Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

CT venography for the diagnosis of postpartum venous thromboembolism: a prospective multi-center cohort study.

OBJECTIVES: To assess the role of CT venography (CTV) in the diagnosis of venous thromboembolism (VTE) during the postpartum period. MATERIALS AND METHODS: This multicenter prospective cohort study was conducted between April 2016 and April 2020 in 14 university hospitals. All women referred for CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE) within the first 6 weeks postpartum were eligible. All CTPAs were performed on multidetector CT machines with the usual parameters and followed by CTV of the abdomen, pelvis, and proximal lower limbs. On-site reports were compared to expert consensus reading, and the added value of CTV was assessed for both. RESULTS: The final study population consisted of 123 women. On-site CTPA reports mentioned PE in seven women (7/123, 5.7%), all confirmed following expert consensus reading, three involving proximal pulmonary arteries and four limited to distal arteries. Positive CTV was reported on-site in nine women, five of whom had negative and two indeterminate CTPAs, bringing the VTE detection rate to 11.4% (14/123) (95%CI: 6.4-18.4, p = 0.03). Expert consensus reading confirmed all positive on-site CTV results, but detected a periuterine vein thrombosis in an additional woman who had a negative CTPA, increasing the VTE detection rate to 12.2% (15/123) (95%CI: 7.0-19.3, p = 0.008). Follow-up at 3 months revealed no adverse events in this woman, who was left untreated. Median Dose-Length-Product was 117 mGy.cm for CTPA and 675 mGy.cm for CTPA + CTV. CONCLUSION: Performing CTV in women suspected of postpartum PE doubles the detection of venous thromboembolism, at the cost of increased radiation exposure. CLINICAL RELEVANCE STATEMENT: CTV can help in the decision-making process concerning curative anticoagulation in women with suspected postpartum PE, particularly those whose CTPA results are indeterminate or whose PE is limited to the subsegmental level. KEY POINTS: Postpartum women are at risk of pulmonary embolism, and CT pulmonary angiography can give equivocal results. CT venography (CTV) positivity increased the venous thromboembolism detection rate from 5.7 to 11.4%. CTV may help clinical decision-making, especially in women with indeterminate CTPA results or subsegmental emboli.

[Translation into French and republication of: "Cancer-related arterial thromboembolic events"]. / Traduction et republication de : « Événements thromboemboliques artériels liés au cancer ¼.

Cancer is associated with a hypercoagulable state and is a well-known independent risk factor for venous thromboembolism, whereas the association between cancer and arterial thromboembolism is less well established. Arterial thromboembolism, primarily defined as myocardial infarction or stroke is significantly more frequent in patients with cancer, independently of vascular risk factors and associated with a three-fold increase in the risk of mortality. Patients with brain cancer, lung cancer, colorectal cancer and pancreatic cancer have the highest relative risk of developing arterial thromboembolism. Antithrombotic treatments should be used with caution due to the increased risk of haemorrhage, as specified in current practice guidelines.

Pulmonary embolism risk stratification: external validation of the 4-level Clinical Pretest Probability Score (4PEPS).

Background: The 4-level clinical pretest probability score (4PEPS) was recently introduced as a clinical decision rule for the diagnosis of pulmonary embolism (PE). Based on the score, patients are classified into clinical pretest probability categories (c-PTP). The "very low" category aims at excluding PE without further testing; "low" and "moderate" categories require D-dimer testing with specific thresholds, while patients with a "high" pretest directly proceed to imaging. Objectives: To provide further external validation of the 4PEPS model. Methods: The 4PEPS was applied to a previously collected prospective database of 756 patients with clinically suspected PE enrolled from European emergency departments in 2002 to 2003. The safety threshold for the failure rate in our study was calculated at 1.95% based on a 26% prevalence of PE in our study, as per the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee guidance. Results: Patients were classified as follows: 90 (12%) in the very low c-PTP group, of whom 5 (5.6%; 95% CI, 2.4%-12.4%) had PE; 363 (49%) in the low c-PTP group, of whom 34 had PE (9.4%); 246 (34%) in the moderate c-PTP group, of whom 124 (50%) had PE; and 35 (5%) in the high c-PTP group of whom 30 (86%) had PE. Overall, the failure rate of the 4PEPS was 9/734 (1.2%; 95% CI, 0.59%-2.23%) Overall, 9 out of 734 patients (1.2%; 95% CI, 0.59%-2.23%) were diagnosed with PE despite a negative 4PEPS rule; 5 (5.6%) from the very low c-PTP group, 3 (1.4%) in the low c-PTP group, and 1 (3.2%) in the moderate c-PTP group. Conclusion: We provide external validation data of the 4PEPS. In this high-prevalence cohort (26% prevalence), PE prevalence in the very low-risk group was higher than expected. A prospective validation study is needed before implementing the 4PEPS model in routine clinical practice.

Acute phase determinant of post-thrombotic syndrome: A review of the literature.

