Financial toxicity and health-related quality of life in long-term survivors of acute promyelocytic leukaemia.

OBJECTIVES: We aimed to investigate the association between financial toxicity (FT) and the health-related quality of life profile of long-term survivors of acute promyelocytic leukaemia (APL) treated within a universal healthcare system. METHODS: We evaluated FT using the financial difficulties item of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). We also compared the prevalence of clinically important problems and symptoms between the survivors of APL with or without FT, using evidence-based thresholds for the EORTC QLQ-C30. A multivariable logistic regression analysis was performed to explore potential risk factors associated with FT. RESULTS: Overall, 352 long-term survivors of APL, with a median age of 53.9 years and a median time since diagnosis of 12.2 years, were analysed. Of these, 71 (20.2%) reported having FT. The prevalence of clinically important problems and symptoms was generally higher across most EORTC QLQ-C30 scales for those survivors who reported FT. The three largest differences between patients with and without FT were observed for emotional functioning (+35.4 percentage points), dyspnoea (+33.1 percentage points) and physical functioning (+27.0 percentage points). The presence of FT was independently associated with having comorbidities and not receiving a salary/pension. CONCLUSIONS: These findings suggest that even many years after being diagnosed, one-fifth of long-term survivors of APL experience FT. Interventions to assist with employment may be critical to minimise the risk of FT in the most vulnerable survivors.

Long-term health-related quality of life and mental health in patients with immune thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially life-threatening disorder. Treatment advances have lowered morbidity rates, but past acute events can still cause long-term consequences, reducing health-related quality of life (HRQoL) and determining cognitive impairment, anxiety, and depression. We aimed to investigate these aspects and the role of caplacizumab and rituximab: 39 patients were evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the FACIT-Fatigue, the Hospital Anxiety and Depression Scale, and the Functional Assessment in Cancer Therapy-Cognitive Function questionnaires. The median age at study inclusion was 50 years (IQR 38-60), and the median follow-up from diagnosis was 97 months (IQR 14-182); 82% of patients were female, and 36% had one or more recurrences. Caplacizumab was administered in 16 patients (41%), as well as rituximab. ITTP patients reported lower physical and mental HRQoL scores than the general population. No differences in physical or mental domains were observed between patients treated or not with caplacizumab, while those who received rituximab reported lower scores in mental health. Neurological impairment at diagnosis correlated with worse fatigue. The majority of patients (72%) reported anxiety or depression (82%). ITTP had a significant impact on the long-term cognitive function, fatigue, depression, and anxiety levels of patients, with a negative effect on their HRQoL. Our findings underscore the need to pay special attention to patients' long-term physical and mental health, regardless of the medical treatments received.

Clinical Outcomes of Incidental Venous Thromboembolism in Cancer and Noncancer Patients: The SWIss Venous ThromboEmbolism Registry (SWIVTER).

OBJECTIVE: In patients with cancer-associated venous thromboembolism (VTE), the risk of recurrence is similar after incidental and symptomatic events. It is unknown whether the same applies to incidental VTE not associated with cancer. METHODS AND RESULTS: We compared baseline characteristics, anticoagulation therapy, all-cause mortality, and VTE recurrence rates at 90 days between patients with incidental (n = 131; 52% without cancer) and symptomatic (n = 1,931) VTE included in the SWIss Venous ThromboEmbolism Registry (SWIVTER). After incidental VTE, 114 (87%) patients received anticoagulation therapy for at least 3 months. The mortality rate was 9.2% after incidental and 8.4% after symptomatic VTE for hazard ratio (HR) 1.10 (95% confidence interval [CI] 0.49-2.50). After adjustment for competing risk of death, recurrence rate was 3.1 versus 2.8%, respectively, for sub-HR 1.07 (95% CI 0.39-2.93). These results were consistent among cancer (mortality: 15.9% vs. 12.6%; HR 1.32, 95% CI 0.67-2.59; recurrence: 4.8% vs. 4.7%; HR 1.02, 95% CI 0.30-3.42) and noncancer patients (mortality: 2.9% vs. 2.1%; HR 1.37, 95% CI 0.33-5.73; recurrence: 1.5% vs. 2.3%; HR 0.63, 95% CI 0.09-4.58). Patients with incidental VTE who received anticoagulation therapy for at least 3 months had lower mortality (4% vs. 41%) and recurrence rate (1% vs. 18%) compared with those who did not. CONCLUSION: In SWIVTER, more than half of incidental VTE events occurred in noncancer patients who often received anticoagulation therapy. Among noncancer patients, early mortality and recurrence rates were similar after incidental versus symptomatic VTE. Our findings suggest that anticoagulation therapy for incidental VTE may be beneficial regardless of the presence of cancer.

