RESUMO
BACKGROUND: The Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning Score (NEWS) is a general prognostic risk score for multiple clinical settings. We investigated whether the NEWS had a comparable performance with the PESI and sPESI, for predicting intensive care unit (ICU) admission and death in patients with acute PE. METHODS: In haemodynamically stable patients with confirmed PE from the YEARS Study (2013-2015), we evaluated the performance of the NEWS, PESI and sPESI for predicting 7-day ICU admission and 30-day mortality. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. RESULTS: Of 352 patients, 12 (3.4%) were admitted to the ICU and 5 (1.4%) died. The AUC of the NEWS for ICU admission was 0.80 (95% CI 0.66 to 0.94) and 0.92 (95% CI 0.82 to 1.00) for 30-day mortality. At a threshold of 3 points, NEWS yielded a sensitivity and specificity of 92% and 53% for ICU admission and 100% and 52% for 30-day mortality. The AUC of the PESI was 0.64 (95% CI 0.48 to 0.79) for ICU admission and 0.94 (95% CI 0.87 to 1.00) for mortality. At a threshold of 66 points, PESI yielded a sensitivity of 75% and a specificity of 38% for ICU admission. For mortality, these were 100% and 37%, respectively. The performance of the sPESI was similar to that of PESI. CONCLUSION: In comparison with PESI and sPESI, NEWS adequately predicted 7-day ICU admission as well as 30-day mortality, supporting its potential relevance for clinical practice.
Assuntos
Escore de Alerta Precoce , Embolia Pulmonar , Humanos , Medição de Risco , Índice de Gravidade de Doença , Valor Preditivo dos Testes , Prognóstico , Embolia Pulmonar/diagnóstico , Doença Aguda , Estudos RetrospectivosRESUMO
BACKGROUND: Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary embolism undergo computed tomographic (CT) pulmonary angiography or ventilation-perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown. METHODS: In a prospective study involving pregnant women with suspected pulmonary embolism, we assessed three criteria from the YEARS algorithm (clinical signs of deep-vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the d-dimer level. Pulmonary embolism was ruled out if none of the three criteria were met and the d-dimer level was less than 1000 ng per milliliter or if one or more of the three criteria were met and the d-dimer level was less than 500 ng per milliliter. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep-vein thrombosis; if the results were positive (i.e., a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. RESULTS: A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep-vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval [CI], 0.04 to 1.2); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% CI, 35 to 44). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. CONCLUSIONS: Pulmonary embolism was safely ruled out by the pregnancy-adapted YEARS diagnostic algorithm across all trimesters of pregnancy. CT pulmonary angiography was avoided in 32 to 65% of patients. (Funded by Leiden University Medical Center and 17 other participating hospitals; Artemis Netherlands Trial Register number, NL5726.).
Assuntos
Algoritmos , Angiografia por Tomografia Computadorizada , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemoptise , Complicações Cardiovasculares na Gravidez/diagnóstico , Embolia Pulmonar/diagnóstico , Tromboembolia Venosa , Doença Aguda , Adulto , Feminino , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Estudos Prospectivos , Embolia Pulmonar/diagnóstico por imagem , Tromboembolia Venosa/diagnóstico , Trombose Venosa/diagnósticoRESUMO
The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) is challenging, because persistent intravascular abnormalities after previous DVT often hinder a diagnosis by compression ultrasonography. Magnetic resonance direct thrombus imaging (MRDTI), a technique without intravenous contrast and with a 10-minute acquisition time, has been shown to accurately distinguish acute recurrent DVT from chronic thrombotic remains. We have evaluated the safety of MRDTI as the sole test for excluding recurrent ipsilateral DVT. The Theia Study was a prospective, international, multicenter, diagnostic management study involving patients with clinically suspected acute recurrent ipsilateral DVT. Treatment of the patients was managed according to the result of the MRDTI, performed within 24 hours of study inclusion. The primary outcome was the 3-month incidence of venous thromboembolism (VTE) after a MRDTI negative for DVT. The secondary outcome was the interobserver agreement on the MRDTI readings. An independent committee adjudicated all end points. Three hundred five patients were included. The baseline prevalence of recurrent DVT was 38%; superficial thrombophlebitis was diagnosed in 4.6%. The primary outcome occurred in 2 of 119 (1.7%; 95% confidence interval [CI], 0.20-5.9) patients with MRDTI negative for DVT and thrombophlebitis, who were not treated with any anticoagulant during follow-up; neither of these recurrences was fatal. The incidence of recurrent VTE in all patients with MRDTI negative for DVT was 1.1% (95% CI, 0.13%-3.8%). The agreement between initial local and post hoc central reading of the MRDTI images was excellent (κ statistic, 0.91). The incidence of VTE recurrence after negative MRDTI was low, and MRDTI proved to be a feasible and reproducible diagnostic test. This trial was registered at www.clinicaltrials.gov as #NCT02262052.
