Antiviral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models.

SARS-CoV-2 variants of concern (VOCs) continue to evolve and reemerge with chronic inflammatory long COVID sequelae, necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the receptor for advanced glycation end products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of RAGE in COVID-19 has not been reported. In the present study, we investigated whether and how the RAGE-Ig fusion protein would have an antiviral and anti-inflammatory therapeutic effect in the COVID-19 system. The protective therapeutic effect of RAGE-Ig was determined in vivo in K18-hACE2 transgenic mice and Syrian golden hamsters infected with six VOCs of SARS-CoV-2. The underlying antiviral mechanism of RAGE-Ig was determined in vitro in SARS-CoV-2-infected human lung epithelial cells (BEAS-2B). Following treatment of K18-hACE2 mice and hamsters infected with various SARS-CoV-2 VOCs with RAGE-Ig, we demonstrated (1) significant dose-dependent protection (i.e., greater survival, less weight loss, lower virus replication in the lungs); (2) a reduction of inflammatory macrophages (F4/80+/Ly6C+) and neutrophils (CD11b+/Ly6G+) infiltrating the infected lungs; (3) a RAGE-Ig dose-dependent increase in the expression of type I IFNs (IFN-α and IFN-ß) and type III IFN (IFNλ2) and a decrease in the inflammatory cytokines (IL-6 and IL-8) in SARS-CoV-2-infected human lung epithelial cells; and (4) a dose-dependent decrease in the expression of CD64 (FcgR1) on monocytes and lung epithelial cells from symptomatic COVID-19 patients. Our preclinical findings revealed type I and III IFN-mediated antiviral and anti-inflammatory therapeutic effects of RAGE-Ig protein against COVID-19 caused by multiple SARS-CoV-2 VOCs.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

Time Savings and Safety of EMS Administration of Antibiotics for Open Fractures.

INTRODUCTION: Early administration of antibiotics for open fractures reduces serious bone and soft tissue infections. The effectiveness of antibiotics in reducing these infections is time-dependent, with various surgical associations recommending administration within one hour of injury, or within one hour of patient arrival to the emergency department (ED). The extent to which prehospital antibiotic administration in these situations might reduce the time to treatment has not been previously reported. The purpose of this study was to describe current prehospital use of antibiotics for traumatic injury, to assess the safety of prehospital antibiotic administration, and to estimate the potential time-savings associated with antibiotic administration by EMS clinicians. METHODS: This was a retrospective analysis of the 2019 through 2022 ESO Data Collaborative research data set. Included subjects were patients that had a linked ICD-10 code indicating an open extremity fracture and who received prehospital antibiotics. Time to antibiotic administration was calculated as the elapsed time from EMS dispatch until antibiotic administration. The minimum potential time saved by EMS antibiotic administration was calculated as the elapsed time from administration until ED arrival. To assess safety, epinephrine and diphenhydramine administration were used as proxies for the adverse events of anaphylaxis and minor allergic reactions. RESULTS: There were 523 patients meeting the inclusion criteria. The median (and interquartile range [IQR]) elapsed time from EMS dispatch until antibiotic administration was 31 (IQR: 24-41) minutes. The median potential time savings associated with prehospital antibiotic administration was 15 (IQR: 8-22) minutes. Notably, 144 (27.5%) of the patients who received prehospital antibiotics had total prehospital times exceeding one hour. None of the patients who received antibiotics also received epinephrine for presumed anaphylaxis. CONCLUSIONS: EMS clinicians were able to safely administer antibiotics to patients with open fractures a median of 15 min before arrival at the hospital, and 99% of the patients receiving antibiotics had them administered within one hour of EMS dispatch. EMS administration of antibiotics may be a safe way to increase compliance with recommendations for early antibiotic administration for open fractures.

Utilizing Nurse Practitioners and Physician Assistants in Academic Emergency Departments Does Not Reduce Residents' Exposure to More Complex Patients.