Venous Thromboembolism and Renal Impairment: Insights from the SWIss Venous ThromboEmbolism Registry (SWIVTER).

Renal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41-3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57-2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41-2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14-0.94; p = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17-2.00; p = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.

Perivascular Perfusion on Contrast-Enhanced Ultrasound (CEUS) Is Associated with Inflammation in Patients with Acute Deep Vein Thrombosis.

Background Inflammatory processes of the venous wall in acute deep vein thrombosis (DVT) play a role in thrombus formation and resolution. However, direct evaluation of the perivascular inflammation is currently not feasible. Objective To assess perivascular perfusion in acute proximal DVT using contrast-enhanced ultrasound (CEUS) reflecting perivenous inflammation and its association with systemic inflammatory markers in a single-centre, prospective observational study. Patients/Methods Twenty patients with proximal DVT underwent CEUS imaging in the thrombosed and contralateral popliteal vein at baseline and after 2 weeks and 3 months. Perfusion was quantified by measuring peak enhancement (PE) and wash-in rate (WiR) in a perivenous region after bolus injection of the contrast agent. High-sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at the time of each CEUS imaging. Results PE and WiR were significantly higher in the thrombosed compared with the unaffected leg at baseline (1,007 vs. 34 au and 103 vs. 4 au/s) and 2-week follow-up (903 vs. 35 au and 70 vs. 4 au/s). Compared with baseline, PE and WiR in the thrombosed leg significantly decreased to 217 au and 18 au/s at 3-month follow-up.At baseline, hsCRP and IL-6 were elevated at 20.1 mg/mL and 8.2 pg/mL and decreased significantly to 2.8 mg/mL and 2.6 pg/mL at 2-week follow-up, remaining low after 3 months. There was a weak association between the level of inflammatory markers and the CEUS parameters at baseline on the thrombosed leg. Conclusion Elevated perivascular perfusion assessed by CEUS imaging is associated with the inflammatory response in acute DVT.

[Endoluminal Treatment of Varicose Veins: Value of Duplex Ultrasound (Part 2)]. / Endoluminale Varikosebehandlung: Stellenwert der Duplexsonografie (Teil 2).

Part one addressed the value of duplex ultrasound in the diagnostic workup of varicosis. The present article discusses the use of preinterventional, intrainterventional and postinterventional duplex ultrasound in endoluminal methods for the treatment of varices. It is a prerequisite for the planning, implementation, and follow-up of this form of therapy.

Clinical Outcomes of Venous Thromboembolism in Patients with and without Cancer: The SWIss Venous ThromboEmbolism Registry (SWIVTER).

Background The association between cancer and venous thromboembolism (VTE) in producing adverse clinical outcomes requires further investigation. Methods In the Swiss Venous ThromboEmbolism Registry (SWIVTER), we compared adverse clinical outcomes between 493 patients with cancer-associated VTE and 1,569 VTE patients without cancer, and identified independent predictors of 90-day mortality. Results Among cancer patients, 351 (71%) had active disease at the time of VTE diagnosis and 232 (47%) had metastatic disease. Cancer patients more frequently had asymptomatic VTE (13 vs. 4%; p < 0.001), iliofemoral deep vein thrombosis (42 vs. 32%; p = 0.017), and upper extremity deep vein thrombosis (16 vs. 7%; p < 0.001). Cancer was associated with an increased risk of cumulative 90-day mortality (13.0 vs. 2.2%; hazard ratio [HR], 6.27; 95% confidence interval [CI], 4.13-9.50; p < 0.001), recurrent VTE (4.7 vs. 2.3%; HR, 2.05; 95% CI, 1.21-3.45; p = 0.007), and bleeding requiring medical attention (5.7 vs. 3.3%; HR, 1.80; 95% CI, 1.13-2.86; p = 0.013). Among cancer patients, the strongest factor associated with mortality was metastatic disease (HR, 4.86; 95% CI, 2.68-8.81; p < 0.001), whereas it was pulmonary embolism among noncancer patients (HR, 4.96; 95% CI, 1.50-16.45; p = 0.009). Symptomatic as compared with asymptomatic VTE predicted neither mortality (12.6 vs. 15.9%; HR, 0.76; 95% CI, 0.39-1.49; p = 0.42) nor recurrent VTE (4.7 vs. 4.8%; HR, 0.98; 95% CI, 0.29-3.31; p = 0.98) in cancer patients. Conclusion In SWIVTER, early mortality of cancer-associated VTE was mainly driven by the extent of cancer disease and not by VTE symptoms or severity.

