Naloxone and Patient Outcomes in Out-of-Hospital Cardiac Arrests in California.

Importance: The incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has grown from less than 1% of OHCA in 2000 to between 7% and 14% of OHCA in recent years; American Heart Association (AHA) protocols suggest that emergency medical service (EMS) clinicians consider naloxone in OA-OHCA. However, it is unknown whether naloxone improves survival in these patients or in patients with undifferentiated OHCA. Objective: To evaluate the association of naloxone with clinical outcomes in patients with undifferentiated OHCA. Design, Setting, and Participants: Retrospective cohort study of EMS-treated patients aged 18 or older who received EMS treatment for nontraumatic OHCA in 3 Northern California counties between 2015 and 2023. Data were analyzed using propensity score-based models from February to April 2024. Exposure: EMS administration of naloxone. Main Outcomes and Measures: The primary outcome was survival to hospital discharge; the secondary outcome was sustained return of spontaneous circulation (ROSC). Covariates included patient and cardiac arrest characteristics (eg, age, sex, nonshockable rhythm, any comorbidity, unwitnessed arrest, and EMS agency) and EMS clinician determination of OHCA cause as presumed drug-related. Results: Among 8195 patients (median [IQR] age, 65 [51-78] years; 5540 male [67.6%]; 1304 Asian, Native Hawaiian, or Pacific Islander [15.9%]; 1119 Black [13.7%]; 2538 White [31.0%]) with OHCA treated by 5 EMS agencies from 2015 to 2023, 715 (8.7%) were believed by treating clinicians to have drug-related OHCA. Naloxone was administered to 1165 patients (14.2%) and was associated with increased ROSC using both nearest neighbor propensity matching (absolute risk difference [ARD], 15.2%; 95% CI, 9.9%-20.6%) and inverse propensity-weighted regression adjustment (ARD, 11.8%; 95% CI, 7.3%-16.4%). Naloxone was also associated with increased survival to hospital discharge using both nearest neighbor propensity matching (ARD, 6.2%; 95% CI, 2.3%-10.0%) and inverse propensity-weighted regression adjustment (ARD, 3.9%; 95% CI, 1.1%-6.7%). The number needed to treat with naloxone was 9 for ROSC and 26 for survival to hospital discharge. In a regression model that assessed effect modification between naloxone and presumed drug-related OHCA, naloxone was associated with improved survival to hospital discharge in both the presumed drug-related OHCA (odds ratio [OR], 2.48; 95% CI, 1.34-4.58) and non-drug-related OHCA groups (OR, 1.35; 95% CI, 1.04-1.77). Conclusions and Relevance: In this retrospective cohort study, naloxone administration as part of EMS management of OHCA was associated with increased rates of ROSC and increased survival to hospital discharge when evaluated using propensity score-based models. Given the lack of clinical practice data on the efficacy of naloxone in OA-OHCA and OHCA in general, these findings support further evaluation of naloxone as part of cardiac arrest care.

Race, Ethnicity, and Gender Differences in Patient Reported Well-Being and Cognitive Functioning Within 3 Months of Symptomatic Illness During COVID-19 Pandemic.

BACKGROUND: Differences in acute COVID-19 associated morbidity based on race, ethnicity, and gender have been well described; however, less is known about differences in subsequent longer term health-related quality of life and well-being. METHODS: This prospective cohort study included symptomatic adults tested for SARS-CoV-2 who completed baseline and 3-month follow-up surveys. Using the PROMIS-29 tool, a validated measure of health and well-being, we compared outcomes at 3 months and change in outcomes from baseline to 3 months among groups with different races, ethnicities, and/or sexes. RESULTS: Among 6044 participants, 4113 (3202 COVID +) were included. Among COVID + participants, compared to non-Hispanic White participants, Black participants had better PROMIS T-scores for cognitive function (3.6 [1.1, 6.2]) and fatigue (- 4.3 [- 6.6, - 2.0]) at 3 months and experienced more improvement in fatigue over 3 months (- 2.7 [- 4.7, - 0.8]). At 3 months, compared with males, females had worse PROMIS T-scores for cognitive function (- 4.1 [- 5.6, - 2.6]), physical function (- 2.1 [- 3.1, - 1.0]), social participation (- 2.8 [- 4.2, - 1.5]), anxiety (2.8 [1.5, 4.1]), fatigue (5.1 [3.7, 6.4]), and pain interference (2.0 [0.9, 3.2]). Females experienced less improvement in fatigue over 3 months (3.1 [2.0, 4.3]). Transgender/non-binary/other gender participants had worse 3-month scores in all domains except for sleep disturbance and pain interference. CONCLUSIONS: Three months after the initial COVID-19 infection, Black participants reported better cognitive function and fatigue, while females and other gender minoritized groups experienced lower well-being. Future studies are necessary to better understand how and why social constructs, specifically race, ethnicity, and gender, influence differences in COVID-19-related health outcomes. Trials Registration ClinicalTrials.gov Identifier: NCT04610515.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection.

