Rapidity of clinical response to adalimumab and improvement of quality of life in luminal Crohn's disease: RAPIDA study.

OBJECTIVE: No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD. PATIENTS AND METHODS: RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation. RESULTS: Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI<5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p<0.0001). CONCLUSION: Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

Incobotulinumtoxin A for Sialorrhea in Neurological Disorders: A Real-Life Experience.

Botulinum toxin type A is one of the most useful treatments of sialorrhea in neurological disorders. Evidence for the use of incobotulinumtoxin A (inco-A) in the treatment of sialorrhea is limited. Thirty-six patients with sialorrhea were treated with infiltrations of inco-A into both parotid glands. The severity of sialorrhea was evaluated by the Drooling Severity Scale (DSS), and the Drooling Frequency Scale (DFS). Patients' perceptions of clinical benefit were recorded via the Patient Global Impression of Improvement (PGI-I) scale. Following treatment, there was a significant difference in both the DFS and the DSS (p < 0.001). Clinical benefits on the basis of the PGI-I were present in up to 90% of patients.

Fish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.

Mercury, lead and cadmium levels in the urine of 170 Spanish adults: a pilot human biomonitoring study.

Human biomonitoring is a well-recognized tool for estimating the exposure of human populations to environmental pollutants. However, information regarding biomarker concentrations of many environmental chemicals in the general population is limited for many countries. The Spanish Environment Ministry has recently funded a human biomonitoring study on the Spanish general population. This study aims to determine reference levels for several biomarkers, especially heavy metals, persistent organic pollutants (POPs) and cotinine, in urine, whole blood, serum and hair, and will involve 2000 volunteers throughout Spain. Samples were taken during 2009-2010 and analyses are currently underway. The results presented herein were obtained in a pilot study carried out in the Madrid region. The study group comprised 170 volunteers, of which 79% were female and 21% male (age: 23-66 years). All participants were asked to complete a questionnaire regarding diet and living habits and provides a morning urine sample. The geometric means for total mercury (Hg), lead (Pb) and cadmium (Cd) were 1.23, 1.11 and 0.25 µg/g creatinine, respectively. Levels of Pb and Hg were higher than those reported for the general population in the USA and Germany, whereas Cd was in the same range (CDC, 2009; Becker et al., 2003). The values reported here are similar to those reported in other Spanish studies.

High-dose etanercept in ankylosing spondylitis: results of a 12-week randomized, double blind, controlled multicentre study (LOADET study).

OBJECTIVES: Etanercept 50 mg a week is approved in the treatment of AS. Increasing the etanercept dose to 100 mg/week improves efficacy in cutaneous psoriasis, a clinical manifestation related to the spondylarthritis family, while maintaining its safety profile. The purpose of this study was to evaluate the efficacy and safety of etanercept 100 vs 50 mg/week in patients with AS. METHODS: Adult patients with AS were randomized to receive etanercept 50 mg twice a week (biw), or etanercept 50 mg once a week (qw) for 12 weeks. The primary efficacy endpoint was Ankylosing Spondylitis Assessment Study (ASAS20) response at Week 12; secondary endpoints included ASAS40, ASAS50, ASAS70 and ASAS5/6 responses, partial remission and quality of life. Safety was assessed until 15 days after the last visit. RESULTS: A total of 108 patients were randomly selected and treated, 54 in each arm. At 12 weeks, ASAS20 response was achieved by 34 (71%) out of 48 patients of the etanercept 50 mg biw group and by 37 (76%) out of 49 patients of the etanercept 50 mg qw group (not statistically significant differences). Other efficacy variables improved significantly over time, but not between treatment groups. Fifty-six patients experienced at least one adverse event (generally, infections and infestations, gastrointestinal disorders and injection site reactions), most of them mild or moderate. CONCLUSIONS: High-dose (100 mg/week) etanercept in the treatment of AS for 12 weeks is as safe as the standard dose (50 mg/week). However, it does not significantly increase its efficacy. Trial Registration. Clinicaltrials.gov, http://clinicaltrials.gov/, NCT00873730.

Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism.

