Background Cancer patients are at risk of developing blood clots in their veins - venous thromboembolism - which often takes the form of a pulmonary embolism or deep vein thrombosis. The risk increases with advanced disease. Evidence based treatment is low molecular weight heparin by daily subcutaneous injection. The aim of this research is to explore the barriers for doctors in the UK when diagnosing and treating advanced cancer patients with VTE. Method Qualitative, in-depth interview study with 45 doctors. Doctors (...) were from three specialties: oncology, palliative medicine and general practice, with a mixture of senior and junior staff. Framework analysis was used. Results Doctors opinions as to whether LMWH treatment was ethically appropriate for patients who were symptomatic from VTE but at end of life existed on a shifting continuum, largely influenced by patient prognosis. A lack of immediate benefit coupled with the discomfort of a daily injection had influenced some doctors not to prescribe LMWH. The point at which LMWH injections should be stopped in patients at the end of life was ambiguous_._ Some perceived ‘overcaution’ in their own and other clinicians’ treatment of patients_._ Viewpoints were divergent on whether dying of a PE was considered a “good way to go”. The interventionalism and ethos of palliative medicine was discussed. Conclusions Decisions are difficult for doctors to make regarding LMWH treatment for advanced cancer patients with VTE. Treatment for this patient group is bounded to the doctors own moral and ethical frameworks. (shrink)

Background: Cancer patients are at risk of developing blood clots in their veins - venous thromboembolism(VTE) - which often takes the form of a pulmonary embolism or deep vein thrombosis. Therisk increases with advanced disease. Evidence based treatment is low molecular weightheparin (LMWH) by daily subcutaneous injection. The aim of this research is to explore thebarriers for doctors in the UK when diagnosing and treating advanced cancer patients withVTE.MethodQualitative, in-depth interview study with 45 doctors (30 across Yorkshire, England and 15across (...) South Wales). Doctors were from three specialties: oncology, palliative medicine andgeneral practice, with a mixture of senior and junior staff. Framework analysis was used. Results: Doctors opinions as to whether LMWH treatment was ethically appropriate for patients whowere symptomatic from VTE but at end of life existed on a shifting continuum, largelyinfluenced by patient prognosis. A lack of immediate benefit coupled with the discomfort of adaily injection had influenced some doctors not to prescribe LMWH. The point at whichLMWH injections should be stopped in patients at the end of life was ambiguous. Someperceived overcaution in their own and other clinicians treatment of patients. Viewpointswere divergent on whether dying of a PE was considered a "good way to go". Theinterventionalism and ethos of palliative medicine was discussed. Conclusions: Decisions are difficult for doctors to make regarding LMWH treatment for advanced cancerpatients with VTE. Treatment for this patient group is bounded to the doctors own moral andethical frameworks. (shrink)

In recent years, a robust body of scholarship has emerged that examines ethical challenges facing the learning health organization model. In “Bystander Ethics and Good Samaritanism,” James Sabin and colleagues make a valuable addition to this scholarship, identifying and exploring the important question of what researchers' obligations are to patients receiving “usual care” if “that care is seen as suboptimal.” The central issue that Sabin et al. faced was whether it would be acceptable for researchers to identify patients with untreated (...) atrial fibrillation but then assign them to a control group that would not receive education about the importance of oral anticoagulation. The authors present this challenge as an issue of “bystander ethics.” To avoid being “bystanders” to identified instances of suboptimal care, the research team decided to instead identify a “delayed intervention” group for which they would not determine the members' anticoagulation status, thereby preventing them from knowing that specific patients met the criteria for oral anticoagulants but were not using them. This “workaround” approach strikes me as disingenuous. (shrink)

The global shortage of organs for transplantation and the development of new and better medical technologies for organ preservation have resulted in a renewed interest in non-heart-beating donation (NHBD). This article discusses ethical questions related to controlled and uncontrolled NHBD. It argues that certain preparative measures, such as giving anticoagulants, should be acceptable before patients are dead, but when they have passed a point where further curative treatment is futile, they are in the process of dying and they are (...) unconscious. Furthermore, the article discusses consequences of technological developments based on improvement of a chest compression apparatus used today to make mechanical heart resuscitation. Such technological development can be used to transform cases of non-controlled NHBD to controlled NHBD. In our view, this is a step forward since the ethical difficulties related to controlled NHBD are easier to solve than those related to non-controlled NHBD. However, such technological developments also evoke other ethical questions. (shrink)

In this issue of the Hastings Center Report, James Sabin and his colleagues ask what responsibility investigators in a learning health organization have to patients when research—particularly research of which patients might be unaware—illuminates problematic aspects of the patients' care. Sabin and his colleagues were confronted by this question in the midst of designing a randomized controlled trial that sought to determine if an educational intervention targeted at patients with atrial fibrillation and their clinicians reduces underuse of oral anticoagulants. (...) Worried about harm that might befall patients in the control group and fearing that they would be negligent bystanders if they knew these patients were at risk and did nothing, the investigators adopted a “workaround.” But the “workaround,” I suggest, was not a solution to the negligent bystander problem. Nor was it a solution to the problem as I would alternatively frame it—how to address instances of suboptimal patient care identified through research within learning health organizations. (shrink)

The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. We present the participation of pre-menopausal women with atrial fibrillation in trials of novel oral (...) anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research. (shrink)

Amyloid beta precursor protein (APP) and prion protein (PrP) are cell membrane elements implicated in neurodegenerative diseases. Both proteins undergo endoproteolysis. Evidence is adduced from the literature hinting that the process in the two proteins could be related, their functions may overlap and their distributions coincide. It is proposed that PrP catalyses its own cleavage, the C-terminal fragment functions as an α secretase and the N-terminal segment chaperones the active site; the α secretase releases anticoagulant and neurotrophic ectodomains from APP. (...) The proposals explain some features of spongiform encephalopathies. BioEssays 23:456–462, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USA: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to (...) pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets, neuronal cells, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs. (shrink)

Robot-assisted retinal cannulation is an eye surgical procedure which can dissolve the obstruction by using robot to inject anticoagulant into occluded vessel. The current research on the critical parameters of cannulation for human is scarce because of the immature technology. Considering the influence of microneedle, this work investigated the effects of drug concentration, injection velocity, injection position, and size of clot on cannulation by theoretical analysis and finite element analysis. For finite element analysis, the multiphysics continuum model was established to (...) demonstrate species transport and reaction which simulates the entire lytic process of the occlusive clot, and four cell zones were established to describe the generation of plasmin with the addition of tissue-type plasminogen activator and fibrinolysis of clot by importing subroutines into each cell zone under the conditions of constant clot size and variable size, respectively. The results imply that the most efficient value of tPA concentration is 50 nM, injection velocity is 60 mm/s for clot length of 0.1 mm, and the best position to insert the cannula is 0.5 mm in front of the thrombus. For different clot lengths of 0.1 mm to 0.6 mm, the optimal range of tPA concentration and injection velocity is from 20 nM to 70 nM and from 40 mm/s to 60 mm/s, respectively, and explores the reasonable injection position of 0.3 mm to 0.5 mm in front of clot in a vein of 100 μm. This conclusion can be used to perform robot-assisted cannulation surgery to improve fibrinolytic efficiency. (shrink)