Rationale Aspirin is typically discontinued in cranial and spinal surgery because of the increased risk of hemorrhagic complications, but comes together with the risk of resulting in an increase of... Show moreRationale Aspirin is typically discontinued in cranial and spinal surgery because of the increased risk of hemorrhagic complications, but comes together with the risk of resulting in an increase of cardiac and neurologic thrombotic perioperative events. Objective The aim of this study is to investigate the non-inferiority of perioperative continuation of aspirin patients undergoing low complex lumbar spinal surgery, compared with the current policy of perioperative discontinuation of aspirin. Study design A randomized controlled trial with two parallel groups of 277 cases (554 in total). Study population Patients undergoing low complex lumbar spinal surgery and using aspirin. All patients are aged >18 years. Intervention Peri-operative continuation of aspirin. Study outcomes Primary study outcome: composite of the following bleeding complications: – Neurological deterioration as a result of hemorrhage in the surgical area with cauda and/or nerve root compression. – Post-surgical anemia with hemoglobin level lower than 5 mmol/l, requiring transfusion. – Subcutaneous hematoma leading to wound leakage and pain higher than NRS=7. – Major and/or minor hemorrhage in any other body system according to the defnition of the International Society on Thrombosis and Haemostasis bleeding scale.Secondary study outcomes: – Each of the individual components of the primary outcome – Absolute mean diference in operative blood loss between the study arms – Thrombo-embolic-related complications: – Myocardial infarction – Venous thromboembolism – Stroke – Arterial thromboembolism Further study outcomes Anticoagulant treatment satisfaction by the Anti-Clot Treatment Scale (ACTS) and general health by the Patient-Reported Outcomes Measurement Information System (PROMIS Global-10) in the pre- and postoperative phase. Nature and extent of the burden and risks associated with participation, beneft, and group related‑ ness Participation in this study imposes no additional risk to patients. Currently, there is no consensus on whether or not aspirin should be discontinued before cranial or spinal surgery. Currently, aspirin is typically discontinued in cranial and spinal surgery, because of a potential increased risk of hemorrhagic complication. An argument not based on a clinical trial. However, this policy might delay surgical procedures or carry the risk of resulting in an increase in cardiac and neurologic thrombotic perioperative events. It is unclear if the possibility of an increase in hemorrhagerelated complications outweighs the risk of an increase in cardiac and neurologic thrombotic perioperative events. Furthermore, the Data Safety Monitoring Board (DSMB) will be asked for safety analysis by monitoring the study. There are no further disadvantages to participating in this study. Outcome measurements are recorded during admission and regular outpatient visits, and thus, do not require additional visits to the hospital. Show less
Geersing, G.J.; Takada, T.; Klok, F.A.; Büller, H.R.; Courtney, D.M.; Freund, Y.; ... ; Es, N. van 2024
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
Background Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening... Show moreBackground Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening programme to detect CTEPH in PE survivors.Methods This was a multicentre cohort study of patients diagnosed with acute symptomatic PE between January 2017 and December 2018 in 16 centres in Spain. Patients were contacted by phone 2 years after the index PE diagnosis. Those with dyspnoea corresponding to a New York Heart Association (NYHA)/WHO scale≥II, visited the outpatient clinic for echocardiography and further diagnostic tests including right heart catheterisation (RHC). The primary outcome was the new diagnosis of CTEPH confirmed by RHC.Results Out of 1077 patients with acute PE, 646 were included in the symptom screening. At 2 years, 21.8% (n=141) reported dyspnoea NYHA/WHO scale≥II. Before symptom screening protocol, five patients were diagnosed with CTEPH following routine care. In patients with NYHA/WHO scale≥II, after symptom screening protocol, the echocardiographic probability of pulmonary hypertension (PH) was low, intermediate and high in 76.6% (n=95), 21.8% (n=27) and 1.6% (n=2), respectively. After performing additional diagnostic test in the latter 2 groups, 12 additional CTEPH cases were confirmed.Conclusions The implementation of this simple strategy based on symptom evaluation by phone diagnosed more than doubled the number of CTEPH cases. Dedicated follow-up algorithms for PE survivors help diagnosing CTEPH earlier. Show less