BACKGROUND: Whether integration of nurse practitioners (NPs) and physician assistants (PAs) into academic emergency departments (EDs) affects emergency medicine (EM) resident clinical learning opportunities is unclear. OBJECTIVE: We sought to compare EM resident exposure to more-complex patients, as well as patients undergoing Accreditation Council for Graduate Medical Education (ACGME)-required procedures, at nonpediatric academic EDs with lower, moderate, and higher levels of NP/PA utilization. METHODS: In this cross-sectional study of National Hospital Ambulatory Medical Care Survey (NHAMCS) data for 2016-2020, nonpediatric academic EDs were classified into the following three groups based on the percentage of patients seen by an NP or PA: lower (≤ 10%), moderate (10.1-30%), and higher (> 30%) NP/PA utilization. The proportion of EM resident-seen patients meeting previously established complex patient criteria was then determined for EDs at each level of NP/PA utilization. The proportion of EM resident-seen patients receiving certain ACGME-required procedures was also determined. Survey analytic procedures and weighting as recommended by NHAMCS were used to calculate and compare proportions using 95% CIs. RESULTS: The weighted 2016-2020 NHAMCS data sets represent 44,130,996 adult resident-seen patients presenting to nonpediatric academic EDs. The proportion of resident-seen patients meeting complex patient criteria did not significantly differ for lower (43.2%; 95% CI 30.6-56.8%), moderate (41.7%; 95% CI 33.0-50.9%), or higher (38.9%; 95% CI 29.3-49.4%) NP/PA utilization EDs. The proportion of patients undergoing an ACGME-required procedure also did not significantly differ across level of NP/PA utilization. CONCLUSIONS: Higher levels of NP/PA utilization in nonpediatric academic EDs do not appear to reduce EM resident exposure to more-complex patients or ACGME-required procedures.

Predisposing, Enabling, and Need Factors Influencing Health-related Quality of Life Among People with Metabolic Syndrome.

INTRODUCTION: Metabolic syndrome (MetS) continues to impact the health-related quality of life (HRQoL) of patients despite various available therapeutic interventions. There is a dearth of information on how patient-centered factors holistically predict HRQoL to provide more insights on addressing MetS. OBJECTIVES: To predict the HRQoL of patients with MetS in the Southern states, using the predisposing, enabling, and need factors. METHOD: The study adopted a cross-sectional approach in collecting 706 complete surveys on HRQoL assessment using the EQ-5D-5L survey and demographic characteristics based on the predisposing, enabling, and need factors of Andersen's Behavioral model. The study focused on people with MetS in the southern states of the United States. Multinomial logistic regression was conducted to investigate the relationship between the number of comorbidities and each HRQoL dimension. Ordinal regression was used to explore factors predicting HRQoL. Sensitivity analysis was conducted using bootstrapping analysis to evaluate the regression's robustness. RESULTS: Over 70% were female and 30% had at least a bachelor's degree, while 47% were married. Most respondents (71.1%) had no problem with self-care. However, 20.0% had severe problems with pain, while the highest proportion (8.6%) was observed for extreme problems with anxiety or depression. A unit increase in comorbidities resulted in higher odds of having extreme problems with mobility (OR = 1.95), usual activities (OR = 1.73), and pain (OR = 1.70). Only 40.8% of the respondents had good HRQoL, compared to 26.2% with poor HRQoL. Age, race, geographical area, marital status, household income, number of prescription drugs, comorbidities, and body mass index were predictors of HRQoL. CONCLUSION: An increase in comorbidities significantly increased the odds of having challenges with the HRQoL dimensions. Demographic, socioeconomic, and health-related factors significantly predicted HRQoL. Therefore, healthcare providers must consider these factors as a component of patient-centered care to address health disparities and promote optimal health outcomes among people with MetS.

Integrated Hepatitis C-Opioid Use Disorder Care Through Facilitated Telemedicine: A Randomized Trial.