Assuntos
Imageamento por Ressonância Magnética/métodos , Trombose Venosa/diagnóstico por imagem , Adulto , Idoso , Anticoagulantes/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Trombose Venosa/tratamento farmacológicoRESUMO
BACKGROUND: Validated diagnostic algorithms in patients with suspected pulmonary embolism are often not used correctly or only benefit subgroups of patients, leading to overuse of computed tomography pulmonary angiography (CTPA). The YEARS clinical decision rule that incorporates differential D-dimer cutoff values at presentation, has been developed to be fast, to be compatible with clinical practice, and to reduce the number of CTPA investigations in all age groups. We aimed to prospectively evaluate this novel and simplified diagnostic algorithm for suspected acute pulmonary embolism. METHODS: We did a prospective, multicentre, cohort study in 12 hospitals in the Netherlands, including consecutive patients with suspected pulmonary embolism between Oct 5, 2013, to July 9, 2015. Patients were managed by simultaneous assessment of the YEARS clinical decision rule, consisting of three items (clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis), and D-dimer concentrations. In patients without YEARS items and D-dimer less than 1000 ng/mL, or in patients with one or more YEARS items and D-dimer less than 500 ng/mL, pulmonary embolism was considered excluded. All other patients had CTPA. The primary outcome was the number of independently adjudicated events of venous thromboembolism during 3 months of follow-up after pulmonary embolism was excluded, and the secondary outcome was the number of required CTPA compared with the Wells' diagnostic algorithm. For the primary outcome regarding the safety of the diagnostic strategy, we used a per-protocol approach. For the secondary outcome regarding the efficiency of the diagnostic strategy, we used an intention-to-diagnose approach. This trial is registered with the Netherlands Trial Registry, number NTR4193. FINDINGS: 3616 consecutive patients with clinically suspected pulmonary embolism were screened, of whom 151 (4%) were excluded. The remaining 3465 patients were assessed of whom 456 (13%) were diagnosed with pulmonary embolism at baseline. Of the 2946 patients (85%) in whom pulmonary embolism was ruled out at baseline and remained untreated, 18 patients were diagnosed with symptomatic venous thromboembolism during 3-month follow-up (0·61%, 95% CI 0·36-0·96) of whom six had fatal pulmonary embolism (0·20%, 0·07-0·44). CTPA was not indicated in 1651 (48%) patients with the YEARS algorithm compared with 1174 (34%) patients, if Wells' rule and fixed D-dimer threshold of less than 500 ng/mL would have been applied, a difference of 14% (95% CI 12-16). INTERPRETATION: In our study pulmonary embolism was safely excluded by the YEARS diagnostic algorithm in patients with suspected pulmonary embolism. The main advantage of the YEARS algorithm in our patients is the absolute 14% decrease of CTPA examinations in all ages and across several relevant subgroups. FUNDING: This study was supported by unrestricted grants from the participating hospitals.
