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1.
BMC Med Educ ; 24(1): 550, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760775

ABSTRACT

BACKGROUND: A recent study found that ethnic minority General Practice (GP)-trainees receive more negative assessments than their majority peers. Previous qualitative research suggested that learning climate-related factors play a pivotal role in unequal opportunities for trainees in post-graduate medical settings, indicating that insufficient inclusivity had put minority students at risk of failure and dropout. STUDY OBJECTIVES: We aimed to develop broadly supported strategies for an inclusive learning climate in Dutch GP-specialty training. METHODS: We employed Participatory Action Research (PAR)-methods, incorporating Participatory Learning and Action (PLA)-techniques to ensure equal voices for all stakeholders in shaping Diversity, Equity, and Inclusion (DEI)-strategies for GP-specialty training. Our approach engaged stakeholders within two pilot GP-specialty training institutes across diverse roles, including management, support staff, in-faculty teachers, in-clinic supervisors, and trainees, representing ethnic minorities and the majority population. Purposeful convenience sampling formed stakeholder- and co-reader groups in two Dutch GP-specialty training institutes. Stakeholder discussion sessions were based on experiences and literature, including two relevant frameworks, and explored perspectives on the dynamics of potential ethnic minority trainees' disadvantages and opportunities for inclusive strategies. A co-reader group commented on discussion outcomes. Consequently, a management group prioritized suggested strategies based on expected feasibility and compatibility. RESULTS: Input from twelve stakeholder group sessions and thirteen co-readers led to implementation guidance for seven inclusive learning environment strategies, of which the management group prioritized three: • Provide DEI-relevant training programs to all GP-specialty training stakeholders; • Appoint DEI ambassadors in all layers of GP-specialty training; • Give a significant voice to minority GP-trainees in their education. CONCLUSION: The study's participatory approach engaged representatives of all GP-specialty training stakeholders and identified seven inclusive learning climate strategies, of which three were prioritized for implementation in two training institutions.


Subject(s)
Education, Medical, Graduate , General Practice , Humans , Cultural Diversity , Ethnicity , General Practice/education , Learning , Minority Groups/education , Netherlands , Stakeholder Participation
3.
Acute Med ; 22(2): 61-66, 2023.
Article in English | MEDLINE | ID: mdl-37306130

ABSTRACT

BACKGROUND: Exact benefits of currently recommended close monitoring in intermediate high risk acute pulmonary embolism (PE) patients are unknown. METHODS: This prospective observational cohort study determined clinical characteristics, and disease course of intermediate high risk acute PE patients in an academic hospital setting . Frequency of hemodynamic deterioration, use of rescue reperfusion therapy and PE related mortality, were outcomes of interest. RESULTS: Of 98 intermediate high risk PE patients included for analysis, 81 patients (83%) were closely monitored. Two deteriorated hemodynamically and were treated with rescue reperfusion therapy. One patient survived after this. CONCLUSIONS: In these 98 intermediate high risk PE patients, hemodynamic deterioration occurred in three patients and rescue reperfusion therapy of two closely monitored patients led to survival of one. Underlining the need for better recognition of patients benefitting from and research in the optimal way of close monitoring.


Subject(s)
Hospitals , Humans , Prospective Studies , Acute Disease , Disease Progression
4.
Thromb Res ; 187: 125-130, 2020 03.
Article in English | MEDLINE | ID: mdl-31986475

