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In the present paper we investigate (p, q)-directed complete bipartite graphs ?K p,q, n-directed paths ?Pn and n-directed cycles ?C n from the perspective of Granular Computing. For each model, we establish the general form of all possible indiscernibility relations, analyze the classical rough approximation functions of rough set theory and provide a close formula for the global accuracy average. Finally, we completely determine the attribute dependency function and the global dependency average for both ?C n and ?Kp,q.

Humans are estimated to consume several grams per week of nanoplastics (NPs) through exposure to a variety of contamination sources. Nonetheless, the effects of these polymeric particles on living systems are still mostly unknown. Here, by means of CD, NMR and TEM analyses, we describe at an atomic resolution the interaction of ubiquitin with polystyrene NPs (PS-NPs), showing how a hard protein corona is formed. Moreover, we report that in human HeLa cells exposure to PS-NPs leads to a sensible reduction of ubiquitination. Our study overall indicates that PS-NPs cause significant structural effects on ubiquitin, thereby influencing one of the key metabolic processes at the base of cell viability.

Following Hurricanes Irma and Maria in September 2017, there were elevated rates of depression and suicide in Puerto Rico. This study evaluates mental health in older and elderly Puerto Ricans 6 months after the hurricanes and suggests strategies for improving future psychosocial responses. Patients attending clinics were evaluated for depression (Patient Health Questionnaire [PHQ-9]) and suicide risk (Ask Suicide-Screening Questions [ASQ]) and were surveyed about their perceived safety, designated as a proxy for anxiety. Used in conjunction, PHQ-9 and ASQ were found to identify a greater proportion of individuals experiencing adverse mental health effects than if each instrument was used in isolation. Patients were also surveyed about time to water and electricity restoration, and it was found that prolonged time to water restoration was associated with increased prevalence and severity of depression and decreased perceived safety. Based on collected patient data (n = 523), using multiple mental health screening tools for diagnosis, improving perceptions of home safety or anxiety, and prioritizing water restoration may reduce mental health sequelae in the elderly and enhance the effect of psychosocial responses following disasters.

BackgroundTimely management of non-convulsive status epilepticus (NCSE) is critical to improving patient outcomes. However, NCSE can only be confirmed using electroencephalography (EEG), which is either significantly delayed or entirely unavailable in emergency departments (EDs). We piloted the use of a new bedside EEG device, Rapid Response EEG (Rapid-EEG, Ceribell), in the ED and evaluated its impact on seizure management when used by emergency physicians.MethodsPatients who underwent Rapid-EEG to rule out NCSE were prospectively enrolled in a pilot project conducted at two ED sites (an academic hospital and a community hospital). Physicians were surveyed on the perceived impact of the device on seizure treatment and patient disposition, and we calculated physicians’ sensitivity and specificity (with 95% CI) for diagnosing NCSE using Rapid-EEG’s Brain Stethoscope function.ResultsOf the 38 patients enrolled, the one patient with NCSE was successfully diagnosed and treated within minutes of evaluation. Physicians reported that Rapid-EEG changed clinical management for 20 patients (53%, 95% CI 37% to 68%), primarily by ruling out seizures and avoiding antiseizure treatment escalation, and expedited disposition for 8 patients (21%, 95% CI 11% to 36%). At the community site, physicians diagnosed seizures by their sound using Brain Stethoscope with 100% sensitivity (95% CI 5% to 100%) and 92% specificity (95% CI 62% to 100%).ConclusionRapid-EEG was successfully deployed by emergency physicians at academic and community hospitals, and the device changed management in a majority of cases. Widespread adoption of Rapid-EEG may lead to earlier diagnosis of NCSE, reduced unnecessary treatment and expedited disposition of seizure mimics.

Introduction: As of October 30, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 44 million people worldwide and killed over 1.1 million people. In the emergency department (ED), patients who need supplemental oxygen or respiratory support are admitted to the hospital, but the course of normoxic patients with SARS-CoV-2 infection is unknown. In our health system, the policy during the coronavirus 2019 (COVID-19) pandemic was to admit all patients with abnormal chest imaging (CXR) regardless of their oxygen level. We also admitted febrile patients with respiratory complaints who resided in congregate living. We describe the rate of decompensation among patients admitted with suspected SARS-CoV-2 infection but who were not hypoxemic in the ED. Methods: This is a retrospective observational study of patients admitted to our health system between March 1–May 5, 2020 with suspected SARS-CoV-2 infection. We queried our registry to find patients who were admitted to the hospital but had no recorded oxygen saturation of