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, Setting, and Participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main Outcomes and Measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and Relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial Registration: ClinicalTrials.gov Identifier: NCT02933970.

Analysis of the Gene Therapies Authorized by the United States Food and Drug Administration and the European Medicines Agency.

BACKGROUND: Gene therapy, altering the genes inside human cells, has recently emerged as an alternative for preventing and treating disease. Concerns have been expressed about the clinical value and the high cost of gene therapies. OBJECTIVE: This study assessed the characteristics of the clinical trials, authorizations, and prices of gene therapies in the United States and the European Union. RESEARCH DESIGN: We collected regulatory information from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and manufacturer-listed prices from the United States, UK, and Germany. Descriptive statistics and t tests were conducted in the study. RESULTS: As of January 1, 2022, the FDA and EMA authorized 8 and 10 gene therapies, respectively. The FDA and EMA granted orphan designation to all gene therapies except talimogene laherparepvec. Pivotal clinical trials were nonrandomized, open level, uncontrolled, phase I-III, and included a limited number of patients. Study primary outcomes were mainly surrogate endpoints without demonstration of direct patient benefit. The price of gene therapies at market entry ranged from $200,064 to $2,125,000 million. CONCLUSIONS: Gene therapy is used to treat incurable diseases that affect only a small number of patients (orphan diseases). Based on this, they are approved by the EMA and FDA with insufficient clinical evidence to ensure safety and efficacy, in addition to the high cost.

Politics and the Public Health Workforce: Lessons Suggested from a Five-State Study.

Policy Points The United States public health system relies on an inadequate and inefficient mix of federal, state, and local funding. Various state-based initiatives suggest that a promising path to bipartisan support for increased public health funding is to gain the support of local elected officials by providing state (and federal) funding directly to local health departments, albeit with performance strings attached. Even with more funding, we will not solve the nation's public health workforce crisis until we make public health a more attractive career path with fewer bureaucratic barriers to entry. CONTEXT: The COVID-19 pandemic exposed the shortcomings of the United States public health system. High on the list is a public health workforce that is understaffed, underpaid, and undervalued. To rebuild that workforce, the American Rescue Plan (ARP) appropriated $7.66 billion to help create 100,000 new public health jobs. As part of this initiative, the Centers for Disease Control and Prevention (CDC) distributed roughly $2 billion to state, local, tribal, and territorial health agencies for use between July 1, 2021, and June 30, 2023. At the same time, several states have enacted (or are considering enacting) initiatives to increase state funding for their local health departments with the goal of ensuring that these departments can deliver a core set of services to all residents. The differences in approach between this first round of ARP funding and theseparate state initiatives offer an opportunity to compare, contrast, and suggest lessons learned. METHODS: After interviewing leaders at the CDC and other experts on the nation's public health workforce, we visited five states (Kentucky, Indiana, Mississippi, New York, and Washington) to examine, by means of interviews and documents, the implementation and impact of both the ARP workforce funds as well as the state-based initiatives. FINDINGS: Three themes emerged. First, states are not spending the CDC workforce funding in a timely fashion; although the specifics vary, there are several organizational, political, and bureaucratic obstacles. Second, the state-based initiatives follow different political paths but rely on the same overarching strategy: gain the support of local elected officials by providing funding directly to local health departments, albeit with performance strings attached. These state initiatives offer their federal counterparts a political roadmap toward a more robust model of public health funding. Third, even with increased funding, we will not meet the nation's public health workforce challenges until we make public health a more attractive career path (with higher pay, improved working conditions, and more training and promotion opportunities) with fewer bureaucratic barriers to entry (most importantly, with less reliance on outdated civil service rules). CONCLUSION: The politics of public health requires a closer look at the role played by county commissioners, mayors, and other local elected officials. We need a political strategy to persuade these officials that their constituents will benefit from a better public health system.

If at First You Do Not Succeed: Consideration of Attempts in Patients With Trauma.