ABSTRACT

BACKGROUND: Evidence for guideline recommendations for the treatment of venous thromboembolism (VTE) during anticoagulant therapy is scarce. We aimed to observe and to describe the management of VTE occurring during anticoagulant therapy. METHODS: This prospective multi-center, observational study included patients with objectively confirmed VTE during anticoagulant therapy (breakthrough event), with a follow-up of 3 months, after the breakthrough event. RESULTS: We registered 121 patients with a breakthrough event, with a mean age of 56 years (range, 19 to 90); 61 were male (50%). Fifty-eight patients (48%) had an active malignancy. At the time of the breakthrough event, 57 patients (47%) were treated with a vitamin K antagonist (VKA), 53 patients (44%) with low-molecular-weight heparin (LMWH) and 11 patients (9%) with direct oral anticoagulants, unfractionated heparin, or VKA plus LMWH. A total of 21 patients (17%) were receiving a subtherapeutic dose of an anticoagulant. The main regimens to treat recurrence in patients on VKA were: switch to LMWH (33%), temporary double treatment with LMWH and VKA (23%), and VKA with a higher target INR (19%). In patients with a breakthrough on LMWH, the most frequently chosen regimen was a permanent dose increase (74%). During 3-month follow-up, 7% of patients had a second breakthrough event and 8% experienced major or clinically relevant non-major bleeding. CONCLUSION: There is wide variation in the management of VTE during anticoagulant treatment, reflecting a heterogeneous and complex clinical situation. Despite intensifying anticoagulation, the risk of a second breakthrough event in this population is 7%.


Subject(s)
Neoplasms , Venous Thromboembolism , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Female , Heparin , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Venous Thromboembolism/drug therapy , Vitamin K , Young Adult
5.
Neth J Med ; 75(8): 328-334, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29219827

ABSTRACT

INTRODUCTION: Venous malformations (VMs) are ubiquitous, low-flow vascular anomalies known to be occasionally painful due to thrombotic episodes within the lesion. The prevalence of superficial or deep vein thrombosis is unclear. METHODS: A cross-sectional study among outpatients aged ≥ 12 years with pure VMs was performed, quantifying the prevalence of thrombosis by screening all patients with compression ultrasonography (CUS). Additionally, we evaluated whether coagulation alterations were related to thrombosis observed with CUS. RESULTS: In total, 69 patients with pure VMs were eligible, median age was 30 years (range 12-63) and 52% were female. A total of 68 patients underwent CUS. Superficial vein thrombosis was observed in 10 (15%) cases; 1 patient had a current asymptomatic deep venous thrombosis. Residual superficial or deep thrombosis was observed in 25 patients (36%). In total, 49% had either a history or current signs of a thrombotic event and overall 10% had venous thromboembolism. In approximately 50% of the patients the D-dimer level was above 0.5 mg/l. Median P-selectin and Von Willebrand factor levels were 29 ng/ml (interquartile range (IQR) 21-34) and 108% (IQR 83-132), respectively. No differences were observed in the coagulation parameters between the patients with and without current clots in their VM. CONCLUSION: This study shows that superficial or deep vein thrombosis is common among patients with a pure VM. Physicians should be aware of this high incidence, especially if other risk factors for thrombosis are present.


Subject(s)
Blood Coagulation Factors/analysis , Blood Coagulation , Vascular Malformations/complications , Venous Thrombosis/etiology , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Male , Middle Aged , Ultrasonography , Vascular Malformations/blood , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/epidemiology , Young Adult
6.
Thromb Res ; 152: 49-51, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28226257

ABSTRACT

BACKGROUND: Cancer patients frequently present with suspected pulmonary embolism (PE). The D-dimer (DD) test is less useful in excluding PE in cancer patients due to the lower specificity. In the general population, the age-adjusted cutoff for DD combined with a clinical decision rule (CDR) improved specificity in the diagnosis of PE. OBJECTIVES: To evaluate the safety and efficacy of the age-adjusted cutoff (defined as age∗10µg/L in patients >50years) combined with a CDR for the exclusion of PE in cancer patients. METHODS: We conducted a prospective study to evaluate the age-adjusted cutoff in patients with suspected PE. Here we report a post-hoc analysis on the performance of the age-adjusted cutoff in patients with and without cancer. The primary outcome was the rate of venous thromboembolic events (VTE) during three-month follow-up. RESULTS: Of 3324 patients with suspected PE, 429 (12.9%) patients had cancer. The prevalence of PE was 25.2% in cancer patients and 18% in patients without cancer (p<0.001). Among cancer patients with an unlikely CDR, 9.9% had a DD <500µg/L as compared with 19.7% using the age-adjusted cutoff. In patients without cancer, these rates were 30.1% and 41.9%. The proportion of cancer patients in whom PE could be excluded by CDR and DD doubled from 6.3% to 12.6%. No VTE occurred during three-month follow-up (failure rate 0.0% (95% CI 0.0-6.9%)). CONCLUSION: Compared with the conventional cutoff, the age-adjusted D-dimer cutoff doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and DD without imaging.


