Optimizing Venous Stenting: Consensus Recommendations for Enhanced Management of Lower Extremity Deep Vein Thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) poses a complex challenge and often leads to postthrombotic syndrome (PTS), a debilitating complication. The emergence of venous stents offers a potential preventive avenue against this complication. This study aimed to provide consensus recommendations on the use of venous stent for DVT. MATERIALS AND METHODS: From June to July 2023, 20 internal medicine, angiology and vascular surgery, and vascular and interventional radiology experts were involved in the Delphi process. Thirty-one recommendations, categorized into three thematic areas, were rigorously evaluated: indications for stent use, stent selection and placement, and monitoring and prevention of complications. Agreement was evaluated using a Likert scale, with consensus defined as agreement by two-thirds of the participants. RESULTS: Consensus was reached for 23 (74.2%) of 31 recommendations. The agreement was centered on considerations, such as stent placement in specific acute DVT scenarios, emphasizing pivotal stent characteristics. However, there were divergences in the recommended stent length to prevent migration and stent characteristics based on iliocaval bifurcation morphology. Notably, there was no consensus on whether patients with DVT caused by a major transient risk factor need more than 3 months of anticoagulation therapy or whether aspirin should be added to anticoagulant treatment after venous stenting. CONCLUSIONS: These consensus recommendations offer practical insights into optimizing venous stent use to prevent PTS in DVT patients. Addressing the critical aspects of stent selection, placement, and postprocedural care, these recommendations contribute to clinical decision-making. The identified divergences underscore the importance of consensus and thus indicate the need for further investigation.

Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis.

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer. METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT. RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58). CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

Errores de medicación en niños que acuden a los servicios de urgencias pediátricas / Medication errors in children visiting pediatric emergency departments

Objetivos: la seguridad de los medicamentos en pediatría supone un verdadero reto. Se dispone de escasos estudios que hayan analizado los errores de medicación en los pacientes pediátricos que acuden a los servicios de urgencias. El objetivo de este estudio ha sido caracterizar los errores detectados en estos pacientes, determinando su gravedad, los procesos afectados, los medicamentos implicados y los tipos de errores y causas asociados. Métodos: estudio multicéntrico observacional prospectivo realizado en los servicios de urgencias de 8 hospitales públicos españoles durante 4 meses. Los errores de medicación detectados por los pediatras de urgencias en pacientes entre 0 y 16 años fueron evaluados por un farmacéutico y un pediatra. Los errores de medicación fueron analizados utilizando la Taxonomía Española de Errores de Medicación actualizada. Resultados: en 99.797 visitas a urgencias se detectaron 218 (0,2%) errores de medicación, de los cuales 74 (33,9%) causaron daños (eventos adversos por medicamentos). Los preescolares fueron el grupo poblacional con mayor número de errores de medicación (126/218). Los errores se originaron mayoritariamente en la prescripción (66,1%), por automedicación (16,5%) y por administración equivocada por parte de los familiares (15,6%). Los tipos de errores más frecuentes fueron: «dosis incorrectas» (51,4%) y «medicamento inapropiado» (46,8%). Los antiinfecciosos (63,5%) fueron los fármacos más comúnmente implicados en los errores con daño. Las causas subyacentes asociadas a una mayor proporción de errores de medicación fueron: «falta de conocimiento del medicamento» (63,8%), «falta de seguimiento de los procedimientos» (48,6%) y «falta de información del paciente» (30,3%). Conclusiones: los errores de medicación en la población pediátrica que acude a urgencias se producen en la prescripción, por automedicación y en la administración, provocando daños a los pacientes en un tercio de las ocasiones. ...(AU)

Objectives: Medication safety represents an important challenge in children. There are limited studies on medication errors in pediatric patients visiting emergency departments. To help bridge this gap, we characterized the medication errors detected in these patients, determining their severity, the stages of the medication process in which they occurred, the drugs involved, and the types and causes associated with the errors. Methods: We conducted a multicenter prospective observational study in the pediatric emergency departments of 8 Spanish public hospitals over a 4-month period. Medication errors detected by emergency pediatricians in patients between 0 and 16 years of age were evaluated by a clinical pharmacist and a pediatrician. Each medication error was analyzed according to the updated Spanish Taxonomy of Medication Errors. Results: In 99,797 visits to pediatric emergency departments, 218 (0.2%) medication errors were detected, of which 74 (33.9%) resulted in harm (adverse drug events). Preschoolers were the age group with the most medication errors (126/218). Errors originated mainly in the prescribing stage (66.1%), and also by self-medication (16.5%) and due to wrong administration of the medication by family members (15.6%). Dosing errors (51.4%) and wrong/improper drugs (46.8%) were the most frequent error types. Anti-infective drugs (63.5%) were the most common drugs implicated in medication errors with harm. Underlying causes associated with a higher proportion of medication errors were “medication knowledge deficit” (63.8%), “deviation from procedures/guidelines” (48.6%) and “lack of patient information” (30.3%). Conclusions: Medication errors presented by children attending emergency departments arise from prescriptions, self-medication, and administration, and lead to patient harm in one third of cases. Developing effective interventions based on the types of errors and the underlying causes identified will improve patient safety. (AU)