Assuntos
Embolia Pulmonar/diagnóstico , Idoso , Algoritmos , Biomarcadores/metabolismo , Angiografia por Tomografia Computadorizada/estatística & dados numéricos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Embolia Pulmonar/terapia , Procedimentos Desnecessários/estatística & dados numéricos , Tromboembolia Venosa/etiologiaAssuntos
Assistência Ambulatorial/normas , Regras de Decisão Clínica , Angiografia por Tomografia Computadorizada , Ventrículos do Coração/diagnóstico por imagem , Embolia Pulmonar/terapia , Triagem/métodos , Disfunção Ventricular Direita/diagnóstico por imagem , Adulto , Idoso , Assistência Ambulatorial/métodos , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Embolia Pulmonar/complicações , Embolia Pulmonar/mortalidade , Recidiva , Medição de Risco , Resultado do Tratamento , Triagem/normas , Disfunção Ventricular Direita/complicaçõesRESUMO
We investigated whether the clinical criteria used in the Hestia study for selection of pulmonary embolism (PE) patients for outpatient treatment could discriminate PE patients with high and low risk for adverse clinical outcome. We performed a cohort study with PE patients who were triaged with 11 criteria for outpatient treatment. Patients not eligible for outpatient treatment were treated in hospital. Study outcomes were recurrent venous thromboembolism, major bleeding and all-cause mortality during 3 months. In total, 530 patients were included, of which 297 were treated at home. In the outpatient group, six patients (2.0%, 95% CI 0.7-4.3%) had recurrent venous thromboembolism versus nine in-patients (3.9%, 95% CI 1.9-7.0%). Three patients (1.0%, 95% CI 0.2-2.9) died during the 3-months follow-up in the outpatient group versus 22 patients (9.6%, 95% CI 6.3-14) in the in-patient group (p<0.05). None of the outpatients died as a result of fatal PE versus five (2.2%) in-patients (p<0.05). In the outpatient group, 0.7% (95% CI 0.08-2.4) had major bleeding events versus 4.8% (95% CI 2.4-8.4) of in-patients (p<0.05). This study showed that the Hestia criteria can discriminate PE patients with low risk from patients with high risk for adverse clinical outcome. The low-risk patients can safely be treated at home.
Assuntos
Embolia Pulmonar/diagnóstico , Embolia Pulmonar/patologia , Pneumologia/normas , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Embolia Pulmonar/mortalidade , Pneumologia/métodos , Recidiva , Estudos Retrospectivos , Risco , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/patologiaRESUMO
BACKGROUND: The recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging testing in patients with clinically suspected pulmonary embolism (PE). AIM: To externally validate the performance of 4PEPS in an independent cohort. METHODS: In this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer <1000 µg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold. RESULTS: Of the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80-0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57-60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86-1.9). CONCLUSION: In this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study.
Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Estudos Prospectivos , Estudos Retrospectivos , Probabilidade , Embolia Pulmonar/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análiseRESUMO
BACKGROUND: Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. OBJECTIVES: The aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis. METHODS: We performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided. RESULTS: We identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127). CONCLUSION: This study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis.
Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Humanos , Feminino , Gravidez , Estudos Prospectivos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Embolia Pulmonar/diagnóstico , Tromboembolia Venosa/diagnóstico , Algoritmos , Doença Aguda , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison. OBJECTIVES: To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients. METHODS: Patient-level data (n = 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared. RESULTS: All six scenarios including reference CUS had higher estimated 1-year costs (1,763-1,913) than the six without reference CUS (1,192-1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8-17.9 per 10,000 patients) and without reference CUS (14.0-18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS. CONCLUSION: One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS.