Subject(s)
Fibrin Fibrinogen Degradation Products/analysis , Neoplasms/complications , Pulmonary Embolism/complications , Pulmonary Embolism/diagnosis , Age Factors , Aged , Decision Support Systems, Clinical , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/blood , Probability , Prospective Studies , Pulmonary Embolism/blood , Venous Thromboembolism/blood , Venous Thromboembolism/complications , Venous Thromboembolism/diagnosis
7.
Oncogene ; 36(13): 1793-1803, 2017 03 30.
Article in English | MEDLINE | ID: mdl-27694902

ABSTRACT

Aberrant Wnt signaling within breast cancer is associated with poor prognosis, but regulation of this pathway in breast tissue remains poorly understood and the consequences of immediate or long-term dysregulation remain elusive. The exact contribution of the Wnt-regulating proteins adenomatous polyposis coli (APC) and APC2 in the pathogenesis of human breast cancer are ill-defined, but our analysis of publically available array data sets indicates that tumors with concomitant low expression of both proteins occurs more frequently in the 'triple negative' phenotype, which is a subtype of breast cancer with particularly poor prognosis. We have used mouse transgenics to delete Apc and/or Apc2 from mouse mammary epithelium to elucidate the significance of these proteins in mammary homeostasis and delineate their influences on Wnt signaling and tumorigenesis. Loss of either protein alone failed to affect Wnt signaling levels or tissue homeostasis. Strikingly, concomitant loss led to local disruption of ß-catenin status, disruption in epithelial integrity, cohesion and polarity, increased cell division and a distinctive form of ductal hyperplasia with 'squamoid' ghost cell nodules in young animals. Upon aging, the development of Wnt activated mammary carcinomas with squamous differentiation was accompanied by a significantly reduced survival. This novel Wnt-driven mammary tumor model highlights the importance of functional redundancies existing between the Apc proteins both in normal homeostasis and in tumorigenesis.


Subject(s)
Adenomatous Polyposis Coli Protein/genetics , Adenomatous Polyposis Coli Protein/metabolism , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Epithelium/metabolism , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinogenesis/genetics , Carcinogenesis/metabolism , DNA Copy Number Variations , Epithelium/pathology , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Homeostasis/genetics , Humans , Hyperplasia , Lactation/genetics , Mammary Neoplasms, Animal , Mice , Mice, Transgenic , Prognosis , beta Catenin/genetics , beta Catenin/metabolism
8.
Neth Heart J ; 24(12): 709-716, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27561279