Introduction Since the beginning of the novel coronavirus (COVID-19) pandemic in the United States, there have been concerns about the potential impact of the pandemic on persons with opioid use disorder. Shelter-in-place (SIP) orders, which aimed to reduce the spread and scope of the virus, likely also impacted this patient population. This study aims to assess the role of the COVID-19 pandemic on the incidence of opioid overdose before and after a SIP order. Methods A retrospective review of the incidence of opioid overdoses in an urban three-hospital system was conducted. Comparisons were made between the first 100 days of a city-wide SIP order during the COVID-19 pandemic and the 100 days during the COVID-19 pandemic preceding the SIP order (Pre-SIP). Differences in observed incidence and expected incidence during the SIP period were evaluated using a Fisher's Exact test. Results Total patient visits decreased 22% from 46,078 during the Pre-SIP period to 35,971 during the SIP period. A total of 1551 opioid overdoses were evaluated during the SIP period, compared to 1665 opioid overdoses during the Pre-SIP period, consistent with a 6.8% decline. A Fisher's Exact Test demonstrated a p, Highlights • Shelter In Place order may have a unique impact on persons with opioid use disorder. • COVID-19 pandemic is associated decreased overall incidence in opioid overdoses. • COVID-19 pandemic is associated with a proportional increase in opioid overdoses.

Background Given the many causes of seizures, emergency physicians often utilize brain computed tomography (CT) to evaluate for intracranial pathology. However, a CT exposes patients to 100 times more radiation than a chest radiograph. Previously, we developed a four-item clinical decision instrument (CDI) to determine which patients with status epilepticus (SE) do not require emergent neuroimaging. In this study, we seek to prospectively validate our CDI in patients with a history of seizures with both SE and generalized tonic-clonic seizures. Methods This was a prospective observational study of 1,739 consecutive patients who were recruited from two urban hospitals in Philadelphia, Pennsylvania. All patients, 18 years and older, who presented with a chief complaint of seizure and had emergency neuroimaging performed were eligible for inclusion. Patients were excluded from analysis if this was a first-time seizure, had a ventriculoperitoneal shunt, or had focal neurologic deficits. Results A total of 376 patients were in the final analysis. Of the 376 patients, 10 patients (3%) had positive CTs. Nine of the 10 of the patients were identified by our CDI, resulting in a negative predictive value (NPV) of 99.5%. On secondary analysis, we refined our CDI from four to three criteria: 1) history of intracranial hemorrhage (ICH), 2) active malignancy, and 3) trauma. These criteria also had a NPV of >99% when applied to patients in SE. Conclusion The validation of our CDI showed improved NPV when compared to the derivation set. Use of the criteria of history of ICH, active malignancy, and trauma could have reduced the use of emergent neuroimaging in our cohort by up to 49%. This CDI should be validated in a larger subset of patients and in multiple centers prior to widespread adoption.

Study question Bisphenol A (BPA) is a constituent of polycarbonate and epoxy resin plastics and is also a by-product of combustion of plastics, resulting harmful for health. Summary answer To evaluate the presence of BPA in the blood and Follicular Fluids, in women, subjected to IVF cycles, living in areas with different environmental impact. What is known already BPA is used in the production of polycarbonate plastics and epoxy resins. 1,3,5-triphenylbenzene is a tracer for burning plastic and has been related to levels of bisphenol A in the air, so the actual release of bisphenol A to the atmosphere could result from burning the plastic. Bisphenol A belongs to the group of endocrine disruptors. Little is known about the effects of BPA on human female reproduction. BPA levels appear to be inversely related to the number of oocytes retrieved in IVF cycles, and it also appears to negatively affect the ovulatory peak of estradiol. Study design, size, duration In the frame of EcoFoodFertility project a cross sectional study conducted in Campania Region (Southern Italy), between January 2019 and December 2020, 74 women, no smokers, no chronic diseases, not exposed to occupational risk factors. living for at least 5 years in areas with low environmental impact (LEI, 31 women), Alto-Medio Sele in province of Salerno and high environmental impact (HEI, 43 women), so-called “Land of Fires” in province of Naples, were selected. Participants/materials, setting, methods Participants have a normal ovarian reserve, average age 32.05 + 3.49, with infertility duration between 26 and 39 months and at the first experience of an IVF cycle. ELISA was used for measuring bisphenol A in blood and Follicular Fluids (FFs), expressed in ng/ mL. 5 mL glass tubes, without additives, not siliconized and kept in a horizontal position were used. FFs were bloodless with a negative albumin test. Main results and the role of chance Differents levels of BPA were found in all processed samples. In the LEI (Low Environmental Impact) group, serum levels vary from a minimum of 3.1 ng/mL to a maximum of 7.7 ng/mL (4.1 ± 1.6) and the Follicular Fluids levels vary from a minimum of 7,1 ng/mL to a maximum of 55.3 ng/mL (13.8 ± 10.9). In the HEI (High Environmental Impact) group, serum levels vary from a minimum of 69.2 ng/mL to a maximum of 167.8 ng/mL (95.5 ± 24.3) and Follicular Fluids levels vary from a minimum of 4.2 ng/mL to a maximum of 34.3 ng/mL (19.9 ± 9.2). Statistical processing of the data shows a highly significant variation in serum levels (p A moderately significant change (p Furthermore, the data did not show any correspondence between serum and Follicular Fluids for any of the participants tested. Limitations, reasons for caution The ELISA method for the determination of BPA seems suitable to us, however, the subject requires further biomonitoring studies, with a larger sample and greater selection of participants, to better understand the effects of BPA and its metabolites in FF and in other districts of the female reproductive system. Wider implications of the findings The results indicate that the greater bioaccumulation in women of the HEI group appears consistent with the environmental condition of the area and with the comparative studies already carried out within the EcoFoodFertility project. This is further evidence that pollution in this area can interfere with female fertility and beyond. Trial registration number G003