BackgroundThe recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging... Show moreBackgroundThe 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).AimTo externally validate the performance of 4PEPS in an independent cohort.MethodsIn 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.ResultsOf 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).ConclusionIn 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. Show less
Background and aimsCancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed... Show moreBackground and aimsCancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed to provide data on the incidence and reasons for interrupting and discontinuing anticoagulant treatment in AF patients with cancer and to assess its contribution to the risk of thromboembolism (TE) and major bleeding (MB).MethodsThis retrospective study identified AF patients with cancer in two hospitals between 2012 and 2017. Data on anticoagulant treatment, TE and MB were collected during two-year follow-up. Incidence rates (IR) per 100 patient-years and adjusted hazard ratios (aHR) were obtained for TE and MB occurring during on- and off-anticoagulant treatment, during interruption and after resumption, and after permanent discontinuation.Results1213 AF patients with cancer were identified, of which 140 patients permanently discontinued anticoagulants and 426 patients experienced one or more interruptions. Anticoagulation was most often interrupted or discontinued due to cancer-related treatment (n = 441, 62 %), bleeding (n = 129, 18 %) or end of life (n = 36, 5 %). The risk of TE was highest off-anticoagulation and during interruptions, with IRs of 19 (14–25)) and 105 (64–13), and aHRs of 3.1 (1.9–5.0) and 4.6 (2.4–9.0), respectively. Major bleeding risk were not only increased during an interruption, but also in the first 30 days after resumption, with IRs of 33 (12–72) and 30 (17–48), and aHRs of 3.3 (1.1–9.8) and 2.4 (1.2–4.6), respectively.ConclusionsInterruption of anticoagulation therapy harbors high TE and MB risk in AF patients with cancer. The high incidence rates call for better (periprocedural) anticoagulant management strategies tailored to the cancer setting. Show less
Jervan, O.; Haukeland-Parker, S.; Gleditsch, J.; Tavoly, M.; Klok, F.A.; Steine, K.; ... ; Ghanima, W. 2023
BackgroundPersistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the... Show moreBackgroundPersistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the scientific evidence is limited.Research QuestionDoes an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea?Study Design and MethodsThis randomized controlled trial was conducted at two hospitals. Patients with persistent dyspnea following PE diagnosed 6 to 72 months earlier, without cardiopulmonary comorbidities, were randomized 1:1 to either the rehabilitation or the control group. The rehabilitation program consisted of two weekly sessions of physical exercise for 8 weeks and one educational session. The control group received usual care. The primary end point was the difference in Incremental Shuttle Walk Test between groups at follow-up. Secondary end points included differences in the Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D and Pulmonary Embolism-QoL questionnaires) and dyspnea (Shortness of Breath questionnaire).ResultsA total of 211 subjects were included: 108 (51%) were randomized to the rehabilitation group and 103 (49%) to the control group. At follow-up, participants allocated to the rehabilitation group performed better on the ISWT compared with the control group (mean difference, 53.0 m; 95% CI, 17.7-88.3; P = .0035). The rehabilitation group reported better scores on the Pulmonary Embolism-QoL questionnaire (mean difference, –4%; 95% CI, –0.09 to 0.00; P = .041) at follow-up, but there were no differences in generic QoL, dyspnea scores, or the ESWT. No adverse events occurred during the intervention.InterpretationIn patients with persistent dyspnea following PE, those who underwent rehabilitation had better exercise capacity at follow-up than those who received usual care. Rehabilitation should be considered in patients with persistent dyspnea following PE. Further research is needed, however, to assess the optimal patient selection, timing, mode, and duration of rehabilitation. Show less
Patient-reported outcome measures (PROMs) are patient-completed instruments that capture patient-perceived health status and well-being. PROMs measure disease impact and outcomes of care as... Show morePatient-reported outcome measures (PROMs) are patient-completed instruments that capture patient-perceived health status and well-being. PROMs measure disease impact and outcomes of care as reported by those who experience the disease. After pulmonary embolism or deep vein thrombosis, patients may face a broad spectrum of complications and long-term sequelae beyond the usual quality-of-care indicators of recurrent venous thromboembolism (VTE), bleeding complications, and survival. The full impact of VTE on individual patients can only be captured by assessing all