Right ventricular-pulmonary artery coupling for prognostication in acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) increases pulmonary pressure and impair right ventricular (RV) function. Echocardiographic investigation can quantify this mismatch as the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) ratio. The aim of the study was to investigate the prognostic capabilities of TAPSE/PASP ratio in patients with acute PE. METHODS: We utilized the RIETE registry to analyze consecutive hemodynamically stable PE patients. We used multivariable logistic regression analyses to assess the association between the TAPSE/PASP ratio and 30-day all-cause mortality across the strata of European Society of Cardiology (ESC) risk categories. RESULTS: We included 4,478 patients, of whom 1,326 (30%) had low-risk, 2,425 (54%) intermediate-low risk, and 727 (16%) intermediate-high risk PE. Thirty-day mortality rates were 0.7%, 2.3% and 3.4%, respectively. Mean TAPSE/PASP ratio was 0.65±0.29 in low-risk patients, 0.46±0.30 in intermediate-low risk, and 0.33±0.19 in intermediate-high risk patients. In multivariable analyses, there was an inverse association between TAPSE/PASP ratio and 30-day mortality (adjusted OR 1.32 [95%CI 1.14-1.52] per 0.1 decrease in TAPSE/PASP). TAPSE/PASP ratio below optimal cut-points was associated with increased mortality in low- (<0.40, aOR: 5.88; 95%CI:1.63-21.2), intermediate-low (<0.43, aOR: 2.96; 95%CI:1.54-5.71) and intermediate-high risk patients (<0.34, aOR: 4.37; 95%CI:1.27-15.0). TAPSE/PASP <0.44 showed net reclassification improvement of 18.2% (95%CI:0.61-35.8) vs. RV/LV ratio >1, and 27.7% (95%CI:10.2-45.1) vs. ESC risk strata. CONCLUSIONS: Decreased TAPSE/PASP ratio was associated with increased mortality. The ratio may aid in clinical decision-making, particularly for intermediate-risk patients for whom the discriminatory capability of the current risk stratification tools is limited.

Validation of Echocardiographic Measurements in Patients with Pulmonary Embolism in the RIETE Registry.

Background In acute pulmonary embolism (PE), echocardiographic identification of right ventricular (RV) dysfunction will inform prognostication and clinical decision-making. Registro Informatizado Enfermedad TromboEmbolica (RIETE) is the world's largest registry of patients with objectively confirmed PE. The reliability of site-reported RV echocardiographic measurements is unknown. We aimed to validate site-reported key RV echocardiographic measurements in the RIETE registry. Methods Fifty-one randomly chosen patients in RIETE who had transthoracic echocardiogram (TTE) performed for acute PE were included. TTEs were de-identified and analyzed by a core laboratory of two independent observers blinded to site-reported data. To investigate reliability, intraclass correlation coefficients (ICCs) and Bland-Altman plots between the two observers, and between an average of the two observers and the RIETE site-reported data were obtained. Results Core laboratory interobserver variations were very limited with correlation coefficients >0.8 for all TTE parameters. Agreement was substantial between core laboratory observers and site-reported data for key parameters including tricuspid annular plane systolic excursion (ICC 0.728; 95% confidence interval [CI], 0.594-0.862) and pulmonary arterial systolic pressure (ICC 0.726; 95% CI, 0.601-0.852). Agreement on right-to-left ventricular diameter ratio (ICC 0.739; 95% CI, 0.443-1.000) was validated, although missing data limited the precision of the estimates. Bland-Altman plots showed differences close to zero. Conclusion We showed substantial reliability of key RV site-reported measurements in the RIETE registry. Ascertaining the validity of such data adds confidence and reliability for subsequent investigations.

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial.

BACKGROUND: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. RESEARCH QUESTION: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? STUDY DESIGN AND METHODS: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. RESULTS: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. INTERPRETATION: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04003116; URL: www. CLINICALTRIALS: gov.

Acute venous thromboembolism in patients with brain cancer: clinical course.

