GLP-1 Receptor Agonist Exposures Are Increasingly Common and Generally Associated with Mild Symptoms: A Single Poison Center Experience.

INTRODUCTION: Glucagon-like peptide-1 receptor agonist use has increased over the last decade for glycemic control in type 2 diabetes mellitus, cardiovascular risk reduction, and weight loss. Clinical trials indicate that gastrointestinal adverse effects are commonly experienced and severe hypoglycemia is rare; however, there is little data regarding glucagon-like peptide-1 receptor agonist in overdose. METHODS: We performed a retrospective chart review evaluating and characterizing glucagon-like peptide-1 receptor agonist exposures reported to a single poison center between 2006 and 2023. Patient demographics, circumstances of exposure, clinical effects, and outcomes were abstracted from charts. Descriptive statistics were utilized to summarize demographic information and clinical factor data. RESULTS: A total of 152 charts met inclusion criteria. Therapeutic errors accounted for 91% of exposures. Most patients (67%) reported no symptoms, although not all patients were followed to a definitive outcome. Nausea, vomiting, generalized weakness, and abdominal pain were the predominant symptoms reported. Most patients (62%) were monitored and closely followed in the home setting. Hypoglycemia was rare but occurred in the setting of a single agent glucagon-like peptide-1 receptor agonist exposure in two patients. Two additional patients who developed hypoglycemia involved co-administration of insulin. 21% of the exposures were related to errors on initial use of the pen. CONCLUSION: Exposures to glucagon-like peptide-1 receptor agonist have increased substantially over the years. Effects from an exposure tended to be mild and primarily involve gastrointestinal symptoms. Hypoglycemia was rare. Therapeutic and administration errors were common. Education on pen administration may help to reduce errors.

A decomposition of the effects of the COVID-19 pandemic on changes in the motor vehicle collision related mortality in Alabama.

BACKGROUND/OBJECTIVE: Motor vehicle collisions are the leading cause of unintentional injury death in Alabama and at various points during the COVID-19 pandemic there were documented increases in the following risk driving behaviors: speeding, driving under the influence, and seat belt citations. Thus, the objective was to characterize the overall motor vehicle collision (MVC)-related mortality rate in Alabama and the contribution of each component over the first two years of the pandemic compared to before the pandemic by three different road classes: urban arterials, rural arterials, and all other road classes. METHODS: MVC data were derived from the Alabama eCrash database, an electronic crash reporting system used by police officers across the state. Data on vehicle miles traveled each year were collected from the U.S. Department of Transportation's Federal Highway Administration estimates of traffic volume trends. MVC-related mortality in Alabama was the primary outcome and year of MVC was the exposure. The novel decomposition method broke down population mortality rate into four parts: deaths per MVC injury, injury per MVC, MVC per vehicle miles traveled (VMT), and VMT per population. Poisson models with scaled deviance were used to estimate rate ratios of each component. Relative contribution (RC) of each component was calculated by taking the absolute value of the component's beta coefficient and dividing by the sum of the absolute values of all components' beta coefficients. Models were stratified by road class. RESULTS: Across all road classes combined, there were no significant changes to the overall MVC-related mortality rate (per population) and its components when comparing 2020-2022 to 2017-2019; this was due to the increased case fatality rate (CFR) being offset by decreases in the VMT rate and MVC injury rate. In 2020, among rural arterials a non-significant increased mortality rate was offset by a decreased VMT rate (RR 0.91, 95% CI 0.84-0.98, RC 19.2%) and MVC injury rate (RR: 0.89, 95% CI: 0.82-0.97, RC: 22.2%) when compared to 2017-2019. For non-arterials, a non-significant decreased MVC mortality rate was observed in 2020 when compared to 2017-2019 (RR 0.86, 95% CI 0.71-1.03). When considering 2021-2022 versus 2020, the only significant component for any road class was a decreased MVC injury rate for non-arterials (RR: 0.90,95% CI: 0.89-0.93) but this was offset by an increased MVC rate and CFR, resulting in no significant change to the mortality rate (per population). CONCLUSIONS: In a state with one of the highest MVC-related mortality rates in the country, despite decreases in VMTs per population and injuries per MVC, the MVC mortality rate per population did not change during the pandemic due in part to the contributions of an increase in the case fatality rate. Future research should determine whether the increase in CFR was associated with risky driving behaviors during the pandemic.