Study question Human exposure to polychlorinated biphenyls (PCBs) exists despite its ceased production since 1977. PCBs congeners harm reproductive health, but data remain inconclusive. Summary answer Evaluate relationship between blood concentrations of specific (PCBs) congeners and abortion rates in women undergoing IVF cycles living in areas with high and low pollution. What is known already PCBs are a class of synthetic chemicals that were widely used in industry until the 1970s and are found in many consumer products as refrigerants in electrical equipment, as flame retardants in plastics production and electronics. Continuous exposure to PCBs is of concern because they fall into the group of endocrine disruptors (EDCs), PCB congeners can spread throughout the female reproductive tract. Indeed, they have been found in human follicle fluids, placenta, amniotic fluid in embryos and fetuses Despite multiple reproductive health effects in women was reported, the results are sometimes inconsistent between experimental and epidemiological studies. Study design, size, duration In the frame of EcoFoodFertility Project, a cross sectional study conducted in Campania Region (Italy) to assess environmental impact on fertility and human health, blood samples were collected during the IVF cycles of the 65 women (aged 27.8 + 3.6) no smokers, BMI 23.5 – 27.9, normal menstruation, in two areas with high and low pollution between 2017 and 2019. The PCBs congeners we investigated were: estrogenic congeners (31,44,52,101,153), anti-estrogenic congeners (77,105,110,114,126,156,169) and other (28,118,138,180). Participants/materials, setting, methods Group A (n = 30) living in low polluted area (LPA), alto Medio Sele in province of Salerno, and group B (n = 35) living in highly polluted area (HPA), known as the “Land of Fires” due to the many sources of pollution. The blood sample was taken on the day of the oocyte pick-up and PCBs were measured by Gas Chromatography Coupled to (tandem) Mass Spectrometry. Statistical analyses were performed by GraphPad Prism 9. Main results and the role of chance Blood concentrations of PCBs are expressed as wet weight (nanograms per gram of serum) and as standardised lipid concentrations (nanograms per gram lipid). The PCB 169 congener was found in the highest concentration, 229.62 ng/g and, on average, accounted for 46.2 % of ΣPCBs tested. The PCB 77 (p Limitations, reasons for caution Although we have set up a strict control and survey protocol, our study also has limitations due to the relatively small sample size of the groups and as with almost all epidemiological studies on environmental impact, there may be confounders or co-exposures that could interfere with the observed associations. Wider implications of the findings Although PCBs are no longer produced, the exposure remains widespread due to their long biological half-life, accumulation in the food chain and human health impacts are still reported. Our findings confirm these concerns, therefore, the study of these old chemicals is still relevant and important and should be expanded. Trial registration number not applicable

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data.

Quality is a multidimensional and transversal concept also in the field of higher education. This and other considerations revealed some problems during application of quality principles to study p...

Background Large vessel occlusion (LVO) strokes are best treated with rapid endovascular therapy (EVT). There are two routes that LVO stroke patients can take to EVT therapy when transported by EMS: primary transport (ambulance transports directly to an endovascular stroke center (ESC) or secondary transport (EMS transports to a non-ESC then transfers for EVT). There is no clear evidence which path to care results in better functional outcomes for LVO stroke patients. To find this answer, an analysis of a large, real-world population of LVO stroke patients must be performed. Methods A pragmatic registry of LVO stroke patients from nine health systems across the United States. The nine health systems span urban and rural populations as well as the spectrum of socioeconomic statuses. We will use univariate and multivariate analysis to explore the relationships between type of EMS transport, socioeconomic factors, and LVO stroke outcomes. We will use geographic information systems and spatial analysis to examine the complex movements of patients in time and space. To detect an 8% difference between groups, with a 3:1 patient ratio of primary to secondary transports, 95% confidence and 80% power, we will need approximately 1600 patients. The primary outcome is the patients with modified Rankin Scale (mRS) ≤ 2 at 90 days. Subgroup analyses include patients who receive intravenous thrombolysis and duration of stroke systems. Secondary analyses include socioeconomic factors associated with poor outcomes after LVO stroke. Discussion Using the data obtained from the OPUS-REACH registry, we will develop evidence based algorithms for prehospital transport of LVO stroke patients. Unlike prior research, the OPUS-REACH registry contains patient-level data spanning from EMS dispatch to ninety day functional outcomes. We expect that we will find modifiable factors and socioeconomic disparities associated with poor outcomes in LVO stroke. OPUS-REACH with its breadth of locations, detailed patient records, and multidisciplinary researchers will design the optimal prehospital stroke system of care for LVO stroke patients.