Background: Patients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH). Objectives: The aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer. Methods: This was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome. Results: Overall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors. Conclusion: In patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

Feasibility of a screening algorithm for chronic thromboembolic pulmonary hypertension: The OSIRIS study.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term sequel to pulmonary embolism (PE) whose incidence varies according to different published studies. We have carried out this study to determine its incidence within 2 years after index pulmonary embolism and to study limitations to an early diagnosis. MATERIAL AND METHODS: OSIRIS is a multicentre, longitudinal cohort study. Patients were followed for 3, 6, 12, and 24 months after pulmonary embolism using a structured three-step algorithm. A physician-centered questionnaire at least one positive response in a screening proceeded to the second step, transthoracic echocardiography. The third step consisted of ventilation/perfusion lung scintigraphy and right heart catheterisation. A transthoracic echocardiography was performed in patients without positive response in the screening questionnaire after 2 years. CTEPH diagnosis required haemodynamic confirmation by right heart catheterisation and mismatched perfusion defects on lung scintigraphy. RESULTS: A total of 1191 patients were enrolled in 18 Spanish hospitals. Cumulative CTEPH incidence after 2-years PE was: 2.49 % (95 % CI: 1.68-3.56) and the incidence rate of CTEPH was 1.1 cases per 1000 person-months (95 % CI: 0.725; 1.60). The CTEPH algorithm presented a lack of adherence of 29 %; patient and physician preferences posed barriers to the triage algorithm The screening questionnaire, in patients who completed the follow-up, shows a specificity of 91.3 % (89.0-93.2 %) and negative predictive value of 99.4 % (98.4-99.8 %).. CONCLUSIONS: OSIRIS provides practiced clinical based data on the chronic thromboembolic pulmonary hypertension incidence and identified barriers to the implementation of a 3-step triage algorithm for its detection. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03134898.

Pulmonary Embolism in Patients with COVID-19: Comparison between Different Care Settings.

The clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) who develop pulmonary embolism (PE) in the full spectrum of patient care settings need to be elucidated. The aim of this study was to compare the clinical characteristics, treatment, and 90-day outcomes in patients diagnosed with PE while recovering from COVID-19 in the outpatient setting versus those who were diagnosed with PE while being hospitalized with COVID-19. Data from the international Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were used. The major study outcomes were all-cause death, major bleeding, and venous thromboembolism (VTE) recurrences during the first 90 days after PE. From March 2020 to March 2021, 737 patients with COVID-19 experienced acute PE. Of these, 340 (46%) were recovering from COVID-19 as outpatients (267 patients who had been treated at home for COVID-19 and 73 discharged after being hospitalized with COVID-19). Compared with inpatients with COVID-19, those recovering in the outpatient setting upon PE were less likely to be men (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.40-0.72) and less likely to have hypertension (OR: 0.55; 95% CI: 0.41-0.74) or diabetes (OR: 0.51; 95% CI: 0.33-0.76). At 90-day follow-up, eight patients (none recovering from COVID-19 as outpatient vs. 2.4% of inpatients with COVID-19) developed recurrent VTE, 34 (1.9 vs. 7.9%) had major bleeding, and 128 (10 vs. 24%) died. On multivariable analysis, inpatients with COVID-19 were at a higher risk of major bleeding (adjusted hazard ratio [HR]: 6.80; 95% CI: 1.52-30.4) or death (adjusted HR: 2.24; 95% CI: 1.40-3.58). In conclusion, using a large multinational registry of patients with COVID-19 who experienced PE, thromboembolic episodes occurring in those recovering from COVID-19 as outpatients were associated with less ominous outcomes than inpatients with COVID-19.

Actions to reduce carbon footprint in materials to healthcare buildings.

