Sexual quality of life of adolescents and young adult breast cancer survivors.

BACKGROUND: With increasing survival rates of adolescents and young adults (AYAs) with breast cancer, health-related quality of life (HRQoL) becomes more important. An important aspect of HRQoL is sexual QoL. This study examined long-term sexual QoL of AYA breast cancer survivors, compared sexual QoL scores with that of other AYA cancer survivors, and identified factors associated with long-term sexual QoL of AYA breast cancer survivors. MATERIALS AND METHODS: Data of the SURVAYA study were utilized for secondary analyses. Sexual QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire (EORTC QLQ-SURV100). Descriptive statistics were used to describe sexual QoL of AYA cancer survivors. Linear regression models were constructed to examine the effect of cancer type on sexual QoL and to identify factors associated with sexual QoL. RESULTS: Of the 4010 AYA cancer survivors, 944 had breast cancer. Mean sexual QoL scores of AYA breast cancer survivors ranged from 34.5 to 60.0 for functional domains and from 25.2 to 41.5 for symptom-orientated domains. AYA breast cancer survivors reported significantly lower sexual QoL compared to AYA survivors of other cancer types on all domains. Age, time since diagnosis, relationship status, educational level, chemotherapy, hormonal therapy, breast surgery, body image, and coping were associated with sexual QoL of AYA breast cancer survivors. CONCLUSIONS: AYA breast cancer survivors experience decreased sexual QoL in the long term (5-20 years) after diagnosis and worse score compared to AYA survivors of other cancer types, indicating a clear need to invest in supportive care interventions for those at risk, to enhance sexual well-being.

Venous and arterial thromboembolism after colorectal cancer in the Netherlands: Incidence, predictors, and prognosis.

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 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.

Real-World Metastatic Renal Cell Carcinoma Treatment Patterns and Clinical Outcomes in The Netherlands.

The number of treatment options for patients with metastatic renal cell carcinoma (mRCC) has significantly grown in the last 15 years. Although randomized controlled trials are fundamental in investigating mRCC treatment efficacy, their external validity can be limited. Therefore, the efficacy of the different treatment options should also be evaluated in clinical practice. We performed a chart review of electronic health records using text mining software to study the current treatment patterns and outcomes. mRCC patients from two large hospitals in the Netherlands, starting treatment between January 2015 and May 2020, were included. Data were collected from electronic health records using a validated text mining tool. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method. Most frequent first-line treatments were pazopanib (n = 70), sunitinib (n = 34), and nivolumab with ipilimumab (n = 28). The overall median PFS values for first-line treatment were 15.7 months (95% confidence interval [95%CI], 8.8-20.7), 16.3 months (95%CI, 9.3-not estimable [NE]) for pazopanib, and 6.9 months (95% CI, 4.4-NE) for sunitinib. The overall median OS values were 33.4 months (95%CI, 28.1-50.9 months), 39.3 months (95%CI, 29.5-NE) for pazopanib, and 28.1 months (95%CI, 7.0-NE) for sunitinib. For nivolumab with ipilimumab, median PFS and median OS were not reached. Of the patients who finished first- and second-line treatments, 64 and 62% received follow-up treatments, respectively. With most patients starting on pazopanib and sunitinib, these real-world treatment outcomes were most likely better than in pivotal trials, which may be due to extensive follow-up treatments.

Lack of diagnostic utility of the ECG-derived ventricular gradient in patients with suspected acute pulmonary embolism.

INTRODUCTION: The YEARS algorithm was successfully developed to reduce the number of computed tomography pulmonary angiography (CTPA) investigations in the diagnostic management of patients with suspected pulmonary embolism (PE), although half of patients still needed to be referred for CTPA. We hypothesized that ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO), an easy to use tool for detecting PE-induced pulmonary hypertension (PH), may further improve the efficiency of the YEARS algorithm. METHODS: In this post-hoc analysis of the Years study, ECGs of 479 patients with suspected PE managed according to the YEARS algorithm were available for analysis. The diagnostic performance of VG-RVPO was assessed and likelihood ratios were calculated. RESULTS: PE was diagnosed in 88 patients (18%). In patients with confirmed PE, 34% had an abnormal VG-RVPO versus 24% of those without PE (odds ratio 1.6; 95%CI 0.94-2.6). The mean VG-RVPO was -22 ± 13 and did not differ between the two patient groups (-22 versus -20; mean difference - 2, 95% CI -4.8 to 1.3). The sensitivity of VG-RVPO for PE was 24% (95%CI 34-45), the specificity 76% (95%CI 71-80) and the c-statistic 0.45 (95% CI 0.38-0.51). When combined with the YEARS algorithm, the likelihood ratios of VG-RVPO remained close to 1.0. Ruling out PE in patients with an indication for CTPA based on a normal VG-RVPO would have resulted in 58 missed cases. CONCLUSIONS: The VG-RVPO has no diagnostic value for suspected acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. CONDENSED ABSTRACT: This post-hoc analysis of the YEARS study failed to demonstrate incremental diagnostic value of VG-RVPO for acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. Nevertheless, the role of VG-RVPO recorded on admission could potentially be valuable in the risk stratification of PE during hospitalization, although this remains to be studied.