INTRODUCTION: Failed extubation in critically ill patients is associated with poor outcomes. In critically ill trauma patients who have failed extubation, providers must decide whether to proceed with tracheostomy or attempt extubation again. The aim of this study was to describe the natural history of failed extubation in trauma patients and determine whether tracheostomy or a second attempt at extubation is more appropriate. METHODS: Trauma patients admitted to our level I trauma center from 2013 to 2019 were identified. Patients who failed extubation, defined as an unplanned reintubation within 48 h of extubation, were included. Patients who immediately underwent tracheostomy were compared with those who had subsequent attempts at extubation. The primary outcome was mortality, and the secondary outcomes were intensive care unit (ICU) length of stay (LOS), ventilator days, and hospital LOS. RESULTS: The population included 93 patients who failed extubation and met inclusion criteria. A total of 53 patients were ultimately successfully extubated, whereas 40 patients underwent a tracheostomy. There was no statistically significant difference in demographics or injury patterns. Patients who underwent tracheostomy had a longer ICU LOS and more ventilator days. There was no difference in mortality or hospital LOS between the two groups. CONCLUSIONS: In trauma patients, those who underwent subsequent attempts at extubation did not experience higher rates of mortality than those who received a tracheostomy. Tracheostomy was associated with longer ICU LOS and ventilator days. In certain situations, it is appropriate to consider subsequent attempts at extubation in trauma patients who fail extubation rather than proceeding directly to tracheostomy.

Prehospital Intervention Improves Outcomes for Patients Presenting in Atrial Fibrillation with Rapid Ventricular Response.

OBJECTIVE: To compare outcomes of patients presenting to emergency medical services (EMS) with atrial fibrillation with rapid ventricular response (AF-RVR) who did and did not receive prehospital advanced life support (ALS) rate or rhythm control intervention(s). METHODS: This retrospective cohort study used the 2021 ESO Data Collaborative (Austin, TX) dataset. We identified 9-1-1 scene responses for patients aged 16 to 100 years old presenting with AF and an initial heart rate ≥ 110 beats per minute (bpm). Prehospital ALS interventions for AF-RVR included medications (e.g., calcium channel blockers, beta blockers, etc.) or electrical cardioversion. Outcome measures included prehospital rate control (i.e., final prehospital heart rate < 110 bpm), emergency department (ED) discharge to home, ED and hospital length of stay, and mortality. We also evaluated prehospital adverse events-specifically bradycardia, hypotension, and cardiac arrest. We used propensity score matching to compare outcomes among treated and untreated patients with similar demographic and clinical characteristics. We determined the average treatment effect on the treated (ATET) with 95% confidence intervals (CI) and the number needed to treat (NNT). RESULTS: After propensity score matching, prehospital outcomes were available for 4,859 treated patients matched with 4,859 similar untreated patients. Prehospital rate control was more frequent for treated than for untreated patients (41.0% vs. 18.2%, ATET +22.8%, CI: +21.1%; +24.6%, NNT = 5). Hospital outcomes were available for 1,347 treated patients matched with 1,347 similar untreated patients. Treated patients were more likely to be discharged from the ED (37.9% vs. 34.0%, ATET +3.9%, CI: +0.2%; +7.5%, NNT = 26) and less likely to die (4.3% vs. 6.7%, ATET -2.5%, CI: -4.2%; -0.8%, NNT = 40) compared to untreated patients. Hypotension occurred more often in treated patients (ATET +2.6%, CI: +1.5%; +3.7%), but resolved before ED arrival in 73% of affected patients. Otherwise, adverse event rates did not significantly differ for the two groups. CONCLUSIONS: In this propensity score matched study of patients presenting to EMS with AF-RVR, prehospital ALS interventions were associated with more frequent prehospital rate control, more frequent discharge to home from the ED, and lower mortality.

Influence of patient-pharmacist relationship on willingness to accept pharmacist-provided services.