RATIONALE: Concomitant deep vein thrombosis (DVT) in patients with acute pulmonary embolism (PE) has an uncertain prognostic significance. OBJECTIVES: In a cohort of patients with PE, this study compared the risk of death in those with and those without concomitant DVT. METHODS: We conducted a prospective cohort study of outpatients diagnosed with a first episode of acute symptomatic PE. Patients underwent bilateral lower extremity venous compression ultrasonography to assess for concomitant DVT. MEASUREMENTS AND MAIN RESULTS: The primary study outcome, all-cause mortality, and the secondary outcome of PE-specific mortality were assessed during the 3 months of follow-up after PE diagnosis. Multivariate Cox proportional hazards regression was done to adjust for significant covariates. Of 707 patients diagnosed with PE, 51.2% (362 of 707) had concomitant DVT and 10.9% (77 of 707) died during follow-up. Patients with concomitant DVT had an increased all-cause mortality (adjusted hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.24 to 3.38; P = 0.005) and PE-specific mortality (adjusted HR, 4.25; 95% CI, 1.61 to 11.25; P = 0.04) compared with those without concomitant DVT. In an external validation cohort of 4,476 patients with acute PE enrolled in the international multicenter RIETE Registry, concomitant DVT remained a significant predictor of all-cause (adjusted HR, 1.66; 95% CI, 1.28 to 2.15; P < 0.001) and PE-specific mortality (adjusted HR, 2.01; 95% CI, 1.18 to 3.44; P = 0.01). CONCLUSIONS: In patients with a first episode of acute symptomatic PE, the presence of concomitant DVT is an independent predictor of death in the ensuing 3 months after diagnosis. Assessment of the thrombotic burden should assist with risk stratification of patients with acute PE.

Association of anaemia and mortality in patients with acute pulmonary embolism.

This study aimed to evaluate the relationship between anaemia and pulmonary embolism (PE) prognosis. We analysed a cohort of 764 patients with acute PE referred to a single center for diagnosis and management. Patients were divided into groups by quartiles of haemoglobin (Hb): Hb < 11.7 g/dl; Hb 11.7 to 12.9 g/dl; Hb 13.0 to 14.1 g/dl; Hb > 14.1 g/dl. Patients had a mean Hb of 12.9 g/dl, and values ranged from to 4.3 to 19.5 g/dl. Lower Hb was associated with recent bleeding, an impaired haemodynamic profile and higher creatinine. Patients in the lower Hb quartiles more commonly had female gender (p < 0.001), a diagnosis of cancer (p < 0.001), and an indication for an inferior vena cava (IVC) filter (p < 0.002), compared to patients in the higher Hb quartiles. Patients in higher Hb quartiles had higher survival at three months (75%, 86%, 90% and 91% for lowest to highest quartiles, respectively). On multivariate analysis, adjusting for known PE prognostic factors, low Hb proved to be an independent predictor of mortality (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.05 to 1.28 for each decrease of 1 g/dl). Hb level remained an independent predictor of all-cause mortality when cancer patients were excluded from the analysis (adjusted HR 0.81; 95% CI, 0.66 to 0.99; p = 0.04). Moreover, patients with anaemia showed a higher risk of fatal PE (unadjusted HR 1.19, 95% CI 1.04 to 1.37). In conclusion, in patients with acute symptomatic PE, anaemia severity is associated with worsened survival.

Enfermedad pulmonar obstructiva crónica en pacientes con tromboembolia de pulmón aguda sintomática / Chronic Obstructive Pulmonary Disease in Patients With Acute Symptomatic Pulmonary Embolism

