Xenotransplantation of porcine islet cells as a potential option for the treatment of type 1 diabetes in the future.

Solid organ and cell transplantation, including pancreatic islets constitute the treatment of choice for chronic terminal diseases. However, the clinical use of allogeneic transplantation is limited by the growing shortage of human organs. This has prompted us to initiate a unique multi-center and multi-team effort to promote translational research in xenotransplantation to bring xenotransplantation to the clinical setting. Supported by the German Research Foundation, an interdisciplinary group of surgeons, internal medicine doctors, diabetologists, material sciences experts, immunologists, cell biologists, virologists, veterinarians, and geneticists have established a collaborative research center (CRC) focusing on the biology of xenogeneic cell, tissue, and organ transplantation. A major strength of this consortium is the inclusion of members of the regulatory bodies, including the Paul-Ehrlich Institute (PEI), infection specialists from the Robert Koch Institute and PEI, veterinarians from the German Primate Center, and representatives of influential ethical and religious institutions. A major goal of this consortium is to promote islet xenotransplantation, based on the extensive expertise and experience of the existing clinical islet transplantation program. Besides comprehensive approaches to understand and prevent inflammation-mediated islet xenotransplant dysfunction [immediate blood-mediated inflammatory reaction (IBMIR)], we also take advantage of the availability of and experience with islet macroencapsulation, with the goal to improve graft survival and function. This consortium harbors a unique group of scientists with complementary expertise under a cohesive program aiming at developing new therapeutic approaches for islet replacement and solid organ xenotransplantation.

[How to Define Good Health Care: An Ethical Framework for the Evaluation of Health Care for the Chronically Ill]. / Was ist gute Versorgung? Ein ethisches Framework zur Bewertung der Versorgung chronisch Kranker.

In Germany we face an increase in chronic illnesses and a health care system not adjusted to the specific needs of this patient group. Innovative health care management programmes (for example, disease management programmes) might be able to play an important role in overcoming the existing deficits. By developing and implementing such programmes we are, how-ever, implicitly touching upon normative issues, but only rarely are the ethical aspects of these programmes discussed explicitly and evaluated in a systematic way. Against this backdrop, we have developed an ethical framework as a tool for evaluating general health care and innovative programmes for the chronically ill. The framework comprises on the one hand a list of criteria that define good health care in the context of chronic illness. Based on a coherentist conception of ethical justification, we developed 8 criteria (among others "the autonomy of patients concerning therapy, use of data and other life choices have to be promoted and respected") for the context of chronic illness. On the other hand, the framework provides a methodological approach to apply the criteria in 6 steps in order to evaluate a specific programme. Thereby, we want to give orienta-tion to policy makers and practitioners concerning the normative underpinnings of their work and support them in identifying relevant ethical requirements and potential problems at an early stage.

[Criteria for an ethically adequate prioritisation of individualised treatment strategies]. / Kriterien für eine ethisch angemessene Priorisierung individualisierter Therapiemaßnahmen.

OBJECTIVES: In view of the constant increase of biomedical innovations as well as the demographic change an explicit regulation of health services is inevitable in the German health-care system. Particularly, this applies to so-called individualised treatment measures, which so far only rarely show significant advantages over "classical" treatment measures with mostly substantially higher costs. Against this background, appropriate prioritisation criteria are developed and possibilities as well as limits of their application in the context of individualised medicine are shown. METHODS: The prioritisation criteria are derived in an analytically ethical manner. RESULTS: Based on a basic need-oriented approach of an ethically adequate health care, five prioritisation criteria have been developed: badness/gravity, entrenchment, urgency, benefit and cost-benefit ratio. CONCLUSIONS: The relative weight of the criteria in individual cases cannot be derived in a purely analytical manner but needs to be determined through fair political decision-making processes. Furthermore, empirical data are necessary in order to interpret and weigh the criteria in prioritisation decisions. In the context of individualised treatment strategies benefit assessment is of special interest.

[Ethical decisions in surgery. Foundations for a principle-oriented case discussion]. / Ethische Entscheidungen in der Chirurgie. Grundlagen einer prinzipienorientierten Falldiskussion.

