ResearchPad - thromboembolism https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Risk of recurrent venous thromboembolism in patients with HIV infection: A nationwide cohort study]]> https://www.researchpad.co/article/elastic_article_14541 The HIV pandemic affects approximately 40 million people and causes significant morbidity, including a markedly increased risk of a venous thromboembolism (VTE).The recurrence risk of VTE in people living with HIV (PWH) is unknown, although this risk drives the anticoagulant therapy duration after a first VTE.Our study determined the recurrent VTE risk in PWH compared to uninfected controls.What did the researchers do and find?We performed an observational cohort study using data from the national ATHENA PWH cohort (2003–2015) in the Netherlands and the Dutch Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) cohort (1999–2009) of HIV-uninfected controls with a first VTE.The recurrent VTE incidence rate per 100 person-years of follow-up (PYFU) was higher in PWH (5.2) compared to controls (3.1) yielding a 1.70 hazard ratio (HR; 95% CI 1.23–2.36). Incidence rates were consistently higher for PWH in subgroups stratified by sex or the cause of the first VTE.PWH with lower cluster of differentiation 4 (CD4)+ T-cell counts at their first VTE had fewer recurrent events, which was driven by PWH experiencing a better CD4+ T-cell recovery on HIV treatment prior to anticoagulant discontinuation.What do these findings mean?The risk of recurrent VTE is apparently increased in PWH but is ameliorated with better immune reconstitution.HIV-associated immunodeficiency reflects a reversible risk factor for VTE specific to PWH and is of relevance for decisions on anticoagulant therapy duration. ]]> <![CDATA[Low relative muscle volume: Correlation with prevalence of venous thromboembolism following total knee arthroplasty]]> https://www.researchpad.co/article/5c8823ced5eed0c484639081

Background

There have been many efforts to find modifiable risk factors for venous thromboembolism (VTE) in the perioperative period of total knee arthroplasty (TKA), while no study has investigated the relationship between the muscle mass and deep vein thrombosis (DVT) or pulmonary embolism frequency following TKA. This study aimed to evaluate the relationship between muscle volume and the prevalence of symptomatic and radiologically confirmed venous thromboembolism (VTE) after total knee arthroplasty (TKA).

Methods

A total of 261 consecutive patients who underwent primary TKA between 2013 and 2015 were enrolled. Computed tomographic venography with pulmonary angiography (CTVPA) was performed between the 5th and 7th postoperative days to assess the presence of VTE. Four parameters of muscle volume at three levels were evaluated on CTVPA: (i) the cross-sectional area of all skeletal muscles (skeletal muscle index) and total psoas area at the level of the third lumbar vertebrae; (ii) the vastus lateralis muscle at the thigh level; and (iii) the posterior crural muscle at the lower leg level. The relationship between the muscle volume at each level and the prevalence of VTE after TKA was evaluated with multivariate adjusted logistic regression models.

Results

The CTVPA scan showed no proximal DVT, and all thrombi were located in muscular, peroneal, and posterior tibial veins. In unilateral TKA, patients with lower muscle volume of the vastus lateralis at the thigh level in the nonoperated limb had significantly higher prevalence of distal DVT in the operated limb (adjusted OR: 2.97 at subclinical DVT revealed by CTVPA and adjusted OR: 2.68 at symptomatic DVT). This finding was also discovered in patients who underwent simultaneous bilateral TKA (adjusted OR: 1.73–2.97 at subclinical DVT and adjusted OR:1.76–1.86 at symptomatic DVT).

Conclusions

The relative muscle volume of the vastus lateralis at the thigh level was negatively associated with the prevalence of symptomatic and radiologically confirmed DVT, suggesting that low thigh muscle mass is an independent risk factor for VTE in the postoperative period of TKA.

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<![CDATA[Comparing the delay with different anticoagulants before elective electrical cardioversion for atrial fibrillation/flutter]]> https://www.researchpad.co/article/5c37b7a2d5eed0c484490753

Aims

To assess the impact of the introduction of direct oral anticoagulants upon the outcomes from elective electrical cardioversion for atrial fibrillation.

Methods

This is a retrospective comparison of delay to elective cardioversion with different anticoagulants. The data was gathered from a large regional hospital from January 2013 to September 2017. There were 3 measured outcomes: 1) the time in weeks from referral to the date of attempted electrical cardioversion; 2) the proportion of patients who were successfully cardioverted; and 3) the proportion of patients who remained in sinus rhythm by the 12 week follow-up. Time-to-cardioversion was non-parametrically distributed so was analysed with Kruskal-Wallis testing and Mann-Whitney-U testing. Maintenance of sinus rhythm was analysed using z-testing.

