Validación de una estrategia diagnóstica basada en aplicación de criterios clínicos, niveles de dímero-D y angio tomografía computarizada torácica para descartar embolia pulmonar en un servicio de urgencias

1.Nuestros resultados han permitido validar una estrategia diagnóstica basada en la combinación de la estimación del riegos clínico de enfermedad tromboembólica venosar, niveles plasmáticos de dímero D angio TC torácica en pacientes que acuden a urgencias con sospecha de embolia pulmonar en nuestro medio. 2.La aplicación del modelo diagnóstico basado en la escala de Wells junto con dímero D negativo permite excluir de forma segura el diagnóstico de embolia pulmonar clínicamente significativa en pacientes atendidos en nuestro medio. 3.La aplicación de dicha estrategia permitiría evitar la realización de una agio TC torácica en una cuarta parte de los pacientes atendidos en urgencias en los que se sospecha embolia pulmonar respecto a la estrategia actual de nuestro centro basada en impresión clínica y angio TC torácica. 4.El beneficio de esta estrategia diagnóstica en términos de poder evitar la realización de angio TC torácica es, según nuestros resultados, menor en pacientes ancianos y con neoplasias. 5.La aplicación de esta estrategia diagnóstica en nuestro medio presenta una buena relación coste-eficacia. 6.El empleo del dímero D sin estimar previamente la probabilidad clínica de EP, puede inducir a errores diagnósticos en pacientes con probabilidad clínica alta de EP. 7.Una angio TC torácica negativa presenta un alto valor predictiva negativo en pacientes atendidos en urgencias en los que sospecha embolia pulmonar, según nuestro estudio. 8.La angio TC realizada en pacientes con sospecha de EP permite identificar diagnósticos alternativos en un tercio de los pacientes en los que no se confirma EP, siendo infecciones respiratorias y neoplasias con diagnósiticos más frecuentes en dichos pacientes

Validación de una estrategia diagnóstica basada en aplicación de criterios clínicos, niveles de dímero-D y angio tomografía computarizada torácica para descartar embolia pulmonar en un servicio de urgencias

1.Nuestros resultados han permitido validar una estrategia diagnóstica basada en la combinación de la estimación del riegos clínico de enfermedad tromboembólica venosar, niveles plasmáticos de dímero D angio TC torácica en pacientes que acuden a urgencias con sospecha de embolia pulmonar en nuestro medio. 2.La aplicación del modelo diagnóstico basado en la escala de Wells junto con dímero D negativo permite excluir de forma segura el diagnóstico de embolia pulmonar clínicamente significativa en pacientes atendidos en nuestro medio. 3.La aplicación de dicha estrategia permitiría evitar la realización de una agio TC torácica en una cuarta parte de los pacientes atendidos en urgencias en los que se sospecha embolia pulmonar respecto a la estrategia actual de nuestro centro basada en impresión clínica y angio TC torácica. 4.El beneficio de esta estrategia diagnóstica en términos de poder evitar la realización de angio TC torácica es, según nuestros resultados, menor en pacientes ancianos y con neoplasias. 5.La aplicación de esta estrategia diagnóstica en nuestro medio presenta una buena relación coste-eficacia. 6.El empleo del dímero D sin estimar previamente la probabilidad clínica de EP, puede inducir a errores diagnósticos en pacientes con probabilidad clínica alta de EP. 7.Una angio TC torácica negativa presenta un alto valor predictiva negativo en pacientes atendidos en urgencias en los que sospecha embolia pulmonar, según nuestro estudio. 8.La angio TC realizada en pacientes con sospecha de EP permite identificar diagnósticos alternativos en un tercio de los pacientes en los que no se confirma EP, siendo infecciones respiratorias y neoplasias con diagnósiticos más frecuentes en dichos pacientes

Accuracy of physicians' intuitive risk estimation in the diagnostic management of pulmonary embolism: An Individual Patient Data Meta-Analysis

