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... Show moreBackground 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 1/4 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. Show less
Boon, G.J.A.M.; Ende-Verhaar, Y.M.; Beenen, L.F.M.; Coolen, J.; Delcroix, M.; Golebiowski, M.; ... ; Klok, F.A. 2021
Objectives Closer reading of computed tomography pulmonary angiography (CTPA) scans of patients presenting with acute pulmonary embolism (PE) may identify those at high risk of developing chronic... Show moreObjectives Closer reading of computed tomography pulmonary angiography (CTPA) scans of patients presenting with acute pulmonary embolism (PE) may identify those at high risk of developing chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to validate the predictive value of six radiological predictors that were previously proposed. Methods Three hundred forty-one patients with acute PE were prospectively followed for development of CTEPH in six European hospitals. Index CTPAs were analysed post hoc by expert chest radiologists blinded to the final diagnosis. The accuracy of the predictors using a predefined threshold for 'high risk' (>= 3 predictors) and the expert overall judgment on the presence of CTEPH were assessed. Results CTEPH was confirmed in nine patients (2.6%) during 2-year follow-up. Any sign of chronic thrombi was already present in 74/341 patients (22%) on the index CTPA, which was associated with CTEPH (OR 7.8, 95%CI 1.9-32); 37 patients (11%) had >= 3 of 6 radiological predictors, of whom 4 (11%) were diagnosed with CTEPH (sensitivity 44%, 95%CI 14-79; specificity 90%, 95%CI 86-93). Expert judgment raised suspicion of CTEPH in 27 patients, which was confirmed in 8 (30%; sensitivity 89%, 95%CI 52-100; specificity 94%, 95%CI 91-97). Conclusions The presence of >= 3 of 6 predefined radiological predictors was highly specific for a future CTEPH diagnosis, comparable to overall expert judgment, while the latter was associated with higher sensitivity. Dedicated CTPA reading for signs of CTEPH may therefore help in early detection of CTEPH after PE, although in our cohort this strategy would not have detected all cases. Show less
Background: Expert reading often reveals radiological signs of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic PE on computed tomography pulmonary angiography (CTPA) performed at... Show moreBackground: Expert reading often reveals radiological signs of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic PE on computed tomography pulmonary angiography (CTPA) performed at the time of acute pulmonary embolism (PE) presentation preceding CTEPH. Little is known about the accuracy and reproducibility of CTPA reading by radiologists in training in this setting. Objectives: To evaluate 1) whether signs of CTEPH or chronic PE are routinely reported on CTPA for suspected PE; and 2) whether CTEPH-non-expert readers achieve comparable predictive accuracy to CTEPH-expert radiologists after dedicated instruction. Methods: Original reports of CTPAs demonstrating acute PE in 50 patients whom ultimately developed CTEPH, and those of 50 PE who did not, were screened for documented signs of CTEPH. All scans were re-assessed by three CTEPH-expert readers and two CTEPH-non-expert readers (blinded and independently) for predefined signs and overall presence of CTEPH. Results: Signs of chronic PE were mentioned in the original reports of 14/50 cases (28%), while CTEPH-expert radiologists had recognized 44/50 (88%). Using a standardized definition (>= 3 predefined radiological signs), moderate-to-good agreement was reached between CTEPH-non-expert readers and the experts' consensus (kstatistics 0.46; 0.61) at slightly lower sensitivities. The CTEPH-non-expert readers had moderate agreement on the presence of CTEPH (Kappa-statistic 0.38), but both correctly identified most cases (80% and 88%, respectively). Conclusions: Concomitant signs of CTEPH were poorly documented in daily practice, while most CTEPH patients were identified by CTEPH-non-expert readers after dedicated instruction. These findings underline the feasibility of achieving earlier CTEPH diagnosis by assessing CTPAs more attentively. Show less
Dam, L.F. van; Hout, W.B. van den; Gautam, G.; Dronkers, C.E.A.; Ghanima, W.; Gleditsch, J.; ... ; Klok, F.A. 2021
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.... Show moreThe 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. Patientlevel 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, (sic)1219-1296) were generally lower than strategies without MRDTI (range, (sic)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 (sic)1529 and (sic)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. Show less
Dam, L.F. van; Gautam, G.; Dronkers, C.E.A.; Ghanima, W.; Gleditsch, J.; Heijne, A. von; ... ; Klok, F.A. 2020
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... Show moreBackground 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. Show less
Dam, L.F. van; Dronkers, C.E.A.; Gautam, G.; Eckerbom, A.; Ghanima, W.; Gleditsch, J.; ... ; Theia Study Grp 2020
The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) is challenging, because persistent intravascular abnormalities after previous DVT often hinder a diagnosis by compression... Show moreThe 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 (k statistic, 0.91). The incidence of VTE recurrence after negative MRDTI was low, and MRDTI proved to be a feasible and reproducible diagnostic test. Show less
