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Background/Aims Fibrinolytic therapy with tenecteplase has been proposed for patients with pulmonary embolism but the optimal dose is unknown. Higher-than-necessary dosing is likely to cause excess bleeding. We designed an adaptive clinical trial to identify the minimum and assumed safest dose of tenecteplase that maintains efficacy. Methods We propose a Bayesian adaptive, placebo-controlled, group-sequential dose-finding trial using response-adaptive randomization to preferentially allocate subjects to the most promising doses, dual analyses strategies (continuous and dichotomized) using a gatekeeping approach to maximize clinical impact, and interim stopping rules to efficiently address competing trial objectives. The operating characteristics of the proposed design were evaluated using Monte Carlo simulation across multiple hypothetical efficacy scenarios. Results Simulation demonstrated response-adaptive randomization can preferentially allocate subjects to doses which appear to be performing well based on interim data. Interim decision-making, including the interim evaluation of both analysis strategies with gatekeeping, allows the trial to continue enrollment when success with the dichotomized analysis strategy appears sufficiently likely and to stop enrollment and declare superiority based on the continuous analysis strategy when there is little chance of ultimately declaring superiority with the dichotomized analysis. Conclusion The proposed design allows evaluation of a greater number of dose levels than would be possible with a non-adaptive design and avoids the need to choose either the continuous or the dichotomized analysis strategy for the primary endpoint.

Background: For surveillance of episodic illness, the emergency department (ED) represents one of the largest interfaces for generalizable data about segments of the US public experiencing a need for unscheduled care. This protocol manuscript describes the development and operation of a national network linking symptom, clinical, laboratory and disposition data provides a public database dedicated to the surveillance of acute respiratory infections (ARIs) in EDs. Methods: The Respiratory Virus Laboratory Emergency Department Network Surveillance (RESP-LENS) network represents the collaboration between 24 investigators, representing 109 hospitals, and the Centers for Disease Control and Prevention (CDC) to survey viral infections. All data originate from electronic medical records (EMRs) accessed by standard query language (SQL) coding. Each Tuesday, data are imported into the standard data form for acute respiratory illness (ARI) visits that occurred the prior week (termed the index file); outcomes at 30 days and ED volume are also recorded. Up to 325 data fields can be populated for each case. Data are transferred from sites into an encrypted Google Cloud Platform, then programmatically checked for compliance, parsed, and aggregated into a central database a second cloud platform prior to transfer to CDC. Results: As of April, 2023, the network has reported index and 30-day data on over 560,000 ARI cases out of over 3.7 million ED encounters. Post-contracting challenges to network execution have included local shifts in testing policies and platforms, delays in ICD-10 coding to detect ARI cases, and site-level personnel turnover. The network is addressing these challenges and is poised to begin streaming weekly data for dissemination. Conclusions: The RESP-LENS network provides a living, weekly updated database that is a public health resource to survey the epidemiology, viral causes, and outcomes of ED patients with acute respiratory infections.

Background The Spanish region of Galicia is one of the most fire-prone areas in Europe. Most wildfires are directly or indirectly related to human activities, suggesting that socioeconomic factors likely can inform wildfire management. Socioeconomic factors, for example, could help explain the causes and distribution of wildfires spatially and temporally within the region. We sought to examine how socioeconomic and biophysical variables and their fluctuations over time (2000–2015) might influence wildfire ignitions and hectares burned in Galicia using municipality-level data describing socioeconomic factors and forest land wildfires. Results We used cluster analysis to characterize socioeconomic variation in our data set and regression analysis of panel data to investigate jointly the temporal and spatial dimensions of correlation between socioeconomic factors and wildfires. Using cluster analysis, we divided the region inter-territorially according to socioeconomic characteristics. Clustering divisions were found to have a similar pattern to that of Galician provinces. Our regression models for each cluster indicate that several socioeconomic factors are at least correlated with and may tend to influence wildfire occurrence and burned area in Galicia. We also found discernible patterns related to our identified clusters, confirming that differences between territories exist regarding the likely influence of socioeconomic factors on the number of wildfire ignitions and hectares burned. Conclusions Results suggest that socioeconomic factors are as crucial as meteorological variables for understanding wildfire ignitions and burned area in Galicia (Spain). Accurate knowledge of inter-territorial socioeconomic differences could help public officials and forest managers to design wildfire prevention policies best suited to the socioeconomic, cultural, and environmental circumstances of each territory.

Older adults represent a disproportionate share of severe COVID-19 presentations and fatalities, but we have limited understanding of the differences in presentation by age and the association between less typical emergency department (ED) presentations and clinical outcomes.This retrospective cohort study used the RECOVER Network registry, a research collaboration of 86 EDs in 27 U.S. states. We focused on encounters with a positive nasopharyngeal swab for SARS-CoV-2, and described their demographics, clinical presentation, and outcomes. Sequential multivariable logistic regressions examined the strength of association between age cohort and outcomes.Of 4536 encounters, median patient age was 55 years, 49% were women, and 34% were non-Hispanic Black persons. Cough was the most common presenting complaint across age groups (18-64, 65-74, and 75+): 71%, 67%, and 59%, respectively (p 0.001). Neurological symptoms, particularly altered mental status, were more common in older adults (2%, 11%, 26%; p 0.001). Patients 75+ had the greatest odds of ED index visit admission of all age groups (adjusted odds ratio [aOR] 6.66; 95% CI 5.23-8.56), 30-day hospitalization (aOR 7.44; 95% CI 5.63-9.99), and severe COVID-19 (aOR 4.26; 95% CI 3.45-5.27). Compared to individuals with alternate presentations and adjusting for age, patients with typical symptoms (fever, cough and/or shortness of breath) had similar odds of ED index visit admission (aOR 1.01; 95% CI 0.81-1.24), potentially higher odds of 30-day hospitalization (aOR 1.23; 95% CI 1.00-1.53), and greater odds of severe COVID-19 (aOR 1.46; 95% CI 1.12-1.90).Older patients with COVID-19 are more likely to have presentations without the most common symptoms. However, alternate presentations of COVID-19 in older ED patients are not associated with greater odds of mechanical ventilation and/or death. Our data highlights the importance of a liberal COVID-19 testing strategy among older ED patients to facilitate accurate diagnoses and timely treatment and prophylaxis.

Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) drugs may modify risk associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we assessed whether baseline therapy with ACEIs or ARBs was associated with lower mortality, respiratory failure (noninvasive ventilation or intubation), and renal failure (new renal replacement therapy) in SARS-CoV-2-positive patients. This retrospective registry-based observational cohort study used data from a national database of emergency department patients tested for SARS-CoV-2. Symptomatic emergency department patients were accrued from January to October 2020, across 197 hospitals in the United States. Multivariable analysis using logistic regression evaluated end points among SARS-CoV-2-positive cases, focusing on ACEIs/ARBs and adjusting for covariates. Model performance was evaluated using the c statistic for discrimination and Cox plotting for calibration. A total of 13 859 (99.9%) patients had known mortality status, of whom 2045 (14.8%) died. Respiratory failure occurred in 2485/13 880 (17.9%) and renal failure in 548/13 813 (4.0%) patients with available data. ACEI/ARB status was associated with a 25% decrease in mortality odds (odds ratio [OR], 0.75; 95%CI, 0.59-0.94; P = .011; c = .82). ACEIs/ARBs were not significantly associated with respiratory failure (OR, 0.89; 95%CI, 0.78-1.06; P = .206) or renal failure (OR, 0.75; 95%CI, 0.55-1.04; P = .083). Adjusting for covariates, baseline ACEI/ARB was associated with 25% lower mortality in SARS-CoV-2-positive patients. The potential mechanism for ACEI/ARB mortality modification requires further exploration.

Background: In the Spanish region of Galicia, one of the most fire-prone areas in Europe, most wildfires are directly or indirectly related to human activities, so socioeconomic conditions and population characteristics become determinant in wildfire management. Socioeconomic factors could also help explain the causes and distribution of wildfires spatially and temporally within the region. We sought to improve the temporal and spatial understanding of the causes of forest land wildfires in Galicia by analyzing the importance of socioeconomic and natural variables over the wildfire ignitions and hectares burned during 2001-2015. We established the municipality as the smallest geographical section with readily available information on socioeconomic factors and forest land wildfires.Results: We used clustering to analyze the spatial dimension and regression analysis of panel data to investigate the temporal dimension. Through the cluster analysis, we divided the region interterritorially according to its socio-economic behavior; nevertheless, our results suggest that the geographical distribution of the municipalities belonging to the four clusters has a similar pattern to that of the Galician provinces. Our regression models for each cluster indicate that several socioeconomic factors are at least correlated with and may tend to influence wildfire occurrence and burned area in Galicia. We also found discernable patterns related to our identified clusters, confirming that differences between territories exist regarding the likely influence of socioeconomic factors on the number of wildfire ignitions and hectares burned.Conclusions: Results suggest that explanatory socioeconomic variables are as crucial as meteorological variables in wildfire ignitions and burned area and that an accurate knowledge of inter-territorial socioeconomic differences could help to design wildfire prevention policies best suited to the socioeconomic, cultural, and environmental circumstances of each territory.

Patients with atrial fibrillation (AF) are frequently admitted from the emergency department (ED), and when discharged, are not reliably prescribed indicated anticoagulation. We report the impact of a novel computerized ED AF pathway orderset on discharge rate and risk-appropriate anticoagulation in patients with primary AF.The orderset included options for rate and rhythm control of primary AF, structured risk assessment for thrombotic complications, recommendations for anticoagulation as appropriate, and follow up with an electrophysiologist. All patients discharged from the ED in whom the AF orderset was utilized over an 18-month period comprised the primary study population. The primary outcome was the rate of appropriate anticoagulation or not according to confirmed CHADS-VASC and HASBLED scores. Additionally, the percentage of primary AF patients discharged directly from the ED was compared in the 18-month periods before and after introduction of the orderset.A total of 56 patients, average age 57.8 years and average initial heart rate 126 beats/minute, were included in the primary analysis. All 56 (100%; 95% confidence interval, 94-100) received guideline-concordant anticoagulation. The discharge rates in the pre- and postorderset implementation periods were 29% and 41%, respectively (95% confidence interval for 12% difference, 5-18).Our novel AF pathway orderset was associated with 100% guideline-concordant anticoagulation in patients discharged from the ED. Availability of the orderset was associated with a significant increase in the proportion of ED AF patients discharged.

Recruitment has been linked to decreases in the ratio of age-specific mortality (M′) to mass-specific growth (G′), and year-class strength may be predicted by the age when M′/G′ = 1. Hydrological stress adversely affects these parameters for species inhabiting floodplains; however, the relationship between M′ and G′ in hydrologically variable environments is poorly understood. We evaluated age-specific mortality for six species from a 20-year time series and growth curves from otolith length-at-age data. We assessed the effect of hydrology on the transitional age (age M′/G′ = 1) at 21 sites representing a hydrological gradient. Disturbance intensity influenced age-specific mortality but had no effect on mass-specific growth. The transitional age was inversely correlated with annual density, but weakly associated with population biomass. Hydrological disturbance shifted the transitional age to older ages, reducing recruitment overall. We demonstrated that the M′/G′ transition was affected adversely by hydrological stress and can be applied to a diverse group of taxa. Growth, survivorship, and the transitional age should be evaluated to improve population modelling efforts used to predict the influence of future restoration actions.