RESUMO
OBJECTIVE: To investigate the inter- and intra-observer reliability of both qualitative and quantitative parameters used in the assessment of nail-fold capillaroscopy images. METHODS: Fifty mosaic nail-fold images of healthy controls (n = 10), patients with primary RP (n = 10) and SSc (n = 30) were assessed in random order by two blinded observers on two occasions at centres in Sweden, UK and The Netherlands. Each image was therefore scored by six observers twice. RESULTS: Inter- and intra-observer reliability of quantitative parameters showed substantial to almost perfect agreement [inter- and intra-observer weighted κ's for the number of widened capillaries was 0.75 and 0.87 and giant capillaries was 0.84 and 0.92, intra-class correlation coefficients (ICCs) for capillary density was 0.87 and 0.92 and total loop width was 0.94 and 0.98, respectively]. Qualitative parameters including architecture, avascularity, haemorrhage, crossed, ramified and bushy capillaries showed moderate to substantial inter-observer reproducibility (weighted κ ranging from 0.47 to 0.73), and substantial intra-observer repeatability (weighted κ ranging from 0.71 to 0.80), whereas the scoring of tortuous and bizarre capillaries showed poor inter-observer and substantial intra-observer agreement (inter-observer weighted κ's was 0.39 and 0.21 and intra-observer weighted κ's was 0.68 and 0.76, respectively). CONCLUSION: All quantitative and certain qualitative parameters are highly reliable in terms of inter- and intra-observer agreement. A combination of parameters with the highest reliability should be incorporated into future capillaroscopic scoring systems in studies of prediction and monitoring of SSc spectrum disorders.
Assuntos
Angioscopia Microscópica/métodos , Unhas/irrigação sanguínea , Doença de Raynaud/patologia , Escleroderma Sistêmico/patologia , Capilares/patologia , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Método Simples-Cego , Gravação em VídeoRESUMO
BACKGROUND: Several clinical decision rules (CDRs) are available to exclude acute pulmonary embolism (PE), but they have not been directly compared. OBJECTIVE: To directly compare the performance of 4 CDRs (Wells rule, revised Geneva score, simplified Wells rule, and simplified revised Geneva score) in combination with d-dimer testing to exclude PE. DESIGN: Prospective cohort study. SETTING: 7 hospitals in the Netherlands. PATIENTS: 807 consecutive patients with suspected acute PE. INTERVENTION: The clinical probability of PE was assessed by using a computer program that calculated all CDRs and indicated the next diagnostic step. Results of the CDRs and d-dimer tests guided clinical care. MEASUREMENTS: Results of the CDRs were compared with the prevalence of PE identified by computed tomography or venous thromboembolism at 3-month follow-up. RESULTS: Prevalence of PE was 23%. The proportion of patients categorized as PE-unlikely ranged from 62% (simplified Wells rule) to 72% (Wells rule). Combined with a normal d-dimer result, the CDRs excluded PE in 22% to 24% of patients. The total failure rates of the CDR and d-dimer combinations were similar (1 failure, 0.5% to 0.6% [upper-limit 95% CI, 2.9% to 3.1%]). Even though 30% of patients had discordant CDR outcomes, PE was not detected in any patient with discordant CDRs and a normal d-dimer result. LIMITATION: Management was based on a combination of decision rules and d-dimer testing rather than only 1 CDR combined with d-dimer testing. CONCLUSION: All 4 CDRs show similar performance for exclusion of acute PE in combination with a normal d-dimer result. This prospective validation indicates that the simplified scores may be used in clinical practice. PRIMARY FUNDING SOURCE: Academic Medical Center, VU University Medical Center, Rijnstate Hospital, Leiden University Medical Center, Maastricht University Medical Center, Erasmus Medical Center, and Maasstad Hospital.
