competency beyond ACGME requirements and prepare them for success in fellowship training and/or leadership within EMS on graduation.

Use of double sequential external defibrillation for refractory ventricular fibrillation during out-of-hospital cardiac arrest.

INTRODUCTION: Survival from out of hospital cardiac arrest (OHCA) is highest in victims with shockable rhythms when early CPR and rapid defibrillation are provided. However, a subset of individuals present with ventricular fibrillation (VF) that does not respond to defibrillation (refractory VF). One intervention that may be a possible option in refractory VF is double sequential external defibrillation (DSD). The objective of this case series was to describe the outcome of prehospital victims with refractory VF treated with DSD in the out-of-hospital setting. METHODS: This evaluation is a retrospective chart review of VF patients treated with DSD in the prehospital setting from August 1st, 2010 through June 30th, 2014. Patients were excluded if less than 17 years of age. The outcomes we evaluated were the number of patients with return of spontaneous circulation, conversion from VF, survival-to-hospital discharge, and Cerebral Performance Category score. RESULTS: Total of 2428 OHCA events were reviewed with twelve patients treated with DSD. Median DSD and prehospital resuscitation times were 27min (IQR 22-33) and 32 (IQR 24-38), respectively. Of the 12 patients treated, return of spontaneous circulation was achieved in three patients, nine patients were converted out of ventricular fibrillation, three patients survived to hospital discharge, and two patients (2/12, 17%) were discharged with Cerebral Performance Category scores of 1 (good cerebral performance). CONCLUSIONS: Double sequential defibrillation may be another tool to improve neurologically intact survival from OHCA. Further studies are needed to demonstrate direct benefits to patient outcomes.

Relationship between fluoroquinolone use and changes in susceptibility to fluoroquinolones of selected pathogens in 10 United States teaching hospitals, 1991-2000.

We retrospectively examined the relationship between fluoroquinolone use and the susceptibilities of 11 bacterial pathogens to fluoroquinolones in 10 US teaching hospitals from 1991 through 2000. Statistical significance was determined by 2-way analysis of variance, with the number of isolates tested each year as a weighting factor. The analysis of baseline-to-end point change in the percentage of susceptibility and the slope of the regression line (trend line) for logit percentage of susceptibility showed that the overall percentage of susceptibility to fluoroquinolones decreased significantly during the study period (P<.05) and that change in percentage of susceptibility was significantly related to change in fluoroquinolone use (P<.05). Particularly notable were the decreases in the susceptibilities of Pseudomonas aeruginosa, Proteus mirabilis, and Escherichia coli (decreases of 25.1%, 11.9%, and 6.8%, respectively).

Tear concentration and safety of levofloxacin ophthalmic solution 1.5% compared with ofloxacin ophthalmic solution 0.3% after topical administration in healthy adult volunteers.

PURPOSE: This study evaluated the tear concentration and safety of levofloxacin ophthalmic solution 1.5%. METHODS: Healthy adult volunteers (N = 125) received a single initial two-drop bilateral dose of either levofloxacin 1.5% (n = 100) or ofloxacin 0.3% (n = 25). Tear-fluid drug concentrations were measured at 15 minutes and at 2, 6, 12, and 24 hours after dosing. Subjects were dosed every 2 hours while awake and 4 and 6 hours after retiring (Days 1-3) and four times daily while awake (Days 4-14). Final measurements and evaluations were done on Day 15. Tear concentrations were determined by high-performance liquid chromatography. Safety and tolerability parameters included visual acuity, ophthalmoscopy, biomicroscopy, rose bengal staining, and adverse effects. RESULTS: Tear concentrations after a single two-drop dose of levofloxacin 1.5% and ofloxacin 0.3% were above 2 microg/mL, a concentration that exceeds the minimum inhibitory concentration90 for levofloxacin in typical ocular bacterial pathogens at all time points through 24 hours. The area under the curve for the first 12 hours for levofloxacin 1.5% was 2703.5 +/- 574.22 microg.h/mL and 414.1 +/- 1179.00 microg.h/mL with ofloxacin 0.3%. Maximal concentrations were 806.9 +/- 8.57 and 73.3 +/- 165.46 microg/mL, respectively. Levofloxacin 1.5% and ofloxacin 0.3% did not differ in adverse event incidence, except for transient mild/moderate dysgeusia (14% of levofloxacin-treated subjects versus 4% of ofloxacin-treated subjects). No corneal epithelial damage or inflammatory changes were associated with levofloxacin. CONCLUSION: A single dose of levofloxacin 1.5% produced tear fluid concentrations that were well above the minimum inhibitory concentration90 for typical ocular pathogens and was safe and well tolerated.

A maritime navigation display that provides visual feedback to improve conning officers' ship-handling during low visibility environments.

Navigating a ship at night in close proximity to another vessel is a dangerous task. To improve conning officers' night time ship-handling performance, a visual navigation display is proposed that is mounted on the stern of the aircraft carrier that will help shipboard conning officers manoeuvre in a battle group formation. To test the effectiveness of the visual navigation display, the Nimitz-class aircraft and plane guard vessel, a Ticonderoga-class cruiser, were modelled in a virtual environment. A navigation display condition had significantly fewer navigational positional errors than a non-navigation display condition. The navigation display provided immediate feedback as to whether the aircraft carrier had changed bearing or speed, thus enabling the operator to initiate the appropriate input to maintain station astern of the carrier. Actual or potential applications of this research include the deployment of a maritime navigation display to assist conning officers' ship handling.

Psychophysical assessments of image-sensor fused imagery.

The goal of this study was to determine the perceptual advantages of multiband sensor-fused (achromatic and chromatic) imagery over conventional single-band nighttime (image-intensified and infrared) imagery for a wide range of visual tasks, including detection, orientation, and scene recognition. Participants were 151 active-duty military observers whose reaction time and accuracy scores were recorded during a visual search task. Data indicate that sensor fusion did not improve performance relative to that obtained with single-band imagery on a target detection task but did facilitate object recognition, judgments of spatial orientation, and scene recognition. Observers' recognition and orientation judgments were improved by the emergent information within the image-fused imagery (i.e., combining dominant information from two or more sensors into a single displayed image). Actual or potential applications of this research include the deployment of image-sensor fused systems for automobile, aviation, and maritime displays to increase operators' visual processing during low-light conditions.