BACKGROUND: Willingness to accept various pharmacist-provided services such as health promotion and medication management is still considered low. Evidence suggests that patient experience and socio-demographics partially explain patient willingness to use pharmacy services. However, the influence of a patient's relationship with their pharmacist may provide additional explanatory power. OBJECTIVES: The aims of the study were to [1] explore the willingness to accept pharmacy services across patients' relationship with pharmacists and [2] evaluate the association between the patient-pharmacist relationship and patients' willingness to accept pharmacist-provided services. METHODS: A total of 1521 respondents' data on the types of patient-pharmacist relationships and willingness to accept dispensing, drug information, medication management, and health promotional services were collected from the 2021 National Consumer Survey on Medication Experience and Pharmacists' Role. Willingness scores across the groups were evaluated using chi-square and analysis of variance. Binary logistic regression was used to investigate the associations between patient-pharmacist relationships and willingness to accept pharmacist-provided services. RESULTS: More respondents were "definitely willing" to accept dispensing services (68.5%) and drug information (68.3%), while 56.5% and 50.1% were "definitely willing" to accept health promotion and medication management services, respectively. While respondents with "customer" and "client" archetype relationships were definitely willing to accept the 4 categories of pharmacy services, the highest proportion of respondents definitely willing to accept the services was observed among those with "partner" archetype relationships. Willingness scores increased significantly across the archetype relationships. Respondents with a "partner" archetype relationship had the highest and most significant odds ratio of accepting all the categories of pharmacist-provided services. CONCLUSION: Willingness to accept services from pharmacists increased as the level of the patient-pharmacist relationship grew. Patients in "partner" archetype relationship were significantly more likely to accept all categories of pharmacist-provided services. Pharmacists are encouraged to embrace the patient-pharmacist relationship continuum to optimize patient care.

Investigation of predictors influencing patient-pharmacist relationship establishment.

BACKGROUND: A strong patient-pharmacist relationship is tied to patients' trust and confidence in pharmacists and pharmacy services. While past research has described patient-pharmacist relationship archetypes (i.e., "customer," "client," "partner") with potential to help pharmacists initially understand patients' preferences and expectations of care and services, little is known about potential factors that underlie these preferences and expectations. OBJECTIVES: This study was aimed to [1] compare the prevalence of the current and desired patient-pharmacist relationships archetypes reported by patients and [2] identify the sociodemographic, health, and medication use and procurement factors predictive of the archetypes representing patients' current relationship with outpatient pharmacists. METHODS: Data from 1521 patients were collected via the 2021 National Consumer Survey on Medication Experience and Pharmacists' Role. Patient-pharmacist relationship distribution across patients' sociodemographic characteristics was explored using crosstabulations. Multinomial logistic regression was also used to investigate the association between patient sociodemographic characteristics and the current patient-pharmacist archetype relationships. RESULTS: The mean age of the patients was 53.9 years and 57.3% were married. Thirty-two percent of the patients reported currently having a "Customer" relationship, while 17.9% and 15.2% reported having a "Client" and "Partner" archetype relationship, respectively. "Client" (25.2%) and "Partner" (20.2%) relationships were the most commonly preferred archetypal relationships. The odds ratios (OR) of having "Client" or "Partner" relationships increased with the number of patients' health conditions and medications. Patients who visited independently owned and clinic pharmacies had a higher OR of building professional relationships with a pharmacist. CONCLUSION: The qualities of a patient-pharmacist relationship may be associated with key patient characteristics. Pharmacists can build relationships with patients informed by a continuum of patient preferences, expectations, and needs to optimize health outcomes.

Cost-effectiveness analysis of androgen deprivation therapy with relugolix for the treatment of advanced prostate cancer.