Assuntos
Técnicas de Apoio para a Decisão , Embolia Pulmonar/diagnóstico , Adulto , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Seguimentos , Humanos , Países Baixos/epidemiologia , Probabilidade , Estudos Prospectivos , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/epidemiologia , Tomografia Computadorizada por Raios X , Tromboembolia Venosa/diagnósticoRESUMO
BACKGROUND: Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home treatment of pulmonary embolism (PE) is associated with a cost reduction. An accurate estimation of cost savings per patient treated at home is currently lacking. AIM: The aim of this study was to compare health care utilization and costs during the first 3 months after a PE diagnosis in patients who are treated at home versus those who are initially hospitalized. METHODS: Patient-level data of the YEARS cohort study, including 383 normotensive patients diagnosed with PE, were used to estimate the proportion of patients treated at home, mean hospitalization duration in those who were hospitalized, and rates of PE-related readmissions and complications. To correct for baseline differences within the two groups, regression analyses was performed. The primary outcome was the average total health care costs during a 3-month follow-up period for patients initially treated at home or in hospital. RESULTS: Mean hospitalization duration for the initial treatment was 0.69 days for those treated initially at home (n = 181) and 4.3 days for those initially treated in hospital (n = 202). Total average costs per hospitalized patient were 3,209 and 1,512 per patient treated at home. The adjusted mean difference was 1,483 (95% confidence interval: 1,181-1,784). CONCLUSION: Home treatment of hemodynamically stable patients with acute PE was associated with an estimated net cost reduction of 1,483 per patient. This difference underlines the advantage of triage-based home treatment of these patients.
Assuntos
Serviços de Assistência Domiciliar , Hospitalização , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Embolia Pulmonar , Triagem , Tromboembolia Venosa/complicações , Redução de Custos/métodos , Duração da Terapia , Feminino , Custos de Cuidados de Saúde/classificação , Custos de Cuidados de Saúde/estatística & dados numéricos , Hemodinâmica , Serviços de Assistência Domiciliar/economia , Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/terapia , Triagem/métodos , Triagem/normasRESUMO
The diagnostic workup of recurrent ipsilateral deep vein thrombosis (DVT) using compression ultrasonography (CUS) can be complicated by persistent intravascular abnormalities after a previous DVT. We showed that magnetic resonance direct thrombus imaging (MRDTI) can exclude recurrent ipsilateral DVT. However, it is unknown whether the application of MRDTI in daily clinical practice is cost effective. The aim of this study was to evaluate the cost effectiveness of MRDTI-based diagnosis for suspected recurrent ipsilateral DVT during first year of treatment and follow-up in the Dutch health care setting. Patient-level data of the Theia study (NCT02262052) were analyzed in 10 diagnostic scenarios, including a clinical decision rule and D-dimer test and imaging with CUS and/or MRDTI. The total costs of diagnostic tests and treatment during 1-year follow-up, including costs of false-positive and false-negative diagnoses, were compared and related to the associated mortality. The 1-year health care costs with MRDTI (range, 1219-1296) were generally lower than strategies without MRDTI (range, 1278-1529). This was because of superior specificity, despite higher initial diagnostic costs. Diagnostic strategies including CUS alone and CUS followed by MRDTI in case of an inconclusive CUS were potential optimal cost-effective strategies, with estimated average costs of 1529 and 1263 per patient and predicted mortality of 1 per 737 patients and 1 per 609 patients, respectively. Our model shows that diagnostic strategies with MRDTI for suspected recurrent ipsilateral DVT have generally lower 1-year health care costs than strategies without MRDTI. Therefore, compared with CUS alone, applying MRDTI did not increase health care costs.
Assuntos
Trombose , Trombose Venosa , Análise Custo-Benefício , Humanos , Imageamento por Ressonância Magnética , Ultrassonografia , Trombose Venosa/diagnóstico por imagemRESUMO
BACKGROUND: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak. METHODS: This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged ≥18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10). FINDINGS: Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0·95 [95% CI 0·76-1·20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0·51 [0·27-0·95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0·52 (95% CI 0·26-1·05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1·07 (0·63-1·80; p=0·81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0·0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events. INTERPRETATION: The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. FUNDING: Amsterdam Medical Center Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ZonMW, and the European Union Innovative Medicines Initiative 2.
