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  • 1
    In: Autophagy, Informa UK Limited, Vol. 17, No. 1 ( 2021-01-02), p. 1-382
    Type of Medium: Online Resource
    ISSN: 1554-8627 , 1554-8635
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2262043-6
    SSG: 12
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  • 2
    In: Health Technology Assessment, National Institute for Health and Care Research, Vol. 19, No. 83 ( 2015-10), p. 1-94
    Abstract: Venous thromboembolism is common in cancer patients and requires anticoagulation with low-molecular-weight heparin (LMWH). Current data recommend LMWH for anticoagulation as far as 6 months, yet guidelines recommend LMWH beyond 6 months in patients who have ongoing or active cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. Objectives (1) To identify the most clinically and cost-effective length of anticoagulation with LMWH in the treatment of cancer-associated thrombosis (CAT); (2) to identify practicalities of conducting a full randomised controlled trial (RCT) with regard to recruitment, retention and outcome measurement; and (3) to explore the barriers for progressing to a full RCT. Design The Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT) trial is a randomised, multicentre, feasibility mixed-methods study with three components: (1) a RCT comparing ongoing LMWH treatment for CAT with cessation of LMWH at 6 months’ treatment (current licensed practice) in patients with locally advanced or metastatic cancer, consulted in three clinical settings (haematology outpatients, oncology outpatients and primary care); (2) a nested qualitative study, including focus groups with clinicians to investigate attitudes for recruiting to the study and identify the challenges of progressing to a full RCT, and semistructured interviews with patients and relatives to explore their attitudes towards participating in the study, and potential barriers and concerns to participation; and (3) a UK-wide survey exercise to develop a classification and enumeration system for the CAT models and pathways of care. Setting A haematology outpatients department, an oncology outpatients department and primary care. Participants Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT. Interventions Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months’ treatment in patients with locally advanced or metastatic cancer. Main outcome measures (i) The number of eligible patients over 12 months; (ii) the number of recruited patients over 12 months (target recruitment rate of 30% of eligible patients); and (iii) the proportion of randomised participants with recurrent venous thromboembolisms (VTEs) during follow-up. Results Following several delays in setting up the RCT component of the study, 5 out of 32 eligible patients consented to be randomised to the RCT suggesting progression to a full RCT was not feasible. Reasons for non-consenting were primarily based on a fixed preference for continuing or discontinuing treatment after 6 months of anticoagulation, and a fear of randomisation to their non-preferred option. Views were largely influenced by patients’ initial experience of CAT. Focus groups with clinicians revealed that they would be reticent to recruit to such a study as they had fixed views of best management despite the lack of evidence. Patient pathway modelling suggested that there is a broad heterogeneity of practice with respect to CAT management and co-ordination, with no consensus on which specialty should best manage such cases. Conclusions The results of the RCT reflect recruitment from the oncology site only and provide no recruitment data from haematology centres. However, it is unlikely that these other sites would have access to more eligible patients. The management of cancer-associated thrombosis beyond 6 months will remain a clinical challenge. As it is unlikely that a prospective study will successfully recruit, other strategies to accrue relevant data are necessary. Currently the LONGHEVA (Long-term treatment for cancer patients with deep-venous thrombosis or pulmonary embolism) registry is in development to prospectively evaluate this important and common clinical scenario. Study registration This study is registered as clinical trials.gov number NCT01817257 and International Standard Randomised Controlled Trial Number (ISRCTN) 37913976. Funding details Funding for the ALICAT trial was provided by the Health Technology Assessment programme (10/145/01) in response to a themed funding call. The study was designed in accordance with the initial funding brief and feedback from the review process.
