Liquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer's Amyloid-ß Oligomers.

Protein phase separation by low-complexity, intrinsically disordered domains generates membraneless organelles and links to neurodegeneration. Cellular prion protein (PrPC) contains such domains, causes spongiform degeneration, and is a receptor for Alzheimer's amyloid-ß oligomers (Aßo). Here, we show that PrPC separates as a liquid phase, in which α-helical Thr become unfolded. At the cell surface, PrPC Lys residues interact with Aßo to create a hydrogel containing immobile Aßo and relatively mobile PrPC. The Aßo/PrP hydrogel has a well-defined stoichiometry and dissociates with excess Aßo. NMR studies of hydrogel PrPC reveal a distinct α-helical conformation for natively unfolded amino-terminal Gly and Ala residues. Aßo/PrP hydrogel traps signal-transducing mGluR5 on the plasma membrane. Recombinant PrPC extracts endogenous Aßo from human Alzheimer's soluble brain lysates into hydrogel, and a PrPC antagonist releases Aßo from endogenous brain hydrogel. Thus, coupled phase and conformational transitions of PrPC are driven by Aß species from Alzheimer's disease.

Comparing Intubation Rates in Patients Receiving Parenteral Olanzapine With and Without a Parenteral Benzodiazepine in the Emergency Department.

STUDY OBJECTIVE: United States prescribing information recommends against coadministration of injectable olanzapine with injectable benzodiazepines due to a risk of cardiorespiratory depression, whereas European prescribing information recommends the 2 drugs not be administered within 60 minutes of each other. In contrast, a recently published American College of Emergency Physicians clinical policy recommends injectable olanzapine and benzodiazepines be coadministered for treating severe agitation. We sought to compare injectable olanzapine with and without injectable benzodiazepines for evidence of cardiorespiratory depression. METHODS: We performed a retrospective study of patients in an urban emergency department from January 2017 through November 2019 who received parenteral olanzapine with or without parenteral benzodiazepines. We included patients receiving 2 total medication doses, either olanzapine+benzodiazepine or 2 doses of olanzapine, coadministered within 60 minutes. The primary outcome was tracheal intubation in the emergency department. Secondary outcomes included hypotension (systolic blood pressure less than 90 mmHg) and hypoxemia (SpO2 less than 90%). RESULTS: We identified 693 patients (median [alcohol]=210 mg/dL, median age=37 years [IQR 29 to 49]). In total, 549 received 2 doses of olanzapine, and 144 patients received olanzapine and a benzodiazepine. We found no difference in intubation rates between the olanzapine-only group (21/549, 3.8%) and the olanzapine+benzodiazepine group (5/144, 3.5%; difference=0.3%, 95% confidence interval -3.0% to 3.7%). Rates of hypoxemia (2% olanzapine-only and 3% olanzapine+benzodiazepine) and hypotension (9% both groups) also were not different between groups. CONCLUSION: We found no difference in cardiorespiratory depression between patients receiving only olanzapine versus olanzapine plus a benzodiazepine.

Parents' and Caregivers' Support for in-School COVID-19 Mitigation Strategies: A Socioecological Perspective.

Informed by the social ecological model, which asserts that health behaviors and beliefs are the result of multiple levels of influence, we examined factors related to parents' support for in-school COVID-19 mitigation strategies. Using data from a survey of 567 parents/caregivers of public elementary and middle school students in eight Maryland counties, we employed regression models to examine relationships between parent-, child-, family-, school-, and community-level factors and acceptability of mitigation strategies. Acceptance of COVID-19 mitigation strategies was positively correlated with child- and family-level factors, including child racial identity (parents of Black children were more accepting than those of White children, odds ratio [OR]: 2.5, 95% confidence interval [CI] = [1.5, 4.1]), parent receipt of the COVID-19 vaccine (OR: 2.4, 95% CI = [1.5, 3.7]), and parent Democrat or Independent political affiliation (compared with Republican affiliation, OR: 4.2, 95% CI = [2.6, 6.7]; OR: 2.2, 95%CI = [1.3, 3.8], respectively). Acceptance was also positively associated with parents' perceptions of their school's mitigation approach, including higher school mitigation score, indicating more intensive mitigation policies (OR: 1.1, 95% CI = [1.0, 1.1]), better school communication about COVID-19 (OR: 1.7, 95% CI = [1.4, 1.9]) and better school capacity to address COVID-19 (OR: 1.9, 95% CI = [1.5, 2.4]). Community-level factors were not associated with acceptance. Child- and parent-level factors identified suggest potential groups for messaging regarding mitigation strategies. School-level factors may play an important role in parents' acceptance of in-school mitigation strategies. Schools' capacity to address public health threats may offer an underappreciated and modifiable setting for disseminating and reinforcing public health guidance.