BACKGROUND: Relugolix treatment of advanced prostate cancer (APC), like other gonadotropin-releasing hormone-antagonists, results in rapid decrease in testosterone concentrations without the risk of flare, as seen in leuprolide. Despite this benefit over leuprolide, no economic evaluation assessment to ascertain the cost-effectiveness of relugolix has been conducted. Therefore, this study aims to assess the cost-effectiveness of androgen deprivation therapy (ADT) with 120 mg relugolix against 7.5 mg leuprolide for the treatment of APC. METHODS: A Markov model was used to assess and compare the costs of APC treatment from a health care payer's perspective and the effectiveness of ADT with relugolix and leuprolide at the 3 lines of APC treatment among modified intent-to-treat patients. Relative progression-free (PFS) and overall survival (OS) rates were estimated. Outcomes measured in the analyses included costs of the drugs and therapies, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), cost-effectiveness acceptability, and probability curves. RESULTS: The cost-effectiveness analysis showed the ICER for ADT with relugolix to be US $49,571.1 per QALY. At the ICER value, the sensitivity analysis indicated that ADT with leuprolide was dominant in 100% of the simulations. ADT acceptance with relugolix was 100% when a willingness-to-pay threshold was set at US $100,000/QALY. At 5-years, the relative PFS and OS rates for relugolix at the first line of therapy were 72.7% and 86.0%, respectively, compared to 61.0% and 85.90% for leuprolide. CONCLUSION: Though the influence of adverse events was not considered in the analysis, ADT with relugolix was not a cost-effective choice for APC management. While the analysis revealed a slight chance of sustaining testosterone suppression with relugolix, ADT with relugolix provided no significant survival advantages over ADT with leuprolide. Therefore, this analysis confirms no need for further assessment of APC interventions to make informed decisions beneficial to the APC patients, oncologists, and other stakeholders.

The EMS Modified Early Warning Score (EMEWS): A Simple Count of Vital Signs as a Predictor of Out-of-Hospital Cardiac Arrests.

Objective: For patients at risk for out-of-hospital cardiac arrest (OHCA) after Emergency Medical Services (EMS) arrival, outcomes may be mitigated by identifying impending arrests and intervening before they occur. Tools such as the Modified Early Warning Score (MEWS) have been developed to determine the risk of arrest, but involve relatively complicated algorithms that can be impractical to compute in the prehospital environment. A simple count of abnormal vital signs, the "EMS Modified Early Warning Score" (EMEWS), may represent a more practical alternative. We sought to compare to the ability of MEWS and EMEWS to identify patients at risk for EMS-witnessed OHCA.Methods: We conducted a retrospect analysis of the 2018 ESO Data Collaborative database of EMS encounters. Patients without cardiac arrest before EMS arrival were categorized into those who did or did not have an EMS-witnessed arrest. MEWS was evaluated without its temperature component (MEWS-T). The performance of MEWS-T and EMEWS in predicting EMS witnessed arrest was evaluated by comparing receiver-operating characteristic curves.Results: Of 369,064 included encounters, 4,651 were EMS witnessed arrests. MEWS-T demonstrated an area under the curve (AUC) of 0.79 (95% CI: 0.79 - 0.80), with 86.8% sensitivity and 51.0% specificity for MEWS-T ≥ 3. EMEWS demonstrated an AUC of 0.74 (95% CI: 0.73 - 0.75), with 81.3% sensitivity and 53.9% specificity for EMEWS ≥ 2.Conclusions: EMEWS showed a similar ability to predict EMS-witnessed cardiac arrest compared to MEWS-T, despite being significantly simpler to compute. Further study is needed to evaluate whether the implementation of EMEWS can aid EMS clinicians in anticipating and preventing OHCA.

Investigation of gene-environment interactions in relation to tic severity.

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.

Virtual Peer-to-Peer Learning to Enhance and Accelerate the Health System Response to COVID-19: The HHS ASPR Project ECHO COVID-19 Clinical Rounds Initiative.