BACKGROUND: Post-thrombotic syndrome (PTS) is the main long-term complication of deep vein thrombosis (DVT). Several therapies are being evaluated to prevent or to treat PTS. Identifying the patients most likely to benefit from these therapies presents a significant challenge. OBJECTIVES: The objective of this review was to identify risk factors for PTS during the acute phase of DVT. ELIGIBILITY CRITERIA: We searched the PubMed and Cochrane databases for studies published between January 2000 and January 2021, including randomized clinical trials, meta-analyses, systematic reviews and observational studies. RESULTS: Risk factors for PTS such as proximal location of DVT, obesity, chronic venous disease, history of DVT are associated with higher risk of PTS. On the initial ultrasound-Doppler, a high thrombotic burden appears to be a predictor of PTS. Among the evaluated biomarkers, some inflammatory markers such as ICAM-1, MMP-1 and MMP-8 appear to be associated with a higher risk of developing PTS. Coagulation disorders are not associated with risk of developing PTS. Role of endothelial biomarkers in predicting PTS has been poorly explored. Lastly, vitamin K antagonist was associated with a higher risk of developing PTS when compared to direct oral anticoagulants and low molecular weight heparin. CONCLUSIONS: Several risk factors during the acute phase of VTE are associated with an increased risk of developing PTS. There is a high-unmet medical need to identify potential biomarkers for early detection of patients at risk of developing PTS after VTE. Inflammatory and endothelial biomarkers should be explored in larger prospective studies to identify populations that could benefit from new therapies.

[Translation into French and republication of: "Home treatment for patients with cancer-associated venous thromboembolism"]. / Traduction et republication de : « Traitement à domicile des patients atteints de maladie veineuse thromboembolique associée au cancer ¼.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

High and intermediate risk pulmonary embolism in the ICU.

Pulmonary embolism (PE) is a common and important medical emergency, encountered by clinicians across all acute care specialties. PE is a relatively uncommon cause of direct admission to the intensive care unit (ICU), but these patients are at high risk of death. More commonly, patients admitted to ICU develop PE as a complication of an unrelated acute illness. This paper reviews the epidemiology, diagnosis, risk stratification, and particularly the management of PE from a critical care perspective. Issues around prevention, anticoagulation, fibrinolysis, catheter-based techniques, surgical embolectomy, and extracorporeal support are discussed.

Contrasting effects of urban trees on air quality: From the aerodynamic effects in streets to impacts of biogenic emissions in cities.

Urban trees are often not considered in air-quality models although they can significantly impact the concentrations of pollutants. Gas and particles can deposit on leaf surfaces, lowering their concentrations, but the tree crown aerodynamic effect is antagonist, limiting the dispersion of pollutants in streets. Furthermore, trees emit Biogenic Volatile Organic Compounds (BVOCs) that react with other compounds to form ozone and secondary organic aerosols. This study aims to quantify the impacts of these three tree effects (dry deposition, aerodynamic effect and BVOC emissions) on air quality from the regional to the street scale over Paris city. Each tree effect is added in the model chain CHIMERE/MUNICH/SSH-aerosol. The tree location and characteristics are determined using the Paris tree inventory, combined with allometric equations. The air-quality simulations are performed over June and July 2022. The results show that the aerodynamic tree effect increases the concentrations of gas and particles emitted in streets, such as NOx (+4.6 % on average in streets with trees and up to +37 % for NO2). This effect increases with the tree Leaf Area Index and it is more important in streets with high traffic, suggesting to limit the planting of trees with large crowns on high-traffic streets. The effect of dry deposition of gas and particles on leaves is very limited, reducing the concentrations of O3 concentrations by -0.6 % on average and at most -2.5 %. Tree biogenic emissions largely increase the isoprene and monoterpene concentrations, bringing the simulated concentrations closer to observations. Over the two-week sensitivity analysis, biogenic emissions induce an increase of O3, organic particles and PM2.5 street concentrations by respectively +1.1, +2.4 and + 0.5 % on average over all streets. This concentration increase may reach locally +3.5, +12.3 and + 2.9 % respectively for O3, organic particles and PM2.5, suggesting to prefer the plantation of low-emitting VOC species in cities.

Hospital at Home Program for the Treatment of Pediatric Osteoarticular Infections.

OBJECTIVES: Hospital at home (HAH) replaces acute inpatient hospital care for selected patients by providing care in their homes. We sought to describe the characteristics, management, and complications of patients with osteoarticular infections (OAIs) treated in an HAH program and its economic impact. METHODS: We conducted a retrospective observational study evaluating an HAH program in a pediatric hospital in Spain, describing the characteristics of patients with confirmed OAIs requiring intravenous antibiotic therapy admitted to this program between January 2019 and December 2022. The program operates as a virtual ward with possible daily visits by physicians and nurses and 24/7 telephone contact. RESULTS: A total of 88 patients (median age, 4.1 years; interquartile range [IQR], 1.7-10.6) with OIAs were admitted to the HAH program. Osteomyelitis (57%) and septic arthritis (29%) were the most frequent infections. Cefuroxime (42%) and cefazolin (39%) were the most frequently prescribed antibiotics. Caregiver self-administration was performed in 99%, allowing multiple daily doses of antimicrobial therapy, 80% by peripheral line. Thirteen patients (15%) had drug-related adverse events, only 3 requiring drug modification. Two patients (2%) were readmitted during HAH, and 1 was readmitted within 30 days of HAH discharge. The median HAH stay was 7 days (IQR, 4-8.75). For osteomyelitis, hospital days lowered from 8.5 days (IQR, 4.5-12) to 4 days (IQR, 3-7) after HAH implementation (P = .005) with 68% per-patient estimated cost savings. CONCLUSIONS: HAH treatment of OAIs is effective and cost-efficient. Patient support by medical and nursing staff, adequate family training, and regular communication are essential to ensure safe home admission.