Background: Low lumbar skeletal muscle mass and density have been associated with adverse outcomes in different populations with colorectal cancer (CRC). We aimed to determine whether skeletal... Show moreBackground: Low lumbar skeletal muscle mass and density have been associated with adverse outcomes in different populations with colorectal cancer (CRC). We aimed to determine whether skeletal muscle mass, density, and physical performance are associated with postoperative complications and overall survival (OS) in older CRC patients.Methods: We analysed consecutive patients (>= 70 years) undergoing elective surgery for non-metastatic CRC (stage I-III). Lumbar skeletal muscle mass and muscle density were measured using abdominal CT-images obtained prior to surgery. Low skeletal muscle mass and low muscle density were defined using commonly used thresholds and by gender-specific quartiles (Q). The preoperative use of a mobility aid served as a marker for physical performance. Cox regression proportional hazard models were used to investigate the association between the independent variables and OS.Results: 174 Patients were included (mean age 78.0), with median follow-up 2.6 years. 36 Patients (21%) used a mobility aid preoperatively. Low muscle density (Q1 vs Q4) and not muscle mass was associated with worse postoperative outcomes, including severe complications (p < 0.05). Use of a mobility aid was associated with more complications, including severe complications (39% vs 17%, p = 0.004) and OS (HR 2.65, CI 1.29-5.44, p = 0.01). However, patients with mobility aid use and low skeletal muscle mass had worse OS (HR 5.68, p = 0.003).Conclusion: Low skeletal muscle density and not muscle mass was associated with more complications after colorectal surgery in older patients. Physical performance has the strongest association for poor surgical outcomes and should be investigated when measuring skeletal muscle mass and density. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Background: Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction.... Show moreBackground: Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction. We determined predictive signs, symptoms and biomarkers for the presence of pneumonia in patients with acute respiratory tract infection in primary care.Methods: From March 2012 until May 2016 we did a prospective observational cohort study in three radiology departments in the Leiden-The Hague area, The Netherlands. From adult patients we collected clinical characteristics and biomarkers, chest X ray results and outcome. To assess the predictive value of C-reactive protein (CRP), procalcitonin and midregional pro-adrenomedullin for pneumonia, univariate and multivariate binary logistic regression were used to determine risk factors and to develop a prediction model.Results: Two hundred forty-nine patients were included of whom 30 (12%) displayed a consolidation on chest X ray. Absence of runny nose and whether or not a patient felt ill were independent predictors for pneumonia. CRP predicts pneumonia better than the other biomarkers but adding CRP to the clinical model did not improve classification (- 4%); however, CRP helped guidance of the decision which patients should be given antibiotics.Conclusions: Adding CRP measurements to a clinical model in selected patients with an acute respiratory infection does not improve prediction of pneumonia, but does help in giving guidance on which patients to treat with antibiotics. Our findings put the use of biomarkers and chest X ray in diagnosing pneumonia and for treatment decisions into some perspective for general practitioners. Show less
Kooiman, J.; Sijpkens, Y.W.J.; Buren, M. van; Groeneveld, J.H.M.; Ramai, S.R.S.; Molen, A.J. van der; ... ; Huisman, M.V. 2014
Background: Knowledge of independent, baseline risk factors for catheter-related thrombosis (CRT) may help select adult cancer patients who are at high risk to receive thromboprophylaxis.... Show moreBackground: Knowledge of independent, baseline risk factors for catheter-related thrombosis (CRT) may help select adult cancer patients who are at high risk to receive thromboprophylaxis. Objectives: We conducted a meta-analysis of individual patient-level data to identify these baseline risk factors. Patients/Methods: MEDLINE, EMBASE, CINAHL, CENTRAL, DARE and the Grey literature databases were searched in all languages from 1995 to 2008. Prospective studies and randomized controlled trials (RCTs) were eligible. Studies were included if original patient-level data were provided by the investigators and if CRT was objectively confirmed with valid imaging. Multivariate logistic regression analysis of 17 prespecified baseline characteristics was conducted. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results: A total sample of 5636 subjects from five RCTs and seven prospective studies was included in the analysis. Among these subjects, 425 CRT events were observed. In multivariate logistic regression, the use of implanted ports as compared with peripherally implanted central venous catheters (PICCs), decreased CRT risk (OR, 0.43; 95% CI, 0.23-0.80), whereas past history of deep vein thrombosis (DVT) (OR, 2.03; 95% CI, 1.05-3.92), subclavian venipuncture insertion technique (OR, 2.16; 95% CI, 1.07-4.34) and improper catheter tip location (OR, 1.92; 95% CI, 1.22-3.02), increased CRT risk. Conclusions: CRT risk is increased with use of PICCs, previous history of DVT, subclavian venipuncture insertion technique and improper positioning of the catheter tip. These factors may be useful for risk stratifying patients to select those for thromboprophylaxis. Prospective studies are needed to validate these findings. Show less
Tan, M.; Velthuis, S.I.; Westerbeek, R.E.; Rooden, C.J. van; Meer, F.J.M. van der; Huisman, M.V. 2010
Venous thrombosis is a well-known complication of central vein catheters (CVCs), which may cause serious morbidity and may result in potentially lethal complications such as pulmonary embolism. In... Show moreVenous thrombosis is a well-known complication of central vein catheters (CVCs), which may cause serious morbidity and may result in potentially lethal complications such as pulmonary embolism. In this thesis the general risk of CVC related thrombosis has been assessed, i.e., what is the overall risk of developing CVC related thrombosis? Which patients are prone to develop thrombosis with its associated morbidity? Are we able to predict this risk by routine surveillance in "high-risk" patients? Better knowledge of the incidence of CVC related thrombosis and identification of high-risk groups will assist clinicians in decision making about CVC use in the various patient-groups and in whom anticoagulant prophylaxis may be warranted. In summary, the a priori determination of common inherited and acquired risk factors may form a basis to guide (prophylactic) treatment decisions. Vulnerable patients may benefit the most, i.e. those who have a high risk of clinically manifest thrombosis, and who are at risk of hemorrhage, such as patients who undergo intensive chemotherapy. Besides, surveillance of these patients with screening by ultrasound, or alternatively surveillances cultures, may be useful to identify patients at high or low risk for clinically manifest CVC related thrombosis, and focused early intervention may be initiated. Show less