Tasked with identifying digital health solutions to support dynamic learning health systems and their response to COVID-19, the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response partnered with the University of New Mexico's Project ECHO and more than 2 dozen other organizations and agencies to create a real-time virtual peer-to-peer clinical education opportunity: the COVID-19 Clinical Rounds Initiative. Focused on 3 "pressure points" in the COVID-19 continuum of care-(1) the out-of-hospital and/or emergency medical services setting, (2) emergency departments, and (3) inpatient critical care environments-the initiative has created a massive peer-to-peer learning network for real-time information sharing, engaging participants in all 50 US states and more than 100 countries. One hundred twenty-five learning sessions had been conducted between March 24, 2020 and February 25, 2021, delivering more than 58,000 total learner-hours of contact in the first 11 months of operation.

Ketamine for Prehospital Pain Management Does Not Prolong Emergency Department Length of Stay.

BACKGROUND: Ketamine is gaining acceptance as an agent for prehospital pain control, but the associated risks of agitation, hallucinations and sedation have raised concern about its potential to prolong emergency department (ED) length of stay (LOS). This study compared ED LOS among EMS patients who received prehospital ketamine, fentanyl or morphine specifically for pain control. We hypothesized ED LOS would not differ between patients receiving the three medications. METHODS: This retrospective observational study utilized the 2018 ESO Research Database, which includes more than 7.5 million EMS events attended by more than 1,200 agencies. Inclusion criteria were a 9-1-1 scene response; age ≥ 18 years; a recorded pain score greater than 4; an initial complaint or use of a treatment protocol indicating a painful condition; prehospital administration of ketamine, fentanyl or morphine; and ED LOS data available. Patients were excluded if they received a combination of the medications, or if there were indications that medication administration could have been for airway management (i.e., altered mental status, head injury, respiratory distress/depression) or agitation control (e.g., behavioral complaints). Kruskal-Wallis test was used to compare ED LOS among patients receiving each of the three medications. Post-hoc evaluations of between-group differences were conducted using Wilcoxon Rank Sum test and a Bonferroni-corrected alpha value of 0.017. RESULTS: Of 9,548 patients who met the inclusion criteria, 119 received ketamine, 1,359 received morphine, and 8,070 received fentanyl. Patient and event characteristics did not significantly differ between the three groups. Median (IQR) ED LOS was 3.5 (2.5-6.1) hours for patients who received ketamine, 4.0 (2.7-6.1) hours for patients who received morphine, and 3.7 (2.6-5.4) hours for patients who received fentanyl (p = 0.002). In post-hoc pairwise comparisons, patients who received morphine had significantly longer ED LOS than patients who received fentanyl (p < 0.001); there was no significant difference in ED LOS for patients who received ketamine vs. morphine (p = 0.161) or for patients who received ketamine vs. fentanyl (p = 0.809). CONCLUSION: ED LOS is not longer for patients who receive prehospital ketamine, versus morphine or fentanyl, for management of isolated painful non-cardiorespiratory conditions.

Development of a Binary End-of-Event Outcome Indicator for the NEMSIS Public Release Research Dataset.

INTRODUCTION: Emergency department and hospital discharge status are available for less than 2% of events recorded in the National EMS Information System (NEMSIS) Public Release Research dataset. The purpose of this project was to develop a binary ("dead" vs. "alive") end-of-event outcome indicator for the NEMSIS dataset. METHODS: The data dictionary for the Version 3 NEMSIS dataset was evaluated to identify elements and codes providing information about a patient's end-of-event status-defined as the point at which EMS providers stopped providing care for an encountered patient, whether at the scene of the event or the transport destination. Those element and code combinations were then used to test the criteria using the NEMSIS-2017 dataset. After revising the criteria based on the NEMSIS-2017 results, the final criteria were then applied to the 2018 NEMSIS dataset. To assess representativeness, the characteristics of events with a determinable outcome were compared to those of the entire dataset. To assess accuracy, the end-of-event indicator was compared with the final reported outcome for patients with a known emergency department disposition. RESULTS: Eighteen NEMSIS element and code combinations suggest a patient was likely "dead" at the end of EMS care, and 15 combinations suggest a patient was likely "alive" at the end of EMS care. A binary end-of-event outcome indicator could be determined for 13,045,887 (98.6%) of the 13,229,079 NEMSIS-2018 9-1-1 initiated ground EMS responses in which patient contact was established, and for 132,728 (89.1%) of the 148,963 events with documented cardiac arrest. The characteristics of the events with determinable end-of-event outcomes did not differ from those of the full dataset. Among patients with a known outcome, 99.6% of those with an "alive" end-of-event indicator were in fact alive at the time of emergency department disposition. CONCLUSION: A binary end-of-event outcome indicator can be determined for 98.6% of 9-1-1 initiated ground EMS scene responses and 89.1% of cardiac arrests included in the NEMSIS dataset. The events with a determinable outcome appear representative of the larger dataset and the end-of-event indicators are generally consistent with reported emergency department outcomes.