The Role of Primary Care in Advancing Civic Engagement and Health Equity: A Conceptual Framework.

Policy Points Health and civic engagement are reciprocally and longitudinally linked: Poor health is associated with less civic engagement. Well-established social drivers of health and health inequality such as inadequate access to health care, poverty, racism, housing instability, and food insecurity are also drivers of lower civic engagement. A robust primary care system can play a key role in advancing civic engagement (e.g., voting, volunteerism, community service, and political involvement) at the population level but has received little attention. Policy and practice solutions at the individual and structural levels should support and leverage potential synergies among health equity, civic engagement, and primary care. CONTEXT: Health and civic engagement are linked. Healthier people may be able to participate more fully in civic life, although those with poorer health may be motivated to address the roots of their health challenges using collective action. In turn, civically active people may experience better health, and societies with more equitable health and health care may experience healthier civic life. Importantly, a robust primary care system is linked to greater health equity. However, the role of primary care in advancing civic engagement has received little study. METHODS: We synthesize current literature on the links among health, civic engagement, and primary care. We propose a conceptual framework to advance research and policy on the role of primary care in supporting civic engagement as a means for individuals to actualize their health and civic futures. FINDINGS: Current literature supports relationships between health equity and civic engagement. However, this literature is primarily cross-sectional and confined to voting. Our integrative conceptual framework highlights the interconnectedness of primary care structures, health equity, and civic engagement and supports the crucial role of primary care in advancing both civic and health outcomes. Primary care is a potentially fruitful setting for cultivating community and individual health and power by supporting social connectedness, self-efficacy, and collective action. CONCLUSIONS: Health and civic engagement are mutually reinforcing. Commonalities between social determinants of health and civic engagement constitute an important convergence for policy, practice, and research. Responsibility for promoting both health and civic engagement is shared by providers, community organizations, educators, and policymakers, as well as democratic and health systems, yet these entities rarely work in concert. Future work can inform policy and practice to bolster primary care as a means for promoting health and civic engagement.

Peer recovery coaches and emergency department utilization in patients with substance use disorders.

BACKGROUND: Although Emergency Departments (ED) frequently provide care for patients with substance use disorders (SUD), there are many barriers to connecting them with appropriate long-term treatment. One approach to subside risk in this population is the Peer Recovery Coach (PRC). PRCs are individuals with a lived experience of the rehabilitation process and are a powerful resource to bridge this gap in care by engaging patients and their families and providing system navigation, self-empowerment for behavior change, and harm reduction strategies. The purpose of this project is to describe an ED-based PRC program, evaluating its feasibility and efficacy. METHODS: This was a retrospective quality improvement project conducted at 3 suburban hospitals. All patients arriving to the ED were screened with a brief questionnaire in triage and patients identified as a high-risk had referral placed to a PRC if the patient consented. The PRC met with the patient at the ED bedside if possible. The PRC program members collected prospective data on patient engagement with the PRC at 30, 60, and 90 days post ED encounter. Using the EMR we identified the number of subsequent ED visits at 30, 60, and 90 days (for both medical and substance use disorder-related visits) from the index PRC visit. RESULTS: There were 448 individuals identified and included in this analysis between January 1, 2019 and June 30, 2020, of which 292 (66%) were male and the mean age was 44 (range 18-80). Most patients identified alcohol as the primary substance they used (289, 65%), followed by heroin/opiates (20%). At 30, 60, and 90 days, there were 110 (25%), 79 (18%), and 71 (16%) patients who were still actively engaged in the program, respectively. Among all patients in the cohort, there was essentially no decrease in mean visits before versus after the PRC engagement visit. However, among patients who had at least one prior ED visit, there were significant differences in mean visits across all visit-types: for patients with 1 prior ED visit, 90 day mean decrease in visits = 1.0 visits (95% CI 0.7-1.2), for patients with 5+ prior ED visits, 90 day mean decrease in visits = 3.6 visits (95% CI 2.4-4.8). CONCLUSION: We describe the implementation of an ED-based PRC program for patients with substance use disorders. While we demonstrated that it is feasible for the PRC to engage the patient while in the ED, there was poor follow-up with the program outpatient. For patients with at least one previous SUD visit to the ED, there was a statistically significant reduction in ED utilization after engaging with a PRC while in the ED, suggesting this may be a population that could be targeted to link patients to long term care and decrease repeated ED utilization.