Logistic regression plays a fundamental role in the production of decision rules, risk assessment, and in establishing cause and effect relationships. This primer is aimed at novice researchers with minimal statistical expertise.Introduce the logit equation and provide a hands-on example to facilitate understanding of its benefits and limitations.This primer reviews the mathematical basis of a logit equation by comparing and contrasting it with the simple straight-line (linear) equation. After gaining an understanding of the meaning of beta coefficients, readers are encouraged to download a free statistical program and database to produce a logistic regression analysis. Using this example, the narrative then discusses commonly used methods to describe model fitness, including the C-statistic, chi square, Akaike and Bayesian Information Criteria, McFadden's pseudo RLogistic regression can provide information about the association of independent variables with important clinical outcomes, which can be the first step to show predictiveness or causation of variables on the outcomes of interest. © 2022 Elsevier Inc.

Venous thromboembolism (VTE) includes the diagnosis of either deep venous thrombosis (DVT) and/or pulmonary embolism (PE). This review discusses an evidence-based approach to the outpatient treatment of VTE in the emergency care setting. Main findings: The majority of patients diagnosed with VTE in the acute care setting are at low risk for an adverse event. Outpatient treatment for patients deemed low-risk by validated clinical decision tools leads to safe, efficacious, patient-centered, and cost-effective care. From a patient perspective, outpatient treatment of VTE can been simplified by the use of direct oral anticoagulant (DOACs) medications, and is supported by clinical trial evidence, and clinical practice guidelines from international societies. Outpatient treatment of patients with DVT has been more widely accepted as a best practice, while adoption of outpatient treatment of low-risk patients with acute PE has lagged. Many acute care clinicians remain wary of discharging patients with PE, concerned about drug access, adherence, and follow-up. Patients with VTE should be risk stratified identically as emerging evidence has demonstrated efficacy and safety in the interdependence of acute care protocols for the outpatient treatment of low-risk DVT and PE. Clinicians who practice in the acute care setting should be comfortable with risk stratification, anticoagulation, and discharge of low-risk VTE.

The use of fibrinolytic agents in acute pulmonary embolism (PE), first described over 50 years ago, hastens the resolution of RV stain, leading to earlier hemodynamic improvement. However, this benefit comes at the increased risk of bleeding. The strongest indication for fibrinolysis is in high-risk PE, or that characterized by sustained hypotension, while its use in patients with intermediate-risk PE remains controversial. Fibrinolysis is generally not recommended for routine use in intermediate-risk PE, although most guidelines advise that it may be considered in patients with signs of acute decompensation and an overall low bleeding risk. The efficacy of fibrinolysis often varies significantly between patients, which may be at least partially explained by several factors found to promote resistance to fibrinolysis. Ultimately, treatment decisions should carefully weigh the risks and benefits of the individual clinical scenario at hand, including the overall severity, the patient's bleeding risk, and the presence of factors known to promote resistance to fibrinolysis. This review aims to further explore the use of fibrinolytic agents in the treatment of PE including specific indications, outcomes, and special considerations.

The Pulmonary Embolism Quality of Life questionnaire (PEmb-QoL) assesses quality of life (QoL) in patients with previous pulmonary embolism (PE).Our aim was to assess the agreement between the PEmb-QoL and interviews and to explore other QoL concerns in patients diagnosed with PE.This mixed-method study included interviews with 21 patients about QoL after PE, followed by the PEmb-QoL questionnaire. In interviews, patients were asked about their lived experiences and impact of PE. Our analysis identified the frequency and severity of decreased QoL in qualitative interviews and compared with the PEmb-QoL score. Excerpts that described the effect of PE on QoL in interview transcripts were transcoded to match the answers corresponding to the 1 to 6 numeric values for each question from the PEmb-QoL using a predetermined matrix (eg, "constant" and "daily" = all of the time = value 1) and directly compared with responses on the PEmb-QoL in the areas of emotional complaints and activities of daily living/social limitations.Interviews showed more functional impairment than predicted by PEmb-QoL. For fear of recurrence, 86% of participants had disagreements between PEmb-QoL scores and transcoded interview scores. We found 42% disagreement between reported descriptions of the inability to do or enjoy hobbies in interviews and the PEmb-QoL score.Patient interviews showed discordances compared with a validated psychometric tool. To capture a more detailed and accurate picture of the effect of PE on QoL, providers and researchers should consider the addition of qualitative methods to assess outcomes.

Increased body mass index (BMI) and metabolic syndrome (MetS) have been associated with adverse outcomes in viral syndromes. We sought to examine associations of increased BMI and MetS on several clinical outcomes in patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).The registry of suspected COVID-19 in emergency care (RECOVER) is an observational study of SARS-CoV-2-tested patients (n=27,051) across 155 United States emergency departments (EDs). We used multivariable logistic regression to test for associations of several predictor variables with various clinical outcomes.We found that a BMI ≥30 kg/mIn this large nationwide sample of ED patients, we report a significant association of both high BMI and composite MetS with poor outcomes in SARS-CoV-2-positive patients. Findings suggest that composite MetS profile may be a more universal predictor of adverse disease outcomes, while the impact of BMI is more heavily modulated by SARS-CoV-2 status.