Importance: Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Objective: To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection-like index illness. Design, Setting, and Participants: This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 years with acute symptoms suggestive of SARS-CoV-2 infection who received a US Food and Drug Administration-approved SARS-CoV-2 test at the time of illness and did not die or withdraw from the study by 3 months. Follow-up surveys were collected through February 28, 2023. Exposure: COVID-19 status (positive vs negative) at enrollment. Main Outcome and Measures: The main outcome was the weighted proportion of participants with ME/CFS-like illness based on the 2015 Institute of Medicine clinical case definition using self-reported symptoms. Results: A total of 4378 participants were included in the study. Most were female (3226 [68.1%]). Mean (SD) age was 37.8 (11.8) years. The survey completion rates ranged from 38.7% (3613 of 4738 participants) to 76.3% (1835 of 4738) and decreased over time. The weighted proportion of participants identified with ME/CFS-like illness did not change significantly at 3 through 12 months of follow-up and was similar in the COVID-19-positive (range, 2.8%-3.7%) and COVID-19-negative (range, 3.1%-4.5%) groups. Adjusted analyses revealed no significant difference in the odds of ME/CFS-like illness at any time point between COVID-19-positive and COVID-19-negative individuals (marginal odds ratio range, 0.84 [95% CI, 0.42-1.67] to 1.18 [95% CI, 0.55-2.51]). Conclusions and Relevance: In this prospective cohort study, there was no evidence that the proportion of participants with ME/CFS-like illness differed between those infected with SARS-CoV-2 vs those without SARS-CoV-2 infection up to 12 months after infection. A 3% to 4% prevalence of ME/CFS-like illness after an acute infection-like index illness would impose a high societal burden given the millions of persons infected with SARS-CoV-2.

Traumatic injury to the posterior fossa: a secondary analysis and description of case series from the NEXUS head injury dataset.

Background: Traumatic brain injuries involving the posterior fossa are rare and case reports indicate they often result in severe outcomes. We seek to describe characteristics and outcomes of traumatic posterior fossa injuries. Methods: We performed a planned secondary analysis of all patients with posterior fossa injuries enrolled in the NEXUS head computed tomography (CT) validation study dataset. The dataset includes prospectively collected data on all patients undergoing non-contrast cranial CT following blunt traumatic head injury from April 2006 to December 2015, at four emergency departments comprising community and university sites, as well as urban, suburban and rural settings in California (Antelope Valley Hospital, San Francisco General Hospital, UCLA Ronald Reagan Medical Center, UCSF Fresno Community Regional Medical Center). We classified each patient into one of three injury patterns: Type I-notable traumatic injuries primarily above the tentorium, with minimal posterior fossa involvement; Type II-notable traumatic injuries both above and within the posterior fossa; and Type III-notable traumatic injuries primarily within the posterior fossa. We extracted demographic data for each patient as well as physician assessments of the NEXUS head CT and Canadian Head CT rule clinical criteria, mechanisms of injury, patient outcomes, and the location and types of intracranial injuries sustained. Findings: Of 11,770 patients in the database, 184 (1.6%) had posterior fossa injuries on CT imaging. Mean age was 55.4 years (standard deviation 22.5 years, range 2-96 years); 131 (71.2%) were males. We identified 63 patients with Type I injuries, 87 with Type II injuries, and 34 Type III injuries. The most common mechanisms of injury were falls (41%), pedestrian vs automobile (15%), and motor vehicle collisions (13%). On presentation most patients had altered mental status (72%), abnormal behavior (53%), or a neurologic deficit (55%). The majority of individuals, 151 (82%), had clinically important injuries and 111 (60%) required neurosurgical intervention. The dispositions for the subjects included 52 deaths (28%), 49 (27%) patients discharged home, and 48 (26%) discharged to rehabilitation facilities. When compared to individuals with Type I and Type II injuries, patients with Type III injuries had lower mortality (6% vs 30% and 35%) and higher percentage of patients discharged home (60% vs 19% and 21%). Interpretation: Patients with Type I and II injury patterns (those that involve both the posterior fossa and supratentorium) experienced high mortality and disability. Patients with Type III injuries (isolated posterior fossa) had a better prognosis. Funding: None.