Building sector is a major contributor to the emissions of pollutant gases, which are responsible for health-damaging effects of climate change. To quantify and reduce these emissions. This comparative study is presented between two buildings that could have a sanitary or any other type of use. Both buildings have similar characteristics, except for their structures, one made of metal and the other of concrete. The design, structural calculation and three-dimensional dimensioning were performed using Building Information Modeling (BIM). The budget and the product carbon footprint study were also carried out, to calculate the level of emissions of each building. The study determined higher emissions for the metal-structured building, with 621.234 tCO2/tmaterial compared to 446.707 tCO2/tmaterial for the concrete building. To reduce these emissions, measures related to the replacement of the previously selected materials, by other materials with lower emission rates and identical functionality were presented, such as the replacement of metal building roof polyurethane, or the composition of cement for the concrete building. Both actions represented a reduction of 84.61% CO2 emissions for metal envelope building and 31.765% for the concrete structure. The results of this work will help to select more sustainable materials to use in the renovation of existing buildings, or in the construction of new buildings. For example, health-related buildings, currently in high demand, given the current pandemic situation caused by COVID-19.

Cancer Histology and Natural History of Patients with Lung Cancer and Venous Thromboembolism.

Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45-214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76-18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09-0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76-1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite.

Statin use and 30-day mortality in patients with acute symptomatic pulmonary embolism.

BACKGROUND: Statins possess antithrombotic and profibrinolytic properties. The association between statin use and short-term outcomes in patients with acute pulmonary embolism (PE) remains unknown. METHODS: We used the data from the Registro Informatizado de Pacientes con Enfermedad TromboEmbólica registry to compare the 30-day all-cause mortality in patients with acute PE according to the use of statins. Secondary outcome was fatal PE. We used cancer-related mortality as a falsification endpoint. RESULTS: From January 2009 to April 2021, 31 169 patients with PE were recruited. Of these, 5520 (18%) were using statins at baseline: low intensity: 829, moderate: 3636, high intensity: 1055. Statin users were older and had a higher frequency of diabetes, hypertension, or atherosclerotic disease than non-users (P <0.001 for all comparisons). During the first 30 days, 1475 patients died (fatal PE, 255). On multivariable analysis, statin users had a lower risk of all-cause death (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.56-0.76) and fatal PE (OR: 0.42; 95% CI: 0.28-0.62) than non-users. The risk for death was lower in patients using either low- (OR: 0.51; 95% CI: 0.34-0.77), moderate- (OR: 0.68; 95% CI: 0.57-0.81), or high-intensity statins (OR: 0.68; 95% CI: 0.51-0.92). Results did not change in mixed effects logistic regression models with hospitals as a random effect. Statins were not associated with a significant chance in cancer mortality (falsification endpoint). CONCLUSIONS: PE patients using statins at baseline had a significantly lower risk of dying within the first 30 days than non-users. Randomized trials are needed to confirm these data.

Effect of Prognostic Guided Management of Patients With Acute Pulmonary Embolism According to the European Society of Cardiology Risk Stratification Model.

Background: A recent trial showed that management driven by prognostic assessment was effective in reducing the length of stay (LOS) for acute stable pulmonary embolism (PE). The efficacy and safety of this strategy in each subgroup of risk stratification remains unknown. Methods: We conducted a post-hoc analysis of the randomized IPEP study to evaluate the effect of a management strategy guided by early use of a prognostic pathway in the low- and intermediate-high risk subgroups defined by the European Society of Cardiology (ESC) model. These subgroups were retrospectively identified in the control arm. The primary outcome was LOS. The secondary outcomes were 30-day clinical outcomes. Results: Of 249 patients assigned to the intervention group, 60 (24%) were classified as low-, and 30 (12%) as intermediate-high risk. Among 249 patients assigned to the control group, 66 (27%) were low-, and 13 (5%) intermediate-high risk. In the low-risk group, the mean LOS was 2.1 (±0.9) days in the intervention group and 5.3 (±2.9) days in the control group (P < 0.001). In this group, no significant differences were observed in 30-day readmissions (0% vs. 3.0%, respectively), all-cause (0% vs. 0%) and PE-related mortality rates (0% vs. 0%), or severe adverse events (0% vs. 1.5%). In the intermediate-high risk group, the mean LOS was 5.3 (±1.8) days in the intervention group and 6.5 (±2.5) days in the control group (P = 0.08). In this group, no significant differences were observed in 30-day readmissions (3.3% vs. 3.0%, respectively), all-cause (6.7% vs. 7.7%) and PE-related mortality rates (6.7% vs. 7.7%), or severe adverse events (16.7% vs. 15.4%). Conclusion: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE without comprising safety across subgroups of risk stratification. Clinical Trial Registration: [ClinicalTrials.gov], Identifier [NCT02733198].