IntroducciónEl diagnóstico de tromboembolia de pulmón (TEP) es a menudo complicado en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Además, algunos estudios indican que la EPOC empeora el pronóstico de los pacientes con TEP.Pacientes y métodosSe incluyó prospectivamente en el estudio a todos los pacientes ambulatorios diagnosticados de TEP aguda sintomática en un hospital universitario terciario. Se compararon las características clínicas, el intervalo de tiempo desde el inicio de los síntomas hasta el diagnóstico y el pronóstico en función de la presencia o ausencia de EPOC. El criterio de evaluación principal fue la muerte por todas las causas a los 3 meses.ResultadosSe incluyó a 882 pacientes con diagnóstico confirmado de TEP aguda sintomática. La prevalencia de EPOC fue de un 8% (intervalo confianza [IC] del 95%, 6–9%). En los pacientes con EPOC, fueron significativamente más frecuentes un retraso diagnóstico de la TEP superior a 3 días y una probabilidad clínica baja según una escala clínica estandarizada. Se produjo el fallecimiento de 128 pacientes (14%; IC del 95%, 12–17%) en los primeros 3 meses de seguimiento. Los antecedentes de cáncer y de inmovilización médica, las cifras de presión arterial sistólica menores de 100mmHg y la saturación de oxígeno inferior al 90% se asociaron de forma significativa a la mortalidad por todas las causas. El antecedente de EPOC se asoció de forma significativa a la mortalidad por TEP en el análisis de regresión logística (riesgo relativo=2,2; IC del 95%, 1,0–5,1).ConclusionesLos pacientes con EPOC y TEP presentan con más frecuencia una probabilidad clínica baja y un mayor retraso en el diagnóstico de la TEP que los pacientes sin EPOC. La EPOC se asocia de manera significativa a mortalidad por TEP en los 3 meses posteriores al diagnóstico(AU)

BackgroundThe diagnosis of pulmonary embolism (PE) is often complicated by the presence of chronic obstructive pulmonary disease (COPD). Some studies have suggested that patients with PE and concomitant COPD have a worse prognosis than patients without COPD.Patients and methodsOutpatients diagnosed with acute symptomatic PE at a university tertiary care hospital were prospectively included in the study. Clinical characteristics, time between onset of symptoms and diagnosis, and outcome were analyzed according to presence or absence of COPD. The primary endpoint was all-cause deaths at 3 months.ResultsOf 882 patients with a confirmed diagnosis of acute symptomatic PE, 8% (95% confidence interval [CI], 6%–9%) had COPD. Patients with COPD were significantly more likely to have a delay in diagnosis of more than 3 days and to have a low pretest probability of pulmonary embolism according to a standardized clinical score. The total number of deaths during 3 months of follow-up was 128 (14%; 95% CI, 12%–17%). Factors significantly associated with mortality from all causes were a history of cancer or immobilization, systolic blood pressure less than 100mm Hg, and arterial oxyhemoglobin saturation less than 90%. COPD was significantly associated with PE-related death in the logistic regression analysis (relative risk, 2.2; 95% CI, 1.0–5.1).ConclusionsPatients with COPD and PE more often have a lower pretest probability and a longer delay in diagnosis of PE. COPD is significantly associated with PE-related death in the 3 months following diagnosis(AU)

[Chronic obstructive pulmonary disease in patients with acute symptomatic pulmonary embolism]. / Enfermedad pulmonar obstructiva crónica en pacientes con tromboembolia de pulmón aguda sintomática.

BACKGROUND: The diagnosis of pulmonary embolism (PE) is often complicated by the presence of chronic obstructive pulmonary disease (COPD). Some studies have suggested that patients with PE and concomitant COPD have a worse prognosis than patients without COPD. PATIENTS AND METHODS: Outpatients diagnosed with acute symptomatic PE at a university tertiary care hospital were prospectively included in the study. Clinical characteristics, time between onset of symptoms and diagnosis, and outcome were analyzed according to presence or absence of COPD. The primary endpoint was all-cause deaths at 3 months. RESULTS: Of 882 patients with a confirmed diagnosis of acute symptomatic PE, 8% (95% confidence interval [CI], 6%-9%) had COPD. Patients with COPD were significantly more likely to have a delay in diagnosis of more than 3 days and to have a low pretest probability of pulmonary embolism according to a standardized clinical score. The total number of deaths during 3 months of follow-up was 128 (14%; 95% CI, 12%-17%). Factors significantly associated with mortality from all causes were a history of cancer or immobilization, systolic blood pressure less than 100mm Hg, and arterial oxyhemoglobin saturation less than 90%. COPD was significantly associated with PE-related death in the logistic regression analysis (relative risk, 2.2; 95% CI, 1.0-5.1). CONCLUSIONS: Patients with COPD and PE more often have a lower pretest probability and a longer delay in diagnosis of PE. COPD is significantly associated with PE-related death in the 3 months following diagnosis.