ABSTRACT

OBJECTIVE: In chronic fatigue syndrome (CFS), only a few imaging and histopathological studies have previously assessed either cardiac dimensions/function or myocardial tissue, suggesting smaller left ventricular (LV) dimensions, LV wall motion abnormalities and occasionally viral persistence that may lead to cardiomyopathy. The present study with cardiac magnetic resonance (CMR) imaging is the first to use a contrast-enhanced approach to assess cardiac involvement, including tissue characterisation of the LV wall. METHODS: CMR measurements of 12 female CFS patients were compared with data of 36 age-matched, healthy female controls. With cine imaging, LV volumes, ejection fraction (EF), mass, and wall motion abnormalities were assessed. T2-weighted images were analysed for increased signal intensity, reflecting oedema (i. e. inflammation). In addition, the presence of contrast enhancement, reflecting fibrosis (i. e. myocardial damage), was analysed. RESULTS: When comparing CFS patients and healthy controls, LVEF (57.9 ± 4.3 % vs. 63.7 ± 3.7 %; p < 0.01), end-diastolic diameter (44 ± 3.7 mm vs. 49 ± 3.7 mm; p < 0.01), as well as body surface area corrected LV end-diastolic volume (77.5 ± 6.2 ml/m2 vs. 86.0 ± 9.3 ml/m2; p < 0.01), stroke volume (44.9 ± 4.5 ml/m2 vs. 54.9 ± 6.3 ml/m2; p < 0.001), and mass (39.8 ± 6.5 g/m2 vs. 49.6 ± 7.1 g/m2; p = 0.02) were significantly lower in patients. Wall motion abnormalities were observed in four patients and contrast enhancement (fibrosis) in three; none of the controls showed wall motion abnormalities or contrast enhancement. None of the patients or controls showed increased signal intensity on the T2-weighted images. CONCLUSION: In patients with CFS, CMR demonstrated lower LV dimensions and a mildly reduced LV function. The presence of myocardial fibrosis in some CFS patients suggests that CMR assessment of cardiac involvement is warranted as part of the scientific exploration, which may imply serial non-invasive examinations.

9.
Thromb Res ; 140 Suppl 1: S179, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27161697

ABSTRACT

INTRODUCTION: Among patients with clinically suspected pulmonary embolism (PE), imaging and anticoagulant treatment can be safely withheld in approximately one-third of patients based on the combination of a "PE unlikely" Wells score and a D-dimer below the age-adjusted threshold. The clinical utility of this diagnostic approach in cancer patients is less clear. AIM: To evaluate the efficiency and failure rate of the original and simplified Wells rules in combination with age-adjusted D-dimer testing in patients with active cancer. MATERIALS AND METHODS: Individual patient data were used from 6 large prospective studies in which the diagnostic management of PE was guided by the original Wells rule and D-dimer testing. Study physicians classified patients as having active cancer if they had new, recurrent, or progressive cancer (excluding basal-cell or squamous-cell skin carcinoma), or cancer requiring treatment in the last 6 months. We evaluated the dichotomous Wells rule and its simplified version (Table). The efficiency of the algorithm was defined as the proportion of patients with a "PE unlikely" Wells score and a negative age-adjusted D-dimer, defined by a D-dimer below the threshold of a patient's age times 10 µg/L in patients aged ≥51 years. A diagnostic failure was defined as a patient with a "PE unlikely" Wells score and negative age-adjusted D-dimer who had symptomatic venous thromboembolism during 3 months follow-up. A one-stage random effects meta-analysis was performed to estimate the efficiency and failure. RESULTS: The dataset comprised 938 patients with active cancer with a mean age of 63 years. The most frequent cancer types were breast (13%), gastrointestinal tract (11%), and lung (8%). The type of cancer was not specified in 42%. The pooled PE prevalence was 29% (95% CI 25-32). PE could be excluded in 122 patients based on a "PE unlikely" Wells score and a negative age-adjusted D-dimer (efficiency 13%; 95% CI 11-15). Two of 122 patients were diagnosed with non-fatal symptomatic venous thromboembolism during follow-up (failure rate 1.5%; 95% CI 0.13-14.8). The simplified Wells score in combination with a negative age-adjusted D-dimer had an efficiency of 3.9% (95% CI 2.0-7.6) and a failure rate of 2.4% (95% CI 0.3-15). CONCLUSIONS: Among cancer patients with clinically suspected PE, imaging and anticoagulant treatment can be withheld in 1 out of every 8 patients by the original Wells rule and age-adjusted D-dimer testing. The simplified Wells rule was neither efficient nor safe in this population.