Results

1,374 patients were submitted to cardioversion. The referrals for cardioversion were either from primary care or from cardiologists. At the time of cardioversion, 789 cases were anticoagulated on warfarin (W), 215 on apixaban (A) and 370 on rivaroxaban (R). All 3 cohorts were initially compared independently using Kruskal-Wallis testing. This demonstrated a significant difference in the delay (measured in weeks) between the A and W group (A = 7, W = 9, P<0.00001); the R and W group (R = 7, W = 9, P<0.00001) and no difference between R and A (A = 7, R = 7, P = 0.92). As there was no difference between the A and R groups, they were combined to form the AR group. The AR group was compared to the W group using Mann-Whitney-U testing which demonstrated a significant delay between the groups (AR = 7, W = 9, P<0.00001). Excluding patients with prior or unknown attempts of cardioversion (n = 791), the W patients (n = 152) were less successful in achieving sinus rhythm at cardioversion than the AR (n = 431) group (W = 95% vs AR = 99% P = 0.04). However at 12 weeks, incidence of sinus rhythm was significantly different (W = 40% vs AR = 49% P = 0.049). These groups were compared by z testing. At 12 weeks' follow-up there was no statistical difference in rate of adverse consequences between the AR group and the W group, but the rate of adverse consequences was too low to draw further conclusions.

Conclusion

DOACs appear to significantly shorten the latency between the decision to cardiovert and the cardioversion procedure by at least 2 weeks compared to warfarin in a real-world setting. In this study, patients who had not previously been cardioverted who were anticoagulated with warfarin had a significantly lower probability of conversion to sinus rhythm and a significantly lower probability to remain in sinus rhythm at the 12 week follow-up compared to the combined apixaban and rivaroxaban group.

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<![CDATA[The efficacy and safety of pharmacologic thromboprophylaxis following caesarean section: A systematic review and meta-analysis]]> https://www.researchpad.co/article/5c181390d5eed0c4847753ff

Objective

Our purpose is to evaluate the efficacy and safety of pharmacologic thromboprophylaxis following caesarean section (CS).

Methods

We searched PubMed, Embase, and the Cochrane Library. Then the systematic review was performed by analysing studies that met the eligibility criteria.

Results

Seven studies with 1243 participants were included, including 6 RCTs and 1 prospective cohort. Results from the meta-analysis showed that low molecular weight heparin (LMWH) was associated with no obvious decrease in the risk of thrombus compared with UHF and negative control. However, LMWH was observed to be associated with a definite increase in the risk of bleeding or haematomas in comparison to negative control (RR: 8.47, CI: 1.52–47.11).

Conclusion

According to current evidences, the efficacy of pharmacologic thromboprophylaxis which increases the risk of bleeding or hematomas remains controversial.

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<![CDATA[The incidence of left atrial appendage thrombi on transesophageal echocardiography after pretreatment with apixaban for cardioversion in the real-world practice]]> https://www.researchpad.co/article/5c141efdd5eed0c484d2925b

The risk of thromboembolisms during the post-cardioversion period is high. For patients with persistent atrial fibrillation (AF), anticoagulation with warfarin (INR 2.0~3.0) is recommended for at least three weeks prior and four weeks after cardioversion. We aimed to evaluate the efficacy of apixaban in preventing thromboembolic events during post-cardioversion. We enrolled 127 consecutive persistent AF patients (83 persistent, 44 longstanding persistent AF), scheduled to undergo cardioversion and were pretreated with apixaban. All patients underwent transesophageal echocardiography (TEE) to rule out thrombi in the left atrium (LA) or LA appendage (LAA) after anticoagulation with apixaban. The median duration of anticoagulation before the TEE was 37 (interquartile range [IQR] 34, 50) days. There were 7 patients (5.5%) with visible thrombi in the LAA. A spontaneous echo contrast was noted in 24 (18.9%) patients. Cardioversion was attempted in 117 patients, and they were prescribed amiodarone before the elective DC cardioversion. Sinus rhythm was achieved in 37 patients (31.6%) by amiodarone itself. DC cardioversion was attempted in 80 patients and was successful in 73 (91.3%). None of the cardioverted patients had any thromboembolic events within one month. Transient ischemic attacks were observed in one patient during a median follow up period of 202 days (IQR 143, 294). In conclusion, apixaban could be used as an anticoagulant for patients scheduled for cardioversion. However, the incidence of thrombi was not negligible. TEE or other imaging modalities should be considered before cardioversion or other invasive procedures.

