Enfermedad tromboembólica venosa idiopática: análisis prospectivo de un registro informatizado de pacientes (RIETE)

La enfermedad tromboembólica venosa (ETEV) idiopática puede suponer hasta la mitad de los pacientes con ETEV y tiene una mayor morbimortalidad, especialmente debido a la mayor frecuencia de recidiva de ETEV. Sin embargo, no se conocen los factores que predicen un mayor riesgo de recidiva y otras complicaciones (hemorragia y muerte) y, en última instancia, no se ha definido la duración óptima del tratamiento anticoagulante. OBJETIVOS: Identificar los factores implicados en la recidiva tromboembólica y la duración óptima del tratamiento anticoagulante en los pacientes con ETEV idiopática. Evaluar la probabilidad acumulada de recidiva post-tratamiento. MÉTODO: El Registro Informatizado de Enfermedad TromboEmbólica (RIETE) consiste en un registro en desarrollo, internacional, multicéntrico, prospectivo, de pacientes consecutivos que se presentan con un evento tromboembólico venoso agudo, confirmado por pruebas objetivas. Se seleccionaron los pacientes con ETEV idiopática y se analizaron la probabilidad de recidiva post-tratamiento, las variables asociadas y la duración optima de anticoagulación recibida. RESULTADOS: De enero-2001 a marzo-2010, 30949 pacientes fueron reclutados. 8939 (28,9%) fueron idiopáticos, de los que 2294 fueron seguidos tras la suspensión de la anticoagulación una mediana de 5,4 meses, habiendo recibido, una duración mediana de anticoagulación de 6,2 meses. La probabilidad acumulada de recidiva post-tratamiento, a los 18 meses, fue del 17,5%. De las 207 recidivas de ETEV, 55,1% fueron TEP y 44,9% TVP. Ninguna variable, incluida la duración del tratamiento anticoagulante, se asoció, significativamente, con la recidiva post-tratamiento en el análisis multivariable. CONCLUSIONES: Los pacientes con ETEV idiopática tienen un alto riesgo de recidiva tras la suspensión del tratamiento anticoagulante. No hay diferencias entre las distintas duraciones de terapias definidas; una vez suspendido el tratamiento, el riesgo de recidiva es igual de elevado. No se han encontrado otros factores que ayuden a predecir un mayor o menor riesgo de recidiva tras la suspensión del tratamiento

Hospital volume and outcomes for acute pulmonary embolism: Multinational population based cohort study

[Objectives] To evaluate the association between experience in the management of acute pulmonary embolism, reflected by hospital case volume, and mortality.[Design] Multinational population based cohort study using data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry between 1 January 2001 and 31 August 2018.[Setting] 353 hospitals in 16 countries.[Participants] 39 257 consecutive patients with confirmed diagnosis of acute symptomatic pulmonary embolism.[Main] outcome measure Pulmonary embolism related mortality within 30 days after diagnosis of the condition.[Results] Patients with acute symptomatic pulmonary embolism admitted to high volume hospitals (>40 pulmonary embolisms per year) had a higher burden of comorbidities. A significant inverse association was seen between annual hospital volume and pulmonary embolism related mortality. Admission to hospitals in the highest quarter (that is, >40 pulmonary embolisms per year) was associated with a 44% reduction in the adjusted odds of pulmonary embolism related mortality at 30 days compared with admission to hospitals in the lowest quarter (<15 pulmonary embolisms per year; adjusted risk 1.3% v 2.3%; adjusted odds ratio 0.56 (95% confidence interval 0.33 to 0.95); P=0.03). Results were consistent in all sensitivity analyses. All cause mortality at 30 days was not significantly reduced between the two quarters (adjusted odds ratio 0.78 (0.50 to 1.22); P=0.28). Survivors showed little change in the odds of recurrent venous thromboembolism (odds ratio 0.76 (0.49 to 1.19)) or major bleeding (1.07 (0.77 to 1.47)) between the low and high volume hospitals.[Conclusions] In patients with acute symptomatic pulmonary embolism, admission to high volume hospitals was associated with significant reductions in adjusted pulmonary embolism related mortality at 30 days. These findings could have implications for management strategies.Peer reviewe