Assuntos
COVID-19/terapia , Mesilato de Imatinib/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/terapia , Idoso , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Permeabilidade Capilar/efeitos dos fármacos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Método Duplo-Cego , Feminino , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Pessoa de Meia-Idade , Países Baixos , Oxigênio/administração & dosagem , Placebos/administração & dosagem , Placebos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/virologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Studies have shown the safety of home treatment of patients with pulmonary embolism (PE) at low risk of adverse events. Management studies focusing on home treatment have suggested that 30% to 55% of acute PE patients could be treated at home, based on the HESTIA criteria, but data from day-to-day clinical practice are largely unavailable. AIM: To determine current practice patterns of home treatment of acute PE in the Netherlands. METHOD: We performed a post-hoc analysis of the YEARS study. The main outcomes were the proportion of patients who were discharged <24 h and reasons for admission if treated in hospital. Further, we compared the 3-month incidence of PE-related unscheduled readmissions between patients treated at home and in hospital. RESULTS: Of the 404 outpatients with PE included in this post-hoc analysis of the YEARS study, 184 (46%) were treated at home. The median duration of admission of the hospitalized patients was 3.0 days. The rate of PE-related readmissions of patients treated at home was 9.7% versus 8.6% for hospitalized patients (crude hazard ratio 1.1 (95% CI 0.57-2.1)). The 3-month incidence of any adverse event was 3.8% in those treated at home (2 recurrent VTE, 3 major bleedings and two deaths) compared to 10% in the hospitalized patients (3 recurrent VTE, 6 major bleedings and fourteen deaths). CONCLUSIONS: In the YEARS study, 46% of patients with PE were treated at home with low incidence of adverse events. PE-related readmission rates were not different between patients treated at home or in hospital.
Assuntos
Pacientes Ambulatoriais , Embolia Pulmonar , Doença Aguda , Assistência Ambulatorial , Humanos , Países Baixos/epidemiologia , Embolia Pulmonar/terapiaRESUMO
BACKGROUND: The Hestia criteria can be used to select pulmonary embolism (PE) patients for outpatient treatment. The subjective Hestia criterion "medical/social reason for admission" allows the treating physician to consider any patient-specific circumstances in the final management decision. It is unknown how often and why this criterion is scored. METHODS: This is a patient-level post hoc analysis of the combined Hestia and Vesta studies. The main outcomes were the frequency of all scored Hestia items in hospitalized patients and the explicit reason for scoring the subjective criterion. Hemodynamic parameters and computed tomography-assessed right ventricular (RV)/left ventricular (LV) ratio of those only awarded with the subjective criterion were compared with patients treated at home. RESULTS: From the 1,166 patients screened, data were available for all 600 who were hospitalized. Most were hospitalized to receive oxygen therapy (45%); 227 (38%) were only awarded with the subjective criterion, of whom 51 because of "intermediate to intermediate-high risk PE." Compared with patients with intermediate risk PE (RV/LV ratio > 1.0) treated at home (179/566, 32%), hospitalized patients with only the subjective criterion had a higher mean RV/LV ratio (mean difference +0.30, 95% confidence interval [CI] 0.19-0.41) and a higher heart rate (+18/min, 95% CI 10-25). No relevant differences were observed for other hemodynamic parameters. CONCLUSION: The most frequent reason for hospital admission was oxygen therapy. In the decision to award the subjective criterion as sole argument for admission, the severity of the RV overload and resulting hemodynamic response of the patient was taken into account rather than just abnormal RV/LV ratio.