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<![CDATA[Rapid and substantial increases in anticoagulant use and expenditure in Australia following the introduction of new types of oral anticoagulants]]> https://www.researchpad.co/article/5c12cf19d5eed0c484913ef6

Objectives

To quantify changes in anticoagulant use in Australia since the introduction of Non-vitamin K antagonist anticoagulants (NOACs) and to estimate government expenditure.

Design

Interrupted-time-series analysis quantifying anticoagulant dispensing, before and after first Pharmaceutical Benefits Scheme (PBS) NOAC listing in August 2009 for venous thromboembolism prevention; and expanded listing for stroke prevention in non-valvular atrial fibrillation (AF) in August 2013, up to June 2016. Estimated government expenditure on PBS-listed anticoagulants.

Setting and participants

PBS dispensing in 10% random sample of Australians, restricted to continuous concessional beneficiaries dispensed oral anticoagulants from July 2005 to June 2016. Total PBS anticoagulant expenditure was calculated using Medicare Australia statistics.

Main outcome measures

Monthly dispensing and initiation of oral anticoagulants (warfarin, rivaroxaban, dabigatran or apixaban). Annual PBS anticoagulant expenditure.

Results

An estimated 149,180 concessional beneficiaries were dispensed anticoagulants (100% warfarin) during July 2005. This increased to 292,550 during June 2016, of whom 47.0%, 27.1%, 18.7% and 7.2% were dispensed warfarin, rivaroxaban, apixaban and dabigatran, respectively. Of 16,500 initiated on anticoagulants in June 2016, 24.3%, 38.2%, 30.0% and 7.5% were initiated on warfarin, rivaroxaban, apixaban, and dabigatran, respectively. Compared to July 2005-July 2013, from August 2013-June 2016, dispensings for all anticoagulants increased by 2,303 dispensings/month (p<0.001, 95%CI = [1,229 3,376]); warfarin dispensing decreased by 1,803 dispensings/month (p<0.001, 95%CI = [–2,606, –1,000]). Total PBS anticoagulant expenditure was $19.5 million (97.0% concessional) in 2008/09, of which 100% was warfarin and $203.3 million (86.2% concessional) in 2015/16, of which 11.2% was warfarin.

Conclusions

The introduction of the NOACs led to substantial increases in anticoagulant use and expenditure in Australia.

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<![CDATA[The association between major complications of immobility during hospitalization and quality of life among bedridden patients: A 3 month prospective multi-center study]]> https://www.researchpad.co/article/5bca48dd40307c0516656415

Purpose

To describe the association between major complications of immobility (pressure ulcer, pneumonia, deep vein thrombosis and urinary tract infection) during hospitalization and the patients’ health-related quality of life after discharge.

Methods

The data were obtained from a multi-center study conducted in 2015. Complications of immobility during hospitalization was measured by case report form and quality of life after discharge was measured using the EQ-5D scale by telephone interview. Multilevel mixed-effects models were used to explore the association of complications and responses in the EQ-5D dimensions after controlling for important covariates.

Results

Among the 20,515 bedridden patients, 2,601(12.72%) patients experienced at least one of the major complications of immobility during hospitalization, including pressure ulcer (527, 2.57%), deep vein thrombosis (343, 1.67%), pneumonia (1647, 8.16%), and urinary tract infection (265, 1.29%). Patients with any of the four complications during hospitalization reported more problems in all EQ-5D dimensions except for pain/discomfort, and had lower mean EQ-VAS scores than those without any complications. The four complications all showed significant associations with the proportion of reported problems in certain dimensions after adjustment for confounding variables.

Conclusions

Major complications of immobility were significantly associated with reduced health related quality of life. Prevention of complications is critical to reduce the burden of decreased quality of life for bedridden patients.

