Displaying publications 1 - 20 of 38 in total

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  1. Sivananthan DK
    J Orthop Surg (Hong Kong), 2013 Aug;21(2):139.
    PMID: 24014768
    Matched MeSH terms: Venous Thromboembolism/etiology; Venous Thromboembolism/prevention & control*
  2. Liew NC, Sim KH, Ng SC, Suhail A, Premchandran N
    Med J Malaysia, 2011 Aug;66(3):278-80; quiz 281.
    PMID: 22111463 MyJurnal
    Venous thromboembolism is a rising concern in Asia especially among patients after surgery where this complication is readily preventable. Despite the availability of several treatment options, the acceptance of prophylaxis and usage of these methods remain low. A possible explanation to this behavior is the limitations attached to the available treatment options: narrow therapeutic window of warfarin and parenteral administration of low molecular weight as well as unfractionated heparins. Newer agents have been researched and introduced to overcome these limitations in the hope of improving the adaptation towards post surgical thromboprophylaxis. Dabigatran and rivaroxaban are two such new agents that are promising in view of efficacy and ease of administration.
    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  3. Das Gupta E
    Malays Fam Physician, 2010;5(1):47-8.
    PMID: 25606188
    Matched MeSH terms: Venous Thromboembolism
  4. Kow CS, Hasan SS
    Rev Esp Cardiol (Engl Ed), 2021 01;74(1):114-115.
    PMID: 32933883 DOI: 10.1016/j.rec.2020.08.009
    Matched MeSH terms: Venous Thromboembolism/blood; Venous Thromboembolism/etiology; Venous Thromboembolism/prevention & control*
  5. ISBN: 978-967-12100-0-0
    Matched MeSH terms: Venous Thromboembolism
  6. Ahmat ANMF, Wan Puteh SE, Yusak S
    Asian Pac J Cancer Prev, 2021 Nov 01;22(11):3601-3606.
    PMID: 34837918 DOI: 10.31557/APJCP.2021.22.11.3601
    OBJECTIVE: Cancer-associated venous thromboembolism (CAT) is a common disease or complication which is associated with reduced survival and incurring a substantial health-care cost. Low molecular weight heparin (LMWH) remained the gold standard treatment option available. Direct oral anticoagulants (DOACs) have recently become more popular in the guidelines, they are still few and inconsistent across the current literature. The aim of this study was to evaluate rivaroxaban in treatment of CAT.

    METHODS: In this prospective real-world study, we recruited and followed up patients diagnosed with CAT treated with rivaroxaban or standard of care as a control for 12 months or until death. Baseline characteristics were collected at the study entry. The primary outcomes were recurrent DVT or PE and death within 12 months after treatment initiation. Safety outcomes were composite outcomes of major and minor bleeding.    Results: A total of 80 patients confirm CAT with radiological imaging were recruited; 39 patients were evaluated in the control arm and 41 patients in the rivaroxaban arm. The 12 months cumulative CAT recurrence rate was 46.2% in control and 39% in rivaroxaban (p=0.519). The 12-month death was not a statistically significant difference between both arms (20.5% vs. 31.7%, p=0.255). The cumulative rate of composite safety outcomes was similar in both groups (17.9% vs. 12.2%, p=0.471).

    CONCLUSION: The result of this small but important real-world evidence proofs that rivaroxaban is an effective and safe alternative to the standard of care for CAT in Malaysia's cancer population.

    Matched MeSH terms: Venous Thromboembolism/drug therapy*; Venous Thromboembolism/etiology; Venous Thromboembolism/mortality
  7. Wan J, Yuan J, Li X, Bao Y, Hou Y, Li Z, et al.
    Complement Ther Med, 2020 Nov;54:102579.
    PMID: 33183675 DOI: 10.1016/j.ctim.2020.102579
    OBJECTIVE: Although many studies have attempted to unravel the relationship between vitamin D deficiency and the incidence of VTE, the results remained inconsistent. To address this discrepancy, we performed a systematic review and meta-analysis to precisely disentangle the relationship between serum vitamin D levels and VTE risk.

    METHODS: The Web of Science, Scopus, PubMed/Medline, Embase, and Google Scholar databases were searched for all available observational studies that reported the risk of venous thromboembolism (VTE) based on serum vitamin D levels categories. The search was performed up to March 2020.