Background Clinical guidelines have supported outpatient treatment of low-risk pulmonary embolism (PE) since 2014, but adoption of this practice has been slow. Direct oral anticoagulant (DOAC) therapy for venous thromboembolism (VTE) is now as common as vitamin K antagonist treatment, but data are sparse regarding outcomes for patients with low-risk PE treated with DOACs as outpatients. We conducted a systematic review of literature on outcomes of outpatient management for PE, including comparisons to inpatient treatment and differences by anticoagulant class. Methods We searched Medline, Embase, PubMed, CENTRAL, clinicaltrials.gov, and ICTRN for studies published from January 1980 through February 2019 using a predefined strategy developed with a medical librarian. We included English-language randomized controlled trials (RCTs) and prospective nonrandomized trials (NRTs) of adult patients diagnosed with acute, symptomatic PE, and discharged from the emergency department or within 48 hours. Our primary outcome included four major adverse outcomes (all-cause mortality, PE-related mortality, recurrent VTE, and major bleeding) within 30 and 90 days. A preplanned subanalysis of high-quality studies assessed outcomes associated with different anticoagulation treatment classes. Results Our initial search identified 6,818 records, of which 12 studies (four RCT, eight NRT) with a total of 3,191 patients were included in the review. All RCTs and six NRTs were determined to have low to moderate risk of bias and were classified as high quality. Outpatients in these studies (n = 1,814) had rates of 90-day major adverse outcomes below 1%, including all-cause mortality (0.7%, 95% confidence interval [CI] = 0.4% to 1.2%), PE-related mortality (0.06%, 95% CI = 0.01% to 0.3%), recurrent VTE (0.8%, 95% CI = 0.5% to 1.4%), and major bleeding (0.8%, 95% CI = 0.5% to 1.4%). Exploratory analysis revealed no association between anticoagulant treatment class and rates of major adverse outcomes. Conclusion Among patients with low-risk PE treated as outpatients, few patients experienced major adverse outcomes such as mortality, recurrent VTE, or major bleeding within 90 days.

This study examined anticoagulant use during and after a hospital encounter for venous thromboembolism (VTE), a transition of care largely uncharacterized in the literature.Adults with a VTE diagnosis code during a hospital encounter (emergency department [ED], observation area [OBS], or inpatient hospital [IP]) from January 2012 to August 2017 were identified in an electronic health records database. The first such hospital encounter was defined as the index VTE encounter. Patients were linked to a claims database and required to be continuously enrolled for six months before the index admission date through six months after the index discharge date. Anticoagulants administered during the index VTE encounter and filled on or within 30 days of discharge were summarized descriptively overall, and by the type of index VTE encounter (IP, No IP) and anticoagulants administered during the index VTE encounter.Among 2,968 eligible patients, mean (SD) age was 64 (16) years, 51% were female, 67% had an IP index VTE encounter, and 77% received anticoagulation therapy during the index VTE encounter. In total, 60% filled a prescription order for anticoagulant within 30 days post-discharge. Of those who received a direct oral anticoagulant (DOAC), warfarin, or parenteral anticoagulant only during the index VTE encounter, 74%, 69%, and 34%, respectively, filled a prescription for the same anticoagulant post-discharge. Patients treated with a DOAC or warfarin during an ED or OBS VTE encounter without a subsequent inpatient hospitalization were more likely to remain on the same anticoagulation therapy post-discharge than those with an inpatient hospitalization (81% vs 69% for DOAC and 75% vs 68% for warfarin).Many patients treated with anticoagulation therapy during a VTE hospital encounter did not fill a prescription for an anticoagulant within 30 days post-discharge, highlighting an opportunity for improved management of care transitions in this patient population.

Solving the opioid crisis requires immediate, innovative, and sustainable solutions. A number of promising strategies are being carried out by U.S. states and territories as part of their Opioid State Targeted Response (STR) plans funded through the 21(st) Century Cures Act, and they provide an opportunity for researchers to assess effectiveness of these interventions using pragmatic approaches. This paper describes a pilot study of Project Planned Outreach, Intervention, Naloxone, and Treatment (POINT), the intervention that served as the basis for Indiana’s STR-funded, emergency department (ED)-based peer specialist expansion that was conducted in preparation for a larger, multisite pragmatic trial. Through the pilot, we identified, documented, and corrected for challenges encountered while implementing planned study protocols. Per the project’s funding mechanism, the ability to move to the larger trial was determined by the achievement of 3 milestones: (1) successful replication of the intervention; (2) demonstrated ability to obtain the necessary sample size; and (3) observe a higher level of engagement in medication for addiction treatment in the POINT group compared to standard care. Overall implementation of the study protocols was successful, with only minor refinements to proposed procedures being required in light of challenges with (1) data access, (2) recruitment, and (3) identification of the expansion hospitals. All three milestones were reached. Challenges in implementing protocols and reaching milestones resulted in refinements that improved the study design overall. The subsequent trial will add to the limited but growing evidence on ED-based peer supports. Capitalizing on STR efforts to study an already scaling and promising intervention is likely to lead to faster and more sustainable results with greater generalizability than traditional, efficacy-focused clinical research.

Background Pulmonary embolism (PE) in children carries a significant morbidity and mortality. We examined previously described factors in 2 cohorts of children tested for PE and identified novel factors. Methods We combined data from 2 retrospective cohorts. Patients up to age 21 years were included who underwent imaging or D‐dimer testing for PE, with positive radiologic testing being the gold standard. Combined predictor variables were examined by univariate analysis and then forward stepwise multivariable logistic regression. Results The combined data set yielded 1103 patients with 42 unique predictor variables, and 93 PE‐positive patients (8.4%), with a median age of 16 years. Univariate analysis retained 17 variables, and multivariable logistic regression found 9 significant variables with increased probability of PE diagnosis: age‐adjusted tachycardia, tachypnea, hypoxia, unilateral limb swelling, trauma/surgery requiring hospitalization in previous 4 weeks, prior thromboembolism, cancer, anemia, and leukocytosis. Conclusion This combined data set of children with suspected PE discovered factors that may contribute to a diagnosis of PE: hypoxia, unilateral limb swelling, trauma/surgery requiring hospitalization in previous 4 weeks, prior thromboembolism, and cancer, age‐adjusted tachycardia, tachypnea, anemia, and leukocytosis. Prospective testing is needed to determine which criteria should be used to initiate diagnostic testing for PE in children.