Promotion of Influenza Vaccination in the Emergency Department.

BACKGROUND: Influenza vaccine uptake is low among underserved populations whose primary health care access occurs in emergency departments. We sought to determine whether implementation of two interventions would increase 30-day influenza vaccine uptake in unvaccinated patients in the emergency department. METHODS: This three-group, prospective, cluster-randomized controlled trial compared two interventions with a control group in noncritically ill, adult patients in the emergency department who were not vaccinated for influenza in the current vaccine season. The unit of randomization was individual calendar days. Participants received either Intervention M (an influenza vaccine messaging platform consisting of a video, one-page flyer, and scripted message, followed by a vaccine acceptance question and provider notification if participants indicated vaccine acceptance), Intervention Q (no messaging but the vaccine acceptance question and provider notification), or control (usual care/no intervention). The primary outcome was receipt of an influenza vaccine at 30 days ascertained by electronic health record review and telephone follow-up, comparing the Intervention M group with the control group. Secondary outcomes included comparisons of 30-day vaccine uptake in Intervention Q versus control and Intervention M versus Intervention Q. RESULTS: Between October 2022 and February 2023, a total of 767 trial participants were enrolled at six emergency departments in five U.S. cities. Median age was 46 years; 353 (46%) participants were female, 274 (36%) were African American, and 158 (21%) were Latinx; 126 (16%) lacked health insurance, and 244 (32%) lacked primary care. The Intervention M, Intervention Q, and control groups had 30-day vaccine uptakes of 41%, 32%, and 15%, respectively (P<0.0001 for Intervention M vs. control). Comparing Intervention M versus Intervention Q, the adjusted difference in 30-day vaccine uptake was 8.7 percentage points (95% confidence interval, -0.1 to 17.6 percentage points). CONCLUSIONS: Implementation of influenza vaccine messaging platforms (video clips, printed materials, and verbal scripts) improved 30-day vaccine uptake among unvaccinated patients in the emergency department. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05836818.).

Characteristics of Intracranial Injuries in Pediatric Patients Following Blunt Head Trauma.

OBJECTIVES: Pediatric head trauma is a frequent reason for presentation to the emergency department. Despite this, there are few reports on specific characteristics and injury patterns in head injured children. The goal of this study was to evaluate head injury patterns in children with blunt head injury and their prevalence by age group. METHODS: This is a planned secondary analysis of the NEXUS II Head CT validation study. Consecutive patients with blunt head trauma were enrolled between 2006 and 2015. Demographics and criteria from 2 clinical decision instruments (NEXUS and Canadian Head CT rules) were gathered at the time of enrollment. We abstracted and cataloged injuries for pediatric patients based on radiologist report. Frequencies of injuries and severity were analyzed by developmental age group. RESULTS: A total of 1018 pediatric patients were enrolled, 128 (12.6%) of whom had an injury on computed tomography scan. Median age was 11.9 (Interquartile range 4.5-15.5) for all patients and 12 (4.8-15.5) for injured patients. Of injured patients, 49 (38.3%) had a significant injury, and 27 (21.1%) received an intervention. Teenagers had the highest rate of significant injury (50%) and intervention (30%). Injuries were most frequently noted in the temporal (46.1%), frontal (45.3%), and parietal (45.3%) regions. Subarachnoid hemorrhage (29.7%) and subdural hematoma (28.9%) were the most common injuries observed.Intraparenchymal hemorrhage and cerebral edema were more prevalent in older age groups. The most common injury mechanism overall was fall from height (24.7%). Motor vehicle accidents and nonmotorized wheeled vehicle accidents were more common in older patients. CONCLUSIONS: Serious injuries requiring intervention were rarely encountered in pediatric patients experiencing blunt head trauma. Mechanisms of injury, type of injury, and rates of intervention varied between developmental age groups.