The females have spoken: A patient-centered national survey on the administration of emergent transfusions with the potential for future fetal harm.

BACKGROUND: Traumatic hemorrhage is the leading cause of preventable death. Early in the resuscitation, only RhD-positive red blood cells are likely to be available, which poses a small risk of causing harm to a future fetus if transfused to an RhD-negative females of childbearing age (CBA), that is, 15 to 49 years old. We sought to characterize how the population, in particular females of CBA, felt about emergency blood administration vis-a-vis potential future fetal harm. METHODS: A national survey was performed using Facebook advertisements in three waves from January 2021 to January 2022. The advertisements directed users to the survey site with seven demographic questions and four questions on accepting transfusion with differing probabilities for future fetal harm (none/any/1:100/1:10,000). Acceptance of transfusion questions were scored on 3-point Likert scale (likely/neutral/unlikely). Only completed responses by females were analyzed. RESULTS: Advertisements were viewed 16,600,430 times by 2,169,805 people with 15,396 advertisement clicks and 2,873 surveys initiated. Most (2,256 of 2,873 [79%]) were fully completed. Majority (2,049 of 2,256 [90%]) of respondents were female. Eighty percent of females (1,645 of 2,049) were of CBA. Most females responded "likely" or "neutral" when asked whether they would accept a lifesaving transfusion if the following risk of fetal harm were present: no risk (99%), any risk (83%), 1:100 risk (85%), and 1:10,000 risk (92%). There were no differences between females of CBA versus non-CBA with respect to the likelihood of accepting lifesaving transfusion with any potential for future fetal harm ( p = 0.24). CONCLUSION: This national survey suggests that most females would accept lifesaving transfusion even with the potential low risk of future fetal harm. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Impact of Emergency Department-Initiated Buprenorphine on Repeat Emergency Department Utilization.

Introduction: Recent studies have demonstrated the promise of emergency department (ED)-initiated buprenorphine/naloxone (bup/nx) for improving 30-day retention in outpatient addiction care programs for patients with opioid use disorder (OUD). We investigated whether ED-initiated bup/nx for OUD also impacts repeat ED utilization. Methods: We performed a retrospective chart review of ED patients discharged with a primary diagnosis of OUD from July 2019-December 2020. Characteristics considered included age, gender, race, insurance status, domicile status, presence of comorbid Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis, presenting chief complaint, and provision of a bup/nx prescription and/or naloxone kit. Primary outcomes included repeat ED visit (opioid or non-opioid related) within 30 days, 90 days, and one year. Statistical analyses included bivariate comparison and Poisson regression. Results: Of 169 participants, the majority were male (67.5%), White (82.8%), uninsured (72.2%), and in opioid withdrawal and/or requesting "detox" (75.7%). Ninety-one (53.8%) received ED-initiated bup/nx, which was independent of age, gender, race, insurance status, presence of comorbid DSM-5 diagnosis, or domicile status. Naloxone was more likely to be provided to patients who received bup/nx (97.8% vs 26.9%; P < 0.001), and bup/nx was more likely to be given to patients who presented with opioid withdrawal and/or requested "detox" (63.3% vs 36.7%; P < 0.001). Bup/nx provision was associated with decreased ED utilization for opioid-related visits at 30 days (P = 0.04). Homelessness and lack of insurance were associated with increased ED utilization for non-opioid-related visits at 90 days (P = 0.008 and P = 0.005, respectively), and again at one year for homelessness (P < 0.001). When controlling for age and domicile status, the adjusted incidence rate ratio for overall ED visits was 0.56 (95% confidence interval [CI] 0.33-0.96) at 30 days, 0.43 (95% CI 0.27-0.69) at 90 days, and 0.60 (95% CI 0.39-0.92) at one year, favoring bup/nx provision. Conclusion: Initiation of bup/nx in the ED setting was associated with decreased subsequent ED utilization. Socioeconomic factors, specifically health insurance and domicile status, significantly impacted non-opioid-related ED reuse. These findings demonstrate the ED's potential as an initiation point for bup/nx and highlight the importance of considering the social risk and social need for OUD patients.