Cancer-Associated Thrombosis: Trends in Clinical Features, Treatment, and Outcomes From 2001 to 2020.

Background: Despite advances in cancer and venous thromboembolism (VTE) management, the epidemiology of cancer-associated thrombosis management over time remains unclear. Objectives: We analyzed data from the RIETE (Registro Informatizado de la Enfermedad Trombo Embólica) registry spanning 2001 to 2020 to investigate temporal trends in clinical characteristics and treatments for cancer-associated thrombosis. Methods: Using multivariable survival regression, we examined temporal trends in risk-adjusted rates of symptomatic VTE recurrences, major bleeding, and death within 30 days after incident VTE. Results: Among the 17,271 patients with cancer-associated thrombosis, there was a progressive increase in patients presenting with pulmonary embolism (from 44% in 2001-2005 to 55% in 2016-2020; P < 0.001 for trend), lung (from 12.7% to 18.1%; P < 0.001) or pancreatic cancer (from 3.8% to 5.6%; P = 0.003), and utilization of immunotherapy (from 0% to 7.4%; P < 0.001). Conversely, there was a decline in patients with prostate cancer (from 11.7% to 6.6%; P < 0.001) or carcinoma of unknown origin (from 3.5% to 0.7%; P < 0.001). At the 30-day follow-up, a reduction was observed in the proportion of patients experiencing symptomatic VTE recurrences (from 3.1% to 1.1%; P < 0.001), major bleeding (from 3.1% to 2.2%; P = 0.004), and death (from 11.9% to 8.4%; P < 0.001). Multivariable analyses revealed a decreased risk over time for VTE recurrence (adjusted subdistribution HR [asHR]: 0.94 per year; 95% CI: 0.92-0.98), major bleeding (asHR: 0.98; 95% CI: 0.96-0.99), and death (aHR: 0.97; 95% CI: 0.96-0.98). Conclusions: In this multicenter study of cancer patients with VTE, there was a decline in thrombotic, hemorrhagic, and fatal events from 2001 to 2020. (Registro Informatizado de la Enfermedad Trombo Embólica [RIETE]; NCT02832245).

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.

Clinical Presentation and Short- and Long-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis vs Proximal Deep Vein Thrombosis in the RIETE Registry.

Importance: Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins without proximal extension or pulmonary embolism (PE). Objective: To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT. Design, Setting, and Participants: This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection. Main Outcomes and Measures: Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE. Results: A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean [SD] age, 61 [17] years; 2975 male patients [50.1%]), and 27 959 (82.5%) had proximal DVT (mean [SD] age, 65 [18] years; 14 315 male patients [51.2%]). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio [OR], 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio [HR], 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%). Conclusions and Relevance: Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.

Enoxaparin versus dalteparin or tinzaparin in patients with cancer and venous thromboembolism: The RIETECAT study.

Background: Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death. Objectives: The objective of the RIETECAT study was to compare the long-term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer. Methods: We used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point. Results: From January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48-1.38), major bleeding (aHR, 1.40; 95% CI, 0.80-2.46), or death (aHR, 1.07; 95% CI, 0.88-1.30) between subgroups. Conclusions: In RIETECAT, in patients with cancer and VTE receiving full-dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6-month period.

Outcome of Cancer-Associated Venous Thromboembolism Is More Favorable among Patients with Hematologic Malignancies than in Those with Solid Tumors.