Comparison of efficacy and frequency of akathisia and dystonia between olanzapine, metoclopramide and prochlorperazine in ED headache patients.

STUDY OBJECTIVE: To compare the efficacy and frequency of akathisia and dystonia between the dopamine antagonist headache medications olanzapine, metoclopramide and prochlorperazine. METHODS: This was a retrospective observational cohort study of patients presenting to a large urban level one trauma center between 2010 and 2018. Inclusion criteria was age ≥ 18 who presented to the emergency department with a chief complaint of headache who received either olanzapine, metoclopramide or prochlorperazine. The primary outcome was need for rescue medication. Secondary outcomes were receiving medication for either akathisia or dystonia. Logistic regression was used to identify differences between the three cohorts up to 72 h from initial presentation. RESULTS: There were 5643 patients who met inclusion criteria. Olanzapine was the most commonly used drug (n = 2994, 53%) followed by prochlorperazine (n = 2100, 37%) and metoclopramide (n = 549, 10%). After adjusting for age and gender, there were no differences in risk for receiving rescue therapy or developing akathisia or dystonia. CONCLUSION: During initial ED visit and up to 72 h after receiving olanzapine, metoclopramide or prochlorperazine, we found no difference in risk for requiring rescue medication or developing akathisia or dystonia.

Financial stress as a mediator of the association between maternal childhood adversity and infant birth weight, gestational age, and NICU admission.

BACKGROUND: To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]). METHODS: Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy. RESULTS: There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 - -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 - -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02-0.08). CONCLUSIONS: Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress.

Using Epigenetic Clocks to Characterize Biological Aging in Studies of Children and Childhood Exposures: a Systematic Review.

Biological age, measured via epigenetic clocks, offers a unique and useful tool for prevention scientists to explore the short- and long-term implications of age deviations for health, development, and behavior. The use of epigenetic clocks in pediatric research is rapidly increasing, and there is a need to review the landscape of this work to understand the utility of these clocks for prevention scientists. We summarize the current state of the literature on the use of specific epigenetic clocks in childhood. Using systematic review methods, we identified studies published through February 2023 that used one of three epigenetic clocks as a measure of biological aging. These epigenetic clocks could either be used as a predictor of health outcomes or as a health outcome of interest. The database search identified 982 records, 908 of which were included in a title and abstract review. After full-text screening, 68 studies were eligible for inclusion. While findings were somewhat mixed, a majority of included studies found significant associations between the epigenetic clock used and the health outcome of interest or between an exposure and the epigenetic clock used. From these results, we propose the use of epigenetic clocks as a tool to understand how exposures impact biologic aging pathways and development in early life, as well as to monitor the effectiveness of preventive interventions that aim to reduce exposure and associated adverse health outcomes.

The Effect of Ketamine Versus Etomidate for Rapid Sequence Intubation on Maximum Sequential Organ Failure Assessment Score: A Randomized Clinical Trial.