BACKGROUND: In patients clinically suspected of having pulmonary embolism (PE), physicians often rely on intuitive estimation ("gestalt") of PE presence. Although shown to be predictive, gestalt is criticized for its assumed variation across physicians and lack of standardization. OBJECTIVES: To assess the diagnostic accuracy of gestalt in the diagnosis of PE and gain insight into its possible variation. METHODS: We performed an individual patient data meta-analysis including patients suspected of having PE. The primary outcome was diagnostic accuracy of gestalt for the diagnosis of PE, quantified as risk ratio (RR) between gestalt and PE based on 2-stage random-effect log-binomial meta-analysis regression as well as gestalts' sensitivity and specificity. The variability of these measures was explored across different health care settings, publication period, PE prevalence, patient subgroups (sex, heart failure, chronic lung disease, and items of the Wells score other than gestalt), and age. RESULTS: We analyzed 20 770 patients suspected of having PE from 16 original studies. The prevalence of PE in patients with and without a positive gestalt was 28.8% vs 9.1%, respectively. The overall RR was 3.02 (95% CI, 2.35-3.87), and the overall sensitivity and specificity were 74% (95% CI, 68%-79%) and 61% (95% CI, 53%-68%), respectively. Although variation was observed across individual studies (I 2, 90.63%), the diagnostic accuracy was consistent across all subgroups and health care settings. CONCLUSION: A positive gestalt was associated with a 3-fold increased risk of PE in suspected patients. Although variation was observed across studies, the RR of gestalt was similar across prespecified subgroups and health care settings, exemplifying its diagnostic value for all patients suspected of having PE

Wells Rule and D-Dimer Testing to Rule Out Pulmonary Embolism A Systematic Review and Individual-Patient Data Meta-analysis

Background: The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear. Purpose: To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted D-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older. Data Sources: MEDLINE and EMBASE from 1 January 1988 to 13 February 2016. Study Selection: 6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative D-dimer testing. Data Extraction: Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. Data Synthesis: The proportion of patients in whom imaging could be withheld based on a "PE-unlikely" Wells score and a negative D-dimer test result (efficiency) was estimated using fixed (50 years) D-dimer thresholds; their 3-month incidence of symptomatic venous thromboembolism (failure rate) was also estimated. Overall, efficiency increased from 28% to 33% when the age-adjusted (instead of the fixed) D-dimer threshold was applied. This increase was more prominent in elderly patients (12%) but less so in inpatients (2.6%). The failure rate of age-adjusted D-dimer testing was less than 3% in all examined subgroups. Limitation: Post hoc analysis, between-study differences in patient characteristics, use of various D-dimer assays, and limited statistical power to assess failure rate. Conclusion: Age-adjusted D-dimer testing is associated with a 5% absolute increase in the proportion of patients with suspected PE in whom imaging can be safely withheld compared with fixed D-dimer testing. This strategy seems safe across different high-risk subgroups, but its efficiency varies

Ruling out pulmonary embolism across different healthcare settings: A systematic review and individual patient data meta-analysis