BACKGROUND: The natural history of patients with hematologic cancer and venous thromboembolism (VTE) has not been consistently evaluated. We aimed to compare the rates of symptomatic recurrent VTE, major bleeding, or death during anticoagulant therapy in patients with VTE associated with hematologic versus solid cancers. METHODS: Consecutive patients with active cancer recruited in RIETE were evaluated. Their baseline characteristics, treatments, and outcomes during the course of anticoagulation were compared. Univariate and multivariate competing-risk analyses were performed. RESULTS: As of December 2020, 16,694 patients with cancer and VTE were recruited. Of these, 1,062 (6.4%) had hematologic cancers. Hematologic patients were less likely to initially present with pulmonary embolism (46 vs. 55%) and more likely with upper extremity deep vein thrombosis (25 vs. 18%). They also were more likely to have severe thrombocytopenia at baseline (5.6 vs. 0.7%) or to receive chemotherapy (67 vs. 41%). During the course of anticoagulation (median, 150 vs. 127 days), 1,071 patients (6.4%) developed VTE recurrences, 806 (4.8%) suffered major bleeding, and 4,136 (24.8%) died. Patients with hematologic cancers had lower rates of recurrent VTE (rate ratio [RR]: 0.73; 95% confidence interval [CI]: 0.56-0.95), major bleeding (RR: 0.72; 95% CI: 0.53-0.98), or all-cause death (RR: 0.49; 95% CI: 0.41-0.57) than those with solid cancers. Patients with multiple myeloma showed the best outcomes. CONCLUSION: Patients with hematologic cancers, particularly multiple myeloma, and VTE had better outcomes than those with solid cancers. These findings are relevant for the interpretation of previous clinical trials and the design of future studies.

Prognostic impact of acute kidney injury in patients with acute pulmonary embolism data from the RIETE registry.

Risk stratification is recommended for patients with pulmonary embolism (PE), and usually starts with the assessment of the hemodynamic status and the simplified Pulmonary Embolism Severity Index (sPESI). The influence of acute kidney injury (AKI) on the prognostic stratification has not been evaluated according to the "Kidney Disease: Improving Global Outcomes" (KDIGO). AKI was computed according to the KDIGO definition in patients with acute PE in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Patients with hemodynamic instability were considered high-risk. Normotensive patients were stratified according to the sPESI score (low-risk: sPESI = 0; intermediate-risk: sPESI > 0). The primary outcome was all-cause 30-day mortality. Secondary outcomes were major bleeding and VTE recurrences during the same period. Among 30,532 patients with PE, 1108 (3.6%) were classified to be at high-risk, 10,577 (34.6%) at low-risk, and the remaining 18,847 (61.8%) at intermediate-risk of adverse events. At baseline, 7879 (26%) had AKI. Overall, 1543 of 30,532 patients (5.1%) died within the first 30 days. The presence of AKI was associated with increased mortality rates in all subgroups of patients: in those at low-risk it increased from 0.46 to 3%, in intermediate-risk from 5.4 to 10%, and in high-risk patients from 9.4 to 18%. The presence of AKI was also associated with an increased risk of major bleeding in all subgroups. The addition of the AKI status to the sPESI score improved the prediction of the 30-day mortality and may be particularly helpful for decisions such as identification of low-risk patient for home discharge.

Machine Learning to Predict Outcomes in Patients with Acute Pulmonary Embolism Who Prematurely Discontinued Anticoagulant Therapy.

BACKGROUND: Patients with pulmonary embolism (PE) who prematurely discontinue anticoagulant therapy (<90 days) are at an increased risk for death or recurrences. METHODS: We used the data from the RIETE (Registro Informatizado de Pacientes con Enfermedad TromboEmbólica) registry to compare the prognostic ability of five machine-learning (ML) models and logistic regression to identify patients at increased risk for the composite of fatal PE or recurrent venous thromboembolism (VTE) 30 days after discontinuation. ML models included decision tree, k-nearest neighbors algorithm, support vector machine, Ensemble, and neural network [NN]. A "full" model with 70 variables and a "reduced" model with 23 were analyzed. Model performance was assessed by confusion matrix metrics on the testing data for each model and a calibration plot. RESULTS: Among 34,447 patients with PE, 1,348 (3.9%) discontinued therapy prematurely. Fifty-one (3.8%) developed fatal PE or sudden death and 24 (1.8%) had nonfatal VTE recurrences within 30 days after discontinuation. ML-NN was the best method for identification of patients experiencing the composite endpoint, predicting the composite outcome with an area under receiver operating characteristic (ROC) curve of 0.96 (95% confidence interval [CI]: 0.95-0.98), using either 70 or 23 variables captured before discontinuation. Similar numbers were obtained for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. The discrimination of logistic regression was inferior (area under ROC curve, 0.76 [95% CI: 0.70-0.81]). Calibration plots showed similar deviations from the perfect line for ML-NN and logistic regression. CONCLUSION: The ML-NN method very well predicted the composite outcome after premature discontinuation of anticoagulation and outperformed traditional logistic regression.