BACKGROUND: The use of induction agents for rapid sequence intubation (RSI) has been associated with hypotension in critically ill patients. Choice of induction agent may be important and the most commonly used agents are etomidate and ketamine. OBJECTIVE: This study aimed to compare the effects of a single dose of ketamine vs. etomidate for RSI on maximum Sequential Organ Failure Assessment (SOFA) score and incidence of hypotension. METHODS: This single-center, randomized, parallel-group trial compared the use of ketamine and etomidate for RSI in critically ill adult patients in the emergency department. The study was performed under Exception from Informed Consent. The primary outcome was the maximum SOFA score within 3 days of hospitalization. RESULTS: A total of 143 patients were enrolled in the trial, 70 in the ketamine group and 73 in the etomidate group. Maximum median SOFA score for the ketamine group was 6.5 (interquartile range [IQR] 5-9) vs. 7 (IQR 5-9) for etomidate with no significant difference (-0.2; 95% CI -1.4 to 1.1; p = 0.79). The incidence of post-intubation hypotension was 28% in the ketamine group vs. 26% in the etomidate group (difference 2%; 95% CI -13% to 17%). There were no significant differences in intensive care unit outcomes. Thirty-day mortality rate for the ketamine group was 11% (8 deaths) and for the etomidate group was 21% (15 deaths), which was not statistically different. CONCLUSIONS: There were no significant differences in maximum SOFA score or post-intubation hypotension between critically ill adults receiving ketamine vs. etomidate for RSI.

Measuring Emergency Department Staff Perceptions of Causes and Management of Violence.

BACKGROUND: Half of all reported violent incidents in health care settings occur in the emergency department (ED) placing all staff members at risk. However, research typically does not include all ED work groups or validated measures beyond nurses and physicians. OBJECTIVE: The aims of this study were to (a) validate an established instrument measuring perceptions of causes of violence and attitudes toward managing violence within an inclusive workforce sample; and (b) explore variation in perceptions, attitudes, and incidence of violence and safety to inform a violence prevention program. METHODS: This is an investigator-initiated single-site cross-sectional survey design assessing the psychometric properties of the Management of Aggression and Violence Attitude Scale (MAVAS) within a convenience sample (n = 134). Construct validity was assessed using exploratory factor analysis and reliability was evaluated by the Cronbach's α estimation. Descriptive, correlational, and inferential estimates explored differences in perceptions, attitudes, and incidence of violence and safety. RESULTS: Exploratory factor analysis indicated validity of the MAVAS with a seven-factor model. Its internal consistency was satisfactory overall (Cronbach's α= 0.87) and across all subscales (Cronbach's α values = 0.52-0.80). Significant variation in incidence of physical assault, perceptions of safety, and causes of violence was found between work groups. CONCLUSIONS: The MAVAS is a valid and reliable tool to measure ED staff members' perceptions of causes of violence and attitudes toward managing violence. In addition, it can inform training according to differences in work group learner needs.

Posterior Globe Depth for Optic Nerve Sheath Diameter Measurement in Ocular Ultrasound in Healthy Volunteers.

BACKGROUND: Point-of-care ultrasound (POCUS) is a readily available imaging modality in many emergency departments and health care facilities globally. Optic nerve sheath diameter (ONSD) measurement via ocular ultrasound has been shown to accurately predict increased intracranial pressure. Classically, the preferred technique for sonographic measurement of ONSD has specified measurement at an optimal position of 3 mm posterior to the globe. This study aims to validate an alternative approach of depth measurement (between 3 and 8 mm), with the hypothesis that ONSD should not change in size as the distance posterior to the globe increases. METHODS: Healthy volunteers aged > 18 years were studied. A point 3 mm posterior to the optic disc was located. This was repeated at a point 5 mm as well as 8 mm posterior to the globe. RESULTS: We enrolled 10 healthy participants. When evaluating variability in ONSD measurements at each of the three distances, we found that the difference in the measurements at each distance was statistically significant. In investigating pairwise comparisons, there was no difference between 3 and 5 mm, but there were differences in ONSD measurements at 3 and 8 mm, as well as at 5 and 8 mm. CONCLUSION: POCUS is readily available in many emergency departments and health care facilities across the world. The classically preferred technique for sonographic measurement of ONSD has specified measurement at an optimal position of 3 mm posterior to the globe. Our results identified that ONSD can be measured between 3 and 5 mm with no significant changes.