    RESULTS: Seven studies were included. The overall analysis showed a significantly increased risk of VTE in subjects with low levels of serum vitamin D compared with those with normal vitamin D levels (RR = 1.34; 95% CI: 1.07-1.69; P = 0.011). In a sensitivity analysis, we did not observe a significant effect of any individual study on the combined effect sizes. Nevertheless, significant heterogeneity was present among the studies (Cochrane Q test, p = 0.018, I2 = 61%). In the stratified analysis, low vitamin D levels were positively associated with an increased risk of VTE in prospective population-based studies (RR = 1.31; 95% CI: 1.06-1.61; P = 0.010) and in subjects below 60 years old (RR = 1.28; 95% CI: 1.07-1.54; P = 0.060).

    CONCLUSION: our systematic review and meta-analysis showed that a low serum vitamin D level was indeed associated with an increased risk of VTE.

    Matched MeSH terms: Venous Thromboembolism/etiology*
  8. Brand JS, Hedayati E, Bhoo-Pathy N, Bergh J, Hall P, Humphreys K, et al.
    Cancer, 2017 02 01;123(3):468-475.
    PMID: 27727456 DOI: 10.1002/cncr.30364
    BACKGROUND: Venous thromboembolism (VTE) is a serious complication of cancer and its treatment. The current study assessed the risk and clinical predictors of VTE in breast cancer patients by time since diagnosis.

    METHODS: This Swedish population-based study included 8338 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region with complete follow-up until 2012. Their incidence of VTE was compared with the incidence among 39,013 age-matched reference individuals from the general population. Cox and flexible parametric models were used to examine associations with patient, tumor, and treatment characteristics, accounting for time-dependent effects.

    RESULTS: Over a median follow-up of 7.2 years, 426 breast cancer patients experienced a VTE event (cumulative incidence, 5.1%). The VTE incidence was 3-fold increased (hazard ratio [HR], 3.28; 95% confidence interval [CI], 2.87-3.74) in comparison with the incidence in the general population and was highest 6 months after diagnosis (HR, 8.62; 95% CI, 6.56-11.33) with a sustained increase in risk thereafter (HR at 5 years, 2.19; 95% CI, 1.80-2.67). Independent predictors of VTE included the following: older age, being overweight, preexisting VTE, comorbid disease, tumor size > 40 mm, progesterone receptor (PR)-negative status, more than 4 affected lymph nodes, and receipt of chemo- and endocrine therapy. The impact of chemotherapy was limited to early-onset VTE, whereas comorbid disease and PR-negative status were more strongly associated with late-onset events.

    CONCLUSIONS: This study confirms the long-term risk of VTE in breast cancer patients and identifies a comprehensive set of clinical risk predictors. Temporal associations with patient, tumor, and treatment characteristics provide insight into the time-dependent etiology of VTE. Cancer 2017;123:468-475. © 2016 American Cancer Society.

    Matched MeSH terms: Venous Thromboembolism/etiology; Venous Thromboembolism/pathology*
  9. Liew NC, Alemany GV, Angchaisuksiri P, Bang SM, Choi G, DE Silva DA, et al.
    Int Angiol, 2017 Feb;36(1):1-20.
    PMID: 27606807 DOI: 10.23736/S0392-9590.16.03765-2
    The Asian venous thromboembolism (VTE) prophylaxis guidelines were first published in 2012. Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors, however, are similar between Asians and Caucasians. The group found no evidence of increased risk of bleeding while using pharmacological agents, including the use of novel anti-coagulants. At present, Caprini risk assessment model is widely used for individual risk assessment. Further validation of this model is needed in Asia. In medically ill patients, pharmacological agents are preferred if there is no bleeding risk. Intermittent pneumatic compression device (IPC) is recommended in patients with bleeding risk but we do not recommend using graduated compressive stockings. In bariatric patients, data on VTE is lacking in Asia. We recommend following current international guidelines. A high index of suspicion should be maintained during postbariatric surgery to detect and promptly treat portomesenteric venous thrombosis. Different cancer types have different thrombotic risks and the types of surgery influence to a large extent the overall VTE risk. Cancer patients should receive further risk assessment. In patients with higher thrombotic risk, either due to predisposing risk or concomitant surgery, low molecular weight heparin is indicated. Different countries appear to have different incidence of VTE following trauma and major orthopedic surgery. We recommend mechanical prophylaxis using IPC as the main method and additional pharmacological prophylaxis if the thrombotic risk is high. As for obstetric practice, we propose adherence to the UK Greentop guideline that is widely accepted and utilized across Asia. To improve VTE thromboprophylaxis implementation in the region, we propose that there should be better health education, establishment of hospital-based guidelines and multidisciplinary collaboration.
    Matched MeSH terms: Venous Thromboembolism/prevention & control*; Venous Thromboembolism/therapy*
  10. Ab Rahman N, Lim MT, Lee FY, Lee SC, Ramli A, Saharudin SN, et al.
    Vaccine, 2022 Jul 30;40(32):4394-4402.
    PMID: 35667917 DOI: 10.1016/j.vaccine.2022.05.075
    BACKGROUND: Rapid deployment of COVID-19 vaccines is challenging for safety surveillance, especially on adverse events of special interest (AESIs) that were not identified during the pre-licensure studies. This study evaluated the risk of hospitalisations for predefined diagnoses among the vaccinated population in Malaysia.