Objective Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. Methods Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. Results Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). Conclusions ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making.

Large vessel occlusion (LVO) strokes are best treated with rapid endovascular therapy (EVT). There are two routes that LVO stroke patients can take to EVT therapy when transported by EMS: primary transport (ambulance transports directly to an endovascular stroke center (ESC) or secondary transport (EMS transports to a non-ESC then transfers for EVT). There is no clear evidence which path to care results in better functional outcomes for LVO stroke patients. To find this answer, an analysis of a large, real-world population of LVO stroke patients must be performed.A pragmatic registry of LVO stroke patients from nine health systems across the United States. The nine health systems span urban and rural populations as well as the spectrum of socioeconomic statuses. We will use univariate and multivariate analysis to explore the relationships between type of EMS transport, socioeconomic factors, and LVO stroke outcomes. We will use geographic information systems and spatial analysis to examine the complex movements of patients in time and space. To detect an 8% difference between groups, with a 3:1 patient ratio of primary to secondary transports, 95% confidence and 80% power, we will need approximately 1600 patients. The primary outcome is the patients with modified Rankin Scale (mRS) ≤ 2 at 90 days. Subgroup analyses include patients who receive intravenous thrombolysis and duration of stroke systems. Secondary analyses include socioeconomic factors associated with poor outcomes after LVO stroke.Using the data obtained from the OPUS-REACH registry, we will develop evidence based algorithms for prehospital transport of LVO stroke patients. Unlike prior research, the OPUS-REACH registry contains patient-level data spanning from EMS dispatch to ninety day functional outcomes. We expect that we will find modifiable factors and socioeconomic disparities associated with poor outcomes in LVO stroke. OPUS-REACH with its breadth of locations, detailed patient records, and multidisciplinary researchers will design the optimal prehospital stroke system of care for LVO stroke patients.

Disparities exist throughout our healthcare system, especially related to access to care. Advanced stroke care for strokes is only available at selected endovascular centers (ESCs) in the United States. Although the number of ESCs increase each year, this does not necessarily reflect increased access to care. Here, we look at the evolution of ESC in four states and disparities in access to advanced stroke care.This is a descriptive study of access to ESCs in four Northeastern states between 2015-2019. Using data from the United States Census Bureau and spatial analysis, we examined the proportion of the population with drive times of less than 60 minutes stratified by income, race/ethnicity, population density, and insurance. We also calculated the mean drive time for each of these socioeconomic groups from their census tracts to the nearest ESC.Between 2015 and 2019, the number of ESCs increased from 15 to 48. The proportion of patients within a 60-minute drive of an ESC increased from 77% to 88%. However, only 66% of the least densely populated quartile lived within 60 min of an ESC. By income, access to ESCs in the wealthiest quartile was 96.6% compared to 83.7% in the lowest quartile. Hispanics and non-Hispanic Blacks had the largest proportions of populations within 60 minutes of an ESC while Non-Hispanic Whites had the smallest.This study underscores the need to evaluate the placement of new ESCs to assure that these hospitals decrease disparities and increase access to advanced stroke care.

BACKGROUNDMost individuals with prior COVID-19 disease manifest long-term protective immune responses against reinfection. Accordingly, we tested the hypothesis that humoral immune and reactogenicity responses to a SARS-CoV-2 mRNA vaccine differ in individuals with and without prior COVID-19 disease.METHODSHealth care workers (n = 61) with (n = 30) and without (n = 31) prior COVID-19 disease received two 30 μg doses of Pfizer BNT162b2 vaccine 3 weeks apart. Serum IgG antibody against the spike receptor-binding domain; serum neutralizing activity; and vaccine reactogenicity were assessed longitudinally every 2 weeks for 56 days after the first injection.RESULTSThe COVID-19 group manifested more rapid increases in spike IgG antibody and serum neutralizing activity after the first vaccine dose but showed little or no increase after the second dose compared with the infection-naive group. In fact, spike IgG was at its maximum level after the first dose in 36% of the COVID-19 group versus 0% of the infection-naive group. Peak IgG antibody levels were lower but appeared to fall more slowly in the COVID-19 group versus the infection-naive group. Finally, adverse systemic reactions, e.g., fever, headache, and malaise, were more frequent and lasted longer after both the first and second injection in the COVID-19 group than in the infection-naive group.CONCLUSIONIndividuals with prior COVID-19 disease demonstrate a robust, accelerated humoral immune response to the first dose but an attenuated response to the second dose of BNT162b2 vaccine compared with controls. The COVID-19 group also experienced greater reactogenicity. Humoral responses and reactogenicity to BNT162b2 differ qualitatively and quantitatively in individuals with prior COVID-19 disease compared with infection-naive individuals.FUNDINGThis work was supported by Temple University institutional funds.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, post-concussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging, because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large scale (n = 5,000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for one year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