BACKGROUND: Due to advanced medical interventions, the multitude of beliefs in our society, and increasing economic pressure, difficult ethical decisions are also part of the surgical care of patients. QUESTION: How can health care personnel address the ethical challenges in a structured, well-founded ethical manner? MATERIALS AND METHODS: Based on the four principles of biomedical ethics beneficence, nonmaleficence, respect for autonomy, and justice, we present a model for the step-wise ethical evaluation of difficult cases. RESULTS: The principle-based model of ethical case discussions consists of five steps: 1) In the medical analysis of the case, the available management strategies are identified, including a detailed description of their benefits and risks. 2) The evaluation starts with the ethical obligations towards the patient: Which treatment strategy is in the patient's best interest? And: Which option does the patient prefer herself after appropriate disclosure? 3) Then it has to be examined whether obligations to third parties (family members, other patients, etc.) have to be taken into account. 4) In the synthesis, the individual evaluations are integrated into an overall assessment of the case; conflicting obligations have to be balanced based on good reasons. 5) A critical review of the case concludes the case discussion. The application of the model is exemplified based on a surgical case discussion. CONCLUSION: Difficult ethical decisions can be supported by structured case discussions, in which all medical disciplines and professional groups involved in the care of the patient should participate.

[Cost-conscious medical decisions. Normative guidance within the conflicting demands of ethics and economics]. / Kostenbewusste ärztliche Entscheidungen. Normative Orientierung im Spannungsfeld zwischen Ethik und Ökonomie.

BACKGROUND: Under the current conditions in the health care system, physicians inevitably have to take responsibility for the cost dimension of their decisions on the level of single cases. This article, therefore, discusses the question how physicians can integrate cost considerations into their clinical decisions at the microlevel in a medically rational and ethically justified way. DISCUSSION: We propose a four-step model for "ethical cost-consciousness": (1) forego ineffective interventions as required by good evidence-based medicine, (2) respect individual patient preferences, (3) minimize the diagnostic and therapeutic effort to achieve a certain treatment goal, and (4) forego expensive interventions that have only a small or unlikely (net) benefit for the patient. Steps 1-3 are ethically justified by the principles of beneficence, nonmaleficence, and respect for autonomy, step 4 by the principles of justice. For decisions on step 4, explicit cost-conscious guidelines should be developed locally or regionally. Following the four-step model can contribute to ethically defensible, cost-conscious decision-making at the microlevel. In addition, physicians' rationing decisions should meet basic standards of procedural fairness. Regular cost-case discussions and clinical ethics consultation should be available as decision support. Implementing step 4, however, requires first of all a clear political legitimation with the corresponding legal framework.

[Cancer screening from the perspective of public health ethics]. / Krebsfrüherkennung aus Sicht der Public-Health-Ethik.

Cancer screening programs aim at reducing the tumor-related morbidity and mortality by early detection of malignant tumors or precancerous lesions. The basic ethical dilemma in cancer screening is, however, that many people have to be exposed to the burdens and risks of the intervention for a few people to benefit from early cancer diagnosis. This article discusses under which conditions it is ethically acceptable to offer or even recommend cancer screening. First, the benefit of the program in terms of a reduced cancer-related mortality should be proven by randomized controlled trials. The risks and burdens of the program related to the side effects of the investigation itself, false-positive findings, as well as overdiagnoses and overtherapy should be in an acceptable relationship to the expected benefit of the program. In addition to a solid empirical scientific basis, the benefit-harm evaluation necessarily involves value judgments. The potential participants in the screening program therefore should receive transparent, objective, unbiased, and understandable information to enable them to make a truly informed choice about participation. Given the complex benefit-risk assessment, it is discussed whether-and if so under which circumstances-it is ethically acceptable to make a recommendation for or against participation in a cancer screening program. Socioempirical research, such as focus group studies and public deliberations, can be used to elicit the preferences and value judgments of members of the target population that should be taken into consideration in recommendations about a cancer screening program.

[German "Triage Act"-Regulation with fatal consequences]. / "Triagegesetz" ­ Regelung mit fatalen Folgen.