    Type of Medium: Online Resource
    ISSN: 1366-5278 , 2046-4924
    Language: English
    Publisher: National Institute for Health and Care Research
    Publication Date: 2015
    detail.hit.zdb_id: 2059206-1
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  • 3
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 121, No. 05 ( 2021-05), p. 616-624
    Abstract: Background Direct oral anticoagulants are recommended for the treatment of cancer-associated thrombosis (CAT) as an alternative to low-molecular-weight heparin (LMWH), but an increased bleeding risk in patients with gastrointestinal cancer was reported. The Caravaggio study compared apixaban and dalteparin for the treatment of patients with CAT. Here we describe sites of bleeding, associated cancer sites, clinical presentation, and course of major bleeding in patients included in the Caravaggio study. Methods The Caravaggio study was a multinational, randomized, open-label, noninferiority study. Bleeding events and the severity of major bleedings were adjudicated by a committee unaware of treatment allocation using predefined criteria; for the purpose of this analysis, data were analyzed in the safety population. Results Major bleeding occurred in 22 of 576 patients on apixaban (3.8%) and in 23 of 579 patients on dalteparin (4.0%). The sites of major bleeding and their distribution according to the type of cancer were similar between the two treatment groups. Major bleeding occurred in nine patients with gastrointestinal cancer in each treatment group. The clinical presentation of major bleeding was severe or fatal in 6 patients on apixaban and in 5 patients on dalteparin, while the clinical course was severe in 5 patients on apixaban and in 7 patients on dalteparin. Conclusion Apixaban is a safe alternative to LMWH for the treatment in patients with CAT. No excess in gastrointestinal bleeding was observed in patients who received apixaban, including those with gastrointestinal cancer.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2021
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  • 4
    In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 196, No. 11 ( 2017-12-01), p. 1396-1403
    Type of Medium: Online Resource
    ISSN: 1073-449X , 1535-4970
    RVK:
    Language: English
    Publisher: American Thoracic Society
    Publication Date: 2017
    detail.hit.zdb_id: 1468352-0
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2013
    In:  Best Practice & Research Clinical Haematology Vol. 26, No. 2 ( 2013-6), p. 183-190
    In: Best Practice & Research Clinical Haematology, Elsevier BV, Vol. 26, No. 2 ( 2013-6), p. 183-190
    Type of Medium: Online Resource
    ISSN: 1521-6926
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 2028865-7
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  • 6
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 2002
    In:  Seminars in Thrombosis and Hemostasis Vol. 28, No. 6 ( 2002), p. 569-576
    In: Seminars in Thrombosis and Hemostasis, Georg Thieme Verlag KG, Vol. 28, No. 6 ( 2002), p. 569-576
    Type of Medium: Online Resource
    ISSN: 0094-6176 , 1098-9064
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2002
    detail.hit.zdb_id: 2072469-X
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  • 7
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2314-2314
    Abstract: Abstract 2314 Venous thromboembolism (VTE) collectively describes the debilitating, painful and potentially fatal conditions of deep vein thrombosis (DVT) and pulmonary embolism (PE). High-risk surgical procedures can lead to VTE, and patients undergoing major orthopaedic surgery, such as total hip or knee replacement (THR and TKR, respectively), are in the highest risk category for VTE. In the absence of anticoagulant prophylaxis the estimated incidence of DVT following orthopaedic surgery ranges from 40–60%, and the overall risk of fatal PE has been estimated to be between 0.2 and 0.9%. Thromboprophylaxis, both mechanical and pharmacological, is current standard practice for the prevention of VTE in patients undergoing orthopaedic surgery.Currently available anticoagulant therapies such as low molecular weight heparins (LMWHs), which are most commonly used, fondaparinux, and warfarin have demonstrated efficacy but have a number of limitations. LMWHs and fondaparinux require parenteral administration and warfarin has a narrow therapeutic window which is difficult to attain. Apixaban, rivaroxaban and dabigatran are new anti-coagulants for thromboprophylaxis after orthopaedic surgery and have the advantages of oral administration and no requirement for routine laboratory monitoring. We compared the efficacy and safety of apixaban versus other anti-coagulants for the prevention of VTE following total hip replacement and total knee replacement surgery. We systematically searched MEDLINE, EMBASE, the Cochrane library and CINAHL up to July 2010 for randomised controlled trials (RCTs) evaluating apixaban, rivaroxaban, dabigatran, fondaparinux and low molecular weight heparins at European licensed doses. A series of direct and indirect comparisons and a network meta-analysis (NMA) were performed where there were sufficient data for analysis, using enoxaparin as the common control. Indirect comparisons found that dabigatran 220mg od was significantly less efficacious than apixaban 2.5mg bd for the prevention of all VTE and all-cause death in THR patients (OR 2.51; 95% CI 1.50–4.21), and in TKR patients (OR 1.72; 95% CI 1.22–2.42). Rivaroxaban 10mg odwas slightly more effective than apixaban 2.5mg bd in both THR and TKR patients (OR 0.69; 95% CI 0.38–1.25, and OR 0.83; 95% CI 0.57–1.19, respectively), but the differences were not statistically significant. For the incidence of major bleeding the adjusted indirect comparison found that dabigatran 220mg od and rivaroxaban 10mg od had higher, but not statistically significant, bleeding rates compared with apixaban 2.5mg bd. Dabigatran versus apixaban: for THR patients OR 1.13; 95% CI 0.50–2.54 and for TKR patients OR 1.75; 95% CI 