Objective In US emergency departments (EDs), the physician has limited ability to evaluate for common and serious conditions of the gastrointestinal (GI) mucosa such as a bleeding peptic ulcer. Although many bleeding lesions are self‐limited, the majority of these patients require emergency hospitalization for upper endoscopy (EGD). We conducted a clinical trial to determine if ED risk stratification with video capsule endoscopy (VCE) reduces hospitalization rates for low‐risk to moderate‐risk patients with suspected upper GI bleeding. Methods We conducted a randomized controlled trial at 3 urban academic EDs. Inclusion criteria included signs of upper GI bleeding and a Glasgow Blatchford score

Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a β-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute. Clinical trial registered with www.clinicaltrials.gov (NCT 04193878).

BackgroundCurrent recommendations in the United States are that subjects with a previous history of COVID-19 disease receive the full 2 dose mRNA vaccine regimen. We tested the hypothesis that humoral immune responses and reactogenicity to a SARS-CoV-2 mRNA vaccine (BNT-162b2) differ qualitatively and quantitatively in subjects with prior SARS-CoV-2 infection versus infection-naïve subjects.MethodsHealth care workers (n=61) from a single academic institution with and without prior COVID-19 received two 30 µg doses of BNT162b2 vaccine 3 weeks apart. The COVID group (n=30) received vaccine approximately 7 months post infection. IgG antibody against the Spike receptor-binding domain (RBD), serum neutralizing activity and vaccine adverse reactions were assessed every 2 weeks for 56 days after the 1st injection. A longitudinal design and long study duration allowed the onset, maximum response and initial decay rate of Spike IgG antibody to be assessed in each subject. In addition, Spike IgG antibody levels are expressed as µg / mL to provide normal values for clinical decision making.FindingsSpike IgG responses were highly variable in both groups. However, the COVID group manifested rapid increases in Spike IgG antibody and serum neutralizing activity post 1st vaccine dose but little or no increase in Spike IgG or serum neutralizing activity after the 2nd dose. In fact, Spike IgG was maximum prior to the 2nd dose in 36% of the COVID group and 0% of controls. Peak IgG antibody was lower but appeared to fall more slowly in the COVID than in the control group. Finally, adverse systemic reactions e.g., fever, headache and malaise, after both the 1st and 2nd injection were more frequent and lasted longer in the COVID group than in the control group.ConclusionsHealth care workers with prior COVID-19 demonstrate a robust, accelerated humoral immune response to the 1st dose of the COVID-19 mRNA vaccine but attenuated response to the 2nd dose. They also experience greater reactogenicity than controls. Accordingly, subjects with prior COVID-19 may require only a single dose of vaccine.

Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. Approach: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. Results: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. Significance: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.

Presence of teeth in a newborn represents a rare finding and a disturbance of biological chronology of teeth. The aim of this paper is to report two cases with neonatal teeth histologically examined.In this paper two cases of patients with neonatal teeth are reported and histological examinations of three extracted teeth are described. We report an exceptional finding in one of the neonatal teeth microscopically examined: a massive inflammatory infiltration in the pulp tissue similar to that in pulpitis.The management of natal and neonatal teeth usually includes the extraction in case of ulceration on the tongue or severe tooth mobility to prevent accidental inhalation or feeding disturbances. The presence of an inflammatory infiltration of pulp tissue in one of teeth histologically examined suggests to review the indications for extraction considered to date.The management of natal and neonatal teeth should consider the presence of an inflammatory infiltration of pulp tissue. An anamnestic interview is advisable in ordert to deeply investigate about possible behaviours of the child due to pain or discomfort.

Study Objectives Many patients in Emergency Departments (EDs) after motor vehicle collisions (MVCs) develop post-traumatic stress disorder (PTSD) or major depressive episode (MDE). This report from the AURORA study focuses on associations of pre-MVC sleep problems with these outcomes 8 weeks after MVC mediated through peritraumatic distress and dissociation and 2-week outcomes. Methods A total of 666 AURORA patients completed self-report assessments in the ED and at 2 and 8 weeks after MVC. Peritraumatic distress, peritraumatic dissociation, and pre-MVC sleep characteristics (insomnia, nightmares, daytime sleepiness, and sleep duration in the 30 days before the MVC, trait sleep stress reactivity) were assessed retrospectively in the ED. The survey assessed acute stress disorder (ASD) and MDE at 2 weeks and at 8 weeks assessed PTSD and MDE (past 30 days). Control variables included demographics, MVC characteristics, and retrospective reports about PTSD and MDE in the 30 days before the MVC. Results Prevalence estimates were 41.0% for 2-week ASD, 42.0% for 8-week PTSD, 30.5% for 2-week MDE, and 27.2% for 8-week MDE. Pre-MVC nightmares and sleep stress reactivity predicted 8-week PTSD (mediated through 2-week ASD) and MDE (mediated through the transition between 2-week and 8-week MDE). Pre-MVC insomnia predicted 8-week PTSD (mediated through 2-week ASD). Estimates of population attributable risk suggest that blocking effects of sleep disturbance might reduce prevalence of 8-week PTSD and MDE by as much as one-third. Conclusions Targeting disturbed sleep in the immediate aftermath of MVC might be one effective way of reducing MVC-related PTSD and MDE.