With the coming into force of § 5c of the Infection Protection Act (IfSG), the so-called Triage Act, on 14 December 2022, a protracted discussion has come to a provisional conclusion, the result of which physicians and social associations but also lawyers and ethicists are equally dissatisfied. The explicit exclusion of the discontinuation of treatment that has already begun in favor of new patients with better chances of success (so-called tertiary or ex-post triage) prevents allocation decisions with the aim of enabling as many patients as possible to beneficially participate in medical care under crisis conditions. The result of the new regulation is de facto a first come first served allocation, which is associated with the highest mortality even among individuals with limitations or disabilities and was rejected by a large margin as unfair in a population survey. Mandating allocation decisions based on the likelihood of success but which are not permitted to be consistently implemented and prohibiting, for example the use of age and frailty as prioritization criteria, although both factors most strongly determine the short-term probability of survival according to evident data, shows the contradictory and dogmatic nature of the regulation. The only remaining possibility is the consistent termination of treatment that is no longer indicated or desired by the patient, regardless of the current resource situation; however, if a different decision is made in a crisis situation than in a situation without a lack of resources, this practice would not be justified and would be punishable. Accordingly, the highest efforts must be set on legally compliant documentation, especially in the stage of decompensated crisis care in a region. The goal of enabling as many patients as possible to beneficially participate in medical care under crisis conditions is in any case thwarted by the new German Triage Act.

[Ethical basis of priority setting in healthcare]. / Ethische Grundlagen der Priorisierung im Gesundheitswesen.

The debate about priorities in healthcare has also started in Germany. Because of the special moral significance of health and healthcare, priority setting in healthcare also involves ethical issues. After clarifying the relationship between priority setting and rationing, I first discuss whether it is ethically acceptable or even mandated to set priorities in healthcare. If this first question is answered with "yes", the following question is how the priorities can be determined in an ethically defensible way. I will try to show that it is impossible to justify priorities in healthcare within a liberal theory of justice that is neutral towards substantive conceptions of the good life. We rather need a deliberative decision process about how we want to live in the face of illness, suffering, and death. Only by reference to a substantial concept of a good life is it possible to define and justify healthcare priorities. A national priority-setting commission could play an important role in stimulating this deliberation and developing general recommendations according to which criteria and procedures priorities should be set in the German healthcare system. The application of this general framework requires the cooperation of medical scientific and physician organizations.

Systematic reviews of empirical bioethics.

BACKGROUND: Publications and discussions of survey research in empirical bioethics have steadily increased over the past two decades. However, findings often differ among studies with similar research questions. As a consequence, ethical reasoning that considers only parts of the existing literature and does not apply systematic reviews tends to be biased. To date, we lack a systematic review (SR) methodology that takes into account the specific conceptual and practical challenges of empirical bioethics. METHODS: The steps of systematically reviewing empirical findings in bioethics are presented and critically discussed. In particular, (a) the limitations of traditional SR methodologies in the field of empirical bioethics are critically discussed, and (b) conceptual and practical recommendations for SRs in empirical bioethics that are (c) based on the authors' review experiences in healthcare ethics are presented. RESULTS: A 7-step approach for SRs of empirical bioethics is proposed: (1) careful definition of review question; (2) selection of relevant databases; (3) application of ancillary search strategies; (4) development of search algorithms; (5) relevance assessment of the retrieved references; (6) quality assessment of included studies; and (7) data analysis and presentation. Conceptual and practical challenges arise because of various peculiarities in reviewing empirical bioethics literature and can lead to biased results if they are not taken into account. CONCLUSIONS: If suitably adapted to the peculiarities of the field, SRs of empirical bioethics provide transparent information for ethical reasoning and decision-making that is less biased than single studies.

[Advance directive consultations - A study of selected consultation services in the Munich region]. / Beratung zur Patientenverfügung.

BACKGROUND: So far, advance directives (AD) are often used ineffectively in Germany. Counseling for advance directives is neither legally required nor are quality standards available. Little is known about the structure and content of the counseling offered by the many different providers. The goal of this study was to assess the current practice and possible improvements of AD consultations by different professional groups in the Munich region in Germany compared to international Advance Care Planning (ACP) programs as best practice models. METHODS: An explorative online survey (using the Likert scale) of general practitioners, notaries, nurses and hospice workers in the Munich area was conducted. The data were analyzed using SPSS and Excel. RESULTS: Content and structure of counseling services differ not only between but also within counseling groups, sometimes considerably. Consultations mostly last up to 60 minutes and included 1-2 sessions. Despite the fact that most counselors (46-79 % in the respective groups) favor routinely offered consultations, most counseling sessions are initiated by the consulted individuals themselves. Among other things, counseling sessions cover the topics of hydration (often / always [o / a] 69-97 %), permanent unconsciousness (o / a 48-94 %) and terminal illnesses (o / a 77-97 %). Especially the participation of future legal representatives in the counseling sessions (o / a 18-85 %), the drafting of emergency plans (0-45 %) and the completion of advance directives within the counseling session (29-51 %) was heterogeneous. CONCLUSIONS: The current counseling practice for advance directives varies considerably and does not yet reliably meet the best practice standards of ACP programs. This study thus underscores the need for comprehensive ACP programs.