10.
Thromb Res ; 140 Suppl 1: S187, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27161718

ABSTRACT

INTRODUCTION: Patients with cancer frequently present with suspected pulmonary embolism (PE). The D-dimer test is less useful to rule out PE in cancer patients due to a lower specificity, whereas the safety of the combination of a clinical decision rule (CDR) and D-dimer test to rule out PE in these patients is unclear. In the general population, use of an age-adjusted cutoff for D-dimer in combination with a CDR has been shown to improve specificity in the diagnosis of PE. AIM: We prospectively analysed the safety and efficacy of the age-adjusted D-dimer (defined as age×10 in patients >50 years) combined with CDR for the exclusion of PE in patients with cancer. MATERIALS AND METHODS: We conducted a multicenter multinational prospective management outcome study in 19 centers in Belgium, France, The Netherlands and Switzerland, the ADJUST-PE study, to validate an age-adjusted D-dimer cut-off in patients with suspected PE. The performance of the age-adjusted D-dimer cut-off and CDR was compared between patients with and without cancer. The primary outcome was the rate of adjudicated thromboembolic events during three-month follow-up. RESULTS: Of the 3,324 patients with suspected PE, 429 (12.9%) patients had cancer. Cancer patients were older and more often had surgery or immobilisation. The prevalence of PE was 108/429 (25.2%) in cancer patients and 522/2894 (18%) in patients without cancer, p<0.001. Among cancer patients with an unlikely CDR, 27/274 (9.9%) had a D-Dimer <500 µg/L as compared with 19.7% using the age-adjusted D-dimer cut-off; in patients without cancer, these rates were 30.1% and 41.9%, respectively. The percentage of cancer patients in whom PE could be excluded based on CDR and age-adjusted D-dimer doubled from 6.3% to 12.6%. None of these cancer patients had a venous thromboembolic event during three-month follow-up, thus the failure rate was 0.0% (95% CI 0.0-6.9%). CONCLUSIONS: Compared with the usual cut-off, the age-adjusted D-dimer cut-off doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and D-dimer without need for CTPA imaging.

11.
Thromb Res ; 136(2): 221-4, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26026636

ABSTRACT

BACKGROUND: Computed tomography pulmonary angiogram (CTPA) has become the standard test in the diagnostic workup of patients with suspected pulmonary embolism (PE). However, young patients may have an increased risk of cancer with CTPA. Perfusion scanning combined with chest X-ray (X/Q) may offer an adequate alternative, but has never been prospectively validated. We directly compared this strategy with CTPA in patients aged ≤50years with suspected PE. METHODS: Consecutive patients with a likely clinical probability or an abnormal D-dimer level underwent both CTPA and X/Q. Two trained and experienced nuclear physicians independently analyzed the X/Q-scans. The accuracy of X/Q according to the PISAPED criteria was calculated in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Seventy-six patients were included, with a PE rate of 33%. The inter-observer agreement for X/Q-scan reading was high (κ=0.89). After consensus reading, 21 patients (28%) were categorized as 'PE present', 53 (70%) as 'PE absent', and two (2.6%) as 'non-diagnostic'. In 22%, there was a discrepancy between the X/Q-scan and CPTA for the diagnosis or exclusion of PE. The PPV and NPV were 71% and 83%, respectively. CONCLUSION: In patients with a high risk of PE, a diagnostic strategy of chest X-ray and perfusion scanning using the PISAPED criteria seems less safe than CTPA. Additional studies should further investigate this diagnostic algorithm.


Subject(s)
Perfusion Imaging/methods , Pulmonary Embolism/diagnostic imaging , X-Ray Therapy/methods , Female , Humans , Male , Radiography
12.
J Thromb Haemost ; 13(8): 1428-35, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25990714