Background The challenging clinical dilemma of detecting pulmonary embolism (PE) in suspected patients is encountered in a variety of healthcare settings. We hypothesized that the optimal diagnostic approach to detect these patients in terms of safety and efficiency depends on underlying PE prevalence, case mix, and physician experience, overall reflected by the type of setting where patients are initially assessed. The objective of this study was to assess the capability of ruling out PE by available diagnostic strategies across all possible settings. Methods and findings We performed a literature search (MEDLINE) followed by an individual patient data (IPD) meta-analysis (MA; 23 studies), including patients from self-referral emergency care (n = 12,612), primary healthcare clinics (n = 3,174), referred secondary care (n = 17,052), and hospitalized or nursing home patients (n = 2,410). Multilevel logistic regression was performed to evaluate diagnostic performance of the Wells and revised Geneva rules, both using fixed and adapted D-dimer thresholds to age or pretest probability (PTP), for the YEARS algorithm and for the Pulmonary Embolism Rule-out Criteria (PERC). All strategies were tested separately in each healthcare setting. Following studies done in this field, the primary diagnostic metrices estimated from the models were the “failure rate” of each strategy—i.e., the proportion of missed PE among patients categorized as “PE excluded” and “efficiency”—defined as the proportion of patients categorized as “PE excluded” among all patients. In self-referral emergency care, the PERC algorithm excludes PE in 21% of suspected patients at a failure rate of 1.12% (95% confidence interval [CI] 0.74 to 1.70), whereas this increases to 6.01% (4.09 to 8.75) in referred patients to secondary care at an efficiency of 10%. In patients from primary healthcare and those referred to secondary care, strategies adjusting D-dimer to PTP are the most efficient (range: 43% to 62%) at a failure rate ranging between 0.25% and 3.06%, with higher failure rates observed in patients referred to secondary care. For this latter setting, strategies adjusting D-dimer to age are associated with a lower failure rate ranging between 0.65% and 0.81%, yet are also less efficient (range: 33% and 35%). For all strategies, failure rates are highest in hospitalized or nursing home patients, ranging between 1.68% and 5.13%, at an efficiency ranging between 15% and 30%. The main limitation of the primary analyses was that the diagnostic performance of each strategy was compared in different sets of studies since the availability of items used in each diagnostic strategy differed across included studies; however, sensitivity analyses suggested that the findings were robust. Conclusions The capability of safely and efficiently ruling out PE of available diagnostic strategies differs for different healthcare settings. The findings of this IPD MA help in determining the optimum diagnostic strategies for ruling out PE per healthcare setting, balancing the trade-off between failure rate and efficiency of each strategy.

17 USC 105 interim-entered record; under temporary embargo. The article of record as published may be found at https://doi.org/10.1016/j.orbis.2022.02.006 or https://www.fpri.org/article/2022/04/a-maritime-conversation-with-america/ Over the last century, the U.S. Navy has encountered critical moments when the emergence of new technologies and competitors cause paradigmatic shifts, undermining established operations and force structure. Today, the rise of an assertive China and its new anti-access and area-denial capabilities threaten the aircraft carrier-based maritime dominance of the U.S. Navy. Citizens and elected officials alike need to be conversant in the process to create the strategy, forces, and metrics needed to guarantee that the United States wins the emerging maritime competition in the Western Pacific. It is time to explain to the American public the enduring considerations and limitations that shape the operations of their global Navy. U.S. Government affiliation is unstated in article text.

Invasive species are one of the greatest threats to ecosystems, disrupting ecosystem function and leading to the collapse and extinction of native species. While populations of native fishes in the Everglades are tied to the system's natural hydrological dynamics, Asian Swamp Eels (Monopterus albus/javanensis) are drought-resistant fish first reported from Florida in 1997 and the Everglades in 2007. Using a 26-year dataset that included a 13-year baseline period prior to swamp eel arrival in Taylor Slough, we assessed population changes of common small fishes and decapods that are important prey for larger vertebrate predators. After invasion, populations of two crayfishes collapsed by95 %, two fishes declined by80 %, two fishes had intermediate declines of 44-66 %, and three species remained unchanged. Species most strongly reduced were those dependent on predator-free habitats at the onset of the wet season, indicating drought-resistant swamp eels have introduced novel predator effects and disrupted the hydrology-mediated production of aquatic animals that are prey for many larger predators. Ongoing Everglades restoration is designed to restore hydrological conditions that support production of crayfishes and fishes, and nesting wading birds reliant on them. Water management may have facilitated the invasion of swamp eels. Our results suggest that the continued spread of swamp eels may result in adverse consequences for Everglades trophic dynamics and potentially diminish benefits expected from the $20B+ restoration.

Background: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. Purpose: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. Data Sources: MEDLINE from 1 January 1995 until 1 January 2021. Study Selection: 16 studies assessing at least 1 diagnostic strategy. Data Extraction: Individual-patient data from 20553 patients. Data Synthesis: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE con -sidered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probabil-ity-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresh-olds, with failure rates varying between 2% and 4% in the pre-defined patient subgroups. Limitations: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verifica-tion bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. Conclusion: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. Primary Funding Source: Dutch Research Council. (PROSPERO: CRD42018089366)

Background COVID-19 has been associated with increased risk of thromboembolism in critically ill patients. Objectives We sought to examine the association of SARS-CoV-2 test positivity and subsequent acute vascular thrombosis, including venous thromboembolism (VTE) or arterial thrombosis (AT) in, a large nationwide registry of emergency department patients tested with a nucleic acid test for suspected SARS-CoV-2. Methods The RECOVER registry includes 155 emergency departments across the US. We performed a retrospective cohort study to produce odds ratios for COVID+ versus COVID- status as a predictor of 30 day VTE or AT, adjusting for age, biological sex, active cancer, intubation, hospital length of stay (LOS), and ICU care. Results Comparing 14,056 COVID+ patients with 12,995 COVID- patients, the overall 30-day prevalence of VTE events was 1.4% versus 1.3%, respectively (p=0.44, χ2). Multivariable analysis identified that testing positive for SAR-CoV-2 status was negatively associated with both VTE (OR 0.76, 95% CI: 0.61-0.94) and AT (0.51, 0.32-0.80), whereas intubation, ICU care, and age>=50 were positively associated with both VTE and AT. Conclusions In contrast to other reports, results from this large, heterogenous national sample of ED patients tested for SARS-CoV-2, showed no association between vascular thrombosis and COVID-19 test positivity.