Hepatitis C active viremia over time in an ED-based testing programme: Impact, disparities and surveillance tool.

Hepatitis C virus (HCV) surveillance is a critical component of a comprehensive strategy to prevent and control HCV infection and HCV-related chronic liver disease. The emergency department (ED) has been increasingly recognized as a vital partner in HCV testing and linkage. We sought to consider active RNA HCV viremia over time in patients participating in an ED-based testing programme as a measure of local HCV surveillance and as a barometer of ED-testing programme impact. We performed a retrospective analysis of individuals participating in our ED-based HCV testing programme between 2015 and 2021. Chi-square tests were used to compare the demographic characteristics of HCV antibody positive tests with active viremia to those without active viremia. Cox proportional hazard models were used to estimate the trend in active viremia risk over time in the overall study population as well as in key subpopulations of interest. Of 5456 HCV antibody positive individuals, 3102 (56.8%) had active viremia. In the overall study population, we found that the risk of active viremia decreased by 4.8% per year during the study period (RR: 0.95, 95% CI: 0.93-0.97|p < .0001). Baby boomers experienced a 9% decrease in active viremia risk per year over the study period while non-baby boomers only had a 2% decrease in risk per year (p = .0009). Compared with insured patients, uninsured patients had a smaller decrease in risk of active HCV viremia per year (p = .003). No significant differences in the risk of active viremia over time were observed for gender (p = .4694) or by primary care provider status (p = .2208). In conclusion, this ED-based testing and linkage programme demonstrates significantly decreased active HCV viremia over time. It also highlights subpopulations, specifically non-baby boomers and uninsured patients, who may benefit from focused interventions to improve access to and adoption of definitive HCV care.

Over-transfusion with blood for suspected hemorrhagic shock is not associated with worse clinical outcomes.

BACKGROUND: We evaluated patient outcomes after early, small volume red blood cell (RBC) transfusion in the setting of presumed hemorrhagic shock. We hypothesized that transfusion with even small amounts of blood would be associated with more complications. STUDY DESIGN AND METHODS: Retrospective review of trauma patients admitted to a Level 1 trauma center between 2016-2021. Patients predicted to require massive transfusion who survived ≥72 h were categorized according to units of RBCs transfused in the first 24 h. A Cox regression model stratified by dichotomized ISS and adjusted for SBP <90 mm Hg and pulse >120 bpm on arrival was used to estimate hazard ratios (HRs) for outcomes of interest. RESULTS: A total of 3121 (24%) received RBC transfusion within the first 24 h. Massive transfusion protocol (MTP) was activated in 38% (1188/3121): 17% received no RBCs, 27.4% 1-3 units, 32.4% 4-9 units, and 22.7% ≥10 units. Mean ISS increased with each category of RBC transfusion. There was no difference in the risk of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), infection, cardiac arrest, venous thromboembolism or stroke for patients receiving 1-3 units compared to the non-transfused group or 4-9 units group (p > 0.05). Compared to those receiving ≥10 units, the 1-3 units group had a significantly lower risk of AKI, ARDS, and cardiac arrest. DISCUSSION: Early empiric RBC transfusion for presumed hemorrhagic shock may subject patients to potential over-transfusion and end-organ damage. Among patients meeting clinical triggers for MTP, 1-3 units of allogeneic RBCs is not associated with worse outcomes.

Balancing enrollment and mortality in hemorrhage control trials: A secondary analysis of the PROPPR trial.