Rivaroxaban for the treatment of venous thromboembolism. The SWIss Venous ThromboEmbolism Registry (SWIVTER).

We investigated three-month clinical outcomes in patients with venous thromboembolism (VTE) treated with rivaroxaban or conventional anticoagulation in routine clinical practice. Between November 2012 and February 2015, 2,062 consecutive patients with VTE from 11 acute care hospitals in Switzerland were enrolled in the SWIss Venous ThromboEmbolism Registry (SWIVTER). Overall, 417 (20 %) patients were treated with rivaroxaban. In comparison to 1,645 patients on conventional anticoagulation, patients on rivaroxaban were younger (56 ± 18 vs. 65 ± 17 years; p<0.001), less often had pulmonary embolism (38 % vs 66 %; p<0.001), hypertension (26 % vs 41 %; p<0.001), cancer (10 % vs 28 %; p<0.001), congestive heart failure (10 % vs 17 %; p=0.001), diabetes (8 % vs 15 %; p<0.001), chronic lung disease (7 % vs 13 %; p=0.001), renal insufficiency (7 % vs 13 %; p=0.001), recent surgery (7 % vs 14 %; p<0.001), and acute coronary syndrome (1 % vs 4 %; p=0.009). VTE reperfusion therapy was more frequently used (28 % vs 9 %; p<0.001) and indefinite-duration anticoagulation treatment less often planned (26 % vs 39 %; p<0.001), respectively. In the propensity score-adjusted population, the risk of recurrent VTE was similar in patients on rivaroxaban vs conventional anticoagulation (1.2 % vs 2.1 %, hazard ratio [HR] 0.55, 95 % confidence interval [CI] 0.18-1.65; p=0.29); the risk of major bleeding was also similar, respectively (0.5 % vs 0.5 %, HR 1.00, 95 %CI 0.14-7.07; p=1.00). Conventional anticoagulation is still frequently used for the treatment of VTE, particularly in the elderly and those with comorbidities. Early clinical outcomes were comparable between propensity score-adjusted patient populations on rivaroxaban and conventional anticoagulation.

Assessment of microcirculation by contrast-enhanced ultrasound: a new approach in vascular medicine.

Contrast-enhanced ultrasound (CEUS) has emerged as a valuable imaging modality that complements and enhances standard vascular ultrasound imaging. Ultrasound contrast agents are gas-filled microbubbles that are injected intravenously and serve as intravascular tracers. Based on the properties to enhance and to quantify the macro- and microcirculation down to the capillary perfusion level in different vascular territories and organs, CEUS imaging has the potential to improve the diagnostic performance in the detection and characterisation of various vascular disorders reviewed in this article. In carotid atherosclerotic disease, CEUS imaging provides additional information on plaque vulnerability by illustrating the presence and extent of intraplaque neovascularisation. This new imaging modality may be helpful for further risk stratification of arteriosclerotic lesions and for detecting patients at risk for vascular events, eventually leading to more specific individually tailored therapeutic recommendations. CEUS imaging is also a helpful tool for the diagnosis and for monitoring of inflammatory vascular diseases. It increases the diagnostic performance of ultrasound in detecting inflammatory changes of the vessel wall such as hypervascularisation and hyperaemia. Changes in vessel wall enhancement may also reflect the response to anti-inflammatory therapy. Moreover, CEUS imaging is also a valuable tool for the assessment of the microcirculation and the tissue perfusion in solid organs including native and transplanted kidneys. The technique provides more accurate information on perfusion deficits of the parenchyma in patients with kidney infarction, necrosis or graft dysfunction. CEUS also has great potential in the assessment of the microcirculation of the skeletal muscle, particularly in patients with peripheral artery disease or diabetic microangiopathy. In the future, the use of targeted on site microbubbles could further enhance and expand the diagnostic capabilities of current vascular ultrasound by assessing specific molecular processes that play a role in the pathophysiology of vascular diseases. Furthermore, ultrasound-directed, site-specific drug and gene delivery using microbubble contrast agents could gain great clinical value in the future. The combination of CEUS for diagnosis and therapy will provide unique opportunities for vascular clinicians to image the microcirculation and directly treat vascular diseases.