Mercury (Hg) contamination has been a persistent concern in the Florida Everglades for over three decades due to elevated atmospheric deposition and the system's propensity for methylation and rapid bioaccumulation. Given declines in atmospheric Hg concentrations in the conterminous United States and efforts to mitigate nutrient release to the greater Everglades ecosystem, it was vital to assess how Hg dynamics responded on temporal and spatial scales. This study used a multimedia approach (water and biota) to examine Hg and methylmercury (MeHg) dynamics across a 76-site network within the southernmost portion of the region, Everglades National Park (ENP), from 2008 to 2018. Hg concentrations across matrices showed that air, water, and biota from the system were inextricably linked. Temporal patterns across matrices were driven primarily by hydrologic and climatic changes in the park and no evidence of a decline in atmospheric Hg deposition from 2008 to 2018 was observed, unlike other regions of the United States. In the Shark River Slough (SRS), excess dissolved organic carbon and sulfate were also consistently delivered from upgradient canals and showed no evidence of decline over the study period. Within the SRS a strong positive correlation was observed between MeHg concentrations in surface water and resident fish. Within distinct geographic regions of ENP (SRS, Marsh, Coastal), the geochemical controls on MeHg dynamics differed and highlighted regions susceptible to higher MeHg bioaccumulation, particularly in the SRS and Coastal regions. This study demonstrates the strong influence that dissolved organic carbon and sulfate loads have on spatial and temporal distributions of MeHg across ENP. Importantly, improved water quality and flow rates are two key restoration targets of the nearly 30-year Everglades restoration program, which if achieved, this study suggests would lead to reduced MeHg production and exposure.

Objectives Identification of patients with coronavirus disease 2019 (COVID‐19) at risk for deterioration after discharge from the emergency department (ED) remains a clinical challenge. Our objective was to develop a prediction model that identifies patients with COVID‐19 at risk for return and hospital admission within 30 days of ED discharge. Methods We performed a retrospective cohort study of discharged adult ED patients (n = 7529) with SARS‐CoV‐2 infection from 116 unique hospitals contributing to the National Registry of Suspected COVID‐19 in Emergency Care. The primary outcome was return hospital admission within 30 days. Models were developed using classification and regression tree (CART), gradient boosted machine (GBM), random forest (RF), and least absolute shrinkage and selection (LASSO) approaches. Results Among patients with COVID‐19 discharged from the ED on their index encounter, 571 (7.6%) returned for hospital admission within 30 days. The machine‐learning (ML) models (GBM, RF, and LASSO) performed similarly. The RF model yielded a test area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI], 0.71–0.78), with a sensitivity of 0.46 (95% CI, 0.39–0.54) and a specificity of 0.84 (95% CI, 0.82–0.85). Predictive variables, including lowest oxygen saturation, temperature, or history of hypertension, diabetes, hyperlipidemia, or obesity, were common to all ML models. Conclusions A predictive model identifying adult ED patients with COVID‐19 at risk for return for return hospital admission within 30 days is feasible. Ensemble/boot‐strapped classification methods (eg, GBM, RF, and LASSO) outperform the single‐tree CART method. Future efforts may focus on the application of ML models in the hospital setting to optimize the allocation of follow‐up resources.

Background: The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism [VTE]; including venous thrombosis and pulmonary embolism [PE]) can be safely and effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial. Methods: This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes. Results: We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% [95% CI, 0.5%–1.7%]), and bleeding requiring hospitalization occurred in 12/1421 (0.8% [0.4%–1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% [0%–0.5%]). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%–9.5%) and was associated with a risk ratio of 6.0 (2.3–15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled. Conclusions: Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03404635

Author(s): Goldberg, Elizabeth M.; Hasegawa, Kohei; Lawrence, Alexis; Kline, Jeffrey A.; Camargo, Jr, Carlos A. | Abstract: Introduction: Coinfection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and another virus may influence the clinical trajectory of emergency department (ED) patients. However, little empirical data exists on the clinical outcomes of coinfection with SARS-CoV-2 Methods: In this retrospective cohort analysis, we included adults presenting to the ED with confirmed, symptomatic coronavirus 2019 who also underwent testing for additional viral pathogens within 24 hours. To investigate the association between coinfection status with each of the outcomes, we performed logistic regression. Results: Of 6,913 ED patients, 5.7% had coinfection. Coinfected individuals were less likely to experience index visit or 30-day hospitalization (odds ratio [OR] 0.57; 95% confidence interval [CI], 0.36-0.90 and OR 0.39; 95% CI, 0.25–0.62, respectively). Conclusion: Coinfection is relatively uncommon in symptomatic ED patients with SARS-CoV-2 and the clinical short- and long-term outcomes are more favorable in coinfected individuals.