[Anti-factor Xa activity of enoxaparin for thromboprophylaxis in nonsurgical patients is dependent on body mass]. / La actividad anti-Xa depende del peso en pacientes médicos que reciben tromboprofilaxis con enoxaparina.

OBJECTIVE: Thromboprophylaxis with a fixed dose of low-molecular-weight heparin is recommended for hospitalized acutely ill medical patients. The purpose of this study was to assess whether the anti-factor Xa (anti-Xa) activity of enoxaparin prescribed for venous thromboembolism prophylaxis depends on body mass index (BMI) in patients hospitalized for an acute respiratory disease. PATIENTS AND METHODS: All patients admitted to the respiratory medicine department (January-December 2006) for an acute respiratory disease, and for whom pharmacologic thromboprophylaxis was indicated, were included in the study. Anti-Xa activity was measured 4 hours after administration of enoxaparin on the third day of hospitalization. The primary outcome was anti-Xa activity in relation to BMI. RESULTS: One hundred twelve patients were enrolled. Mean anti-Xa activity decreased with each BMI quartile (0.28, 0.23, 0.15, and 0.13 U/mL for quartiles 1, 2, 3, and 4, respectively). In the multivariate analysis, BMI was the only predictor of inadequate anti-Xa activity (odds ratio, 1.14; 95% confidence interval, 10.5-1.24; P< .002) after adjustment for age, sex, and serum creatinine levels. Two episodes of symptomatic proximal deep vein thrombosis were diagnosed in the month after hospitalization; both occurred in patients who had inadequate anti-Xa activity. CONCLUSIONS: Anti-Xa activity is dependent on BMI in hospitalized acute medical patients receiving enoxaparin for thromboprophylaxis.

[Prognostic value of electrocardiographic findings in hemodynamically stable patients with acute symptomatic pulmonary embolism]. / Valor pronóstico de los hallazgos electrocardiográficos en pacientes estables hemodinámicamente con tromboembolia de pulmón aguda sintomática.

INTRODUCTION AND OBJECTIVES: The aim of this study was to determine the prognostic value of electrocardiography in hemodynamically stable patients with a diagnosis of acute symptomatic pulmonary embolism (PE). METHODS: This prospective study included all hemodynamically stable outpatients who were diagnosed with PE at a university hospital. The electrocardiographic abnormalities investigated were: a) sinus tachycardia (>100 beats/min); b) ST-segment or T-wave abnormalities; c) right bundle branch block; d) an S1Q3T3 pattern, and e) recent-onset atrial arrhythmia. RESULTS: The study included 644 patients. Overall, 5% of those with an ECG abnormality died due to PE in the 15 days after diagnosis compared with 2% of those with normal ECG findings (relative risk [RR]=2.4; 95% confidence interval [CI], 1-5,8; P=.05). Multivariate analysis showed that sinus tachycardia was associated with a 2.2-fold increased risk of death due to all causes in the month after PE diagnosis. After adjusting for age, a history of cancer, immobility, ECG abnormalities, and sinus tachycardia, the presence of recent-onset atrial arrhythmia was significantly associated with death due to PE in the first 15 days (RR=2.8; 95% CI, 1-8.3; P=.05). The negative predictive value of atrial arrhythmia for 15-day PE-related mortality was 97%, while the negative likelihood ratio was 0.79. CONCLUSIONS: In hemodynamically stable patients with acute symptomatic PE, the presence of sinus tachycardia and atrial arrhythmia were independent predictors of a poor prognosis. However, the usefulness of these factors for stratifying risk in PE patients is limited.

Valor pronóstico de los hallazgos electrocardiográficos en pacientes estables hemodinámicamente con tromboembolia de pulmón aguda sintomática / Prognostic value of electrocardiographic findings in hemodynamically stable patients with acute symptomatic pulmonary embolism