Electrocardiogram Before Tricyclic Antidepressant Use: Minimal Impact in Pediatric Functional Gastrointestinal Disorders.

OBJECTIVES: The aim of this study was to determine the effect of electrocardiogram (ECG) findings on the initiation of tricyclic antidepressants (TCAs) for functional gastrointestinal disorders (FGIDs) and to evaluate cardiac outcomes related to low dose TCA use. METHODS: We performed a retrospective chart review of all pediatric outpatients at a tertiary pediatric hospital with an ECG ordered by a pediatric gastroenterologist when considering initiation of a TCA between January 2011 and February 2018. We collected demographics, previous cardiovascular testing results, TCA dosing, and pertinent outcomes, including cardiology referrals, emergency department, and hospital admissions, and death during the study period. All ECGs were reviewed for corrected QT (QTc) interval, heart rate, and other abnormalities. RESULTS: Of 233 patients with screening ECGs, most (84.1%) were prescribed a TCA. Functional abdominal pain or dyspepsia account for 82.0% of diagnoses. Initial TCA dosing of amitriptyline varied widely, 10-50 mg/day, and the dose was not associated with QTc intervals. TCAs were not started in only 1.7% (4/233) due to ECG results. A significant ECG abnormality prompting cardiology referral was found in eight (3.4%) with a prolonged QTc interval in one (0.4%). In 10.7% (25/233) of patients, screening ECG was obtained despite available ECG in the chart. No deaths and no emergency department or hospital visits for arrhythmia or drug overdose occurred. CONCLUSION: Screening ECGs infrequently influence TCA initiation and may lead to increased resource utilization. The overall frequency of cardiology referral due to ECG results is low. Serious adverse cardiac events are unlikely with low dose TCA administration.

Emergency cricothyrotomy in morbid obesity: comparing the bougie-guided and traditional techniques in a live animal model.

BACKGROUND: Cricothyrotomy is a rare, time sensitive procedure that is more challenging to perform when anatomical landmarks are not easily palpated before the initial incision. There is a paucity of literature describing the optimal technique for cricothyrotomy in patients with impalpable airway structures, such as in morbid obesity. In this study, we used a live sheep model of morbid obesity to compare the effectiveness of two common cricothyrotomy techniques. METHODS: We randomly assigned emergency medicine residents to perform one of two cricothyrotomy techniques on a live anesthetized sheep. To simulate the anterior soft tissue neck thickness of an adult with morbid obesity we injected 120 mL of a mixture of autologous blood and saline into the anterior neck of the sheep. The traditional technique (as described in the New England Journal Video titled "Cricothyroidotomy") used a Shiley tracheostomy tube and no bougie, and the bougie-guided technique used a bougie and a standard endotracheal tube. The primary outcome was the total procedure time; the secondary outcome was first attempt success. RESULTS: 23 residents were included, 11 assigned to the bougie-guided technique and 12 to the traditional technique. After injection of blood and saline, the median depth from skin to cricothyroid membrane was 3.0 cm (IQR 2.5-3.4 cm). The median time for the bougie technique was 118 s (IQR 77-200 s) compared to 183 s (IQR 134-270 s) for the traditional technique (median difference 62 s, 95% CI 10-144 s). Success on the first attempt occurred in 7/11 (64%) in the bougie group and 6/12 (50%) in the traditional technique group. CONCLUSION: In this study, which simulated morbid obesity on a living animal model complete with active hemorrhage and time pressure caused by extubation before the procedure, the bougie-guided technique was faster than the traditional technique using a tracheostomy tube without a bougie.

Validation of a decision rule to predict patients at low risk of variceal upper gastrointestinal hemorrhage.