    METHODS: Hospital admissions for selected diagnoses between 1 February 2021 and 30 September 2021 were linked to the national COVID-19 immunisation register. We conducted self-controlled case-series study by identifying individuals who received COVID-19 vaccine and diagnosis of thrombocytopenia, venous thromboembolism, myocardial infarction, myocarditis/pericarditis, arrhythmia, stroke, Bell's Palsy, and convulsion/seizure. The incidence of events was assessed in risk period of 21 days postvaccination relative to the control period. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI) with adjustment for calendar period.

    RESULTS: There was no increase in the risk for myocarditis/pericarditis, Bell's Palsy, stroke, and myocardial infarction in the 21 days following either dose of BNT162b2, CoronaVac, and ChAdOx1 vaccines. A small increased risk of venous thromboembolism (IRR 1.24; 95% CI 1.02, 1.49), arrhythmia (IRR 1.16, 95% CI 1.07, 1.26), and convulsion/seizure (IRR 1.26; 95% CI 1.07, 1.48) was observed among BNT162b2 recipients. No association between CoronaVac vaccine was found with all events except arrhythmia (IRR 1.15; 95% CI 1.01, 1.30). ChAdOx1 vaccine was associated with an increased risk of thrombocytopenia (IRR 2.67; 95% CI 1.21, 5.89) and venous thromboembolism (IRR 2.22; 95% CI 1.17, 4.21).

    CONCLUSION: This study shows acceptable safety profiles of COVID-19 vaccines among recipients of BNT162b2, CoronaVac, and ChAdOx1 vaccines. This information can be used together with effectiveness data for risk-benefit analysis of the vaccination program. Further surveillance with more data is required to assess AESIs following COVID-19 vaccination in short- and long-term.