Introducción y objetivos. El objetivo de este estudio es evaluar el valor pronóstico del electrocardiograma (ECG) en pacientes estables hemodinámicamente con diagnóstico de tromboembolia pulmonar (TEP) aguda sintomática. Métodos. Se incluyó de forma prospectiva a todos los pacientes ambulatorios estables hemodinámicamente diagnosticados de TEP aguda sintomática en un hospital universitario terciario. Las anomalías electrocardiográficas consideradas fueron: a) taquicardia sinusal (> 100 lat/min); b) alteraciones del segmento ST o de la onda T; c) bloqueo de la rama derecha del haz de His (BRDHH); d) patrón S1Q3T3, y e) arritmias auriculares de reciente comienzo. Resultados. Se incluyó a 644 pacientes en el estudio. Un 5% de los pacientes con ECG anormal fallecieron por TEP en los 15 días posteriores al diagnóstico, comparado con un 2% de los pacientes con ECG normal (razón de riesgo [RR] = 2,4; intervalo de confianza [IC] del 95%, 1-5,8; p = 0,05). En el análisis multivariable, la taquicardia sinusal multiplicó por 2,2 el riesgo de muerte por todas las causas en el mes posterior al diagnóstico de TEP. Tras ajustar por edad, antecedentes de cáncer, inmovilización, un ECG alterado y la presencia de taquicardia sinusal, las arritmias auriculares de reciente diagnóstico se asociaron de forma significativa a la muerte por TEP durante los primeros 15 días (RR = 2,8; IC del 95%, 1-8,3; p = 0,05). Las arritmias auriculares mostraron un alto valor predictivo negativo de muerte por TEP a los 15 días (97%), pero la razón de probabilidad negativa fue 0,79. Conclusiones. En pacientes estables hemodinámicamente con TEP aguda sintomática, la taquicardia sinusal y las arritmias auriculares son predictoras independientes de mal pronóstico. Sin embargo, su utilidad en la estratificación pronóstica de estos pacientes es limitada

Introduction and objectives. The aim of this study was to determine the prognostic value of electrocardiography in hemodynamically stable patients with a diagnosis of acute symptomatic pulmonary embolism (PE). Methods. This prospective study included all hemodynamically stable outpatients who were diagnosed with PE at a university hospital. The electrocardiographic abnormalities investigated were: a) sinus tachycardia (>100 beats/min); b) ST-segment or T-wave abnormalities; c) right bundle branch block; d) an S1Q3T3 pattern, and e) recent-onset atrial arrhythmia. Results. The study included 644 patients. Overall, 5% of those with an ECG abnormality died due to PE in the 15 days after diagnosis compared with 2% of those with normal ECG findings (relative risk [RR]=2.4; 95% confidence interval [CI], 1­5,8; P=.05). Multivariate analysis showed that sinus tachycardia was associated with a 2.2-fold increased risk of death due to all causes in the month after PE diagnosis. After adjusting for age, a history of cancer, immobility, ECG abnormalities, and sinus tachycardia, the presence of recent-onset atrial arrhythmia was significantly associated with death due to PE in the first 15 days (RR=2.8; 95% CI, 1­8.3; P=.05). The negative predictive value of atrial arrhythmia for 15-day PE-related mortality was 97%, while the negative likelihood ratio was 0.79. Conclusions. In hemodynamically stable patients with acute symptomatic PE, the presence of sinus tachycardia and atrial arrhythmia were independent predictors of a poor prognosis. However, the usefulness of these factors for stratifying risk in PE patients is limited

[Prognostic value of transthoracic echocardiography in hemodynamically stable patients with acute symptomatic pulmonary embolism]. / Valor pronóstico de la ecocardiografía transtorácica en pacientes estables hemodinámicamente con tromboembolia de pulmón aguda sintomática.

OBJECTIVE: To determine the prognostic value of transthoracic echocardiography in hemodynamically stable patients diagnosed with acute symptomatic pulmonary embolism. PATIENTS AND METHODS: Hemodynamically stable outpatients diagnosed with acute symptomatic pulmonary embolism at a tertiary university hospital were prospectively included in the study. All patients underwent transthoracic echocardiography within 48 hours of diagnosis. The primary endpoint was all-cause mortality at 1 month. RESULTS: Right ventricular dysfunction was documented by echocardiography in 86 of the 214 patients (40%) in our series. In the first month of follow-up, 7 patients died--4 with positive echocardiographic findings and 3 with negative findings (odds ratio, 2.0; 95% confidence interval, 0.4-9.3; P=.41). For the primary endpoint, the negative predictive value of transthoracic echocardiography was 98%, the positive predictive value was 5%, and the negative likelihood ratio was 0.7. The negative predictive value was 100% and the positive predictive value was 3% when we analyzed death due to pulmonary embolism only. CONCLUSIONS: In our setting, transthoracic echocardiography is not useful for prognostic stratification of hemodynamically stable patients with pulmonary embolism.