BACKGROUND: Determining the likelihood of a variceal versus nonvariceal source of upper gastrointestinal bleeding (UGIB) guides ED therapy, but can be difficult to determine on clinical grounds. A simple decision rule, using only platelet and international normalized ratio (INR) values, was previously derived in a single center and had high sensitivity (97%). We sought to validate this decision rule using multi-center data. MATERIALS AND METHODS: We performed this decision rule validation using data collected from 21 Canadian hospitals, comprising 2020 patients. The parent study enrolled patients aged ≥18 years at participating hospitals with nonvariceal or variceal UGIB from January 2004 through May 2005. To validate the existing decision rule, we computed the test characteristics of the rule on this study population. The existing decision rule, in order to predict patients at low risk for variceal hemorrhage, is designed to be highly sensitive for variceal UGIB. In the previously derived rule, patients are not low risk if either is present: INR ≥1.3 or platelet count ≤200 × 109/L. We additionally added a third common-sense criterion to the decision rule in a separate analysis: whether the patient has previously had variceal hemorrhage. RESULTS: 2001 patients were eligible for analysis, including 214 (10.7%) with a variceal source of gastrointestinal hemorrhage. Median age was 69 (IQR 55-79), and 764 (38%) were women. The two-step rule correctly identified 204 of the 214 (95.3%) patients with variceal hemorrhage; adding prior variceal hemorrhage as a variable identified 5 more patients (209/214 [97.7%]). Of the 2001 patients, 953 (47%) would have been classified as low risk for variceal hemorrhage; of these patients, 5 (0.5%) experienced variceal hemorrhage. The sensitivity of the rule in this validation cohort was 95.3% (95% CI 91.6-97.7%), with a negative likelihood ratio of 0.09 (95% CI 0.05-0.16). Adding prior variceal hemorrhage increased sensitivity to 97.7% (95% CI 94.6-99.2%), with a negative likelihood ratio of 0.04 (95% CI 0.02-0.11). CONCLUSION: We have validated a simple decision rule to identify patients at low risk for variceal UGIB. This two-step (three-step if prior history of variceal hemorrhage is known) rule is simple to use, and may enable safe deferment of unnecessary or harmful therapies.

The feasibility of bedside transvaginal ultrasonography in non-pregnant women in the emergency department.

STUDY OBJECTIVE: We recorded data on the routine use of point-of-care transvaginal ultrasound (POC TVUS) for the evaluation of non-pregnant women with pelvic complaints in the Emergency Department (ED), and sought to determine how it altered the diagnostic impression and management. METHODS: This was a prospective observational study. Adult non-pregnant women with pelvic complaints undergoing POC TVUS were enrolled. Pre and post ultrasound, the treating physician completed a data collection form indicating the most likely cause of the patient's pain, current treatment plan, and expected ultrasound findings. Immediately after the ultrasound, the treating physician completed another form to indicate details about the sonographic process and findings, and whether a radiologyperformed TVUS was planned. RESULTS: Of 113 women enrolled, 79% had both ovaries visualized and the POC TVUS led to changes in plan in 43% of patients, including 3 emergent/urgent interventions; 48% of patients had unexpected findings. Of the 25% who had an additional radiology exam, there were no instances of discordant findings when both ovaries were assessed to be normal on ED Ultrasound. The ultrasound added <10 minutes in 92% of patients. With an ED ultrasound only (n = 85), the median length of stay (LOS) was 282 (IQR 197-323) minutes, compared to 437 (IQR 367-500) minutes when a radiology ultrasound was required (n = 28) (median difference,170 minutes [95% CI 122-212 min]). CONCLUSION: In this study, emergency physicians were able to efficiently obtain and interpret POC TVUS images that changed assessment of non-pregnant women with pelvic pain without significantly increasing the ED length of stay.

Medical needs of emergency department patients presenting with acute alcohol and drug intoxication.