Combination of Pulmonary Embolism Rule-out Criteria and YEARS Algorithm in a European Cohort of Patients with Suspected Pulmonary Embolism.

BACKGROUND: Both the YEARS algorithm and the pulmonary embolism (PE) rule-out criteria (PERC) were created to exclude PE with limited diagnostic tests. A diagnostic strategy combining both scores might save additional computed tomography pulmonary angiography (CTPA) scans, but they have never been evaluated in conjunction. AIM: The aim of this study was to determine the safety and efficiency of combining YEARS and PERC in a single diagnostic strategy for suspected PE. METHODS: The PERC rule was assessed in 1,316 consecutive patients with suspected PE who were managed according to YEARS. We calculated the absolute difference (with 95% confidence interval [CI]) in failure rate and the number of 'saved' CTPAs for the scenario that PE would have been ruled out without CTPA in the absence of all PERC items. RESULTS: Using the YEARS algorithm, PE was diagnosed in 189 patients (14%), 680 patients (52%) were managed without CTPA and the 3-month rate of venous thromboembolism in patients in whom PE was ruled out was 0.44% (95% CI: 0.19-1.0). Only 6 of 154 patients (3.9%; 95% CI: 1.4-8.2) with no YEARS items who were referred for CTPA would have been PERC negative, of whom none were diagnosed with PE at baseline or during follow-up (0%; 95% CI: 0-64). Applying PERC before YEARS in all patients would have led to a failure rate of 1.42% (95% CI: 0.87-2.3%), 0.98% (95% CI: 0.17-1.9) more than shown in patients managed by YEARS. CONCLUSION: Combining YEARS with PERC would have yielded only a modest improvement of efficiency in patients without a YEARS item and an unacceptable failure rate in patients with ≥ 1 YEARS item.

The YEARS algorithm for suspected pulmonary embolism: shorter visit time and reduced costs at the emergency department.

Essentials The YEARS algorithm was designed to simplify the diagnostic workup of suspected pulmonary embolism. We compared emergency ward turnaround time of YEARS and the conventional algorithm. YEARS was associated with a significantly shorter emergency department visit time of ˜60 minutes. Treatment of pulmonary embolism was initiated 53 minutes earlier with the YEARS algorithm SUMMARY: Background Recently, the safety of the YEARS algorithm, designed to simplify the diagnostic work-up of pulmonary embolism (PE), was demonstrated. We hypothesize that by design, YEARS would be associated with a shorter diagnostic emergency department (ED) visit time due to simultaneous assessment of pre-test probability and D-dimer level and reduction in number of CT scans. Aim To investigate whether implementation of the YEARS diagnostic algorithm is associated with a shorter ED visit time compared with the conventional algorithm and to evaluate the associated cost savings. Methods We selected consecutive outpatients with suspected PE from our hospital included in the YEARS study and ADJUST-PE study. Different time-points of the diagnostic process were extracted from the to-the-minute accurate electronic patients' chart system of the ED. Further, the costs of the ED visits were estimated for both algorithms. Results All predefined diagnostic turnaround times were significantly shorter after implementation of YEARS: patients were discharged earlier from the ED; 54 min (95% CI, 37-70) for patients managed without computed tomography pulmonary angiography (CTPA) and 60 min (95% CI, 44-76) for the complete study population. Importantly, patients diagnosed with PE by CTPA received the first dose of anticoagulants 53 min (95% CI, 22-82) faster than those managed according to the conventional algorithm. Total costs were reduced by on average €123 per visit. Conclusion YEARS was shown to be associated with a shorter ED visit time compared with the conventional diagnostic algorithm, leading to faster start of treatment in the case of confirmed PE and savings on ED resources.

Sex-specific performance of pre-imaging diagnostic algorithms for pulmonary embolism.