Benefits and Process of Providing Peer Support for Pediatric Burn Survivors and Caregivers during Inpatient and Outpatient Phases of Recovery.

The World Health Organization reveals that pediatric burns represent a large portion of burns globally (61). Increases in survival rates have guided clinical and research focus on physical, psychological, and social outcomes. Research on other childhood illnesses has shown the efficacy of social support throughout recovery. In the pediatric burn literature, studies have shown the efficacy of burn camps for promoting positive interactions among survivors, learning coping skills, and facilitating socialization and reintegration. However, few studies have focused on the benefits of peer support for pediatric burn survivors and their caregivers in the inpatient and outpatient phases of recovery. This descriptive paper identifies options for building resilience for pediatric burn survivors through peer support in the inpatient and outpatient phases of recovery. The authors discuss options for providing peer support during the coronavirus disease 2019 pandemic on the pediatric intensive care unit, general pediatric floor, and outpatient setting.

Availability and use of institutional support programs for emergency department healthcare personnel during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic placed health care personnel (HCP) at risk for stress, anxiety, burnout, and post-traumatic stress disorder (PTSD). To address this, hospitals developed programs to mitigate risk. The objectives of the current study were to measure the availability and use of these programs in a cohort of academic emergency departments (EDs) in the United States early in the pandemic and identify factors associated with program use. METHODS: Cross-sectional survey of ED HCP in 21 academic EDs in 15 states between June and September 2020. Site investigators provided data on the availability of 28 programs grouped into 9 categories. Individual support programs included: financial, workload mitigation, individual COVID-19 testing, emotional (e.g., mental health hotline), and instrumental (e.g., childcare) Clinical work support programs included: COVID-19 team communication (e.g., debriefing critical incident), patient-family communication facilitation, patient services (e.g., social work, ethics consultation), and system-level exposure reduction. Participants provided corresponding data on whether they used the programs. We used generalized linear mixed models clustered on site to measure the association between demographic and facility characteristics and program use. RESULTS: We received 1,541 survey responses (96% response rate) from emergency physicians or advanced practice providers, nurses, and nonclinical staff. Program availability in each of the 9 categories was high (>95% of hospitals). Program use was variable, with clinical work support programs used more frequently (28-50% of eligible HCP across categories) than individual employee support programs (6-13% of eligible HCP across categories). Fifty-seven percent of respondents reported that the COVID-19 pandemic had affected their stress and anxiety, and 12% were at elevated risk for PTSD. Program use did not significantly differ for HCP who reported symptoms of anxiety and/or stress compared to those who did not. CONCLUSIONS: Early in the pandemic, support programs were widely available to ED HCP, but program use was low. Future work will focus on identifying barriers and facilitators to use and specific programs most likely to be effective during periods of highest occupational stress.

Missed Opportunities to Diagnose and Treat Asymptomatic Hypertension in Emergency Departments in the United States, 2016-2019.

BACKGROUND: Fewer than one-half of U.S. adults with hypertension (HTN) have it controlled and one-third are unaware of their condition. The emergency department (ED) represents a setting to improve HTN control by increasing awareness of asymptomatic hypertension (aHTN) according to the 2013 American College of Emergency Physicians asymptomatic elevated blood pressure clinical policy. OBJECTIVE: The aim of the study was to estimate the prevalence and management of aHTN in U.S. EDs. METHODS: We examined the 2016-2019 National Hospital Ambulatory Medical Care Surveys to provide a more valid estimate of aHTN visits in U.S. EDs. aHTN is defined as adult patients with blood pressure ≥ 160/100 mm Hg at triage and discharge without trauma or signs of end organ damage. We then stratified aHTN into a 160-179/100-109 mm Hg subgroup and > 180/110 mm Hg subgroup and examined diagnosis and treatment outcomes. RESULTS: Approximately 5.9% of total visits between 2016 and 2019 met the definition for aHTN and 74% of patients were discharged home, representing an estimated 26.5 million visits. Among those discharged home, emergency physicians diagnosed 13% (95% CI 10.6-15.8%) and treated aHTN in 3.9% (95% CI 2.8-5.5%) of patients in the higher aHTN subgroup. In the lower aHTN subgroup, diagnosis and treatment decreased to 3.1% (95% CI 2.4-4.1%) and 1.2% (95% CI 0.7-2.0%), respectively. CONCLUSIONS: Millions of ED patients found to have aHTN are discharged home without diagnosis or treatment. Although management practices follow clinical policy to delay treatment of aHTN, there are missed opportunities to diagnosis aHTN.