Assuntos
Tomada de Decisão Clínica , Hospitalização , Admissão do Paciente , Embolia Pulmonar/epidemiologia , Índice de Gravidade de Doença , Doença Aguda , Ventrículos do Coração/diagnóstico por imagem , Hemodinâmica , Hospitalização/estatística & dados numéricos , Humanos , Tamanho do Órgão , Oxigenoterapia , Embolia Pulmonar/complicações , Embolia Pulmonar/terapia , Tomografia Computadorizada por Raios X , Disfunção Ventricular Direita/etiologiaRESUMO
BACKGROUND: The diagnostic accuracy of clinical probability assessment and D-dimer testing for clinically suspected recurrent deep vein thrombosis (DVT) is largely unknown. AIM: To evaluate the safety of ruling out acute recurrent DVT based on an unlikely Wells score for DVT and a normal D-dimer test. METHODS: This was a predefined endpoint of the Theia study in which the diagnostic accuracy of magnetic resonance direct thrombus imaging in acute recurrent ipsilateral DVT was validated. The Wells rule and D-dimer test, performed as part of the study protocol, were not used for management decisions. The primary outcome of this analysis was the incidence of recurrent DVT at baseline or during 3-month follow-up for patients with an unlikely Wells score and a normal D-dimer test. RESULTS: Results of both Wells score and D-dimer tests were available in 231 patients without anticoagulant treatment. The recurrent DVT prevalence was 45% (103/231). Forty-nine patients had an unlikely Wells score and normal D-dimer test, of whom 3 (6.1%, 95% confidence interval [CI] 1.3%-18%) had recurrent DVT at baseline/follow-up, yielding a sensitivity of 97% (95% CI 92%-99%) and specificity of 36% (95% CI 28%-45%). Thus, if clinical probability scoring and D-dimer testing would have been applied, radiological imaging could have been omitted in 21% of patients with a diagnostic failure rate of 6.1%. CONCLUSION: By applying clinical probability scoring and D-dimer testing, radiological imaging could be spared in one fifth of patients with suspected recurrent ipsilateral DVT. However, the high failure rate does not support implementation of this strategy in daily practice.
Assuntos
Trombose , Trombose Venosa , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Valor Preditivo dos Testes , Trombose Venosa/diagnóstico por imagemRESUMO
OBJECTIVE: The objective of this study was to assess the interobserver agreement between on-call radiology residents and radiology specialists in the evaluation of pulmonary embolism (PE) using computed tomographic pulmonary angiography (CTPA). MATERIALS AND METHODS: Single center, prospective cohort study of 119 consecutive inpatients and outpatients with clinically suspected PE in whom CTPA was performed during out-of-office hours and weekends. The on-call radiology resident interpreted the CTPA for the presence of PE. An experienced radiology specialist, without knowledge of earlier reading, reviewed the CTPA the following morning. In discordant cases, a consensus reading was conducted. The radiology specialists' assessment and the consensus reading in case of discordance were considered as the gold standard. RESULTS: Five CTPA studies were excluded from the analysis. In the remaining cases, radiology residents and radiology specialists agreed on the interpretations of CTPAs (no PE vs PE present) in 106 (93%) of the 114 cases, with a kappa value of 0.84 (95% confidence interval, 0.74-0.95). The consensus reading equally disagreed with both radiology resident and radiology specialist in 8 (7%) of the 114 discordant cases. Seven out of 8 discordant cases had suboptimal scan quality. CONCLUSIONS: The assessment of CTPA in patients with suspected PE by radiology residents seems reliable during out-of-office hours.
Assuntos
Angiografia/métodos , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Competência Clínica , Meios de Contraste , Humanos , Internato e Residência , Iohexol/análogos & derivados , Medicina , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Serviço Hospitalar de RadiologiaRESUMO
A 26-year-old man presented at the emergency department with confusion and decreased consciousness after several days of vomiting. In the preceding 6 months, he had used a 2-litre tank of nitrous oxide (N2O) weekly. His metabolic encephalopathy was caused by hyperammonaemia which probably resulted from interference of N2O-induced vitamin B12 deficiency with ammonia degradation. A catabolic state might have contributed to the hyperammonaemia in this case. After treatment with vitamin B12 and lactulose, both his consciousness and hyperammonaemia improved. He reported no residual complaints after 3 months of follow-up. Since N2O is increasingly used as a recreational drug, we recommend considering hyperammonaemia as a cause of metabolic encephalopathy in cases of N2O use and altered mental status.