BACKGROUND: Designing clinical trials on hemorrhage control requires carefully balancing the need for high enrollment numbers with the need of focusing on the sickest patients. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial enrolled patients within 2 hours of arrival to the emergency department for a trial of injured patients at risk for massive transfusion. We conducted a secondary analysis to determine how time-to-randomization affected patient outcomes and the balance between enrollment and mortality. METHODS: Patients from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were compared based on 30-minute time to randomization intervals. Outcomes included 24-hour and 30-day mortality, time to hemostasis, adverse events, and operative procedures. Additional analyses were conducted based on treatment arm allocation, mechanism of injury, and variation in start time (arrival vs. randomization). RESULTS: Randomization within 30 minutes of arrival was associated with higher injury severity (median Injury Severity Score, 29 vs. 26 overall; p < 0.01), lower systolic blood pressure (median, 91 vs. 102 mm Hg overall; p < 0.01), and increased penetrating mechanism (50% vs. 47% overall; p < 0.01). Faster time-to-randomization was associated with increased 24-hour (20% for 0- to 30 minute entry, 9% for 31-minute to 60-minute entry, 10% for 61-minute to 90-minute entry, 0% for 91-minute to 120-minute entry; p < 0.01) and 30-day mortality (p < 0.01). There were no significant associations between time-to-randomization and adverse event occurrence, operative interventions, or time to hemostasis. CONCLUSION: Increasing time to randomization in this large multicenter randomized trial was associated with increased survival. Fastest randomization (within 0-30 minutes) was associated with highest 24-hour and 30-day mortality, but only 57% of patients were enrolled within this timeframe. Only 3% of patients were enrolled within the last 30-minute window (91-120 minutes), with none of them dying within the first 24 hours. For a more optimal balance between enrollment and mortality, investigators should consider shortening the time to randomization when planning future clinical trials of hemorrhage control interventions. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level II.

Patient-level interventions to reduce alcohol-related harms in low- and middle-income countries: A systematic review and meta-summary.

BACKGROUND: Disease and disability from alcohol use disproportionately impact people in low- and middle-income countries (LMICs). While varied interventions have been shown to reduce alcohol use in high-income countries, their efficacy in LMICs has not been assessed. This systematic review describes current published literature on patient-level alcohol interventions in LMICs and specifically describes clinical trials evaluating interventions to reduce alcohol use in LMICs. METHODS AND FINDINGS: In accordance with PRISMA, we performed a systematic review using an electronic search strategy from January 1, 1995 to December 1, 2020. Title, abstract, as well as full-text screening and extraction were performed in duplicate. A meta-summary was performed on randomized controlled trials (RCTs) that evaluated alcohol-related outcomes. We searched the following electronic databases: PubMed, EMBASE, Scopus, Web of Science, Cochrane, WHO Global Health Library, and PsycINFO. Articles that evaluated patient-level interventions targeting alcohol use and alcohol-related harm in LMICs were eligible for inclusion. No studies were excluded based on language. After screening 5,036 articles, 117 articles fit our inclusion criteria, 75 of which were RCTs. Of these RCTs, 93% were performed in 13 middle-income countries, while 7% were from 2 low-income countries. These RCTs evaluated brief interventions (24, defined as any intervention ranging from advice to counseling, lasting less than 1 hour per session up to 4 sessions), psychotherapy or counseling (15, defined as an interaction with a counselor longer than a brief intervention or that included a psychotherapeutic component), health promotion and education (20, defined as an intervention encouraged individuals' agency of taking care of their health), or biologic treatments (19, defined as interventions where the biological function of alcohol use disorder (AUD) as the main nexus of intervention) with 3 mixing categories of intervention types. Due to high heterogeneity of intervention types, outcome measures, and follow-up times, we did not conduct meta-analysis to compare and contrast studies, but created a meta-summary of all 75 RCT studies. The most commonly evaluated intervention with the most consistent positive effect was a brief intervention; similarly, motivational interviewing (MI) techniques were most commonly utilized among the diverse array of interventions evaluated. CONCLUSIONS: Our review demonstrated numerous patient-level interventions that have the potential to be effective in LMICs, but further research to standardize interventions, populations, and outcome measures is necessary to accurately assess their effectiveness. Brief interventions and MI techniques were the most commonly evaluated and had the most consistent positive effect on alcohol-related outcomes. TRIAL REGISTRATION: Protocol Registry: PROSPERO CRD42017055549.

Perception of risk in massive transfusion as it relates to fetal outcomes: A survey of surgeons and nurses at one American trauma center.