relevant health outcomes from the patient’s perspective in addition to the traditionally recognized complications. Defining and measuring all important outcomes will help facilitate treatment tailored to the needs and preferences of patients and may improve health outcomes. The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease endorsed the International Consortium for Health Outcomes Measurement (ICHOM) VTE project on development of a standardized set of patient-centered outcome measures for patients with VTE. In this communication, the course and result of the project are summarized, and based on these findings, we propose recommendations for the use of PROMs during clinical follow-up of patients with VTE. We describe challenges to implementation of PROMs and explore barriers and enablers. Show less
Maanen, R. van; Martens, E.S.L.; Takada, T.; Roy, P.M.; Wit, K. de; Parpia, S.; ... ; Luijken, K. 2023
BackgroundIn patients clinically suspected of having pulmonary embolism (PE), physicians often rely on intuitive estimation (“gestalt”) of PE presence. Although shown to be predictive, gestalt is... Show moreBackgroundIn patients clinically suspected of having pulmonary embolism (PE), physicians often rely on intuitive estimation (“gestalt”) of PE presence. Although shown to be predictive, gestalt is criticized for its assumed variation across physicians and lack of standardization.ObjectivesTo assess the diagnostic accuracy of gestalt in the diagnosis of PE and gain insight into its possible variation.MethodsWe performed an individual patient data meta-analysis including patients suspected of having PE. The primary outcome was diagnostic accuracy of gestalt for the diagnosis of PE, quantified as risk ratio (RR) between gestalt and PE based on 2-stage random-effect log-binomial meta-analysis regression as well as gestalts’ sensitivity and specificity. The variability of these measures was explored across different health care settings, publication period, PE prevalence, patient subgroups (sex, heart failure, chronic lung disease, and items of the Wells score other than gestalt), and age.ResultsWe analyzed 20 770 patients suspected of having PE from 16 original studies. The prevalence of PE in patients with and without a positive gestalt was 28.8% vs 9.1%, respectively. The overall RR was 3.02 (95% CI, 2.35-3.87), and the overall sensitivity and specificity were 74% (95% CI, 68%-79%) and 61% (95% CI, 53%-68%), respectively. Although variation was observed across individual studies (I2, 90.63%), the diagnostic accuracy was consistent across all subgroups and health care settings.ConclusionA positive gestalt was associated with a 3-fold increased risk of PE in suspected patients. Although variation was observed across studies, the RR of gestalt was similar across prespecified subgroups and health care settings, exemplifying its diagnostic value for all patients suspected of having PE. Show less
This population-based cohort study aimed to describe changes in incidence of cardiovascular disease (CVD) hospital diagnoses during the COVID-19 pandemic in The Netherlands compared with the pre... Show moreThis population-based cohort study aimed to describe changes in incidence of cardiovascular disease (CVD) hospital diagnoses during the COVID-19 pandemic in The Netherlands compared with the pre-pandemic period. We used Dutch nationwide statistics about hospitalizations to estimate incidence rate ratios (IRR) of hospital diagnoses of CVD during the first and second COVID-19 waves in The Netherlands in 2020 versus the same periods in 2019. Compared with 2019, the incidence rate of a hospital diagnosis of ischemic stroke (IRR 0.87; 95% CI 0.79-0.95), major bleeding (IRR 0.74; 95% CI 0.68-0.82), atrial fibrillation (IRR 0.73; 95% CI 0.65-0.82), myocardial infarction (IRR 0.78; 95% CI 0.72-0.84), and heart failure (IRR 0.74; 95% CI 0.65-0.85) declined during the first wave, but returned to pre-pandemic levels throughout 2020. However, the incidence rate of a hospital diagnosis of pulmonary embolism (PE) increased during both the first and second wave in 2020 compared with 2019 (IRR 1.30; 95% CI 1.15-1.48 and IRR 1.31; 95% CI 1.19-1.44, respectively). In conclusion, we observed substantial declines in incidences of CVD during the COVID-19 pandemic in The Netherlands in 2020, especially during the first wave, with an exception for an increase in incidence of PE. This study contributes to quantifying the collateral damage of the COVID-19 pandemic. Show less
AimsRisk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that... Show moreAimsRisk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations.Methods and resultsAn individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85–0.89; 95% PI, 0.77–0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87–1.14; 95% PI, 0.55–1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70–0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76–0.81).ConclusionThe present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. Show less