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<![CDATA[Effects of thrombolysis on outcomes of patients with deep venous thrombosis: An updated meta-analysis]]> https://www.researchpad.co/article/5bb3df3440307c54ff8ce8ef

Background

Small randomized controlled studies and meta-analyses have shown that thrombolysis, especially catheter-directed thrombolysis, can reduce the incidence of post-thrombotic syndrome (PTS). However, the recent ATTRACT trial did not demonstrate the same effects. Given this confusing situation, we performed an updated meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of thrombolysis, especially catheter-directed thrombolysis, on the outcomes of deep venous thrombosis (DVT).

Methods

We searched PubMed, Embase, and the Cochrane Library for relevant studies comparing thrombolysis in combination with anticoagulation and with anticoagulation alone. The primary endpoint was PTS during the longest follow-up period. The safety endpoint was the incidence of major bleeding events. We also evaluated the outcomes of catheter-directed thrombolysis as a subgroup analysis.

Results

Six RCTs, including 1418 patients with DVT, were included in our meta-analysis. Thrombolysis in combination with anticoagulation did not reduce PTS (RR: 0.90, [0.80–1.01], P = 0.19) and increased major bleeding (RR: 2.07, [1.12–3.81], P = 0.02). However, trial sequential analysis (TSA) showed that more patients are needed to support the conclusion that thrombolysis in combination with anticoagulation increased major bleeding. Catheter-directed thrombolysis did not reduce the incidence of PTS (RR: 0.88, [0.68–1.13], P = 0.31) and did increase the incidence of major bleeding events (RR: 1.89, [1.00–3.59], P = 0.05).

Conclusion

Thrombolysis, including catheter-directed thrombolysis, did not reduce the incidence of PTS and increased the incidence of major bleeding. However, the results were not supported by TSA and sensitivity analysis, so more relevant studies are needed.

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<![CDATA[Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial]]> https://www.researchpad.co/article/5c032e02d5eed0c4844f8af1

Introduction

There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial.

Methods

We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression.

Results

In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant.

Conclusions

In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone.

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<![CDATA[Protein C Mutation (A267T) Results in ER Retention and Unfolded Protein Response Activation]]> https://www.researchpad.co/article/5989da2cab0ee8fa60b82a74

Background

Protein C (PC) deficiency is associated with a high risk of venous thrombosis. Recently, we identified the PC-A267T mutation in a patient with PC deficiency and revealed by in vitro studies decreased intracellular and secreted levels of the mutant. The aim of the present study was to characterize the underlying mechanism(s).

Methodology/Principal Findings

CHO-K1 cells stably expressing the wild-type (PC-wt) or the PC mutant were generated. In order to examine whether the PC mutant was subjected to increased intracellular degradation, the cells were treated with several inhibitors of various degradation pathways and pulse-chase experiments were performed. Protein-chaperone complexes were analyzed by treating the cells with a cross-linker followed by Western blotting (WB). Expression levels of the immunoglobulin-binding protein (BiP) and the phosphorylated eukaryotic initiation factor 2α (P-eIF2α), both common ER stress markers, were determined by WB to examine if the mutation induced ER stress and unfolded protein response (UPR) activation. We found no major differences in the intracellular degradation between the PC variants. The PC mutant was retained in the endoplasmic reticulum (ER) and had increased association with the Grp-94 and calreticulin chaperones. Retention of the PC-A267T in ER resulted in UPR activation demonstrated by increased expression levels of the ER stress markers BiP and P-eIF2α and caused also increased apoptotic activity in CHO-K1 cells as evidenced by elevated levels of DNA fragmentation.

Conclusions/Significance

The reduced intracellular level and impaired secretion of the PC mutant were due to retention in ER. In contrast to other PC mutations, retention of the PC-A267T in ER resulted in minor increased proteasomal degradation, rather it induced ER stress, UPR activation and apoptosis.

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<![CDATA[Caution in Interpreting Results from Imputation Analysis When Linkage Disequilibrium Extends over a Large Distance: A Case Study on Venous Thrombosis]]> https://www.researchpad.co/article/5989db21ab0ee8fa60bcf400

By applying an imputation strategy based on the 1000 Genomes project to two genome-wide association studies (GWAS), we detected a susceptibility locus for venous thrombosis on chromosome 11p11.2 that was missed by previous GWAS analyses that had been conducted on the same datasets. A comprehensive linkage disequilibrium and haplotype analysis of the whole locus where twelve SNPs exhibited association p-values lower than 2.23 10−11 and the use of independent case-control samples demonstrated that the culprit variant was a rare variant located ∼1 Mb away from the original hits, not tagged by current genome-wide genotyping arrays and even not well imputed in the original GWAS samples. This variant was in fact the rs1799963, also known as the FII G20210A prothrombin mutation. This work may be of major interest not only for its scientific impact but also for its methodological findings.