Major bleeding in patients with pulmonary embolism presenting with syncope.

INTRODUCTION: Syncope has been shown to be a risk factor of bleeding in patients receiving thrombolytic therapy for acute pulmonary embolism (PE). Whether syncope predicts bleeding in a broader population of patients with PE remains unknown. METHODS: We used the RIETE registry data to assess whether initial presentation with syncope could predict bleeding in PE patients receiving anticoagulant therapy, and to explore the association between presence of syncope and timing and site of major bleeding events. RESULTS: Among 45,765 patients with acute PE from March 2001 to January 2021, 6760 (14.8%) had syncope. Patients with syncope were older and more likely to have hypotension, tachycardia, hypoxaemia or elevated troponin levels than those without syncope. They also were more likely to receive thrombolytics. During the first 90 days, 1097 patients (2.4%) suffered major bleeding (gastrointestinal 335, hematoma 271 and intracranial 163) and 3611 died (158 had fatal bleeding). Patients with syncope had a higher rate of major bleeding (odds ratio [OR]: 1.63; 95% CI: 1.41-1.89) and a nonsignificantly higher rate of fatal bleeding (OR: 1.47; 95% CI: 0.99-2.17) than those without syncope. Multivariable analysis confirmed that patients with syncope were at increased risk for major bleeding (adjusted hazard ratio [aHR]: 1.34; 95% CI: 1.15-1.55). On sensitivity analysis, the increased risk for major bleeding was confirmed in patients initially receiving anticoagulant therapy without thrombolytics at 7 days (aHR: 1.47; 95% CI: 1.13-1.91) and 90 days (aHR: 1.33; 95%CI: 1.13-1.56). DISCUSSION: Syncope is a predictor of major bleeding events in patients with PE, even among those receiving anticoagulation monotherapy.

Adjusted D-dimer cutoff levels to rule out pulmonary embolism in patients hospitalized for COPD exacerbation: results from the SLICE trial.

BACKGROUND: For patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined. METHODS: We ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial. Using the conventional strategy as the reference, we compared the proportion of patients with a negative D-dimer result, and the negative predictive value and sensitivity of three D-dimer threshold strategies for initial PE or subsequent diagnosis of venous thromboembolism (VTE): the age-adjusted strategy, the Wells-adjusted strategy, and the YEARS-adjusted strategy. RESULTS: We included 368 patients. Using a conventional threshold, 182 (49.5%) patients had negative D-dimer values, of whom 1 (0.6%) had PE (sensitivity, 94.1%). The use of an age-adjusted threshold increased the number of patients in whom PE could be excluded from 182 to 233 patients (63.3%), and the proportion of false-negative findings increased from 0.5% to 1.7% (sensitivity, 76.5%). With the use of the Wells or YEARS strategies, 64.4% and 71.5% had negative values, and the proportion of false-negative findings was 2.5% (sensitivity, 64.7%) and 2.7% (sensitivity, 58.8%), respectively. CONCLUSIONS: In patients hospitalized for COPD exacerbation, compared with the conventional strategy, age- or clinically-adjusted strategies of D-dimer interpretation were associated with a larger proportion of patients in whom PE was ruled out with a higher failure rate. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02238639 .

Multidisciplinary Consensus for the Management of Pulmonary Thromboembolism. / Consenso multidisciplinar para el manejo de la tromboembolia de pulmón.