Background and Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. Methods: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. Results: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09–1.21]; P =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32–1.34]; P =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia ( P =0.36) or stroke ( P =0.33). Conclusions: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.

Invasive Cervical Root Resorption (ICRR) has a poor known aetiology, compared with typical external root resorption it appears very aggressive, posing a high risk of tooth loss. ICCR is often misdiagnosed, the resorption is caused by cells of the peridontium penetrating the outer surface of the root in the cervical region, spreading out throughout the root dentin. ICCR is usually detected in the adulthood on permanent teeth, anyway in a small amount of cases is possible to observe ICCR on impacted permanent canines during the adolescence and first adulthood.The aim of this paper is to present our experience with a ICCR case occurred in a young woman previously treated for an impacted canine with orthodontic therapy.

Introduction: Mechanical ventilation is a commonly performed procedure in the emergency department (ED). Approximately 240,000 patients per year receive mechanical ventilation in the ED representing 0.23% of ED visits. An ED-based trial published in 2017 showed that a bundle of interventions in mechanically ventilated patients, including low tidal volume ventilation, reduced the development of acute respiratory distress syndrome by nearly 50%. Prior literature has shown that as many as 40% of ED patients do not receive lung protective ventilation. Our goal was to determine whether differences exist between the percent of males vs females who are ventilated at ≥ 8 milliliters per kilogram (mL/kg) of predicted body weight. Methods: We conducted this study at Temple University Hospital, a tertiary care center located in Philadelphia, Pennsylvania. This was a planned subgroup analysis of study looking at interventions to improve adherence to recommended tidal volume settings. We used a convenience sample of mechanically ventilated patients in our ED between September 1, 2017, and September 30, 2018. All adult patient > 18 years old were eligible for inclusion in the study. Our primary outcome measure was the number of patients who had initial tidal volumes set at > 8 mL/kg of predicted body weight. Our secondary outcome was the number of patients who had tidal volumes set at ≥ 8 mL/kg at 60 minutes after initiation of mechanical ventilation. Results: A total of 130 patients were included in the final analysis. We found that significantly more females were initially ventilated with tidal volumes ≥ 8 mL/kg compared to men: 56% of females vs 9% of males (p=

Introduction Given the many causes of seizures, emergency physicians often utilize brain computed tomography (CT) to evaluate for intracranial pathology. Previously, we have validated the LIMIT (Let's Image Malignancy, Intracranial Hemorrhage, and Trauma) clinical decision instrument (CDI) study to determine which patients with recurrent seizures require emergent neuroimaging. The LIMIT CDI had a negative predictive value (NPV) of 99.9%. Here, we seek to compare the LIMIT CDI to unstructured physician judgement. Methods This was an observational study of patients who presented with a complaint of seizure. A research assistant reviewed the electronic medical record (EMR) for each patient and applied the LIMIT CDI. Brain CT was used as a proxy for physician judgement. If no brain CT was ordered and the patient was discharged from the emergency department (ED), the EMR was searched to determine whether patient had any medical visits within one year of the index visit. If the patient had no new neurological findings on follow up or abnormalities on follow up neuroimaging, this was considered a patient who did not require a brain CT in the ED. Patients who did not have a CT on their ED visit and had no follow up visits were excluded. Results 1739 patients were screened and 1108 patients were in the final analysis. 24 patients who did not have a brain CT and no follow up visits were excluded. 10 patients (0.9%) had positive CTs. 9/10 of the patients were identified by the CDI resulting in a sensitivity of 90%, specificity of 81.1% and a negative predictive value (NPV) of 99.9%, and a negative likelihood ratio (LR) of 0.12. Clinician judgement identified all 10 patients with a positive brain CT for a sensitivity of 100%, specificity of 67.8%, and a NPV and negative LR of 100% and 0, respectively. Using unstructured clinical judgement, EPs ordered 364 brain CTs while only 217 brain CTs would have been ordered using the CDI, a reduction of 13.3%. Discussion When compared to unstructured physician judgement, the LIMIT CDI would have reduced brain CT usage by more than 13%. Although the LIMIT CDI needs to be validated in a larger set of patients, it performed better than unstructured physician judgement for evaluating need for emergent neuroimaging after recurrent seizures.