Physiological responses to acute cold exposure in young lean men

The aim of this study was to comprehensively describe the physiological responses to an acute bout of mild cold in young lean men (n = 11, age: 23 ± 2 years, body mass index: 23.1 ± 1.2 kg/m2) to better understand the underlying mechanisms of non-shivering thermogenesis and how it is regulated. Resting energy expenditure, substrate metabolism, skin temperature, thermal comfort perception, superficial muscle activity, hemodynamics of the forearm and abdominal regions, and heart rate variability were measured under warm conditions (22.7 ± 0.2ÊC) and during an individualized cooling protocol (air-conditioning and water cooling vest) in a cold room (19.4 ± 0.1ÊC). The temperature of the cooling vest started at 16.6ÊC and decreased ~ 1.4ÊC every 10 minutes until participants shivered (93.5 ± 26.3 min). All measurements were analysed across 4 periods: warm period, at 31% and at 64% of individualÂs cold exposure time until shivering occurred, and at the shivering threshold. Energy expenditure increased from warm period to 31% of cold exposure by 16.7% (P = 0.078) and to the shivering threshold by 31.7% (P = 0.023). Fat oxidation increased by 72.6% from warm period to 31% of cold exposure (P = 0.004), whereas no changes occurred in carbohydrates oxidation. As shivering came closer, the skin temperature and thermal comfort perception decreased (all P<0.05), except in the supraclavicular skin temperature, which did not change (P>0.05). Furthermore, the superficial muscle activation increased at the shivering threshold. It is noteworthy that the largest physiological changes occurred during the first 30 minutes of cold exposure, when the participants felt less discomfort.The study was supported by the Spanish Ministry of Economy and Competitiveness (PTA 12264-I), Fondo de InvestigacioÂn Sanitaria del Instituto de Salud Carlos III (PI13/01393), and Retos de la Sociedad (DEP2016-79512-R), Fondos Estructurales de la UnioÂn Europea (FEDER), by the Spanish Ministry of Education (FPU 13/04365 and 15/04059), by the FundacioÂn Iberoamericana de NutricioÂn (FINUT), by the Redes temaÂticas de investigacioÂn cooperativa RETIC (Red SAMI

Prediction of Major Bleeding in Anticoagulated Patients for Venous Thromboembolism : Comparison of the RIETE and the VTE-BLEED Scores

The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).The performance of validated bleeding risk scores in patients with venous thromboembolism (VTE) could be different depending on the time after index event or the site of bleeding. In this study we compared the "classic" Registro Informatizado de Enfermedad TromboEmbólica (RIETE) score and the more recently developed VTE-BLEED score for the prediction of major bleeding in patients under anticoagulant therapy in different time intervals after VTE diagnosis. Out of 82,239 patients with acute VTE, the proportion of high-risk patients according to the RIETE and VTE-BLEED scores was 7.1 and 62.3%, respectively. The performance of both scores across the different study periods (first 30 days after VTE diagnosis, days 31-90, days 91-180, and days 181-360) was similar, with areas under the receiving operating characteristics (ROC) curve (AUC) ranging between 0.69 and 0.72. However, the positive predictive values were low, ranging between 0.6 and 3.9 (better for early major bleeding than for later periods). A sensitivity analysis limited to patients with unprovoked VTE showed comparable results. Both scores showed a trend toward a better prediction of extracranial than intracranial major bleeding, the RIETE score resulting more useful for early extracranial bleeding and the VTE-BLEED for late intracranial hemorrhages. Our study reveals that the usefulness of available bleeding scores may vary depending on the characteristics of the patient population and the time frame evaluated. Dynamic scores could be more useful for this purpose.publishersversionPeer reviewe

The rationale, design, and methods of a randomized, controlled trial to evaluate the efficacy and safety of an active strategy for the diagnosis and treatment of acute pulmonary embolism during exacerbations of chronic obstructive pulmonary disease

Introduction: Some previous studies have suggested a high prevalence of pulmonary embolism (PE) during exacerbations of chronic obstructive pulmonary disease (ECOPD). The SLICE trial aims to assess the efficacy and safety of an active strategy for the diagnosis and treatment of PE (vs usual care) in patients hospitalized because of ECOPD. Methods: SLICE is a phase III, prospective, international, multicenter, randomized, open-label, and parallel-group trial. A total of 746 patients hospitalized because of ECOPD will be randomized in a 1:1 fashion to receive either an active strategy for the diagnosis and anticoagulant treatment of PE or usual care (ie, standard care without any diagnostic test for diagnosing PE). The primary outcome is a composite of all-cause death, non-fatal (recurrent) venous thromboembolism (VTE), or readmission for ECOPD within 90 days after enrollment. Secondary outcomes are (a) death from any cause within 90 days after enrollment, (b) non-fatal (recurrent) VTE within 90 days after enrollment, (c) readmission within 90 days after enrollment, and (d) length of hospital stay. Results: Enrollment started in September 2014 and is expected to proceed until 2020. Median age of the first 443 patients was 71 years (interquartile range, 64-78), and 26% were female. Conclusions: This multicenter trial will determine the value of detecting PEs in patients with ECOPD. This has implications for COPD patient morbidity and mortality