Anijs, R.J.S.; Chen, Q.; Hulle, T. van der; Versteeg, H.H.; Klok, F.A.; Lijfering, W.M.; Cannegieter, S.C. 2023
Background: Colorectal cancer (CRC) is the third most prevalent cancer type. CRC-patients are at increased risk of venous and arterial thromboembolism (TE), but the magnitude of the risks, their... Show moreBackground: Colorectal cancer (CRC) is the third most prevalent cancer type. CRC-patients are at increased risk of venous and arterial thromboembolism (TE), but the magnitude of the risks, their predictors and consequences are not exactly known.Objectives: We aimed to determine incidence, predictors and prognosis of TE after incident CRC in a large, unselected population. Methods: Using data from Statistics Netherlands and the Netherlands Comprehensive Cancer Organization, all incident CRC-patients were identified between 2013 and 2018 plus a sample of 1:2 age- and sex-matched control subjects. Incidence rates and cumulative incidences for TE were estimated. Predictor variables for TE were explored by univariable Cox regression. The association between TE and all-cause mortality was evaluated by multivariable time-dependent Cox regression.Results: 68,238 incident CRC-patients were matched to 136,476 controls. CRC-patients had a 1-year cumulative venous TE (VTE) incidence of 1.93 % (95%CI 1.83-2.04), versus 0.24 % (95%CI 0.21-0.27) in controls (HR 8.85; 95%CI 7.83-9.99). For arterial TE (ATE), this was 2.74 % (95%CI 2.62-2.87) in CRC versus 1.88 % (95%CI 1.81-1.95) in controls (HR 1.57; 95%CI 1.47-1.66). Cancer stage, surgery, chemotherapy and asthma were predictors for VTE, whereas age, prior ATE and Parkinson's disease were predictors for ATE. CRC patients with TE had an increased risk of all-cause mortality (VTE HR; 3.68 (95%CI 3.30-4.10, ATE HR; 3.05 (95%CI 2.75-3.39)) compared with CRC-patients without TE.Conclusions: This Dutch nationwide cohort study adds detailed knowledge on the risk of VTE and ATE, their predictors and prognosis in CRC-patients. These findings may drive TE prophylactic management decisions. Show less
Lee, J.Y.; Es, N. van; Takada, T.; Klok, F.A.; Geersing, G.J.; Blume, J.; ... ; IPD study team 2023
ObjectivesWe present an illustrative application of methods that account for covariates in receiver operating characteristic (ROC) curve analysis, using individual patient data on D-dimer testing... Show moreObjectivesWe present an illustrative application of methods that account for covariates in receiver operating characteristic (ROC) curve analysis, using individual patient data on D-dimer testing for excluding pulmonary embolism.Study Design and SettingBayesian nonparametric covariate-specific ROC curves were constructed to examine the performance/positivity thresholds in covariate subgroups. Standard ROC curves were constructed. Three scenarios were outlined based on comparison between subgroups and standard ROC curve conclusion: (1) identical distribution/identical performance, (2) different distribution/identical performance, and (3) different distribution/different performance. Scenarios were illustrated using clinical covariates. Covariate-adjusted ROC curves were also constructed.ResultsAge groups had prominent differences in D-dimer concentration, paired with differences in performance (Scenario 3). Different positivity thresholds were required to achieve the same level of sensitivity. D-dimer had identical performance, but different distributions for YEARS algorithm items (Scenario 2), and similar distributions for sex (Scenario 1). For the later covariates, comparable positivity thresholds achieved the same sensitivity. All covariate-adjusted models had AUCs comparable to the standard approach.ConclusionSubgroup differences in performance and distribution of results can indicate that the conventional ROC curve is not a fair representation of test performance. Estimating conditional ROC curves can improve the ability to select thresholds with greater applicability. Show less
BackgroundThere is limited information on short- and long-term effects of venous thromboembolism (VTE) on health-related quality of life (HRQoL) in the elderly.ObjectivesTo assess change in generic... Show moreBackgroundThere is limited information on short- and long-term effects of venous thromboembolism (VTE) on health-related quality of life (HRQoL) in the elderly.ObjectivesTo assess change in generic HRQoL and disease-specific HRQoL in patients 1 year after the VTE.MethodsThe Age and Thrombosis, Acquired and Genetic risk factors in the elderly (AT-AGE) study is a 2-center case-control study performed in Leiden, the Netherlands, and Vermont, United States, among individuals aged ≥70 years. We measured generic HRQoL using the 36-item Short Form Health Survey (SF-36) and disease-specific HRQoL using the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms Questionnaire (VEINES-QoL/Sym) and the