STUDY OBJECTIVE: Some contend that patients with acute alcohol or illicit substance intoxication should be treated in outpatient detoxification centers rather than in the ED. However, these patients often have underlying acute medical needs. We sought to determine the frequency of medical interventions required by ED patients with alcohol or illicit substance intoxication. METHODS: This was a prospective observational study of consecutive ED patients presenting to an urban tertiary care ED with altered mental status due to alcohol or illicit substance use. We performed data collection for patients deemed to be low-risk for complications, as defined by receiving care in an intoxication observation unit. Trained staff observed and recorded all medical interventions, including medications administered, diagnostic testing, procedures performed, and airway interventions. The incidence of agitation was recorded using the Altered Mental Status Scale (AMSS, ordinal scale from -4 to +4, where +4 is most agitated). The data analysis is descriptive. RESULTS: This analysis included 2685 encounters (1645 unique patients; median age 39; 73% male) from January to May 2019. Average breath alcohol concentration was 0.20 g/dL (range 0.00-0.47). There were 89% encounters with alcohol intoxication, and in 17% encounters the patient was suspected or known to have drug intoxication (either alone or in conjunction with alcohol use). On arrival to the ED, 372 (14%) had agitation (AMSS +1 or higher) and 32 (1%) were profoundly agitated (AMSS +4). In total, 1526 (56%) received at least one intervention that could not be provided by a local detoxification or sobering facility. Of the study population, 955 (36%) received a sedating medication, 903 (34%) required physical restraints for patients or staff safety, 575 (21%) underwent imaging studies, 318 (12%) underwent laboratory testing, 367 (13%) received another intervention (IV access, EKG, splinting, wound care, etc). Additionally, 111 (4%) patients received an airway intervention (19 intubation, 23 nasal airway, 85 supplemental oxygen) and 275 (10%) required repositioning to protect the airway. There were 168 (6%) patients admitted to the hospital. CONCLUSION: In this population of relatively low-risk ED patients with drug and alcohol intoxication, a substantial proportion of patients received medical interventions.

Utility of plain abdominal radiography in adult ED patients with suspected constipation.

BACKGROUND: Abdominal radiographs are often obtained in ED patients with suspected constipation, although their utility in adults is not well understood. We sought to compare ED management when an abdominal radiograph is and is not obtained. METHODS: We performed a retrospective chart review study of adult ED patients with a chief complaint of constipation from 2010 through 2016. Trained abstractors recorded radiologic tests ordered, treatments received, and final diagnosis. We determined the physician interpretation of the abdominal radiograph and its use in clinical decision making. RESULTS: Of 1142 eligible patients, 481 (42%) patients underwent abdominal radiography. Stool burden rated moderate or large was observed in 271 patients (46%). Sixteen patients (3%) were diagnosed with small bowel obstruction; 15/16 of these patients had high risk features such as old age, complex surgical history, history of small bowel obstruction, abdominal malignancy, or presented with vomiting or inability to pass flatus. Of the 197 patients with no or mild stool burden or normal radiograph, 109 (55%) were diagnosed with constipation and 89 (45%) received constipation treatment in the ED. Conversely, of the 271 patients with moderate or greater stool burden, 114 (42%) received no treatment for constipation in the ED and 104 (38%) were prescribed no discharge medications for constipation; 77 of these 271 patients (28%) were diagnosed with something other than constipation. CONCLUSION: Plain abdominal radiography did not appear to significantly affect the ED management of patients presenting with constipation; it was common for patients to receive treatment that was in direct opposition to radiographic findings. Though a small number of patients had concerning diagnoses identified on plain radiography, the history and physical examination should have sufficiently excluded simple constipation, prompting an alternate diagnostic approach. Fecal loading on radiography does not preclude a more serious diagnosis. In conclusion, abdominal radiography appears to have low value in patients with constipation.

The Use, Safety, and Efficacy of Olanzapine in a Level I Pediatric Trauma Center Emergency Department Over a 10-Year Period.