Clinical Characteristics and Outcomes of Patients with Lung Cancer and Venous Thromboembolism

Background. The natural history of patients with lung cancer and venous thromboembolism (VTE) has not been consistently evaluated. Methods  We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics, time course, and outcomes during anticoagulation of lung cancer patients with acute, symptomatic VTE. Results  As of May 2017, a total of 1,725 patients were recruited: 1,208 (70%) presented with pulmonary embolism (PE) and 517 with deep vein thrombosis (DVT). Overall, 865 patients (50%) were diagnosed with cancer <3 months before, 1,270 (74%) had metastases, and 1,250 (72%) had no additional risk factors for VTE. During anticoagulation (median, 93 days), 166 patients had symptomatic VTE recurrences (recurrent DVT: 86, PE: 80), 63 had major bleeding (intracranial 11), and 870 died. The recurrence rate was twofold higher than the major bleeding rate during the first month, and over threefold higher beyond the first month. Fifty-seven patients died of PE and 15 died of bleeding. Most fatal PEs (84%) and most fatal bleeds (67%) occurred within the first month of therapy. Nine patients with fatal PE (16%) died within the first 24 hours. Of 72 patients dying of PE or bleeding, 15 (21%) had no metastases and 29 (40%) had the VTE shortly after surgery or immobility. Conclusion  Active surveillance on early signs and/or symptoms of VTE in patients with recently diagnosed lung cancer and prescription of prophylaxis in those undergoing surgery or during periods of immobilization might likely help prevent VTE better, detect it earlier, and treat it more efficiently.publishersversionPeer reviewe

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

SLICE Trial Group.[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.Peer reviewe

Hospital emergency room diagnosis of acute appendicitis in patients aged 2 to 20 years: the INFURG-SEMES score from the emergency infections study of the Spanish Society of Emergency Medicine

Objetivo. Derivar una escala clínico-analítica diagnóstica de apendicitis aguda (AA) en pacientes entre 2 y 20 años atendidos por dolor abdominal con sospecha de AA en servicios de urgencias hospitalarios (SUH), y comparar su capacidad diagnóstica con la Escala de Alvarado (EA). Métodos. Estudio observacional de cohorte prospectivo que incluyó de forma consecutiva pacientes entre 2 y 20 años con dolor abdominal sospechoso de AA de menos de 72 horas de evolución atendidos en 4 SUH españoles entre junio y diciembre de 2014. Se recogieron datos demográficos, clínicos, analíticos (recuento leucocitario, fórmula y proteína C reactiva) y radiológicos (ecografía y/o TC) y, si procedía, quirúrgicos. La variable resultado principal fue el diagnóstico final de AA en los 14 días desde la visita índice. Resultados. Se incluyeron 331 pacientes con edad media de 11,8 (DE 3,8) años, siendo 175 (52,9%) hombres. Ciento dieciséis (35,0%) tuvieron diagnóstico final de AA. La escala INFURG-SEMES incluye sexo masculino, dolor en fosa ilíaca derecha a la exploración, dolor a la percusión, dolor al caminar, presencia de neutrofilia y proteína C reactiva elevada. El área bajo la curva (ABC) de la característica operativa del receptor (COR) de dicha escala fue 0,84 (IC 95% 0,79-0,88) y para la EA 0,77 (IC95% 0,72-0,82) siendo la diferencia estadísticamente significativa (p = 0,002). Conclusiones. La escala INFURG-SEMES podría ser una herramienta de ayuda para el diagnóstico de AA en los pacientes entre 2 y 20 años atendidos con dolor abdominal sospechoso de apendicitis en los SUH, y ha mostrado una mayor capacidad discriminativa que la EA

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.Peer reviewe

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

publishersversionPeer reviewe