Novel applications of contrast-enhanced ultrasound imaging in vascular medicine.

The use of contrast-enhanced ultrasound (CEUS) for vascular imaging indications has increased dramatically during the last decade. Ultrasound contrast agents are gas-filled microbubbles that are injected into the bloodstream and serve as strict intravascular reflectors of ultrasound waves. Numerous studies have addressed the potential clinical use of CEUS in different vascular fields including the carotid arteries, the abdominal aorta, renal arteries and the kidneys. In this review article we discuss the clinical value of contrast agents in vascular ultrasound by enhancing the vascular lumen, and more important, their role as a tool to deliver high resolution, real-time images of microvascular perfusion. Specifically, CEUS imaging of the carotid artery provides a novel, non-invasive method not only to improve the delineation of the vessel wall, but also for the assessment of the vasa vasorum and the ectopic vascularization of the atherosclerotic plaque (intraplaque neovascularization); probably providing a "window" to risk stratify atherosclerotic lesions and individuals by identifying "vulnerable" plaques prone to rupture causing vascular events. CEUS imaging has also emerged as a novel diagnostic tool in various aortic pathologies and particularly for the detection of endoleaks following endovascular treatment of abdominal aortic aneurysms. It is also a valuable tool for the assessment of the tissue perfusion in native and transplanted kidneys providing information on perfusion deficits of the parenchyma. Furthermore, a real-time CEUS method has recently been developed to assess the skeletal muscle microcirculation which could be used to study patients with peripheral arterial occlusive disease or diabetic microangiopathy. In the future, the use of targeted microbubbles could further enhance and expand the diagnostic capabilities of current vascular ultrasound imaging by detecting specific molecular processes that play a role in the pathophysiology of vascular disease.

Contrast-enhanced ultrasound for assessing carotid atherosclerotic plaque lesions.

OBJECTIVE: Contrast-enhanced ultrasound that is used to assess atherosclerotic carotid plaques improves visualization of vessel wall irregularities and provides direct visualization of intraplaque neovascularization. This article illustrates the use of contrast-enhanced ultrasound in the assessment of carotid atherosclerotic lesions. CONCLUSION: Contrast-enhanced ultrasound is a new, noninvasive, and safe procedure for imaging carotid atherosclerotic lesions. It is a valuable tool for evaluating the vulnerable plaque at risk for rupture and for evaluating both the development and severity of systemic atherosclerotic disease.

Predictors of in-hospital mortality in elderly patients with acute venous thrombo-embolism: the SWIss Venous ThromboEmbolism Registry (SWIVTER).

AIMS: Although acute venous thrombo-embolism (VTE) often afflicts patients with advanced age, the predictors of in-hospital mortality for elderly VTE patients are unknown. METHODS AND RESULTS: Among 1247 consecutive patients with acute VTE from the prospective SWIss Venous ThromboEmbolism Registry (SWIVTER), 644 (52%) were elderly (≥65 years of age). In comparison to younger patients, the elderly more often had pulmonary embolism (PE) (60 vs. 42%; P< 0.001), cancer (30 vs. 20%; P< 0.001), chronic lung disease (14 vs. 8%; P= 0.001), and congestive heart failure (12 vs. 2%; P< 0.001). Elderly VTE patients were more often hospitalized (75 vs. 52%; P< 0.001), and there was no difference in the use of thrombolysis, catheter intervention, or surgical embolectomy between the elderly and younger PE patients (5 vs. 6%; P= 0.54), despite a trend towards a higher rate of massive PE in the elderly (8 vs. 4%; P= 0.07). The overall in-hospital mortality rate was 6.6% in the elderly vs. 3.2% in the younger VTE patients (P= 0.033). Cancer was associated with in-hospital death both in the elderly [hazard ratio (HR) 4.91, 95% confidence interval (CI) 2.32-10.38; P< 0.001] and in the younger patients (HR 4.90, 95% CI 1.37-17.59; P= 0.015); massive PE was a predictor of in-hospital death in the elderly only (HR 3.77, 95% CI 1.63-8.74; P= 0.002). CONCLUSION: Elderly patients had more serious VTE than younger patients, and massive PE was particularly life-threatening in the elderly.