Essentials Decision rules for pulmonary embolism are used indiscriminately despite possible sex-differences. Various pre-imaging diagnostic algorithms have been investigated in several prospective studies. When analysed at an individual patient data level the algorithms perform similarly in both sexes. Estrogen use and male sex were associated with a higher prevalence in suspected pulmonary embolism. SUMMARY: Background In patients suspected of pulmonary embolism (PE), clinical decision rules are combined with D-dimer testing to rule out PE, avoiding the need for imaging in those at low risk. Despite sex differences in several aspects of the disease, including its diagnosis, these algorithms are used indiscriminately in women and men. Objectives To compare the performance, defined as efficiency and failure rate, of three pre-imaging diagnostic algorithms for PE between women and men: the Wells rule with fixed or with age-adjusted D-dimer cut-off, and a recently validated algorithm (YEARS). A secondary aim was to determine the sex-specific prevalence of PE. Methods Individual patient data were obtained from six studies using the Wells rule (fixed D-dimer, n = 5; age adjusted, n = 1) and from one study using the YEARS algorithm. All studies prospectively enrolled consecutive patients with suspected PE. Main outcomes were efficiency (proportion of patients in which the algorithm ruled out PE without imaging) and failure rate (proportion of patients with PE not detected by the algorithm). Outcomes were estimated using (multilevel) logistic regression models. Results The main outcomes showed no sex differences in any of the separate algorithms. With all three, the prevalence of PE was lower in women (OR, 0.66, 0.68 and 0.74). In women, estrogen use, adjusted for age, was associated with lower efficiency and higher prevalence and D-dimer levels. Conclusions The investigated pre-imaging diagnostic algorithms for patients suspected of PE show no sex differences in performance. Male sex and estrogen use are both associated with a higher probability of having the disease.

No added value of the age-adjusted D-dimer cut-off to the YEARS algorithm in patients with suspected pulmonary embolism.

Essentials Imaging is warranted in the majority of patients to confirm or rule out pulmonary embolism (PE). The age-adjusted D-dimer (ADJUST) reduced the number of required imaging tests in patients ≥ 50 years. The YEARS algorithm was designed to improve the efficiency in patients with suspected PE. There was no added value of implementing ADJUST in the YEARS algorithm in our cohort. SUMMARY: Background The YEARS algorithm was designed to simplify the diagnostic work-up of pulmonary embolism (PE) and to reduce the number of necessary computed tomography pulmonary angiography (CTPA) scans. An alternative strategy to reduce the number of CTPAs is the age-adjusted D-dimer cut-off (ADJUST) in patients aged 50 years or older. We aimed to investigate whether a combination of both diagnostic strategies might save additional CTPAs. Methods The YEARS algorithm consists of three items (clinical signs of deep venous thrombosis, hemoptysis, 'PE most likely diagnosis') with simultaneous D-dimer testing using a pre-test dependent threshold. We performed a post hoc analysis in 3465 patients managed according to YEARS to compare the number of patients managed without CTPA scans and associated diagnostic failures in hypothetical scenarios with different YEARS-ADJUST combinations. Results Following the YEARS algorithm, 1651 patients (48%) were managed without CTPA; PE was diagnosed in 456 (13%) patients at baseline and 18 patients with initial normal testing suffered venous thromboembolism (VTE) during 3-month follow-up (failure rate 0.61%; 95% confidence interval [CI], 0.36-0.96). If ADJUST had been fully integrated in YEARS, 1627 patients (47%) would have been managed without CTPA (absolute decrease of 0.69%; 95% CI -1.7 to 3.0), at cost of four additional missed PE diagnoses at baseline, for a projected 3-month VTE failure rate of 0.75% (95% CI, 0.49-1.13). None of the other studied scenarios showed relevant improvements in efficiency as well, but all led to more missed diagnoses. Conclusion In our cohort, there was no added value of implementing ADJUST in the YEARS algorithm.

Is stand-alone D-dimer testing safe to rule out acute pulmonary embolism?