Pulmonary Embolism–Specific Quality of Life Questionnaire (PEmb-QoL). All patients completed these questionnaires shortly after their VTE and 1 year later, while controls completed the 36-item Short Form Health Survey questionnaire once. Linear regression for change in quality of life scores was performed and adjusted for potential confounders.ResultsFor the current analysis, we included patients who were visited twice (n = 316) and controls (n = 427) with HRQoL information. Mean age of patients and controls was similar (78.8 vs 75.5 years). In patients who survived at least 1 year after the VTE, generic HRQoL improved for both summary scores, but it did not reach the level of the age-matched controls: physical and mental summary scores increased by 5.6 and 5.5 points, respectively, but compared with controls, remained 8.2 and 6.4 points lower. For disease-specific HRQoL, the Pulmonary Embolism–Specific Quality of Life Questionnaire overall score decreased from 21.7% to 15.2%, indicating improved HRQoL. Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms Questionnaire scores did not change over time.ConclusionOverall, the quality of life of patients with VTE was worse than that of controls after 1 year, indicating a long-term impact of VTE diagnosis in the elderly. Show less
Jervan, O.; Dhayyat, A.; Gleditsch, J.; Haukeland-Parker, S.; Tavoly, M.; Klok, F.A.; ... ; Steine, K. 2023
Background: Residual perfusion defects (RPD) after pulmonary embolism (PE) are common. Primary aim: This study aimed to determine the prevalence of RPD in a cohort diagnosed with PE 6–72 months... Show moreBackground: Residual perfusion defects (RPD) after pulmonary embolism (PE) are common. Primary aim: This study aimed to determine the prevalence of RPD in a cohort diagnosed with PE 6–72 months earlier, and to determine demographic, clinical, and echocardiographic variables associated with RPD. Methods: Patients aged 18–75 years with prior PE, confirmed by computed tomography pulmonary angiography 6–72 months earlier, were included. Participants (N = 286) completed a diagnostic work-up consisting of transthoracic echocardiography and ventilation/perfusion scintigraphy. Demographic, clinical, and echocardiographic characteristics between participants with RPD and those without RPD were explored in univariate analyses using t-test or Mann-Whitney U test. Multiple logistic regression analysis was used to assess the association between selected variables and RPD. Results: RPD were detected in 72/286 patients (25.2 %, 95 % CI:20.5 %–30.5 %). Greater tricuspid annular plane systolic excursion (TAPSE) (adjusted odds ratio (aOR) 1.10, 95 % CI:1.00–1.21, p = 0.048) at echocardiographic follow-up, greater thrombotic burden at diagnosis, as assessed by mean bilateral proximal extension of the clot (MBPEC) score 3–4 (aOR 2.08, 95 % CI:1.06–4.06, p = 0.032), and unprovoked PE (aOR 2.25, 95 % CI:1.13–4.48, p = 0.021) were independently associated with increased risk of RPD, whereas increased pulmonary artery acceleration time was associated with a lower risk of RPD (aOR 0.72, 95 % CI:0.62–0.83, p < 0.001, per 10 ms). Dyspnoea was not associated with RPD. Conclusion: RPD were common after PE. Reduced pulmonary artery acceleration time and greater TAPSE on echocardiography at follow-up, greater thrombotic burden at diagnosis, and unprovoked PE were associated with RPD. Show less
BACKGROUNDS: planchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis. There is no consensus on whether therapeutic anticoagulation should be started in... Show moreBACKGROUNDS: planchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis. There is no consensus on whether therapeutic anticoagulation should be started in patients with acute pancreatitis and SVT. AIM: To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis. METHODS: A total of 139 pancreatologists of the Dutch Pancreatitis Study Group and Dutch Pancreatic Cancer Group were approached to complete an online survey and case vignette survey. The threshold to assume group agreement was set at 75%. RESULTS: The response rate was 67% (n = 93). Seventy-one pancreatologists (77%) regularly prescribed therapeutic anticoagulation in case of SVT, and 12 pancreatologists (13%) for narrowing of splanchnic vein lumen. The most common reason to treat SVT was to avoid complications (87%). Acute thrombosis was the most important factor to prescribe therapeutic anticoagulation (90%). Portal vein thrombosis was chosen as the most preferred location to initiate therapeutic anticoagulation (76%) and splenic vein thrombosis as the least preferred location (86%). The preferred initial agent was low molecular weight heparin (LMWH; 87%). In the case vignettes, therapeutic anticoagulation was prescribed for acute portal vein thrombosis, with or without suspected infected necrosis (82% and 90%), and thrombus progression (88%). Agreement was lacking regarding the selection and duration of long-term anticoagulation, the indication for thrombophilia testing and upper endoscopy, and about whether risk of bleeding is a major barrier for therapeutic anticoagulation. CONCLUSION: In this national survey, the pancreatologists seemed to agree on the use of therapeutic anticoagulation, using LMWH in the acute phase, for acute portal thrombosis and in the case of thrombus progression, irrespective of the presence of infected necrosis. Show less