Outpatient management of cancer-associated pulmonary embolism: A post-hoc analysis from the HOME-PE trial.

INTRODUCTION: Cancer-related pulmonary embolism (PE) is associated with poor prognosis. Some decision rules identifying patients eligible for home treatment categorize cancer patients at high risk of complications, precluding home treatment. We sought to assess the effectiveness and the safety of outpatient management of patients with low-risk cancer-associated PE. METHODS: In the HOME-PE trial, hemodynamically stable patients with symptomatic PE were randomized to either triaging with Hestia criteria or sPESI score. We analyzed 3 groups of low-risk PE patients: 47 with active cancer treated at home (group 1), 691 without active cancer treated at home (group 2), and 33 with active cancer as the only sPESI criterion qualifying them for hospitalization (group 3). The main outcome was the composite of recurrent venous thromboembolism, major bleeding, and all-cause death within 30 days after randomization. RESULTS: Patients treated at home had composite outcome rates of 4.3 % (2/47) for those with cancer vs. 1.0 % (7/691) for those without (odds ratio (OR) 4.98, 95%CI 1.15-21.49). Patients with cancer had rates of complications of 4.3 % when treated at home vs. 3.0 % (1/33) when hospitalized (OR 1.19, 95%CI 0.15-9.47). In multivariable analysis, active cancer was associated with an increased risk of complications for patients treated at home (OR 7.95; 95%CI 1.48-42.82). For patients with active cancer, home treatment was not associated with the primary outcome (OR 1.19, 95%CI 0.15-9.74). CONCLUSIONS: Among patients treated at home, active cancer was a risk factor for complications, but among patients with active cancer, home treatment was not associated with adverse outcomes.

Human metapneumovirus infection is associated with a substantial morbidity and mortality burden in adult inpatients.

Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients. Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used. Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62-84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2-7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course. Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients.

Enoxaparin versus Placebo to Prevent Symptomatic Venous Thromboembolism in Hospitalized Older Adult Medical Patients.

BACKGROUND: Admission to the hospital is a major risk factor for the development of venous thromboembolism (VTE). Whether thromboprophylaxis with low-molecular-weight heparin prevents symptomatic VTE in medically ill, hospitalized older adults remains debated. METHODS: In a prospective, randomized, placebo-controlled, double-blind, multicenter trial, older adults (>70 years of age) hospitalized for acute medical conditions were randomly assigned to receive 40 mg a day of low-molecular-weight heparin (enoxaparin) or placebo for 6 to 14 days. The primary efficacy outcome was the cumulative incidence of symptomatic VTE (distal or proximal deep vein thrombosis, fatal or nonfatal pulmonary embolism) at 30 days. The primary safety outcome was major bleeding. Secondary outcomes included efficacy and safety outcomes at 90 days. RESULTS: The trial was prematurely discontinued in September 2020, 5 years after enrollment began, because of drug supply issues. By the time of trial discontinuation, 2559 patients had been randomly assigned at 47 centers. Median age was 82 years and 60% of patients were female. In the intention-to-treat population, the primary efficacy outcome occurred in 22 out of 1278 (cumulative incidence, 1.8%) patients in the enoxaparin group and in 27 out of 1263 (cumulative incidence, 2.2%) patients in the placebo group (cumulative incidence difference, −0.4 percentage points; 95% confidence interval, −1.5 to 0.7), with no significant difference in time to VTE (P=0.46). The incidence of major bleeding was 0.9% in the enoxaparin group and 1.0% in the placebo group. At 90 days there were 14 symptomatic pulmonary emboli in the enoxaparin group and 25 in the placebo group; all 39 pulmonary embolism events resulted in hospital readmission and/or death, with 5 deaths from pulmonary embolism in the enoxaparin group and 11 deaths in the placebo group. CONCLUSIONS: This trial of thromboprophylaxis in medically ill, hospitalized older adults did not demonstrate that enoxaparin reduced the risk of symptomatic VTE after 1 month. Because the trial was prematurely discontinued, larger trials are needed to definitively address this question. (Funded by the French Ministry of Health Programme Hospitalier de Recherche Clinique, grant number PHRC-N-13-0283; ClinicalTrials.gov number, NCT02379806.)