Valor pronóstico de la ecocardiografía transtorácica en pacientes estables hemodinámicamente con tromboembolia de pulmón aguda sintomática / Prognostic value of transthoracic echocardiography in hemodynamically stable patients with acute symptomatic pulmonary embolism

Objetivo: El objetivo de este estudio ha sido evaluar el valor pronóstico de la ecocardiografía transtorácica en pacientes estables hemodinámicamente con diagnóstico de tromboembolia pulmonar (TEP) aguda sintomática. Pacientes y métodos: Se incluyó prospectivamente en el estudio a todos los pacientes ambulatorios, estables hemodinámicamente, diagnosticados de TEP aguda sintomática en un hospital universitario terciario. Se realizó a todos ellos una ecocardiografía transtorácica en las 48 h posteriores al diagnóstico. El criterio de evaluación principal fue la muerte por todas las causas a un mes. Resultados: La prevalencia de criterios ecocardiográficos de disfunción del ventrículo derecho fue de un 40% en nuestra serie (86/214). Durante el primer mes de seguimiento se produjeron 7 fallecimientos, 4 en el grupo con ecocardiografía positiva y 3 en el grupo con ecocardiografía negativa (odds ratio = 2,0; intervalo de confianza del 95%, 0,4-9,3; p = 0,41). La ecocardiografía transtorácica demostró un valor predictivo negativo del 98%, un valor predictivo positivo del 5% y un cociente de probabilidad negativo de 0,7 respecto al parámetro de valoración principal. Cuando sólo se consideró la muerte por TEP, el valor predictivo negativo fue del 100% y el valor predictivo positivo, del 3%. Conclusiones: En nuestro medio la ecocardiografía transtorácica carece de utilidad en la estratificación pronóstica de los pacientes estables hemodinámicamente con TEP

Objective: To determine the prognostic value of transthoracic echocardiography in hemodynamically stable patients diagnosed with acute symptomatic pulmonary embolism. Patients and Methods: Hemodynamically stable outpatients diagnosed with acute symptomatic pulmonary embolism at a tertiary university hospital were prospectively included in the study. All patients underwent transthoracic echocardiography within 48 hours of diagnosis. The primary endpoint was all-cause mortality at 1 month. Results: Right ventricular dysfunction was documented by echocardiography in 86 of the 214 patients (40%) in our series. In the first month of follow-up, 7 patients died--4 with positive echocardiographic findings and 3 with negative findings (odds ratio, 2.0; 95% confidence interval, 0.4-9.3; P=.41). For the primary endpoint, the negative predictive value of transthoracic echocardiography was 98%, the positive predictive value was 5%, and the negative likelihood ratio was 0.7. The negative predictive value was 100% and the positive predictive value was 3% when we analyzed death due to pulmonary embolism only. Conclusions: In our setting, transthoracic echocardiography is not useful for prognostic stratification of hemodynamically stable patients with pulmonary embolism

Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy.

OBJECTIVE: To assess the performance of two prognostic models in predicting short-term mortality in patients with pulmonary embolism (PE). SUBJECTS AND METHODS: We compared the test characteristics of two prognostic models for predicting 30-day outcomes (mortality, thromboembolic recurrences, and major bleeding) in a cohort of 599 patients with objectively confirmed PE. Patients were stratified into the PE severity index (PESI) risk classes I-V and the Geneva low-risk and high-risk strata. We compared the discriminatory power of both prognostic models. RESULTS: The PESI classified fewer patients as low risk (strata I and II) [36%; 216 of 599 patients; 95% confidence interval (CI), 32 to 40%] compared to the Geneva prediction rule (84%; 502 of 599 patients; 95% CI, 81 to 87%) [p < 0.0001]. Using either prediction rule, the low-risk groups showed statistically relevant 30-day mortality difference (PESI, 0.9%; 95% CI, 0.3 to 2.2; vs Geneva, 5.6%; 95% CI, 3.6 to 7.6) [p < 0.0001], although nonfatal recurrent venous thromboembolism or major bleeding rates were statistically similar (PESI, 2.8%; 95% CI, 0.6 to 5.0%; vs Geneva, 4.2%; 95% CI, 2.4 to 5.9%). The area under the receiver operating characteristic curve was higher for the PESI (0.76; 95% CI, 0.69 to 0.83) than for the Geneva score (0.61; 95% CI, 0.51 to 0.71) [p = 0.002]. CONCLUSIONS: The PESI quantified the prognosis of patients with PE better than the Geneva score. This study demonstrated that PESI can select patients with very low adverse event rates during the initial days of acute PE therapy and assist in selecting patients for treatment in the outpatient setting.