Objective Facilities that process and package meat for consumer sale and consumption (meatpacking plants) were early sites of coronavirus disease 2019 (COVID‐19) outbreaks. The aim of this study was to characterize the association between meatpacking plant exposure and clinical outcomes among emergency department (ED) patients with COVID‐19 symptoms. Methods This was a retrospective cohort study of patients presenting to a single ED, from March 1 to May 31, 2020, who had: 1) symptoms consistent with COVID‐19 and 2) a COVID‐19 test performed. The primary outcome was COVID‐19 positivity, and secondary outcomes included hospital admission from the ED, ventilator use, intensive care unit (ICU) admission, hospital length of stay (LOS

Supplemental Digital Content is Available in the Text., Background: There is a need to characterize patients with HIV with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Setting: Multicenter registry of patients from 116 emergency departments in 27 US states. Methods: Planned secondary analysis of patients with suspected SARS-CoV-2, with (n = 415) and without (n = 25,306) HIV. Descriptive statistics were used to compare patient information and clinical characteristics by SARS-CoV-2 and HIV status. Unadjusted and multivariable models were used to explore factors associated with death, intubation, and hospital length of stay. Kaplan–Meier curves were used to estimate survival by SARS-CoV-2 and HIV infection status. Results: Patients with both SARS-CoV-2 and HIV and patients with SARS-CoV-2 but without HIV had similar admission rates (62.7% versus 58.6%, P = 0.24), hospitalization characteristics [eg, rates of admission to the intensive care unit from the emergency department (5.0% versus 6.3%, P = 0.45) and intubation (10% versus 13.3%, P = 0.17)], and rates of death (13.9% versus 15.1%, P = 0.65). They also had a similar cumulative risk of death (log-rank P = 0.72). However, patients with both HIV and SARS-CoV-2 infections compared with patients with HIV but without SAR-CoV-2 had worsened outcomes, including increased mortality (13.9% versus 5.1%, P < 0.01, log-rank P < 0.0001) and their deaths occurred sooner (median 11.5 versus 34 days, P < 0.01). Conclusions: Among emergency department patients with HIV, clinical outcomes associated with SARS-CoV-2 infection are not worse when compared with patients without HIV, but SARS-CoV-2 infection increased the risk of death in patients with HIV.

We demonstrate an application evaluating carbon sequestration benefits from federal policy alternatives. Using detailed forest inventory data, we projected carbon sequestration outcomes in the coterminous 48 states for a baseline scenario and three policy scenarios through 2050. Alternatives included (1) reducing deforestation from development, (2) afforestation in the eastern United States and reforestation in the western United States, and (3) reducing stand-replacing wildfires. We used social cost of carbon estimates to evaluate the present value of carbon sequestration benefits gained with each policy. Results suggest that afforestation and reforestation would provide the greatest marginal increase in carbon benefit, far exceeding policy cost.

Advanced solid-state quantum bits (qubits) are likely to require a variety of dielectrics for wiring crossovers, substrates, and Josephson junctions. Microwave superconducting resonators are an excellent tool for measuring the internal dielectric loss of materials. We report the dielectric loss of boron-based dielectric films using a microwave coplanar waveguide (CPW) resonator with heterostructure geometry. Power-dependent internal quality factors of magnetron-sputtered boron carbide ( $$\hbox {B}_{{4}}\hbox {C}$$ ) and boron nitride (BN) were measured and are compared to silicon oxide ( $$\hbox {SiO}_{{2}}$$ ), a common material used in wiring crossovers. The internal dielectric loss due to two-level systems for $$\hbox {B}_{{4}}\hbox {C}$$ , and BN is less than silicon dioxide ( $$\hbox {SiO}_{{2}}$$ ), which demonstrates the existence of low-loss sputtered materials. We also found that niobium (Nb) CPW resonators suffer a decrease in internal quality factor after deposition of $$\hbox {B}_{{4}}\hbox {C}$$ at temperatures above 150 $$^{\circ }\hbox {C}$$ . This result is consistent with the idea that the oxidation of the surface of the superconducting metal can contribute to loss in a device.

Laboratory studies suggest elevated blood pressure after resuscitation from cardiac arrest may be protective; however, clinical data are limited. We sought to test the hypothesis that elevated postresuscitation mean arterial blood pressure is associated with neurologic outcome.Preplanned analysis of a prospective cohort study.Six academic hospitals in the United States.Adult, nontraumatic cardiac arrest patients treated with targeted temperature management after return of spontaneous circulation.Mean arterial blood pressure was measured noninvasively after return of spontaneous circulation and every hour during the initial 6 hours after return of spontaneous circulation.We calculated the mean arterial blood pressure and a priori dichotomized subjects into two groups: mean arterial blood pressure 70-90 and greater than 90 mm Hg. The primary outcome was good neurologic function, defined as a modified Rankin Scale less than or equal to 3. The modified Rankin Scale was prospectively determined at hospital discharge. Of the 269 patients included, 159 (59%) had a mean arterial blood pressure greater than 90 mm Hg. Good neurologic function at hospital discharge occurred in 30% of patients in the entire cohort and was significantly higher in patients with a mean arterial blood pressure greater than 90 mm Hg (42%) as compared with mean arterial blood pressure 70-90 mm Hg (15%) (absolute risk difference, 27%; 95% CI, 17-37%). In a multivariable Poisson regression model adjusting for potential confounders, mean arterial blood pressure greater than 90 mm Hg was associated with good neurologic function (adjusted relative risk, 2.46; 95% CI; 2.09-2.88). Over ascending ranges of mean arterial blood pressure, there was a dose-response increase in probability of good neurologic outcome, with mean arterial blood pressure greater than 110 mm Hg having the strongest association (adjusted relative risk, 2.97; 95% CI, 1.86-4.76).Elevated blood pressure during the initial 6 hours after resuscitation from cardiac arrest was independently associated with good neurologic function at hospital discharge. Further investigation is warranted to determine if targeting an elevated mean arterial blood pressure would improve neurologic outcome after cardiac arrest.