ABSTRACT

BACKGROUND: An 'unlikely' clinical decision rule with a negative D-dimer result safely excludes pulmonary embolism (PE) in 30% of presenting patients. We aimed to simplify this diagnostic approach and to increase its efficiency. METHODS: Data for 723 consecutive patients with suspected PE were analyzed (prevalence of PE, 22%). After constructing a logistic regression model with the D-dimer test result and items from the Wells' score, we identified the most prevalent combinations of influential items and selected new D-dimer positivity thresholds. The performance was separately validated with data from 2785 consecutive patients with suspected PE. RESULTS: Three Wells items significantly added incremental value to the D-dimer test: hemoptysis, signs of deep vein thrombosis and 'PE most likely'. Based on the most frequent combinations of these three items, we identified two groups: (i) none of these three items positive (41%); (ii) one or more of these items positive (59%). When applying a 1000 µg/L D-dimer threshold in group 1 and 500 µg/L in group 2, PE could be excluded without CT scanning in 36%, at a false-negative rate of 1.2% (95%, 0.04-3.3%). In the validation set, these proportions were 46% and 1.9% (95% CI, 1.2-2.7%), respectively. Using the conventional Wells score with a normal D-dimer result, these rates were, respectively, 22% and 0.6% (95% CI, 0.10-2.4%). CONCLUSION: Combining Wells items with the D-dimer test resulted in a simplified decision rule, which reduces the need for CT scanning in patients with suspected PE. A prospective validation is required before it can be implemented in clinical practice.


Subject(s)
Decision Support Techniques , Fibrin Fibrinogen Degradation Products/analysis , Patient Selection , Pulmonary Embolism/diagnosis , Tomography, X-Ray Computed , Adult , Aged , Area Under Curve , Biomarkers/blood , Comorbidity , Female , Hemoptysis/diagnosis , Hemoptysis/epidemiology , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Netherlands/epidemiology , Predictive Value of Tests , Prevalence , Pulmonary Embolism/blood , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/epidemiology , ROC Curve , Reproducibility of Results , Retrospective Studies , Risk Factors , Venous Thrombosis/diagnosis , Venous Thrombosis/epidemiology
13.
Neth J Med ; 71(9): 466-71, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24218420

ABSTRACT

BACKGROUND: In critically ill patients, dosing of unfractionated heparin (UFH) is difficult due to unpredictable pharmacokinetics, which has an impact on the time to reach therapeutic anticoagulation. We evaluated the quality of UFH therapy in critically ill patients in terms of activated partial thromboplastin time (APTT) test values and time to therapeutic range. METHODS: Patients admitted to the Intensive Care Unit (ICU) and Medium Care Unit (MCU) were screened for intravenous UFH administration. Time to therapeutic range was categorised into 0-12, 13-24 and >24 hours. APTT results were classified into categories of subtherapeutic, supratherapeutic and therapeutic tests. We identified to what extent the sub- and upratherapeutic values were aberrant of the limit of the therapeutic range (15%). RESULTS: In 101 patients admitted to the ICU and MCU, time to therapeutic range was 24 hours in 56% of the population, whereas in 10% of the patients no therapeutic APTT was achieved during UFH treatment. Among the APTT levels, 29% of all test results measured in 24 hours were within the therapeutic range. Subtherapeutic values were found in 53% of the test results, of which 160/203 were more than 15% under the lower limit, whereas 18% of the test results were supratherapeutic, of which 40/69 more than 15% above the upper limit. CONCLUSION: In this cohort of critically ill patients, therapeutic APTT values were reached within 24 hours in 56% of the patients. We conclude that intravenous UFH therapy can be improved in critically ill patients.


Subject(s)
Anticoagulants/therapeutic use , Critical Illness/therapy , Drug Monitoring/methods , Heparin/therapeutic use , Partial Thromboplastin Time , Adult , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Anticoagulants/pharmacokinetics , Dose-Response Relationship, Drug , Female , Heparin/administration & dosage , Heparin/pharmacokinetics , Humans , Infusions, Intravenous , Intensive Care Units , Male , Middle Aged , Patient Admission , Thromboembolism/prevention & control , Time Factors , Young Adult
14.
J Thromb Haemost ; 11(11): 1986-92, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23965032