COVID-19 Vaccine Uptake in Undocumented Latinx Patients Presenting to the Emergency Department.

This cross-sectional study examines COVID-19 infection status, vaccination uptake, and perceptions about the vaccine among Latinx patients presenting to the emergency department in California.

Coronavirus Disease 2019 Infections Among Emergency Health Care Personnel: Impact on Delivery of United States Emergency Medical Care, 2020.

STUDY OBJECTIVE: In the early months of the coronavirus disease 2019 (COVID-19) pandemic and before vaccine availability, there were concerns that infected emergency department (ED) health care personnel could present a threat to the delivery of emergency medical care. We examined how the pandemic affected staffing levels and whether COVID-19 positive staff were potentially infectious at work in a cohort of US ED health care personnel in 2020. METHODS: The COVID-19 Evaluation of Risks in Emergency Departments (Project COVERED) project was a multicenter prospective cohort study of US ED health care personnel conducted from May to December 2020. During surveillance, health care personnel completed weekly electronic surveys and underwent periodic serology and nasal reverse transcription polymerase chain reaction testing for SARS-CoV-2, and investigators captured weekly data on health care facility COVID-19 prevalence and health care personnel staffing. Surveys asked about symptoms, potential exposures, work attendance, personal protective equipment use, and behaviors. RESULTS: We enrolled 1,673 health care personnel who completed 29,825 person weeks of surveillance. Eighty-nine (5.3%) health care personnel documented 90 (0.3%; 95% confidence interval [CI] 0.2% to 0.4%) person weeks of missed work related to documented or concerns for COVID-19 infection. Health care personnel experienced symptoms of COVID-19 during 1,256 (4.2%) person weeks and worked at least one shift whereas symptomatic during 1,042 (83.0%) of these periods. Seventy-five (4.5%) participants tested positive for SARS-CoV-2 during the surveillance period, including 43 (57.3%) who indicated they never experienced symptoms; 74 (98.7%; 95% CI 90.7% to 99.9%) infected health care personnel worked at least one shift during the initial period of infection, and 71 (94.7%) continued working until laboratory confirmation of their infection. Physician staffing was not associated with the facility or community COVID-19 levels within any time frame studied (Kendall tau's 0.02, 0.056, and 0.081 for no shift, one-week time shift, and 2-week time shift, respectively). CONCLUSIONS: During the first wave of the pandemic, COVID-19 infections in ED health care personnel were infrequent, and the time lost from the workforce was minimal. Health care personnel frequently reported for work while infected with SARS-CoV-2 before laboratory confirmation. The ED staffing levels were poorly correlated with facility and community COVID-19 burden.

Trends in presumed drug overdose out-of-hospital cardiac arrests in San Francisco, 2015-2023.

INTRODUCTION: Estimates of the prevalence of drug-related out of hospital cardiac arrest (OHCA) vary, ranging from 1.8% to 10.0% of medical OHCA. However, studies conducted prior to the recent wave of fentanyl deaths likely underestimate the current prevalence of drug-related OHCA. We evaluated recent trends in drug-related OHCA, hypothesizing that the proportion of presumed drug-related OHCA treated by emergency medical services (EMS) has increased since 2015. METHODS: We conducted a retrospective analysis of OHCA patients treated by EMS providers in San Francisco, California between 2015 and 2023. Participants included OHCA cases in which resuscitation was attempted by EMS. The study exposure was the year of arrest. Our primary outcome was the occurrence of drug-related OHCA, defined as the EMS impression of OHCA caused by a presumed or known overdose of medication(s) or drug(s). RESULTS: From 2015 to 2023, 5044 OHCA resuscitations attended by EMS (average 561 per year) met inclusion criteria. The median age was 65 (IQR 50-79); 3508 (69.6%) were male. The EMS impression of arrest etiology was drug-related in 446/5044 (8.8%) of OHCA. The prevalence of presumed drug-related OHCA increased significantly each year from 1% in 2015 to 17.6% in 2023 (p-value for trend = 0.0001). After adjustment, presumed drug-related OHCA increased by 30% each year from 2015-2023. CONCLUSION: Drug-related OHCA is an increasingly common etiology of OHCA. In 2023, one in six OHCA was presumed to be drug related. Among participants less than 60 years old, one in three OHCA was presumed to be drug related.