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<![CDATA[D-Dimer Use and Pulmonary Embolism Diagnosis in Emergency Units: Why Is There Such a Difference in Pulmonary Embolism Prevalence between the United States of America and Countries Outside USA?]]> https://www.researchpad.co/article/5989dae7ab0ee8fa60bbdb85

Objective

Although diagnostic guidelines are similar, there is a huge difference in pulmonary embolism (PE) prevalence between the United States of America (US) and countries outside the USA (OUS) in the emergency care setting. In this study, we prospectively analyze patients’ characteristics and differences in clinical care that may influence PE prevalence in different countries.

Methods

An international multicenter prospective diagnostic study was conducted in a standard-of-care setting. Consecutive outpatients presenting to the emergency unit and suspected for PE were managed using the Wells score, STA-Liatest® D-Dimers and imaging.

Results

The prevalence of PE in the study was 7.9% in low and moderate risk patients. Among the 1060 patients with low or moderate pre-test probability (PTP), PE prevalence was four times higher in OUS (10.7%) than in the US (2.5%) (P < 0.0001). The mean number of imaging procedures performed for one new PE diagnosis was 3.3 in OUS vs 17 in the US (P < 0.001). Stopping investigation in the case of negative D-dimers (DD combined) with low/moderate PTP was more frequent in OUS (92.7%) than in the US (75.7%) (P < 0.01). Moreover, the use of imaging was much higher in the US (44.4% vs 19.2% in OUS) in the case of moderate PTP combined with negative DD.

Conclusion

Differences between US and OUS PE prevalence in emergency setting might be explained by differences in patients' characteristics and mostly in care patterns. US physicians performed computed tomographic pulmonary angiography more often than in Europe in cases of low/moderate PTP combined with negative DD.

Trial Registration

ClinicalTrials.gov NCT01221805

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<![CDATA[Patient Preferences for Receiving Education on Venous Thromboembolism Prevention – A Survey of Stakeholder Organizations]]> https://www.researchpad.co/article/5989da4aab0ee8fa60b8c883

Importance

Venous thromboembolism (VTE) is a major cause of morbidity and mortality among hospitalized patients and is largely preventable. Strategies to decrease the burden of VTE have focused on improving clinicians’ prescribing of prophylaxis with relatively less emphasis on patient education.

Objective

To develop a patient-centered approach to education of patients and their families on VTE: including importance, risk factors, and benefit/harm of VTE prophylaxis in hospital settings.

Design, Setting and Participants

The objective of this study was to develop a patient-centered approach to education of patients and their families on VTE: including importance, risk factors, and benefit/harm of VTE prophylaxis in hospital settings. We implemented a three-phase, web-based survey (SurveyMonkey) between March 2014 and September 2014 and analyzed survey data using descriptive statistics. Four hundred twenty one members of several national stakeholder organizations and a single local patient and family advisory board were invited to participate via email. We assessed participants’ preferences for VTE education topics and methods of delivery.

Participants wanted to learn about VTE symptoms, risk factors, prevention, and complications in a context that emphasized harm. Although participants were willing to learn using a variety of methods, most preferred to receive education in the context of a doctor-patient encounter. The next most common preferences were for video and paper educational materials.

Conclusions

Patients want to learn about the harm associated with VTE through a variety of methods. Efforts to improve VTE prophylaxis and decrease preventable harm from VTE should target the entire continuum of care and a variety of stakeholders including patients and their families.

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<![CDATA[Dabigatran for the Treatment and Secondary Prevention of Venous Thromboembolism; A Cost-Effectiveness Analysis for the Netherlands]]> https://www.researchpad.co/article/5989da25ab0ee8fa60b806ce

Background

Dabigatran was proven to have similar effect on the prevention of recurrence of venous thromboembolism (VTE) and a lower risk of bleeding compared to vitamin K antagonists (VKA). The aim of this study is to assess the cost-effectiveness (CE) of dabigatran for the treatment and secondary prevention in patients with VTE compared to VKAs in the Dutch setting.