ABSTRACT

BACKGROUND: Computed tomography pulmonary angiography (CTPA) is frequently requested using diagnostic algorithms for suspected pulmonary embolism (PE). For suspected deep vein thrombosis, it was recently shown that doubling the D-dimer threshold in patients with low pretest probability safely decreased the number of ultrasonograms. We evaluated the safety and efficiency of a similar strategy in patients with suspected PE. METHODS: We performed a post-hoc analysis of 2213 consecutive patients of two cohort studies with suspected PE who were managed according to current standards: PE ruled out in case of unlikely probability (Wells rule ≤ 4 points) and a D-dimer level < 0.5 µg mL(-1) . CTPA was performed in all other cases. All patients were followed for 3 months. We calculated 3-month venous thromboembolism (VTE) incidence and the number of required CTPAs for selective D-dimer thresholds in patients with low clinical probability (< 2 points, D-dimer threshold < 1.0 µg mL(-1) ) and intermediate probability (2-6 points, D-dimer threshold < 0.5 µg mL(-1) ). RESULTS: Using standard management, PE could be excluded without CTPA in 26% of patients, with a 3-month VTE incidence of 0.88% (95% confidence interval [CI] 0.29-2.1%). Using selective D-dimer thresholds, PE could be excluded without CTPA in 36% of patients, with a 3-month VTE incidence of 2.1% (95% CI 1.2-3.4%) in patients managed without CTPA, an increase of 1.2 percentage points (95% CI -0.3 to 2.2). CONCLUSIONS: Applying selective D-dimer thresholds reduces the need for CTPA by 11 percentage points but is associated with an increased failure rate. Prospective studies should evaluate the safety and net clinical benefit of this approach.


Subject(s)
Fibrin Fibrinogen Degradation Products/metabolism , Pulmonary Embolism/blood , Pulmonary Embolism/diagnosis , Adult , Aged , Algorithms , Angiography , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Probability , Tomography, X-Ray Computed , Treatment Outcome , Venous Thromboembolism/blood , Venous Thromboembolism/diagnosis
15.
J Thromb Haemost ; 11(4): 679-85, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23347140

ABSTRACT

INTRODUCTION: Little is known about the natural history of clot resolution in the initial weeks of anticoagulant therapy in patients with acute pulmonary embolism (PE). Clot resolution of acute PE was assessed with either computed tomography pulmonary angiography scan (CT-scan) or perfusion scintigraphy scan (Q-scan) after 3 weeks of treatment. METHODS: This was a predefined safety analysis of the Einstein PE study, including PE patients, randomized to either enoxaparin with vitamin K antagonist (VKA) or rivaroxaban. A similar scan as at baseline was repeated after 3 weeks. The percentage of vascular obstruction (PVO) was calculated on the basis of a weighted semiquantitative estimation of obstruction. Clot resolution was assessed blindly by calculating the relative change after 3 weeks. RESULTS: PE was diagnosed in 264 patients with CT-scan and in 83 with Q-scan. Baseline characteristics were similar. At baseline, the mean PVO assessed with CT-scan (PVO-CT) and the mean PVO assessed with Q-scan (PVO-Q) were both 21% (standard deviation [SD] 13%) (P = 0.9). The mean relative decrease in PVO was 71% (SD 33%) for PVO-CT, and 62% (SD 36%) for PVO-Q (P = 0.02); complete resolution was observed in 44% (116/264; 95% confidence interval [CI] 38-50%) and 31% (26/83; 95% CI 22-42%) with CT-scan and Q-scan, respectively (P = 0.04). No difference in clot resolution between enoxaparin/VKA and rivaroxaban was found. CONCLUSION: In patients with acute PE, only 3 weeks of anticoagulant treatment leads to complete clot resolution in a considerable proportion of patients, and normalization is more often observed with CT-scan than with Q-scan.