Blunt Head Injury in the Elderly: Analysis of the NEXUS II Injury Cohort.

BACKGROUND: Changes with aging make older patients vulnerable to blunt head trauma and alter the potential for injury and the injury patterns seen among this expanding cohort. High-quality care requires a clear understanding of the factors associated with blunt head injuries in the elderly. Our objective was to develop a detailed assessment of the injury mechanisms, presentations, injury patterns, and outcomes among older blunt head trauma patients. METHODS: We conducted a planned secondary analysis of patients aged 65 or greater who were enrolled in the National Emergency X-Radiography Utilization Study (NEXUS) Head Computed Tomography validation study. We performed a detailed assessment of the demographics, mechanisms, presentations, injuries, interventions, and outcomes among older patients. RESULTS: We identified 3,659 patients aged 65 years or greater, among the 11,770 patients enrolled in the NEXUS validation study. Of these older patients, 325 (8.9%) sustained significant injuries, as compared with significant injuries in 442 (5.4%) of the 8,111 younger patients. Older females (1,900; 51.9%) outnumbered older males (1,753; 47.9%), and occult presentations (exhibiting no high-risk clinical criteria beyond age) occurred in 48 (14.8%; 95% confidence interval (CI) 11.1 to 19.1) patients with significant injuries. Subdural hematomas (377 discreet lesions in 299 patients) and subarachnoid hemorrhages (333 discreet instances in 256 patients) were the most frequent types of injuries occurring in our elderly population. A ground-level fall was the most frequent mechanism of injury among all patients (2,211; 69.6%), those sustaining significant injuries (180; 55.7%), and those who died of their injuries (37; 46.3%), but mortality rates were highest among patients experiencing a fall from a ladder (11.8%; 4 deaths among 34 cases [95% CI 3.3% to 27.5%]) and automobile versus pedestrian events (10.7%; 16 deaths among 149 cases [95% CI 6.3% to 16.9%]). Among older patients who required neurosurgical intervention for their injuries, only 16.4% (95% CI 11.1% to 22.9%) were able to return home, 32.1% (95% CI 25.1% to 39.8%) required extended facility care, and 41.8% (95% CI 34.2% to 49.7%) died from their injuries. CONCLUSIONS: Older blunt head injury patients are at high risk of sustaining serious intracranial injuries even with low-risk mechanisms of injury, such as ground-level falls. Clinical evaluation is unreliable and frequently fails to identify patients with significant injuries. Outcomes, particularly after intervention, can be poor, with high rates of long-term disability and mortality.

Discrete class I molecules on brain endothelium differentially regulate neuropathology in experimental cerebral malaria.

Cerebral malaria is the deadliest complication that can arise from Plasmodium infection. CD8 T-cell engagement of brain vasculature is a putative mechanism of neuropathology in cerebral malaria. To define contributions of brain endothelial cell major histocompatibility complex (MHC) class I antigen-presentation to CD8 T cells in establishing cerebral malaria pathology, we developed novel H-2Kb LoxP and H-2Db LoxP mice crossed with Cdh5-Cre mice to achieve targeted deletion of discrete class I molecules, specifically from brain endothelium. This strategy allowed us to avoid off-target effects on iron homeostasis and class I-like molecules, which are known to perturb Plasmodium infection. This is the first endothelial-specific ablation of individual class-I molecules enabling us to interrogate these molecular interactions. In these studies, we interrogated human and mouse transcriptomics data to compare antigen presentation capacity during cerebral malaria. Using the Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we observed that H-2Kb and H-2Db class I molecules regulate distinct patterns of disease onset, CD8 T-cell infiltration, targeted cell death and regional blood-brain barrier disruption. Strikingly, ablation of either molecule from brain endothelial cells resulted in reduced CD8 T-cell activation, attenuated T-cell interaction with brain vasculature, lessened targeted cell death, preserved blood-brain barrier integrity and prevention of ECM and the death of the animal. We were able to show that these events were brain-specific through the use of parabiosis and created the novel technique of dual small animal MRI to simultaneously scan conjoined parabionts during infection. These data demonstrate that interactions of CD8 T cells with discrete MHC class I molecules on brain endothelium differentially regulate development of ECM neuropathology. Therefore, targeting MHC class I interactions therapeutically may hold potential for treatment of cases of severe malaria.