Methods

Previously published Markov model was modified and updated to assess the CE of dabigatran and VKAs for the treatment and secondary prevention in patients with VTE from a societal perspective in the base-case analysis. The model was populated with efficacy and safety data from major dabigatran trials (i.e. RE-COVER, RECOVER II, RE-MEDY and RE-SONATE), Dutch specific costs, and utilities derived from dabigatran trials or other published literature. Univariate, probabilistic sensitivity and a number of scenario analyses evaluating various decision-analytic settings (e.g. the perspective of analysis, use of anticoagulants only for treatment or only for secondary prevention, or comparison to no treatment) were tested on the incremental cost-effectiveness ratio (ICER).

Results

In the base-case scenario, patients on dabigatran gained an additional 0.034 quality adjusted life year (QALY) while saving €1,598. Results of univariate sensitivity analysis were quite robust. The probability that dabigatran is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 98.1%. From the perspective of healthcare provider, extended anticoagulation with dabigatran compared to VKAs was estimated at €2,158 per QALY gained. The ICER for anticoagulation versus no treatment in patients with equipoise risk of recurrent VTE was estimated at €33,379 per QALY gained. Other scenarios showed dabigatran was cost-saving.

Conclusion

From a societal perspective, dabigatran is likely to be a cost-effective or even cost-saving strategy for treatment and secondary prevention of VTE compared to VKAs in the Netherlands.

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<![CDATA[Asthma–Chronic Obstructive Pulmonary Disease Overlap Syndrome Associated with Risk of Pulmonary Embolism ]]> https://www.researchpad.co/article/5989da1aab0ee8fa60b7ca9b

Purpose

We conducted a cohort study to clarify this relationship between asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and pulmonary embolism (PE).

Methods

From the National Health Insurance Research Database of Taiwan, we identified patients who had a diagnosis of asthma and a diagnosis of COPD (defined as ACOS) and concurrent treatment between January 1999 and December 2009 (ACOS cohort: n = 14,150; non-ACOS cohort: n = 55,876). Cox proportional hazards regression analysis was performed to determine the adjusted hazard ratios (aHRs) for PE of the ACOS cohort compared with the non-ACOS cohort.

Results

Comparing the ACOS cohort with the non-ACOS cohort, the aHR of PE was 2.08 (95% confidence intervals [CIs]: 1.56–2.76). The risk of PE was higher in ACOS cohort than non-ACOS cohort, regardless of age, sex, comorbidity, inhaled corticosteroids (ICSs) and oral steroids (OSs) used. For ages ranging from 20 to 65 years, the aHR of PE was 2.53 (95% CI: 1.44–4.44) in the ACOS cohort. ACOS patients using ICSs (aHR: 1.97, 95% CI: 1.29–3.01) or OSs (aHR: 1.97, 95% CI: 1.46–2.65), the risk of PE was higher than in the non-ACOS cohort. The risk of PE increased with the number of outpatient visits and hospitalizations necessitated, ranging from 2.32 (95% CI: 1.54–3.52) in patients having 3–9 visits to 4.20 (95% CI: 2.74–6.44) for those having >9 visits.

Conclusions

ACOS is associated with increased risk of PE, particularly patients with a high frequency of AE—even in young adults or people without comorbidities.

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<![CDATA[High Frequency of Pulmonary Hypertension-Causing Gene Mutation in Chinese Patients with Chronic Thromboembolic Pulmonary Hypertension]]> https://www.researchpad.co/article/5989d9f4ab0ee8fa60b6fb70

The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. Histopathologic studies revealed that pulmonary vasculature lesions similar to idiopathic pulmonary arterial hypertension (PAH) existed in CTEPH patients as well. It’s well-known that genetic predisposition plays an important role in the mechanism of PAH. So we hypothesized that PAH-causing gene mutation might exist in some CTEPH patients and act as a background to facilitate the development of CTEPH. In this study, we analyzed 7 PAH-causing genes including BMPR2, ACVRL1, ENG, SMAD9, CAV1, KCNK3, and CBLN2 in 49 CTEPH patients and 17 patients recovered from pulmonary embolism (PE) but without pulmonary hypertension(PH). The results showed that the nonsynonymous mutation rate in CTEPH patients is significantly higher than that in PE without PH patients (25 out of 49 (51%) CTEPH patients vs. 3 out of 17 PE without PH patients (18%); p = 0.022). Four CTEPH patients had the same point mutation in ACVRL1 exon 10 (c.1450C>G), a mutation approved to be associated with PH in a previous study. In addition, we identified two CTEPH associated SNPs (rs3739817 and rs55805125). Our results suggest that PAH-causing gene mutation might play an important role in the development of CTEPH.