OBJECTIVES: Neurovascular and neurocritical care emergencies constitute a leading cause of morbidity/mortality. There has been great evolution in this field, including but not limited to extended time‐window therapeutic interventions for acute ischemic stroke. The intent of this article is to evaluate the goals and future direction of clinical rotations in neurovascular and neurocritical care for emergency medicine (EM) residents. METHODS: A panel of 13 board‐certified emergency physicians from the Society for Academic Emergency Medicine (SAEM) neurologic emergencies interest group (IG) convened in response to a call for publications—three with fellowship training/board certification in stroke and/or neurocritical care; five with advanced research degrees; three who have been authors on national practice guidelines; and six who have held clinical duties within neurology, neurosurgery, or neurocritical care. A mixed‐methods analysis was performed including a review of the literature, a survey of Council of Emergency Medicine Residency Directors (CORD) residency leaders/faculty and SAEM neuro‐IG members, and a consensus review by this panel of select neurology rotations provided by IG faculty. RESULTS: Thirteen articles for residency neurovascular education were identified: three studies on curriculum, three studies evaluating knowledge, and seven studies evaluating knowledge after an educational intervention. Intervention outcomes included the ability to recognize and manage acute strokes, manage intracerebral hemorrhage, calculate National Institutes of Health Stroke Scale (NIHSS), and interpret images. In the survey sent to CORD residency leaders and neuro‐IG faculty, response was obtained from 48 programs. A total of 52.1% indicated having a required rotation (6.2% general neurology, 2% stroke service, 18.8% neurologic intensive care unit, 2% neurosurgery, 22.9% on a combination of services). The majority of programs with required rotations have a combination rotation (residents rotate through multiple services) and evaluations were positive. CONCLUSIONS: Variability exists in the availability of neurovascular/neurocritical care rotations for EM trainees. Dedicated clinical time in neurologic education was beneficial to participants. Given recent advancements in the field, augmentation of EM residency training in this area merits strong consideration.

Background: Patients with cancer are at higher risk of developing COVID-19 disease, adverse outcomes, and increased mortality. Phase III COVID-19 vaccine trials have demonstrated safety/efficacy against COVID-19 and prevented hospitalizations and deaths;however, most excluded ptcpts with cancer. We present phase 3 tozinameran mRNA COVID-19 vaccine trial results from ptcpts with a cancer history at baseline, either ongoing or not, per the Charlson Comorbidity Index and up to 6 months of follow-up. Methods: Between Jul 2020-Jan 2021, 46429 ptcpts ≥12 y at 152 sites in 6 countries were randomized in a placebo-controlled, observer-blinded trial of 2-dose tozinameran, showing 95% protection against COVID-19 and favorable safety (Polack et al NEJM, Dec 2020). After emergency use authorization, ptcpts were allowed to unblind and placebo recipients received vaccine. Data prior to unblinding for crossover up to 13 Mar 2021 are presented for ptcpts ≥16 y for safety and ≥12 y for efficacy. Adverse event (AE) data are controlled for follow-up time before unblinding and reported as incidence rate (IR) per 100-person-y of follow-up. Results: Of ptcpts ≥16 y, 1647 had a prior diagnosis of cancer and were not on active immunosuppressive treatment (755 M;892 F;median age 66 y [range 22-91]). Most common solid cancers included breast (n=458), prostate (n=360), and melanoma (n=210). AEs were reported at IRs of 94.0 (vaccine) and 49.3 (placebo) per 100-person-y;most common AEs were reactogenicity events (injection-site pain [IR: 40.2 vaccine;4.2 placebo];fatigue [IR: 21.4 vaccine;7.6 placebo];pyrexia [IR: 19.8 vaccine;0.7 placebo]). 1 vaccine ptcpt withdrew due to a vaccine-related AE. No vaccine-related deaths were reported. Among ptcpts ≥12 y with cancer, 3 vaccine and 27 placebo recipients developed COVID-19 from 7 days post-Dose 2;vaccine efficacy (VE) was 89.7% (95% CI 66.5-98.0%). This compares favorably with overall VE of 91.1%. Updated results will be presented. Conclusions: Tozinameran has similar efficacy/safety in ptcpts with cancer as in the overall population. These results inform tozinameran use in COVID-19 and in future trials in patients with cancer. Clinical trial identification: NCT04368728. Editorial acknowledgement: Editorial assistance was provided by Erin Bekes, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer. Legal entity responsible for the study: Study sponsored by BioNTech, managed by Pfizer. Funding: Pfizer and BioNTech. Disclosure: S.J. Thomas: Financial Interests, Personal and Institutional, Research Grant, Advisory role: Pfizer. J.L. Perez: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S.P. Lockhart: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S. Hariharan: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. N. Kitchin: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. R. Bailey: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. K. Liau: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. E. Lagkadinou: Financial Interests, Personal, Full or part-time Employment: BioNTech. O. Tureci: Financial Interests, Personal, Research Grant: BioNTech. U. Sahin: Financial Interests, Personal, Research Grant: BioNTech. X. Xu: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S.S. Dychter: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. C. Lu: Financial Interests, Personal, Full or part-time Employment: Pfizer. W. Gruber: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. All other authors have declared no conflicts of interest.