    Matched MeSH terms: Venous Thromboembolism/chemically induced; Venous Thromboembolism/epidemiology
  11. Liew NC, Chang YH, Choi G, Chu PH, Gao X, Gibbs H, et al.
    Int Angiol, 2012 Dec;31(6):501-16.
    PMID: 23222928
    Venous thromboembolism (VTE) prophylaxis is under-utilized in Asia because of the misconception that its incidence is lower in Asians as compared to the Caucasians. The available data on VTE in Asia is limited due to the lack of well-designed multicenter randomized controlled trials as well as non-standardized research designs, making data comparison difficult. Emerging data indicates that the VTE incidence is not low in Asia, and is comparable to that reported in the Western literature in some instances. There is also a trend towards increasing incidence of VTE, as demonstrated by a number of hospital-based studies in Asia. This could be attributed to lifestyle changes, ageing population, increasing awareness of VTE and wider availability of Duplex ultrasound. The risk of VTE in hospitalized patients remain the same in Asians and Caucasians, even though there may be factors that are inherent to patients in Asia that influence the slight variation in incidence. The utilization rate of VTE prophylaxis remains suboptimal in Asia. The Asian Venous Thrombosis Forum (AVTF) comprises participants from various countries such as China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand and experts from Australia and Europe. The forum evaluated the available data on VTE from the Asian region and formulated guidelines tailored to meet the needs of the region. We recommend that serious considerations are given to VTE prophylaxis especially in the at-risk group and a formal hospital policy be established to facilitate the implementation. On admission to the hospital, we recommend assessing the patients for both VTE and bleeding risk. We recommend mechanical prophylaxis for patients at increased risk of bleeding and utilizing it as an adjunctive measure in combination with pharmacological prophylaxis in patients with high risk of VTE. For patients undergoing general or gynecological surgery and with moderate risk for VTE, we recommend prophylaxis with one of the following: low dose unfractionated heparin (LDUH), low molecular weight heparin (LMWH), fondaparinux or intermittent pneumatic compression (IPC). For the same group of patients at high risk of VTE, we recommend pharmacological or combination of pharmacological and mechanical prophylaxis. For patients undergoing major orthopedic surgeries like total hip replacement, total knee replacement and proximal hip fracture surgery, we recommend using one of the following: LMWH, fondaparinux, rivaroxaban, apixaban, edoxaban, dabigatran, warfarin or aspirin with IPC. For patients admitted to the hospital with acute medical illness and has moderate risk of VTE, we recommend prophylaxis with LDUH, LMWH or Fondaparinux. For the same group at high risk of VTE, we recommend combination of pharmacological and mechanical prophylaxis.
    Matched MeSH terms: Venous Thromboembolism/diagnosis; Venous Thromboembolism/ethnology; Venous Thromboembolism/prevention & control*
  12. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al.
    Circulation, 2019 03 05;139(10):e56-e528.
    PMID: 30700139 DOI: 10.1161/CIR.0000000000000659
    Matched MeSH terms: Venous Thromboembolism/complications; Venous Thromboembolism/epidemiology; Venous Thromboembolism/pathology
  13. Huei TJ, Henry TCL, Ho CA, Mohamad Y
    J Clin Diagn Res, 2017 Jul;11(7):PD03-PD04.
    PMID: 28892968 DOI: 10.7860/JCDR/2017/27923.10192
    Venous thromboembolism in tuberculosis is not a well recognised entity. It is a less frequently reported complication of severe pulmonary tuberculosis. It is exceedingly rare when it complicates extrapulmonary tuberculosis. Here, we present a case of 22-year-old young female with abdominal tuberculosis complicated with reverse ileocecal intussusception, deep vein thrombosis and pulmonary embolism. An emergency vena cava filter was inserted prior to a limited right hemicolectomy. In this article, we discuss the rare association of venous thromboembolism with ileocecal tuberculosis.
    Matched MeSH terms: Venous Thromboembolism
  14. Liew NC, Lee L
    World J Surg, 2016 07;40(7):1788-9.
    PMID: 26464151 DOI: 10.1007/s00268-015-3273-4
    Matched MeSH terms: Venous Thromboembolism/drug therapy*
  15. Gan R, Rosoman NP, Henshaw DJE, Noble EP, Georgius P, Sommerfeld N
    Med Hypotheses, 2020 Nov;144:110024.
    PMID: 32758871 DOI: 10.1016/j.mehy.2020.110024
    SARS-CoV-2, the agent of COVID-19, shares a lineage with SARS-CoV-1, and a common fatal pulmonary profile but with striking differences in presentation, clinical course, and response to treatment. In contrast to SARS-CoV-1 (SARS), COVID-19 has presented as an often bi-phasic, multi-organ pathology, with a proclivity for severe disease in the elderly and those with hypertension, diabetes and cardiovascular disease. Whilst death is usually related to respiratory collapse, autopsy reveals multi-organ pathology. Chronic pulmonary disease is underrepresented in the group with severe COVID-19. A commonality of aberrant renin angiotensin system (RAS) is suggested in the at-risk group. The identification of angiotensin-converting-enzyme 2 (ACE2) as the receptor allowing viral entry to cells precipitated our interest in the role of ACE2 in COVID-19 pathogenesis. We propose that COVID-19 is a viral multisystem disease, with dominant vascular pathology, mediated by global reduction in ACE2 function, pronounced in disease conditions with RAS bias toward angiotensin-converting-enzyme (ACE) over ACE2. It is further complicated by organ specific pathology related to loss of ACE2 expressing cells particularly affecting the endothelium, alveolus, glomerulus and cardiac microvasculature. The possible upregulation in ACE2 receptor expression may predispose individuals with aberrant RAS status to higher viral load on infection and relatively more cell loss. Relative ACE2 deficiency leads to enhanced and protracted tissue, and vessel exposure to angiotensin II, characterised by vasoconstriction, enhanced thrombosis, cell proliferation and recruitment, increased tissue permeability, and cytokine production (including IL-6) resulting in inflammation. Additionally, there is a profound loss of the "protective" angiotensin (1-7), a vasodilator with anti-inflammatory, anti-thrombotic, antiproliferative, antifibrotic, anti-arrhythmic, and antioxidant activity. Our model predicts global vascular insult related to direct endothelial cell damage, vasoconstriction and thrombosis with a disease specific cytokine profile related to angiotensin II rather than "cytokine storm". Our proposed mechanism of lung injury provides an explanation for early hypoxia without reduction in lung compliance and suggests a need for revision of treatment protocols to address vasoconstriction, thromboprophylaxis, and to minimize additional small airways and alveolar trauma via ventilation choice. Our model predicts long term sequelae of scarring/fibrosis in vessels, lungs, renal and cardiac tissue with protracted illness in at-risk individuals. It is hoped that our model stimulates review of current diagnostic and therapeutic intervention protocols, particularly with respect to early anticoagulation, vasodilatation and revision of ventilatory support choices.
    Matched MeSH terms: Venous Thromboembolism/complications
  16. Lee YJ, Zakaria R, Manaf ZA, Mohamed Z, Lee YY
    Chin Med J (Engl), 2013;126(11):2049-53.
    PMID: 23769556
    There is increasing evidence that CT pulmonary arteriography and venography allow a better diagnostic yield for deep vein thrombosis (DVT) in suspected acute pulmonary embolism (PE). The aim was to investigate the value for using such an approach in a multiracial Asian population.
    Matched MeSH terms: Venous Thromboembolism/radiography*
  17. Hasan SS, Radford S, Kow CS, Zaidi STR
    J Thromb Thrombolysis, 2020 Nov;50(4):814-821.
    PMID: 32748122 DOI: 10.1007/s11239-020-02235-z
    Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19). We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units. Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic). The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model. Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation. We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis. All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses. Seven studies reported on the proportion of patients with the previous history of VTE (range 0-10%). The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20-43%). Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10-70%) and 27% (95% CI 17-40%) respectively. With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim.
    Matched MeSH terms: Venous Thromboembolism/blood; Venous Thromboembolism/epidemiology; Venous Thromboembolism/prevention & control*; Venous Thromboembolism/virology
  18. Pillai P, Joseph JP, Fadzillah NHM, Mahmod M
    J Stroke Cerebrovasc Dis, 2021 Jan;30(1):105427.
    PMID: 33137615 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105427
    COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to cause multisystemic damage. We undertook a systematic literature review and comprehensive analysis of a total of 55 articles on arterial and venous thromboembolism in COVID-19 and articles on previous pandemics with respect to thromboembolism and compared the similarities and differences between them. The presence of thrombosis in multiple organ systems points to thromboembolism being an integral component in the pathogenesis of this disease. Thromboembolism is likely to be the main player in the morbidity and mortality of COVID -19 in which the pulmonary system is most severely affected. We also hypothesize that D-dimer values could be used as an early marker for prognostication of disease as it has been seen to be raised even in the pre-symptomatic stage. This further strengthens the notion that thromboembolism prevention is necessary. We also examined literature on the neurovascular and cardiovascular systems, as the manifestation of thromboembolic phenomenon in these two systems varied, suggesting different pathophysiology of damage. Further research into the role of thromboembolism in COVID-19 is important to advance the understanding of the virus, its effects and to tailor treatment accordingly to prevent further casualties from this pandemic.
    Matched MeSH terms: Venous Thromboembolism/diagnosis; Venous Thromboembolism/etiology*; Venous Thromboembolism/mortality; Venous Thromboembolism/prevention & control
  19. Lee L, Liew NC, Gee T
    Int Angiol, 2012 Dec;31(6):526-33.
    PMID: 23222930
    This survey was conducted to determine the opinions and practices of peri-operative venous thromboembolism (VTE) prophylaxis among surgical and intensive care specialists in Asia.
    Matched MeSH terms: Venous Thromboembolism/etiology; Venous Thromboembolism/prevention & control*
  20. Kotirum S, Chongmelaxme B, Chaiyakunapruk N
    J Thromb Thrombolysis, 2017 Feb;43(2):252-262.
    PMID: 27704332 DOI: 10.1007/s11239-016-1433-5
    To analyze the cost-utility of oral dabigatran etexilate, enoxaparin sodium injection, and no intervention for venous thromboembolism (VTE) prophylaxis after total hip or knee replacement (THR/TKR) surgery among Thai patients. A cost-utility analysis using a decision tree model was conducted using societal and healthcare payers' perspectives to simulate relevant costs and health outcomes covering a 3-month time horizon. Costs were adjusted to year 2014. The willingness-to-pay threshold of THB 160,000 (USD 4926) was used. One-way sensitivity and probabilistic sensitivity analyses using a Monte Carlo simulation were performed. Compared with no VTE prophylaxis, dabigatran and enoxaparin after THR and TKR surgery incurred higher costs and increased quality adjusted life years (QALYs). However, their incremental cost-effectiveness ratios were high above the willingness to pay. Compared with enoxaparin, dabigatran for THR/TKR lowered VTE complications but increased bleeding cases; dabigatran was cost-saving by reducing the costs [by THB 3809.96 (USD 117.30) for THR] and producing more QALYs gained (by 0.00013 for THR). Dabigatran (vs. enoxaparin) had a 98 % likelihood of being cost effective. Dabigatran is cost-saving compared to enoxaparin for VTE prophylaxis after THR or TKR under the Thai context. However, both medications are not cost-effective compared to no thromboprophylaxis.
    Matched MeSH terms: Venous Thromboembolism/economics; Venous Thromboembolism/prevention & control*
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