International audienceBackground The challenging clinical dilemma of detecting pulmonary embolism (PE) in suspected patients is encountered in a variety of healthcare settings. We hypothesized that the optimal diagnostic approach to detect these patients in terms of safety and efficiency depends on underlying PE prevalence, case mix, and physician experience, overall reflected by the type of setting where patients are initially assessed. The objective of this study was to assess the capability of ruling out PE by available diagnostic strategies across all possible settings. Methods and findings We performed a literature search (MEDLINE) followed by an individual patient data (IPD) meta-analysis (MA; 23 studies), including patients from self-referral emergency care ( n = 12,612), primary healthcare clinics ( n = 3,174), referred secondary care ( n = 17,052), and hospitalized or nursing home patients ( n = 2,410). Multilevel logistic regression was performed to evaluate diagnostic performance of the Wells and revised Geneva rules, both using fixed and adapted D-dimer thresholds to age or pretest probability (PTP), for the YEARS algorithm and for the Pulmonary Embolism Rule-out Criteria (PERC). All strategies were tested separately in each healthcare setting. Following studies done in this field, the primary diagnostic metrices estimated from the models were the “failure rate” of each strategy—i.e., the proportion of missed PE among patients categorized as “PE excluded” and “efficiency”—defined as the proportion of patients categorized as “PE excluded” among all patients. In self-referral emergency care, the PERC algorithm excludes PE in 21% of suspected patients at a failure rate of 1.12% (95% confidence interval [CI] 0.74 to 1.70), whereas this increases to 6.01% (4.09 to 8.75) in referred patients to secondary care at an efficiency of 10%. In patients from primary healthcare and those referred to secondary care, strategies adjusting D-dimer to PTP are the most efficient (range: 43% to 62%) at a failure rate ranging between 0.25% and 3.06%, with higher failure rates observed in patients referred to secondary care. For this latter setting, strategies adjusting D-dimer to age are associated with a lower failure rate ranging between 0.65% and 0.81%, yet are also less efficient (range: 33% and 35%). For all strategies, failure rates are highest in hospitalized or nursing home patients, ranging between 1.68% and 5.13%, at an efficiency ranging between 15% and 30%. The main limitation of the primary analyses was that the diagnostic performance of each strategy was compared in different sets of studies since the availability of items used in each diagnostic strategy differed across included studies; however, sensitivity analyses suggested that the findings were robust. Conclusions The capability of safely and efficiently ruling out PE of available diagnostic strategies differs for different healthcare settings. The findings of this IPD MA help in determining the optimum diagnostic strategies for ruling out PE per healthcare setting, balancing the trade-off between failure rate and efficiency of each strategy

Accuracy of physicians' intuitive risk estimation in the diagnostic management of pulmonary embolism : an individual patient data meta-analysis

Background: In patients clinically suspected of having pulmonary embolism (PE), physicians often rely on intuitive estimation ("gestalt") of PE presence. Although shown to be predictive, gestalt is criticized for its assumed variation across physicians and lack of standardization. Objectives: To assess the diagnostic accuracy of gestalt in the diagnosis of PE and gain insight into its possible variation. Methods: We performed an individual patient data meta-analysis including patients suspected of having PE. The primary outcome was diagnostic accuracy of gestalt for the diagnosis of PE, quantified as risk ratio (RR) between gestalt and PE based on 2-stage random-effect log-binomial meta-analysis regression as well as gestalts' sensitivity and specificity. The variability of these measures was explored across different health care settings, publication period, PE prevalence, patient subgroups (sex, heart failure, chronic lung disease, and items of the Wells score other than gestalt), and age. Results: We analyzed 20 770 patients suspected of having PE from 16 original studies. The prevalence of PE in patients with and without a positive gestalt was 28.8% vs 9.1%, respectively. The overall RR was 3.02 (95% CI, 2.35-3.87), and the overall sensitivity and specificity were 74% (95% CI, 68%-79%) and 61% (95% CI, 53%-68%), respectively. Although variation was observed across individual studies (I2, 90.63%), the diagnostic accuracy was consistent across all subgroups and health care settings. Conclusion: A positive gestalt was associated with a 3-fold increased risk of PE in suspected patients. Although variation was observed across studies, the RR of gestalt was similar across prespecified subgroups and health care settings, exemplifying its diagnostic value for all patients suspected of having PE.</p

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis

Aims: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. Methods and results: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value &lt;0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). Conclusion: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. Registration: PROSPERO ID 89366.</p

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis

AIMS: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. METHODS AND RESULTS: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). CONCLUSION: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. REGISTRATION: PROSPERO ID 89366

Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis

Background: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. Purpose: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. Data sources: MEDLINE from 1 January 1995 until 1 January 2021. Study selection: 16 studies assessing at least 1 diagnostic strategy. Data extraction: Individual-patient data from 20 553 patients. Data synthesis: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. Limitations: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. Conclusion: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds.</p