Subject(s)
Anticoagulants/therapeutic use , Perfusion Imaging/methods , Pulmonary Embolism/drug therapy , Thrombosis/drug therapy , Tomography, X-Ray Computed/methods , Adult , Aged , Female , Humans , Male , Middle Aged
16.
J Thromb Thrombolysis ; 36(1): 47-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23263991

ABSTRACT

Patients with venous-thromboembolism (VTE) and myocardial infarction (MI) have elevated prothrombin fragment 1+2 (F1+2) levels. In patients with postoperative VTE, urinary F1+2 (uF1+2) was higher than in individuals without VTE. To explore the relationship between plasma and uF1+2 we performed a pilot study in patients with thrombotic events and healthy controls. In 40 patients with VTE or MI, and 25 age- and sex-matched healthy controls, F1+2 and D-dimer levels were measured in urine and plasma within 48 h after diagnosis. In addition, in all subjects renal function was assessed. Plasma and uF1+2 levels were positively correlated. Compared to controls, patients with VTE had higher levels of both plasma F1+2 (271 vs 160 pmol L(-1), p < 0.05) and uF1+2 levels (38 vs 28 pmol L(-1)), the latter, however, was not statistically significant. Patients with acute MI had similar F1+2 levels as controls in both plasma and urine. Differences in urinary F1+2 levels could not be attributed to differences in concentrations of creatinine or albumin in spot urine samples. Overall, D-dimer and F1+2 levels in urine were extremely low in all groups.


Subject(s)
Fibrin Fibrinogen Degradation Products/urine , Myocardial Infarction/urine , Venous Thromboembolism/urine , Adult , Aged , Biomarkers/blood , Biomarkers/urine , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Middle Aged , Myocardial Infarction/blood , Pilot Projects , Prothrombin , Time Factors , Venous Thromboembolism/blood
19.
Heart Vessels ; 27(3): 250-7, 2012 May.
Article in English | MEDLINE | ID: mdl-21598029

ABSTRACT

Histopathological studies have suggested that early revascularization for acute myocardial infarction (MI) limits the size, transmural extent, and homogeneity of myocardial necrosis. However, the long-term effect of early revascularization on infarct tissue characteristics is largely unknown. Cardiovascular magnetic resonance (CMR) imaging with contrast enhancement (CE) allows non-invasive examination of infarct tissue characteristics and left ventricular (LV) dimensions and function in one examination. A total of 69 patients, referred for cardiac evaluation for various clinical reasons, were examined with CE-CMR >1 month (median 6, range 1-213) post-acute MI. We compared patients with (n = 33) versus without (n = 36) successful early revascularization for acute MI. Cine-CMR measurements included the LV end-diastolic and end-systolic volumes (ESV), LV ejection fraction (LVEF, %), and wall motion score index (WMSI). CE images were analyzed for core, peri, and total infarct size (%), and for the number of transmural segments. In our population, patients with successful early revascularization had better LVEFs (46 ± 16 vs. 34 ± 14%; P < 0.01), superior WMSIs (0.53, range 0.00-2.29 vs. 1.42, range 0.00-2.59; P < 0.01), and smaller ESVs (121 ± 70 vs. 166 ± 82; P = 0.02). However, there was no difference in core (9 ± 6 vs. 11 ± 6%), peri (9 ± 4 vs. 10 ± 4%), and total infarct size (18 ± 9 vs. 21 ± 9%; P > 0.05 for all comparisons); only transmural extent (P = 0.07) and infarct age (P = 0.06) tended to be larger in patients without early revascularization. CMR wall motion abnormalities are significantly better after revascularization; these differences are particularly marked later after infarction. The difference in scar size is more subtle and does not reach significance in this study.


Subject(s)
Contrast Media , Magnetic Resonance Imaging, Cine , Myocardial Infarction/therapy , Myocardial Revascularization , Myocardium/pathology , Aged , Chi-Square Distribution , Female , Humans , Linear Models , Male , Middle Aged , Myocardial Contraction , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Netherlands , Predictive Value of Tests , Recovery of Function , Stroke Volume , Time Factors , Treatment Outcome , Ventricular Function, Left , Ventricular Remodeling
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