Vedovati, M.C.; Giustozzi, M.; Munoz, A.; Bertoletti, L.; Cohen, A.T.; Klok, F.A.; ... ; Agnelli, G. 2023
Risks of recurrence and treatment-emergent bleeding are high in patients with cancer-associated venous thromboembolism (VTE) but factors associated with these risks remain substantially undefined... Show moreRisks of recurrence and treatment-emergent bleeding are high in patients with cancer-associated venous thromboembolism (VTE) but factors associated with these risks remain substantially undefined.The aim of this analysis in patients with cancer-associated VTE included in the Caravaggio study was to identify risk factors for recurrent VTE and major bleeding. Variables potentially predictive for recurrent VTE or major bleeding were evaluated in a Cox proportional hazard multivariable analysis with backward variable selection.Recurrent VTE occurred in 78 patients (6.8%) and major bleeding in 45 (3.9%). Independent risk factors for recurrent VTE were deep vein thrombosis (DVT) as index event (Hazard ratio (HR) 1.84, 95% CI 1.17–2.88), ECOG status of 1 or more (HR 1.95, 95% CI 1.11–3.43), pancreatic or hepatobiliary cancer site (HR 2.20, 95% CI 1.19–4.06), concomitant anti-cancer treatment (HR 1.98, 95% CI 1.03–3.81) and creatinine clearance (HR 1.10, 95% CI 1.00–1.20 for every 10 ml/min absolute increase). Independent risk factors for major bleeding were ECOG status of 2 (HR 2.31, 95% CI 1.24–4.29), genitourinary cancer site (HR 2.72, 95% CI 1.28–5.77), upper gastrointestinal cancer site (HR 3.17, 95% CI 1.22–8.23), and non-resected luminal gastrointestinal cancer (HR 2.77, 95% CI 1.38–5.56).This analysis of the Caravaggio study in patients with cancer-associated VTE who were on standardized anticoagulant treatment identified five independent predictors for recurrent VTE and four independent predictors of treatment-emergent major bleeding. Considering these risks could help clinicians to optimize the anticoagulant treatment in patients with cancer-associated VTE. Show less
Background In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care... Show moreBackground In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days.Methods This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale.Results In the primary analysis, 587 patients were included (age: 57 [Q1–Q3: 45–68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60–1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42–0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41–1.01, p = 0.05).Conclusion Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508). Show less
BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is considered a complication of pulmonary embolism (PE). However, signs of CTEPH may exist in patients with a first symptomatic PE... Show moreBackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is considered a complication of pulmonary embolism (PE). However, signs of CTEPH may exist in patients with a first symptomatic PE.Research QuestionWhich radiologic findings on CT pulmonary angiography (CTPA) at the time of acute PE could indicate the presence of preexisting CTEPH?Study Design and MethodsThis study included unselected patients with acute PE who were prospectively followed up for 2 years with a structured visit schedule. Two expert radiologists independently assessed patients’ baseline CTPAs for preexisting CTEPH; in case of disagreement, a decision was reached by a 2:1 majority with a third expert radiologist. In addition, the radiologists checked for predefined individual parameters suggesting chronic PE and pulmonary hypertension.ResultsSigns of chronic PE or CTEPH at baseline were identified in 46 of 303 included patients (15%). Intravascular webs, arterial narrowing or retraction, dilated bronchial arteries, and right ventricular hypertrophy were the main drivers of the assessment. Five (1.7%) patients were diagnosed with CTEPH during follow-up. All four patients diagnosed with CTEPH early (83-108 days following acute PE) were found in enriched subgroups based on the experts’ overall assessment or fulfilling a minimum number of the predefined radiologic criteria at baseline. The specificity of preexisting CTEPH diagnosis and the level of radiologists’ agreement improved as the number of required criteria increased.InterpretationSearching for predefined radiologic parameters suggesting preexisting CTEPH at the time of acute PE diagnosis may allow for targeted follow-up strategies and risk-adapted CTEPH screening, thus facilitating earlier CTEPH diagnosis. Show less