OBJECTIVES: Olanzapine is a second-generation antipsychotic increasingly used in emergency medicine for many indications. Literature on its use in children is sparse. Our objectives were to describe the use, safety, and efficacy of olanzapine in pediatric emergency patients. METHODS: A structured chart review was performed of patients 18 years old or younger receiving olanzapine from 2007 to 2016 in the emergency department of a pediatric level I trauma center. RESULTS: A total of 285 children received olanzapine. Mean age was 16.4 years (range, 9-18 years); 121 were male (42.8%). Primary indications for olanzapine included agitation (n = 166, 58.3%), headache (n = 58, 20.4%), nausea/vomiting/abdominal pain (n = 37, 12.5%), unspecified pain (n = 20, 7%), and other (n = 4, 1.4%). Route of olanzapine administration was intramuscular (n = 160, 56%; median dose, 10 mg; range, 2.5-20), intravenous (n = 101, 36%; median dose, 5 mg; range, 1.25-5), and oral (n = 24, 8%; median dose, 10 mg; range, 5-10). For agitated patients, 28 (17%) received another sedative within 1 hour. For headache patients, 5 (8.6%) received another analgesic. For gastrointestinal complaints, 5 patients (13.5%) received another analgesic/antiemetic. Adverse respiratory events were hypoxia (pulse oximetry reading, in percentage, <92%; n = 7, 2.4%), supplemental oxygen placement (n = 9, 3.2%), and intubation (n = 2, 0.7%). No patient died or had a dysrhythmia. One patient experienced dystonia. CONCLUSIONS: Olanzapine seems safe when used for a variety of conditions in pediatric emergency patients. It may be effective for acute agitation, primary headache, and gastrointestinal complaints.

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration: ClinicalTrials.gov Identifier: NCT01990768.

A comparative study of conducted electrical weapon incapacitation during a goal-directed task.

Conducted electrical weapons (CEW) are ubiquitous in law enforcement given their unique ability to physically incapacitate violently resisting subjects. Early use of animal models to study CEW incapacitation effectiveness (e.g. porcine model with 4-limb strain gauges) proved to be poorly predictive of human incapacitation effectiveness. In a previously published human study, we developed a methodology for the prospective assessment of the incapacitation effectiveness of CEWs in highly motivated human subjects. Here we use this methodology in Part 1 to compare the incapacitation effectiveness of the newly released Axon® (formerly TASER® International) T(ASER) 7 to the TASER X26E, the "gold standard", and the TASER X2, a current model. The T7 has a new "adaptive cross-connect" technology that may improve incapacitation effectiveness in the scenario of small spreads between probe pairs, a common cause of weapon "failure" in the field. In Part 2, we use our methodology to test the functionality of the T7 cross-connect technology by comparing different bay and probe configurations. This is the first published study in the literature comparing different CEW models using this human model. For Part 1, 29 subjects completed the study and had data available for analysis. For Part 2, 21 subjects completed the study and had data available for analysis. The subjects were motivated to complete the task of reaching a suspended martial arts dummy 3.4 m (11 ft) away while being exposed "under power" to the CEW. In Part 1, subjects were assigned to 1 of 6 groups with probe spreads of 10, 20, and 30 cm (4, 8, 12 in). Subjects were exposed to a "control" CEW (either the X2 or X26E) and the T7 on alternating sides. Exposures with the X2 and T7 included 2 bay-exposures. In Part 2, 21 subjects were assigned to 1 of 5 groups of different T7 bay and probe configurations all with a theoretical effective spread of 30 cm (12 in). Subjects were rated on their progress towards successfully reaching the dummy and on the extent of limb incapacitation using a quasi-blinded expert-observer scoring panel based on high-speed video review. In Part 1, all CEW models achieved maximal or near-maximal subject control with the 30 cm probe spread. With probe spreads of 10 and 20 cm the pooled data showed the T7 to be superior to the X2 for goal achievement (p < 0.001) and limb incapacitation (p = 0.002) mostly driven by differences seen with the 10 cm spread (2-bay exposures). The T7 was non-inferior to the X26E. In Part 2, there was no statistical significance between the limb capture scores, but there was a statistically significant difference in goal scores. The results overall validate that the T7 CEW cross-connect feature performed as expected. The T7 adaptive cross-connect feature with two simultaneous deployed probe pairs demonstrated a significant improvement in incapacitation effectiveness compared to the current X2 CEW with two simultaneously deployed probe pairs. Small probe spreads are a common reason for limited incapacitation effectiveness in the field and this study suggests the T7 may offer an improvement in this scenario. The T7, with single-bay exposures, was non-inferior to the single-bay X26E.