Using Red Lights and Sirens for Emergency Ambulance Response: How Often Are Potentially Life-Saving Interventions Performed?

BACKGROUND: Emergency Medical Services (EMS) often respond to 911 calls using red lights and sirens (RLS). RLS is associated with increased collisions and increased injuries to EMS personnel. While some patients might benefit from time savings, there is little evidence to guide targeted RLS response strategies. OBJECTIVE: To describe the frequency and nature of 911 calls that result in potentially life-saving interventions (PLSI) during the call. METHODS: Using data from ESO (Austin, Texas, USA), a national provider of EMS electronic health records, we analyzed all 911 calls in 2018. We abstracted the use of RLS, call nature, and interventions performed. A liberal definition of PLSI was developed a priori through a consensus process and included both interventions, medications, and critical hospital notifications. We calculated the proportion of calls with RLS response and with PLSI performed, both overall and stratified by call nature. RESULTS: There were 5,977,612 calls from 1,187 agencies included in the analysis. The majority (85.8%) of calls utilized RLS, yet few (6.9%) resulted in PLSI. When stratified by call nature, cardiac arrest calls had the highest frequency PLSI (45.0%); followed by diabetic problems (37.0%). Glucose was the most frequently given PLSI, n = 69,036. When including multiple administrations to the same patient, epinephrine was given most commonly PLSI, n = 157,282 administrations). CONCLUSION: In this large national dataset, RLS responses were very common (86%) yet potentially life-saving interventions were infrequent (6.9%). These data suggest a methodology to help EMS leaders craft targeted RLS response strategies.

Injury rates per mile of travel for electric scooters versus motor vehicles.

OBJECTIVE: This study determined the vehicle-miles-traveled (VMT)-based injury rate for stand-up, dockless electric rental scooters (e-scooters), and compare it with the VMT-based injury rate for motor vehicle travel. METHODS: In this secondary analysis of existing data, the e-scooter injury rate was calculated based on e-scooter injuries presenting to an emergency department or the emergency medical services system in Austin, TX between September and November 2018. Injuries were identified by Austin Public Health through a targeted e-scooter epidemiological injury investigation; e-scooter VMT data were reported by e-scooter vendors as a condition of their city licensing. Comparative injury rates for motor vehicle travel in Texas, and specifically in Travis County were calculated using annual motor vehicle crash (MVC) injury and VMT data reported by the Texas Department of Transportation. RESULTS: There were 160 confirmed e-scooter injuries identified by the e-scooter injury investigation, with 891,121 reported miles of e-scooter travel during the study period. This produces an injury rate estimate of 180 injuries/million VMT (MVMT). The injury rates for motor vehicle travel for Texas and for Travis County were 0.9 injuries/MVMT and 1.0 injuries/MVMT, respectively. CONCLUSION: The observed VMT-based e-scooter injury rate was approximately 175 to 200 times higher than statewide or county specific injury rates for motor vehicle travel. These findings raise concerns about the potential higher injury rate associated with e-scooters, and highlight the need for further injury surveillance, research and prevention activities addressing this emerging transportation technology.