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<![CDATA[CT Pulmonary Angiography at Reduced Radiation Exposure and Contrast Material Volume Using Iterative Model Reconstruction and iDose4 Technique in Comparison to FBP]]> https://www.researchpad.co/article/5989da1bab0ee8fa60b7cde8

Purpose

To assess image quality of CT pulmonary angiography (CTPA) at reduced radiation exposure (RD-CTPA) and contrast medium (CM) volume using two different iterative reconstruction (IR) algorithms (iDose4 and iterative model reconstruction (IMR)) in comparison to filtered back projection (FBP).

Materials and Methods

52 patients (body weight < 100 kg, mean BMI: 23.9) with suspected pulmonary embolism (PE) underwent RD-CTPA (tube voltage: 80 kV; mean CTDIvol: 1.9 mGy) using 40 ml CM. Data were reconstructed using FBP and two different IR algorithms (iDose4 and IMR). Subjective and objective image quality and conspicuity of PE were assessed in central, segmental, and subsegmental arteries.

Results

Noise reduction of 55% was achieved with iDose4 and of 85% with IMR compared to FBP. Contrast-to-noise ratio significantly increased with iDose4 and IMR compared to FBP (p<0.05). Subjective image quality was rated significantly higher at IMR reconstructions in comparison to iDose4 and FBP. Conspicuity of central and segmental PE significantly improved with the use of IMR. In subsegmental arteries, iDose4 was superior to IMR.

Conclusions

CTPA at reduced radiation exposure and contrast medium volume is feasible with the use of IMR, which provides improved image quality and conspicuity of pulmonary embolism in central and segmental arteries.

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<![CDATA[Measurement of Warfarin in the Oral Fluid of Patients Undergoing Anticoagulant Oral Therapy]]> https://www.researchpad.co/article/5989dab3ab0ee8fa60bac122

Background

Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls.

Methodology

A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm.

Findings

The method was free from interference and matrix effect, linear in the range 0.2–100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8–7.6 ng/mL). Dosage was not correlated to INR (r = −0.03, p = 0.85) but positively correlated to warfarin concentration in the oral fluid (r = 0.39, p = 0.006). The correlation between warfarin concentration and pH in the oral fluid (r = 0.37, p = 0.009) confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ≥7.2 (r = 0.84, p = 0.004).

Conclusions

Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters.

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<![CDATA[Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study]]> https://www.researchpad.co/article/5989da30ab0ee8fa60b84324

Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes.

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<![CDATA[Benchmark for Time in Therapeutic Range in Venous Thromboembolism: A Systematic Review and Meta-Analysis]]> https://www.researchpad.co/article/5989db25ab0ee8fa60bd02f1

Introduction

The percentage of time within the target INR range 2.0 to 3.0 (TTR) in patients treated with vitamin K antagonists varies considerably among efficacy-studies of novel anticoagulants. In order to properly asses the quality of anticoagulant control in upcoming cost-effectiveness studies and real life registries this systematic review reports a benchmark of TTR for different treatment durations in patients with venous thromboembolism and discusses ways to calculate TTR.

Methods

Medline and Embase were searched for studies published between January 1990 and May 2012. Randomized controlled trials and cohort studies reporting the TTR in patients with objectively confirmed venous thromboembolism treated with vitamin K antagonists (VKA) were eligible. Duplicate reports, studies only reporting INR during initial treatment or with VKA treatment less than 3 months were excluded. Three authors assessed trials for inclusion and extracted data independently. Discrepancies were resolved by discussion between the reviewers. A meta-analysis was performed by calculating a weighted mean, based on the number of participants in each included study, for each time-period in which the TTR was measured since the confirmation of the diagnosis of VTE.

Results

Forty studies were included (26064 patients). The weighted means of TTR were 54.0% in the first month since the start of treatment, 55.6% in months 1 to 3, 60.0% in months 2 to 3, 60.0% in the months1 to 6+ and 75.2% in months 4 to 12+. Five studies reported TTR in classes. The INR in these studies was ≥67% of time in therapeutic range in 72.0% of the patients.

Conclusion

Reported quality of VKA treatment is highly dependent on the time-period since the start of treatment, with TTR ranging from approximately 56% in studies including the 1st month to 75% in studies excluding the first 3 months.

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