Essentials A stand-alone D-dimer below 750 µg/L has been proposed to rule out acute pulmonary embolism (PE). This was a post-hoc analysis on data from 6 studies comprising 7268 patients with suspected PE. The negative predictive value of a D-dimer <750 µg/L ranged from 79% to 96% in various subgroups. Stand-alone D-dimer testing seems to be unsafe to rule out PE in all patients. SUMMARY: Background Recently, stand-alone D-dimer testing at a positivity threshold of 750 µg L-1 has been proposed as a safe and efficient approach to rule out acute pulmonary embolism (PE), without additional imaging, but this approach needs validation. Objectives To evaluate stand-alone D-dimer testing at a positivity threshold of 750 µg L-1 to rule out PE. Methods Individual data from 7268 patients with suspected PE previously enrolled in six prospective management studies were used. Patients were assessed by the Wells rule followed by quantitative D-dimer testing in those with a 'PE unlikely' score. Patients were classified post hoc as having a negative (< 750 µg L-1 ) or positive (≥ 750 µg L-1 ) D-dimer. Using a one-stage meta-analytic approach, the negative predictive value (NPV) of stand-alone D-dimer testing was evaluated overall and in different risk subgroups. Results The pooled incidence of PE was 23% (range, 13-42%). Overall, 44% of patients had a D-dimer < 750 µg L-1 , of whom 2.8% were diagnosed with PE at baseline or during 3-month follow-up (NPV, 97.2%; 95% confidence interval [CI], 94.9-98.5). The NPV was highest in patients with a low probability of PE according to the Wells rule (99.2%; 95% CI, 98.6-99.5%) and lowest in those with a high probability of PE (79.3%; 95% CI, 53.0-92.8%). The NPVs in patients with active cancer, patients with previous venous thromboembolism and inpatients were 96.2% (95% CI, 85.6-99.1%), 94.7% (95% CI, 88.6-97.6%) and 92.7% (95% CI, 79.3-97.7%), respectively. Conclusions Our findings suggest that stand-alone D-dimer testing at a positivity threshold of 750 µg L-1 is not safe to rule out acute PE.

PO-07 - Excluding pulmonary embolism in cancer patients using the Wells rule and age-adjusted D-dimer testing: an individual patient data meta-analysis.

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

Current standings in diagnostic management of acute venous thromboembolism: Still rough around the edges.

Signs and symptoms of acute deep vein thrombosis (DVT) and pulmonary embolism (PE) are notoriously non-specific. Therefore, diagnostic management algorithms have been developed, consisting of a clinical decision rule (CDR), D-dimer testing and an imaging test, that allow safe diagnostic management and the exclusion of VTE in clinical practice. However, several challenges still remain: adherence to the diagnostic algorithms, accurate diagnosis of recurrent VTE and reducing the radiation exposure associated with computed tomography pulmonary angiography for suspected PE. In this clinically oriented review, we will provide an overview of current diagnostic algorithms for suspected DVT and PE and focus on recent advances including strategies to improve adherence to recommended algorithms, age-dependent D-dimer threshold and novel imaging techniques.

Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients.

UNLABELLED: ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE. BACKGROUND: Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. METHODS: Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed. RESULTS: In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4). CONCLUSION: These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.

Recent developments in the diagnosis and treatment of pulmonary embolism.

Due to the nonspecific symptoms of the condition, a diagnosis of acute pulmonary embolism (PE) is frequently considered. However, PE will only be confirmed in 10-20% of patients. Because the imaging test of choice, computed tomography pulmonary angiography (CTPA), is costly and associated with radiation exposure and other complications, a validated diagnostic algorithm consisting of a clinical decision rule and D-dimer test should be used to safely exclude PE in 20-30% of patients without the need for CTPA. Recently, the age-adjusted D-dimer threshold has been validated, and this has increased the proportion of patients at older age in whom PE can be excluded without CTPA. Initial therapeutic management of PE depends on the risk of short-term PE-related mortality. Haemodynamically unstable patients should be closely monitored and receive thrombolytic therapy unless contraindicated because of an unacceptably high bleeding risk, whereas patients with low-risk PE may be safely discharged early from hospital or receive only outpatient treatment. The PESI score and Hestia decision rule are available to select patients in whom early discharge or outpatient treatment will be safe, although the safety of these strategies should be confirmed in additional studies. Standard PE therapy consists of low molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs). Recently, several nonvitamin K-dependent oral anticoagulants have been shown to be as effective as LMWH/VKAs, and maybe safer. Determining the optimal duration of treatment for a first unprovoked PE remains a challenge, although clinical prediction rules for estimating the risk of recurrence of venous thromboembolism and anticoagulation-associated haemorrhage are under investigation. Using these prediction rules may lead to both more standardized and more individualized long-term treatment of PE.

The post-PE syndrome: a new concept for chronic complications of pulmonary embolism.

Long-term follow-up studies have consistently demonstrated that after an episode of acute pulmonary embolism (PE), half of patients report functional limitations and/or decreased quality of life up to many years after the acute event. Incomplete thrombus resolution occurs in one-fourth to one-third of patients. Further, pulmonary artery pressure and right ventricular function remain abnormal despite adequate anticoagulant treatment in 10-30% of patients, and 0.5-4% is diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) which represents the most severe long term complication of acute PE. From these numbers, it seems that CTEPH itself is the extreme manifestation of a much more common phenomenon of permanent changes in pulmonary artery flow, pulmonary gas exchange and/or cardiac function caused by the acute PE and associated with dyspnea and decreased exercise capacity, which in analogy to post-thrombotic syndrome after deep vein thrombosis could be referred to as the post-pulmonary embolism syndrome. The acknowledgement of this syndrome would both be relevant for daily clinical practice and also provide a concept that aids in further understanding of the pathophysiology of CTEPH. In this clinically oriented review, we discuss the established associations and hypotheses between the process of thrombus resolution or persistence, lasting hemodynamic changes following acute PE as well as the consequences of a PE diagnosis on long-term physical performance and quality of life.

Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism.

INTRODUCTION: Treatment of acute venous thromboembolism (VTE) in cancer patients is challenging, owing to a high risk of recurrent VTE and bleeding complications. The anticoagulants of choice are low molecular weight heparins (LMWHs), because of a proven higher efficacy than vitamin K antagonists (VKAs) and a similar bleeding profile. The recently introduced new oral anticoagulants (NOACs) have the potential to be alternative options for these patients, as these drugs share practical advantages with LMWH, are administered orally, and had similar efficacy to VKAs but a lower bleeding risk in phase 3 studies in the general VTE population. METHODS: A systematic literature search was performed to identify phase 3 trials investigating NOACs for the treatment of VTE. The efficacy outcome was recurrent VTE, and the safety outcome was major and clinically relevant non-major bleeding. Pooled incidence rates and risk ratios (RRs) were calculated for cancer patients and non-cancer patients separately. RESULTS AND DISCUSSION: Five studies were included, with 19 060 patients, of whom 973 (5.1%) had active cancer. The pooled incidence rates of recurrent VTE were 4.1% (95% confidence interval [CI] 2.6-6.0) in cancer patients treated with NOACs, and 6.1% (95% CI 4.1-8.5) in patients treated with VKAs (RR 0.66, 95% CI 0.38-1.2). The pooled incidence rates of major or non-major clinically relevant bleeding were 15% (95% CI 12-18) in cancer patients treated with NOACs, and 16% (95% CI 9.9-22) in patients treated with VKAs (RR 0.94, 95% CI 0.70-1.3). These results form a solid basis for the initiation of a head-to-head comparison of NOACs with LMWH in cancer patients.

Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis.

INTRODUCTION: New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta-analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE. METHODS: We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials Registry up to October 2013. Eligible studies included phase 3 trials comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs), absolute risk differences and numbers needed to treat (NNTs) to prevent one event were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall mortality, major bleeding, and other bleeding complications, with random-effects models. RESULTS: Five studies were included, investigating four NOACs (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and 0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI 0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149. The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed-effect network analysis did not demonstrate significant differences between individual NOACs and rivaroxaban. CONCLUSIONS: NOACs have comparable efficacy to that of VKAs, and are associated with a significantly lower risk of bleeding complications, although the NNT to prevent one major bleed was relatively high.

Computed tomography-assessed right ventricular dysfunction and risk stratification of patients with acute non-massive pulmonary embolism: systematic review and meta-analysis.

BACKGROUND: The ability of computed tomography (CT)-assessed right ventricular dysfunction (RVD) to identify normotensive patients with acute pulmonary embolism (PE) at high risk of mortality or adverse outcome lacks clarity. METHODS AND RESULTS: We performed a systematic review and a meta-analysis of studies in normotensive patients with acute PE to assess the prognostic value of CT-assessed RVD for death and a predefined composite outcome of PE-related complications. We conducted unrestricted searches of MEDLINE and EMBASE from 1980 to March 2013, and used the terms 'computed tomography', 'pulmonary embolism', and 'prognos*'. We used a random-effects model to pool study results, funnel-plot inspection to evaluate for publication bias, and I(2) testing to assess for heterogeneity. The analysis included data from 10 studies (2288 patients). Overall, 99 of 1268 patients with RVD assessed by CT died (7.8%; 95% confidence interval [CI] 6.3-9.3) as compared with 52 of 1020 without RVD (5.1%; 95% CI 3.7-6.4). CT-assessed RVD had significant associations with mortality (odds ratio [OR] 1.8; 95% CI 1.3-2.6), with death resulting from PE (OR 7.4; 95% CI 1.4-39.5), and with PE-related complications (OR 2.4; 95% CI 1.2-4.7). Pooled likelihood ratios (LRs) were not extreme (negative LR 0.71; 95% CI 0.57-0.89; and positive LR 1.27; 95% CI 1.12-1.43). CONCLUSIONS: Although RVD assessed by CT showed an association with an increased risk of mortality in patients with hemodynamically stable PE, it resulted in only small increases in the ability to classify risk.