BACKGROUND: The use of blood products early in the resuscitation of bleeding trauma patients is widely accepted, but made difficult by limited supplies of D- red blood cell (RBC)-containing products. Use of D+ RBC-containing products would alleviate this issue, but could lead to alloimmunization. Risk associated with transfusing D+ RBC in emergency bleeding situations is being reconsidered. The level of concern surrounding emergency transfusion as it relates to future fetal harm was surveyed among surgeons and nurses. METHODS: Faculty and staff in the Departments of Surgery and Nursing were surveyed on the risks of receiving an emergency RBC transfusion and the subsequent potential for fetal harm. Answers were grouped as likely to accept (likely/very likely) or refuse transfusion (unlikely/very unlikely). Participants were compared by sex, and women by child-bearing age, ([15-50 years] vs. [>50 years]). RESULTS: Ninety surveys were initiated with 76 fully completed. Male (n = 39) and female (n = 37) respondents were comparable. Most female respondents (30/37, 81%) were of childbearing age. Overall, both males (38/39, 95%) and females (33/37, 89%; p = .19) were likely to accept a transfusion in an emergency. There was no difference in transfusion acceptance if the risk of fetal harm was presented as 1% (p = .73) or 0.1% (p = .51). Most females (34/37, 92%) were not opposed to transfusion even if there was an unspecified risk of future fetal harm. CONCLUSION: Most of the surgeons and nurses who responded would accept a transfusion in an emergency situation even if it might lead to harming a future fetus.

Access to care solutions in healthcare for obstetric care in Africa: A systematic review.

BACKGROUND: Emergency Medical Services (EMS) systems exist to reduce death and disability from life-threatening medical emergencies. Less than 9% of the African population is serviced by an emergency medical services transportation system, and nearly two-thirds of African countries do not have any known EMS system in place. One of the leading reasons for EMS utilization in Africa is for obstetric emergencies. The purpose of this systematic review is to provide a qualitative description and summation of previously described interventions to improve access to care for patients with maternal obstetric emergencies in Africa with the intent of identifying interventions that can innovatively be translated to a broader emergency context. METHODS: The protocol was registered in the PROSPERO database (International Prospective Register of Systematic Reviews) under the number CRD42018105371. We searched the following electronic databases for all abstracts up to 10/19/2020 in accordance to PRISMA guidelines: PubMed/MEDLINE, Embase, CINAHL, Scopus and African Index Medicus. Articles were included if they were focused on a specific mode of transportation or an access-to-care solution for hospital or outpatient clinic care in Africa for maternal or traumatic emergency conditions. Exclusion criteria included in-hospital solutions intended to address a lack of access. Reference and citation analyses were performed, and a data quality assessment was conducted. Data analysis was performed using a qualitative metasynthesis approach. FINDINGS: A total of 6,457 references were imported for screening and 1,757 duplicates were removed. Of the 4,700 studies that were screened against title and abstract, 4,485 studies were excluded. Finally, 215 studies were assessed for full-text eligibility and 152 studies were excluded. A final count of 63 studies were included in the systematic review. In the 63 studies that were included, there was representation from 20 countries in Africa. The three most common interventions included specific transportation solutions (n = 39), community engagement (n = 28) and education or training initiatives (n = 27). Over half of the studies included more than one category of intervention. INTERPRETATION: Emergency care systems across Africa are understudied and interventions to improve access to care for obstetric emergencies provides important insight into existing solutions for other types of emergency conditions. Physical access to means of transportation, efforts to increase layperson knowledge and recognition of emergent conditions, and community engagement hold the most promise for future efforts at improving emergency access to care.

Predictors of ambulance transport to first health facility among injured patients in southern Sri Lanka.

BACKGROUND: Injuries account for about 13% of all registered deaths in Sri Lanka and are the leading cause of admission to public hospitals. Prehospital trauma care is new to Sri Lanka, and in 2016, a free ambulance service was launched in the Western and Southern provinces. OBJECTIVE: The aim of this study was to identify the proportion of admitted injury patients at a tertiary hospital who used an ambulance to get to the first health facility and examine patient demographics, injury event, and injury type as predictors of ambulance transport. METHODS: A cross-sectional survey was administered to 405 patients who were admitted to the emergency trauma center at Teaching Hospital Karapitiya (THK) in Galle, Sri Lanka. Descriptive statistics were tabulated to summarize prehospital transportation variables. Logistic regression models were created to examine predictors of ambulance transport, and ArcGIS Pro was used to calculate the distance between injury location and first facility and THK. RESULTS: The proportion of patients with injuries who used an ambulance to get to the first health facility was 20.5%. Factors that were significantly associated with ambulance use were older age, injury mechanism, alcohol use prior to injury, location type, open wound, abrasion, and chest/abdomen injury. Distance from injury location to THK or nearest health facility were not significantly associated with ambulance transport to the first health facility. CONCLUSION: Among lower acuity injury patients in southern Sri Lanka, 20.5% traveled in an ambulance to the first health facility, while over half used a tuk tuk. Older age and injuries at home were associated with lower odds of ambulance transport. Future studies on predictors of ambulance transport should include patients with more severe injuries, gather detailed data on care provided while in transport and examine the association between prehospital care and clinical outcomes.