A practice-based approach to emergency department evaluation and management of patients with postacute sequelae after COVID-19 infection: long COVID.

Afflicting millions of people across the world, "long COVID" is a new disease entity that can present with a diverse array of symptoms of variable severity, affecting nearly every organ system. The presumptive diagnosis of long COVID is largely clinical, and should be made only after other serious etiologies have been excluded. Workup is driven by the patient's presenting acute symptoms, comorbidities, and physical examination findings. This issue reviews the research and current evidence on the etiology of COVID-19 infection and long COVID and presents a practice-based approach to the management of patients presenting with its postacute sequelae.

The Impact of the COVID-19 Shelter-in-Place Order on Traumatic Brain Injuries in San Francisco, California.

BACKGROUND: In response to the COVID-19 pandemic, San Francisco, California issued a shelter-in-place (SIP) order in March 2020, during which emergency physicians noted a drop in trauma cases, as well as a change in traditional mechanisms of trauma. OBJECTIVES: Our objective was to determine the epidemiology of traumatic brain injury (TBI) pre- and post-COVID-19 SIP. METHODS: We reviewed the electronic medical record of the only trauma center in the city of San Francisco, to determine the number of and characteristics of patients with a diagnosis of head injury presenting to the emergency department between December 16, 2019 and June 16, 2020. Using chi-squared and Fisher's exact tests when appropriate, we compared pre- and post- COVID-19 lockdown epidemiology. RESULTS: There were 1246 TBI-related visits during the 6-month study period. Bi-weekly TBI cases decreased by 36.64% 2 weeks after the COVID-19 SIP and then increased to near baseline levels by June 2020. TBI patients during SIP were older (mean age: 53.3 years pre-SIP vs. 58.2 post-SIP; p < 0.001), more likely to be male (odds ratio 1.43, 95% confidence interval 1.14-1.81), and less likely to be 17 or younger (8.9% vs. 0.5%, pre- to post-SIP respectively, p = 0.003). Patients were less likely to be Hispanic (27.2% vs. 21.7% pre- to post-SIP, respectively, p = 0.029). The proportion of TBI visits attributable to cycling accidents increased (14.1% to 52.7%, p < 0.001), whereas those attributable to pedestrians involved in road traffic accidents decreased (37.2% to 12.7%, p = 0.003). CONCLUSIONS: Understanding the changing epidemiology of TBI during the COVID-19 pandemic can aid in immediate and future disaster resource planning.

Impact of a hypothetical COVID-19 vaccine mandate on parental likelihood to vaccinate children: Exploring school-related concerns and vaccination decision-making.

OBJECTIVE: We assessed the impact of a hypothetical school-entry COVID-19 vaccine mandate on parental likelihood to vaccinate their child. METHODS: We collected demographics, COVID-19-related school concerns, and parental likelihood to vaccinate their child from parents of patients aged 3-16 years seen across nine pediatric Emergency Departments from 06/07/2021 to 08/13/2021. Wilcoxon signed-rank test compared pre- and post-mandate vaccination likelihood. Multivariate linear and logistic regression analyses explored associations between parental concerns with baseline and change in vaccination likelihood, respectively. RESULTS: Vaccination likelihood increased from 43% to 50% with a hypothetical vaccine mandate (Z = -6.69, p < 0.001), although most parents (63%) had no change, while 26% increased and 11% decreased their vaccination likelihood. Parent concerns about their child contracting COVID-19 was associated with greater baseline vaccination likelihood. No single school-related concern explained the increased vaccination likelihood with a mandate. CONCLUSION: Parental school-related concerns did not drive changes in likelihood to vaccinate with a mandate.