We have updated recommendations on 12 controversial topics that were published in the 2013 National Consensus on the diagnosis, risk stratification and treatment of patients with pulmonary embolism (PE). A comprehensive review of the literature was performed for each topic, and each recommendation was evaluated in two teleconferences. For diagnosis, we recommend against using the Pulmonary Embolism Rule Out Criteria (PERC) rule as the only test to rule out PE, and we recommend using a D-dimer cutoff adjusted to age to rule out PE. We suggest using computed tomography pulmonary angiogram as the imaging test of choice for the majority of patients with suspected PE. We recommend using direct oral anticoagulants (over vitamin K antagonists) for the vast majority of patients with acute PE, and we suggest using anticoagulation for patients with isolated subsegmental PE. We recommend against inserting an inferior cava filter for the majority of patients with PE, and we recommend using full-dose systemic thrombolytic therapy for PE patients requiring reperfusion. The decision to stop anticoagulants at 3 months or to treat indefinitely mainly depends on the presence (or absence) and type of risk factor for venous thromboembolism, and we recommend against thrombophilia testing to decide duration of anticoagulation. Finally, we suggest against extensive screening for occult cancer in patients with PE.

Randomised controlled trial of a prognostic assessment and management pathway to reduce the length of hospital stay in normotensive patients with acute pulmonary embolism.

BACKGROUND: The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown. METHODS: We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes. RESULTS: Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7-4.2 days) in the intervention group and 6.1 days (IQR 5.7-6.5 days) in the control group (p<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR -58.37, 95% CI EUR -84.34- to -32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR -1147.31, 95% CI EUR -1414.97- to -879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates. CONCLUSIONS: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.

Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding.

INTRODUCTION: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. METHODS: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. RESULTS: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68-0.79) for major bleeding, 0.73 (95% CI: 0.67-0.78) for non-major bleeding and 0.82 (95% CI: 0.76-0.87) for bleeding-related death. CONCLUSIONS: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.

Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes in Patients Hospitalized for COPD Exacerbation: A Randomized Clinical Trial.

Importance: Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD). Objective: To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation. Design, Setting, and Participants: Randomized clinical trial conducted across 18 hospitals in Spain. A total of 746 patients were randomized from September 2014 to July 2020 (final follow-up was November 2020). Interventions: Usual care plus an active strategy for diagnosing PE (D-dimer testing and, if positive, computed tomography pulmonary angiogram) (n = 370) vs usual care (n = 367). Main Outcomes and Measures: The primary outcome was a composite of nonfatal symptomatic venous thromboembolism (VTE), readmission for COPD, or death within 90 days after randomization. There were 4 secondary outcomes, including nonfatal new or recurrent VTE, readmission for COPD, and death from any cause within 90 days. Adverse events were also collected. Results: Among the 746 patients who were randomized, 737 (98.8%) completed the trial (mean age, 70 years; 195 [26%] women). The primary outcome occurred in 110 patients (29.7%) in the intervention group and 107 patients (29.2%) in the control group (absolute risk difference, 0.5% [95% CI, -6.2% to 7.3%]; relative risk, 1.02 [95% CI, 0.82-1.28]; P = .86). Nonfatal new or recurrent VTE was not significantly different in the 2 groups (0.5% vs 2.5%; risk difference, -2.0% [95% CI, -4.3% to 0.1%]). By day 90, a total of 94 patients (25.4%) in the intervention group and 84 (22.9%) in the control group had been readmitted for exacerbation of COPD (risk difference, 2.5% [95% CI, -3.9% to 8.9%]). Death from any cause occurred in 23 patients (6.2%) in the intervention group and 29 (7.9%) in the control group (risk difference, -1.7% [95% CI, -5.7% to 2.3%]). Major bleeding occurred in 3 patients (0.8%) in the intervention group and 3 patients (0.8%) in the control group (risk difference, 0% [95% CI, -1.9% to 1.8%]; P = .99). Conclusions and Relevance: Among patients hospitalized for an exacerbation of COPD, the addition of an active strategy for the diagnosis of PE to usual care, compared with usual care alone, did not significantly improve a composite health outcome. The study may not have had adequate power to assess individual components of the composite outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02238639.