Temporal Dysregulation of the Angiopoietin-2/-1 Ratio After Trauma and Associations With Injury Characteristics and Outcomes.

Traumatic injury and hemorrhagic shock result in endothelial cell activation and vascular dysfunction that, if not corrected, can propagate multiorgan failure. Angiopoietin-1 and angiopoietin-2 are important regulators of endothelial cell function, and the ratio of plasma angiopoietin-2-to-1 is a useful indicator of overall vascular health. We therefore characterized plasma angiopoietin-2/-1 ratios over time after trauma in adults in an effort to gain insight into the pathophysiology that may drive post-traumatic vasculopathy and organ injury. We performed a single-center prospective observational study to measure plasma angiopoietin-1 and -2 levels and determine angiopoietin-2/-1 ratios in adult trauma patients upon hospital arrival and after 12, 24, and 48 h. Compared with levels in healthy adults, angiopoietin-1 levels were significantly elevated at hospital arrival, and angiopoietin-2 levels were significantly elevated at 12, 24, and 48 h. These kinetics translated in angiopoietin-2/-1 ratios that were significantly greater than controls at 24 and 48 h. After regression analysis, elevated angiopoietin-2 levels were independently associated with blunt injuries at admission, with coagulopathy at admission and 12 h, and with hemorrhagic shock at 24 and 48 h. Significant correlations were observed between both angiopoietins and 24-h transfusion requirements. Angiopoietin-2/-1 ratios correlated with mechanical ventilation duration and intensive care unit and hospital lengths of stay. In this study, we demonstrate novel temporal associations between angiopoietin dysregulation and blunt injuries, acute coagulopathy, and hemorrhagic shock. Moreover, our findings highlight the presence of endothelial activation following traumatic insults in adults that may contribute to worse clinical outcomes.

The global pool of simulation exercise materials in health emergency preparedness and response: a scoping review with a health system perspective.

Simulation Exercises (SimEx) are an established tool in defence and allied security sectors, applied extensively in health security initiatives under national or international legislative requirements, particularly the International Health Regulations (2005). There is, however, a paucity of information on SimEx application to test the functionality of health systems alongside emergency preparedness, response and recovery. Given the important implications health services resilience has for the protection and improvement of human life, this scoping review was undertaken to determine how the publicly available body of existing global SimEx materials considers health systems, together with health security functions in the event of disruptive emergencies. The global review identified 668 articles from literature and 73 products from institutional sources. Relevant screening identified 51 materials suitable to examine from a health system lens using the six health system building blocks as per the WHO Health System Framework. Eight materials were identified for further examination of their ability to test health system functionality from a resilience perspective. SimEx are an effective approach used extensively within health security and emergency response sectors but is not yet adequately used to test health system resilience. Currently available SimEx materials lack an integrated health system perspective and have a limited focus on the quality of services delivered within the context of response to a public health emergency. The materials do not focus on the ability of systems to effectively maintain core services during response. Without adjustment of the scope and focus, currently available SimEx materials do not have the capacity to test health systems to support the development of resilient health systems. Dedicated SimEx materials are urgently needed to fill this gap and harness their potential as an operational tool to contribute to improvements in health systems. They can act as effective global goods to allow testing of different functional aspects of health systems and service delivery alongside emergency preparedness and response. The work was conducted within the scope of the Tackling Deadly Diseases in Africa Programme, funded by the UK Department for International Development, which seeks to strengthen collaboration between the health system and health security clusters to promote health security and build resilient health systems.