ImportanceDiagnosis of cancer in the emergency department (ED) may be associated with poor outcomes, related to socioeconomic (SES) disparities, however data are limited.ObjectiveTo examine the morality and associated disparities for cancer diagnoses made less than six months after an ED visit.DesignThis study is case-control analysis of the Indiana State Department of Health Cancer Registry, and the Indiana Network for Patient Care. First time diagnoses of ICD-“cancer” appearing in the registry between January 2013 and December 2017 were included. Cases were patients who had an ED visit in the 6 months before their cancer diagnosis; controls had no recent ED visits.Main Outcome(s) and Measure(s)Primary outcome was mortality, comparing ED-associated mortality to non-ED-associated. Secondary outcomes include SES and demographic disparities.Results134,761 first-time cancer patients were identified, including 15,432 (11.5%) cases. In cases and controls, the mean age was same at 65 and the Charlson Comorbidity Index (CCI) was the same at 2.0 in both groups. More of the ED cohort were Black than the non-ED cohort (12.4% vs 7.4%, PConclusion and RelevanceThis study found that an ED visit within 6 months prior to the first time of ICD-coded cancer is associated with Black race, low income and an overall three-fold increased risk of death. The mortality rates for ED-associated cancers are uniformly worse for all cancer types. These data suggest that additional work is needed in order to reduce disparities among ED-associated cancer diagnoses, including increased surveillance and improved transitions of care.Key PointsQuestionDo patients diagnosed with cancer, shortly after an emergency department (ED) visit have worsened outcomes than patients with diagnoses not associated with an ED visit.FindingsIn this retrospective, epidemiological assessment, 134,761 patients were diagnosed with cancer, 11.5% (15,432) were seen in the ED within 6 months prior to their diagnosis. They had increased mortality, associated with racial and socioeconomic disparities.MeaningThese findings imply an urgent need for improved transitions of care for minority and low-income patients with suspected cancer in the ED.

As avian reproductive success is generally prey limited, identifying important prey types or sizes and understanding mechanisms governing prey availability are important objectives for avian conservation ecology. Irruptive White Ibis (Eudocimus albus) nesting at coastal colonies in the southern Everglades numbered over 100,000 nests in the 1930s. A century of drainage and altered hydrologic patterns reduced aquatic prey availability and eliminated large nesting events; nesting activity in recent decades has been typically less than 5% of historical peaks. Hydrologic restoration is expected to increase ibis nesting activity, but which prey types will support high nesting effort is less clear. In 2017 and 2018, we collected food boluses from White Ibis chicks at coastal colonies in Everglades National Park. We also monitored regional nesting activity from 1999 to 2018. In 2017, the region had 1,075 nests, typical of the past several decades; but in 2018, there were 30,420 nests, representing the highest recorded nesting activity in 87 yr. Prey composition varied between years; estuarine crabs dominated nestling boluses in 2017, while crayfish and fish were dominant prey in 2018. Crayfish, especially Procambarus alleni, were heavily exploited by ibis early in the 2018 breeding season, while fish were used more at the end. Crayfish abundances in wetlands near the colonies were higher prior to 2018, and more crayfish-producing short-hydroperiod wetlands remained available for ibis foraging in 2018. Our results support previous studies indicating that crayfish are important prey for breeding ibises and suggest that unprecedented, extensive flooding of seasonal wetlands promoted crayfish production and initiated the irruptive breeding in 2018. Our observations indicate that rehydration of the southern Everglades could restore ibis nesting activity at coastal colonies, but further investigations of hydrologic variation, crayfish production, and ibis foraging and nesting activity will be helpful to understand these dynamics and the importance of short-hydroperiod wetlands.LAY SUMMARYIncreasing White Ibis breeding in the southern Everglades and increasing the frequency of large nesting events (tens of thousands of nest attempts) are stated ecological goals of Everglades restoration.Little is known about which prey support White Ibis breeding and large nesting events in the southern Everglades.We found that White Ibis nesting in the southern Everglades used freshwater crayfish heavily in a year with extraordinarily high breeding activity and used estuarine crabs heavily in a year with poor breeding activity.Extensive flooding of seasonal wetlands, following hurricane Irma, was correlated with higher crayfish abundances an foraging habitat availability in the year with higher White Ibis breeding activity.Our observations indicate that ecological processes supporting large nesting events of White Ibis could be restored with additional freshwater flooding of the southwestern Everglades.

ObjectivesAccurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction rule for SARS-CoV-2 infection that uses simple criteria widely available at the point of care.MethodsData came from the Registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical predictors and 30-day outcomes were abstracted from medical records of 19,850 emergency department (ED) patients tested for SARS-CoV-2. The criterion standard for diagnosis of SARS-CoV-2 required a positive molecular test from a swabbed sample or positive antibody testing within 30 days. The prediction rule was derived from a 50% random sample (n=9,925) using unadjusted analysis of 107 candidate variables as a screening step, followed by stepwise forward logistic regression on 72 variables.ResultsMultivariable regression yielded a 13-variable score, which was simplified to 13-point rule: +1 point each for age>50 years, measured temperature>37.5°C, oxygen saturation75% probability with +5 or more points).ConclusionCriteria that are available at the point of care can accurately predict the probability of SARS-CoV-2 infection. These criteria could assist with decision about isolation and testing at high throughput checkpoints.Key pointsQuestionCan clinical criteria, derived solely from interview and vital signs accurately estimate the probability of infection from the novel coronavirus (SARS-CoV-2) that causes COVID-19?FindingsFrom derivation sample (n=9,925), we derived a set of 13 clinical criteria that produced an area under the receiver operating characteristic curve of 0.80 (0.79-0.81) in a validation sample (n=9,925). At a score of zero, the simplified version of the criteria produced sensitivity of 95.6% (94.8 to 96.3%), and specificity of 20.0% (19.0 to 21.0%).MeaningClinical criteria can estimate the probability of SARS-CoV-2 infection.