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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.

Objectives Accurate estimation of the risk of SARS‐CoV‐2 infection based on bedside data alone has importance to emergency department (ED) operations and throughput. The 13‐item CORC (COVID [or coronavirus] Rule‐out Criteria) rule had good overall diagnostic accuracy in retrospective derivation and validation. The objective of this study was to prospectively test the inter‐rater reliability and diagnostic accuracy of the CORC score and rule (score ≤ 0 negative, > 0 positive) and compare the CORC rule performance with physician gestalt. Methods This noninterventional study was conducted at an urban academic ED from February 2021 to March 2021. Two practitioners were approached by research coordinators and asked to independently complete a form capturing the CORC criteria for their shared patient and their gestalt binary prediction of the SARS‐CoV‐2 test result and confidence (0%–100%). The criterion standard for SARS‐CoV‐2 was from reverse transcriptase polymerase chain reaction performed on a nasopharyngeal swab. The primary analysis was from weighted Cohen's kappa and likelihood ratios (LRs). Results For 928 patients, agreement between observers was good for the total CORC score, κ = 0.613 (95% confidence interval [CI] = 0.579–0.646), and for the CORC rule, κ = 0.644 (95% CI = 0.591–0.697). The agreement for clinician gestalt binary determination of SARs‐CoV‐2 status was κ = 0.534 (95% CI = 0.437–0.632) with median confidence of 76% (first–third quartile = 66–88.5). For 425 patients who had the criterion standard, a negative CORC rule (both observers scored CORC < 0), the sensitivity was 88%, and specificity was 51%, with a negative LR (LR−) of 0.24 (95% CI = 0.10–0.50). Among patients with a mean CORC score of >4, the prevalence of a positive SARS‐CoV‐2 test was 58% (95% CI = 28%–85%) and positive LR was 13.1 (95% CI = 4.5–37.2). Clinician gestalt demonstrated a sensitivity of 51% and specificity of 86% with a LR− of 0.57 (95% CI = 0.39–0.74). Conclusion In this prospective study, the CORC score and rule demonstrated good inter‐rater reliability and reproducible diagnostic accuracy for estimating the pretest probability of SARs‐CoV‐2 infection.

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.

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.