0.51–5.99. Rivaroxaban versus apixaban: for THR patients OR 2.48; 95%CI 0.44–13.8 and for TKR patients OR 1.86; 95% CI0.47–7.30. Trials comparing fondaparinux with enoxaparin were only available in THR patients, and for the outcomes any DVT and major bleeding. The adjusted indirect comparison found that fondaparinux 2.5mg od had higher but non-significant rates of any DVT (OR 1.29; 95% CI 0.69–2.43) and major bleeding (OR 1.22; 95% CI 0.56–2.67) compared with apixaban 2.5mg bd. The NMA showedno significant differences between the treatments for the outcomes evaluated. Apixaban, rivaroxaban and dabigatran have demonstrated similar or improved efficacy and similar safety compared with current therapies for the prevention of VTE in patients undergoing orthopaedic surgery. Apixaban may be more effective than dabigatran and similar to rivaroxaban, whilst all three have a comparable safety profile. Considering practical and economic advantages, such as the ease of oral dosing and the substantial reduction in costs related to this, these new anti-coagulants represent an appealing alternative to conventional thromboprophylaxis regimens in patients undergoing THR and TKR surgery and may improve patient compliance and standard of care.Figure 1:Pooled estimates of the results of randomised controlled trials comparing the effects of apixaban, rivaroxaban and dabigatran versus enoxaparin on; the composite of all VTE and all-cause death for patients undergoing (A) total hip replacement and (B) total knee replacement and; major bleeding for patients undergoing (C) total hip replacement and (D) total knee replacementFigure 1:. Pooled estimates of the results of randomised controlled trials comparing the effects of apixaban, rivaroxaban and dabigatran versus enoxaparin on; the composite of all VTE and all-cause death for patients undergoing (A) total hip replacement and (B) total knee replacement and; major bleeding for patients undergoing (C) total hip replacement and (D) total knee replacement Disclosures: Cohen: Pfizer Ltd: Consultancy. Pieter:Pfizer/BMS: Employment. Marchant:Pfizer Ltd: Employment. Mitchell:Pfizer Ltd: Consultancy. Orme:Pfizer Ltd: Consultancy. Simon:BMS: Employment. Sutton:Pfizer Ltd: Consultancy. Rublee:Pfizer Ltd: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Research and Practice in Thrombosis and Haemostasis, Elsevier BV, Vol. 4, No. 2 ( 2020-02), p. 230-237
    Type of Medium: Online Resource
    ISSN: 2475-0379
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2901840-7
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  • 9
    Online Resource
    Online Resource
    Future Medicine Ltd ; 2017
    In:  Future Cardiology Vol. 13, No. 3 ( 2017-05), p. 207-209
    In: Future Cardiology, Future Medicine Ltd, Vol. 13, No. 3 ( 2017-05), p. 207-209
    Abstract: Ander Cohen speaks to Adam Price-Evans, Commissioning Editor of Future Cardiology: Alexander (Ander) Cohen MBBS (Hons), MSc, MD, FRACP is a vascular physician and epidemiologist at Guy's and St Thomas’ Hospital, King's College (London, UK). He graduated with honors in medicine and honors in surgery from the University of Melbourne, Australia, and became a fellow of the Royal Australasian College of Physicians in 1990. He was awarded an MSc in Epidemiology from the London School of Hygiene and Tropical Medicine, University of London in 1991 with a thesis on the metabolic syndrome in South-Asian populations. In 1998, he was awarded an MD with a thesis on the epidemiology of venous thromboembolism and thromboprophylaxis. In addition to his clinical work, he is involved in designing, managing and analyzing clinical trials from Phase I to IV. He is the Chairman and a member of many international steering committees for multicenter trials, epidemiological and pharmacoeconomic studies, and was previously the Director of Clinical Research and an Epidemiologist in Thrombosis Research at King's College Hospital.
    Type of Medium: Online Resource
    ISSN: 1479-6678 , 1744-8298
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2017
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  • 10
    Online Resource
    Online Resource
    Wiley ; 2015
    In:  Annals of Clinical and Translational Neurology Vol. 2, No. 1 ( 2015-01), p. 1-11
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 2, No. 1 ( 2015-01), p. 1-11
    Abstract: Stroke is a leading cause of long‐term motor disability. Stroke patients with severe hand weakness do not profit from rehabilitative treatments. Recently, brain‐controlled robotics and sequential functional electrical stimulation allowed some improvement. However, for such therapies to succeed, it is required to decode patients' intentions for different arm movements. Here, we evaluated whether residual muscle activity could be used to predict movements from paralyzed joints in severely impaired chronic stroke patients. Methods Muscle activity was recorded with surface‐electromyography ( EMG ) in 41 patients, with severe hand weakness (Fugl‐Meyer Assessment [ FMA ] hand subscores of 2.93 ± 2.7), in order to decode their intention to perform six different motions of the affected arm, required for voluntary muscle activity and to control neuroprostheses. Decoding of paretic and nonparetic muscle activity was performed using a feed‐forward neural network classifier. The contribution of each muscle to the intended movement was determined. Results Decoding of up to six arm movements was accurate ( 〉 65%) in more than 97% of nonparetic and 46% of paretic muscles. Interpretation These results demonstrate that some level of neuronal innervation to the paretic muscle remains preserved and can be used to implement neurorehabilitative treatments in 46% of patients with severe paralysis and extensive cortical and/or subcortical lesions. Such decoding may allow these patients for the first time after stroke to control different motions of arm prostheses through muscle‐triggered rehabilitative treatments.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2740696-9
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