Outpatient management of acute deep vein thrombosis: results from the OTIS-DVT registry.

OBJECTIVES: We aimed to investigate clinical practice patterns for the outpatient management of acute deep vein thrombosis (DVT). METHODS: In the prospective Outpatient Treatment of Deep Vein Thrombosis in Switzerland (OTIS-DVT) registry, 534 consecutive outpatients with acute DVT (49% proximal, 24% recurrent, and 12% cancer-associated) were enrolled: 41% patients were managed in private angiology practice, 34% in an outpatient hospital department, and 25% in private general or internal medicine practice. RESULTS: For diagnosis, ultrasound was used in 95% and D-dimer testing in 53%. Low-molecular-weight heparin (LMWH) was prescribed for a median (IQR) duration of 7 (5-12) days in 83% of patients, and vitamin K-antagonists for 163 (92-183) days in 81%. Mechanical measures to prevent post-thrombotic syndrome were prescribed in 83%; compression stockings or bandages for a median (IQR) duration of 364 (101-730) days from hospital physicians, and 92 (45-183) days from private practice physicians (p < 0.001). Among patients with symptomatic proximal DVT, mechanical measures were prescribed for at least 2 years in 24% patients; 55% in hospital, and 6% in private practice (p < 0.001). Among patients with cancer-associated DVT, the median (IQR) duration of LMWH therapy was 16 (8-45) days, and 35% received LMWH for less than 90 days. CONCLUSIONS: The OTIS-DVT registry provides representative information on clinical practice patterns for outpatients with acute DVT managed by hospital or private practice physicians. The use of mechanical measures in patients with symptomatic proximal DVT and the administration of LMWH for a long-term therapy of cancer-associated DVT require improvement to comply with current guidelines.

Inconsistencies in the planning of the duration of anticoagulation among outpatients with acute deep-vein thrombosis. Results from the OTIS-DVT Registry.

Three-month anticoagulation is recommended to treat provoked or first distal deep-vein thrombosis (DVT), and indefinite-duration anticoagulation should be considered for patients with unprovoked proximal, unprovoked recurrent, or cancer-associated DVT. In the prospective Outpatient Treatment of Deep Vein Thrombosis in Switzerland (OTIS-DVT) Registry of 502 patients with acute objectively confirmed lower extremity DVT (59% provoked or first distal DVT; 41% unprovoked proximal, unprovoked recurrent, or cancer-associated DVT) from 53 private practices and 11 hospitals, we investigated the planned duration of anticoagulation at the time of treatment initiation. The decision to administer limited-duration anticoagulation therapy was made in 343 (68%) patients with a median duration of 107 (interquartile range 91-182) days for provoked or first distal DVT, and 182 (interquartile range 111-184) days for unprovoked proximal, unprovoked recurrent, or cancer-associated DVT. Among patients with provoked or first distal DVT, anticoagulation was recommended for < 3 months in 11%, ≥ 3 months in 63%, and for an indefinite period in 26%. Among patients with unprovoked proximal, unprovoked recurrent, or cancer-associated DVT, anticoagulation was recommended for < 6 months in 22%, 6-12 months in 38%, and for an indefinite period in 40%. Overall, there was more frequent planning of indefinite-duration therapy from hospital physicians as compared with private practice physicians (39% vs. 28%; p=0.019). Considerable inconsistency in planning the duration of anticoagulation therapy mandates an improvement in risk stratification of outpatients with acute DVT.