Prognostic significance of delays in diagnosis of pulmonary embolism.

STUDY OBJECTIVE: To investigate the prognostic significance of a diagnostic delay of greater than 1 week after symptom onset in patients with pulmonary embolism (PE). DESIGN: Prospective cohort study. LOCATION: Emergency Department of Ramón y Cajal Hospital, a 1500-bed tertiary-care center in Madrid, Spain. PATIENTS: Diagnosed with PE by objective testing between January 1, 2003, and June 30, 2005. INTERVENTIONS: All patients received standard anticoagulation therapy during follow-up. ENDPOINTS: Death from any cause or symptomatic recurrent venous thromboembolism (VTE), confirmed by standard objective testing, within 3 months after PE diagnosis. RESULTS: Of the 397 patients with acute PE, 72 (18%) had a diagnostic delay while 325 (82%) did not. The all-cause mortality rate was 13.1% at 3 months (95% CI=9.8-16.4%); due to 9 (12.5%) deaths in the diagnostic delay group and 43 (13.2%) deaths in the group without diagnostic delay (OR 0.9; 95% CI=0.4-2.0). Though multivariate analysis of clinical variables at the time of PE diagnosis identified active cancer, heart failure and immobility for more than 4 days as independent risk factors for death, diagnostic delay was not predictive. Recurrent VTE was observed in 3 (4.2%) of 72 patients with diagnostic delay and in 15 (4.6%) of 325 patients without diagnostic delay (odds ratio: 0.9; 95% CI=0.2-3.2). None of the variables analysed, including diagnostic delay, was associated with an increased risk of recurrent VTE during follow-up. CONCLUSIONS: Among survivors diagnosed with acute PE in the Emergency Department, we did not detect an association between a delay in diagnosis and an increased risk of death or VTE recurrence during the ensuing 3 months of treatment.

Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism.

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.

[Thromboembolic events in patients after a negative computed tomography pulmonary angiogram: A retrospective study of 165 patients]. / Aparición de episodios tromboembólicos en pacientes con angiotomografía axial computarizada simple negativa. Estudio retrospectivo de 165 pacientes.

OBJECTIVE: To determine the value of computed tomography (CT) angiography of the chest as a diagnostic test to exclude pulmonary embolism and to assess compliance with diagnostic protocols for thromboembolic disease. PATIENTS AND METHODS: We retrospectively studied patients who underwent CT angiography of the chest because of suspected pulmonary embolism in 2004. All the patients were followed for 3 months. The percentage of patients diagnosed with a thromboembolic event based on an objective test during the follow-up period was determined. We analyzed the percentage of patients with a negative CT angiogram on whom additional diagnostic tests (ultrasound of the lower limbs and/or ventilation-perfusion lung scintigraphy) were performed. RESULTS: One hundred sixty-five patients underwent CT angiography of the chest because of suspected pulmonary embolism in 2004. Four of the patients were excluded from the study because they were on chronic anticoagulation therapy and a further 2 were excluded because they had a life expectancy of under 3 months. Of the remaining 159 patients, 60 had CT angiograms that were interpreted as high probability for pulmonary embolism (prevalence of 38%). Thirty-nine of the 99 patients with a negative CT angiogram experienced an objectively confirmed thromboembolic event (63% sensitivity; 95% confidence interval, 53%-73%). Other diagnostic tests were not performed in 46% of the cases. CONCLUSIONS: In our setting, a negative single-detector helical CT angiogram was not sensitive enough to exclude the diagnosis of pulmonary embolism. Furthermore, compliance with internationally accepted diagnostic protocols was far from optimal.