Objective The assessment of the severity of upper gastrointestinal hemorrhage in emergency department (ED) patients is difficult to assess with commonly available diagnostic tools. Small studies have shown that video capsule endoscopy (VCE) is a promising risk-stratification method and may be better than current clinical decision rules such as the Rockall score and the Glasgow Blatchford score. This review aims to assess the accuracy of VCE to detect active upper gastrointestinal hemorrhage compared to a reference standard. Methods The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology was used to perform a review of studies that have measured the diagnostic accuracy of VCE. Studies were included if they measured ED use of VCE for upper GI hemorrhage as compared to a reference standard of an esophagogastroduodenoscopy (EGD). A meta-analysis was performed on select patients using a fixed effects and random-effects model to determine the primary outcome of diagnostic test accuracy. Results 40 studies were screened for eligibility and five studies representing 193 patients met the inclusion and exclusion criteria. All patients received both a VCE and an EGD. The sensitivity and specificity of VCE were 0.724 and 0.748, respectively. The diagnostic odds ratio was 6.29 (95% CI: 3.23–12.25) and the summary receiver operating characteristic curve was 0.782. Conclusions VCE demonstrated high accuracy for detecting upper GI hemorrhage in this meta-analysis of existing studies. In light of the potential advantages of VCE in the ED, further research is warranted to further establish its role.

Background Studies have shown the value of CT brain imaging in adults with first-time seizures, but there are no recommendations regarding emergent brain CTs in persons with an established seizure disorders. Our study aimed to derive a clinical decision instrument (CDI) to determine which patients with status epilepticus (SE) require emergent brain imaging. Methods This was a retrospective chart review of patients who presented to our emergency department with SE between 2010 and 2018. Patients with first-time seizures were excluded. A priori, we defined high risk criteria for emergent imaging as well as positive findings on brain CT. High risk criteria included known malignancy, trauma, and immunosuppression. Positive CT scans included findings such as intracranial hemorrhage (ICH) and mass. Results We identified 214 patients who met inclusion criteria Of the 181 patients without high risk criteria, 3% had positive CT scans. Of the 33 patients with high risk criteria, 10% had positive CT scans. The sensitivity, specificity, PPV, and NPV for our initial CDI were 38%, 85%, 9%, and 97%. Adding the criterion of prior ICH would have lowered our miss rate to 0.6%. Modifying our CDI to 1) History of ICH, 2) Malignancy, 3) Immunosuppression, and 4) Trauma would result in a CDI with sensitivity, specificity, PPV, and NPV of 87.5%, 87.4%, 21.2%, and 99.5%. Conclusions By using four criteria to identify high risk patients, we can defer CT scanning in the vast majority of patients with SE and known seizure disorders. This CDI should be prospectively validated before adoption.

Objectives There is limited knowledge of the relationship between mechanical thrombectomy (MT) and endothelial inflammation in large-vessel occlusion (LVO) acute ischemic stroke (AIS). Intimal arterial damage releases tissue factor, a precipitant of the clotting cascade and thrombosis. We report changes in blood coagulation markers after MT treated with and without tissue plasminogen activator for AIS. Materials and Methods Cases of LVO-AIS treated with MT were included. Blood coagulation marker levels were measured within 10 h of stroke onset as a baseline and then 48 h later. Assayed biomarkers included: tissue factor procoagulant activity (TFPCA), factor VII (FVII), activated factor VII (FVIIa), factor VIII (FVIII), d-dimer, thrombin-antithrombin complex (TAT), plasminogen activator inhibitor-1 (PAI-1), and tissue factor pathway inhibitor (TFPI). Biomarker levels of MT with tissue plasminogen activator (TPA) or without (non-TPA) are reported. Results Biomarker levels from five patients with LVO-AIS treated with MT (three non-TPA, two TPA) were included. In non-TPA cases, TFPCA and PAI-1 increased while FVII, FVIIa, TAT, d-dimer, and TFPI decreased from baseline to 48 h. In TPA cases, TFPCA, FVIIa, d-dimer, TFPI, and PAI-1 decreased while FVIII increased from baseline to 48 h. Conclusions TFPCA increased after MT in non-TPA but decreased in TPA treated patients. This finding suggests that MT is associated with elevated inflammation and procoagulation which may be reduced with TPA treatment. With further validation, the increase in TFPCA levels could help guide anticoagulant management of patients with MT without TPA.