Recommendations for the ethical development and use of medical decision-support systems.

Medical decision support systems (MDSS) play an increasingly important role in medical practice. By assisting physicians with making clinical decisions, MDSS are expected to improve the quality of medical care. However, there are also concerns that malfunctioning or inappropriate use of MDSS could jeopardize the well-being of the patient. While several authors have already discussed ethical issues arising with the use of computer-assisted medical decision making, there is still no consensus about the ethically appropriate use of MDSS. Based on a review and synthesis of previous relevant work, this paper proposes a comprehensive set of recommendations for the ethical development and application of MDSS.

[Nosocomial measles infections]. / Nosokomiale Maserninfektionen.

Measles is re-emerging in several developed countries because of suboptimal vaccination coverage. Health-care facilities play a crucial role in the transmission of measles infection. Nosocomial measles may contribute for an important part of cases in measles epidemics, especially in countries where measles is largely under control. The risk of acquiring measles is estimated to be 2 to 19 times higher for susceptible healthcare personnel (HCP) than for the general population. Measles vaccination of HCP should be included by all health care facilities as part of a strict occupational health program. All HCP should have documented evidence of measles immunity. Immunity against measles should be a prerequisite for working in areas where the most vulnerable patients are cared for. Both occupational and public health measures are needed to ensure that nosocomial measles should be comprehensively monitored and consistently prevented.

[Does patient safety justify mandatory vaccinations?]. / Rechtfertigt der Patientenschutz verpflichtende Impfungen?

BACKGROUND AND OBJECTIVES: Medical and dental students belong to a group of health care workers (HCWs) who are frequently exposed to patients with occupationally transmissible infectious diseases. Vaccinations are the most effective interventions to protect HCWs and patients from vaccine-preventable infectious diseases. Despite decades of effort to encourage HCWs to be immunized, vaccination levels (e. g. influenza) remain insufficient. METHODS: To assess the attitudes of German medical and dental students towards mandatory immunizations, an anonymous questionnaire was offered to medical and dental students of the University of Frankfurt/Main, Germany. Overall, 56.9 % (1823/3200) of all medical and dental students attended to the study. RESULTS: This study - so far the largest study done on this issue - showed that almost 88.5 % of the responding medical and dental students would accept mandatory vaccinations for HCWs. CONCLUSION: Contrary to the widespread concern that a vaccination requirement would cause resistance, our data support that mandatory vaccinations (at least for HCWs who care for immunocompromised patients) might be widely accepted.

[Is there health care rationing in German hospitals? How exactly do we know and why should it not be the most important question?]. / Wird in deutschen Kliniken rationiert oder nicht? Wie genau wir es wissen und warum es nicht die wichtigste Frage sein sollte.

A questionnaire study, conducted by the authors among a representative sample of hospital doctors in Germany, showed that health care rationing in German hospitals is already a fact. But since the results were published in 2009 the validity of its findings has been questioned. This article provides empirical data to demonstrate that the findings are not biased to any significant extent by misunderstandings or political motivation of the responding doctors. There is thus an urgent need for action in support of medical professionals to make it possible for them to deal with implicit rationing and with the potential disadvantages to which vulnerable groups of patients may be exposed. Taking into account health opportunity costs, increased funding in the health sector should not be the primary demand. The availability and critical appraisal of scientific evidence on the risk/benefit ratio of medical interventions must first be improved in order to optimize the administration of scarce health care resources in a medically rational way so that it is ethically and legally acceptable as well as economically reasonable.

[Limiting life-prolonging treatments: a practical guidance reflecting the current legislation in Germany]. / Begrenzung lebenserhaltender Massnahmen: Eine Handreichung für die Praxis auf der Grundlage der aktuellen Gesetzgebung.

From the general ethical and legal requirements of medical interventions it can be inferred when life-prolonging treatments can or should be limited: If the intervention has no benefit for the patient and/or the properly informed patient refuses to consent to the intervention. Two questions are especially challenging: When are medical interventions futile? And: How should decisions be made on behalf of incompetent patients? In accordance with prior high court rulings, the new Civil Law legislation in Germany provides three standards for proxy decision making: (1) the patients' written advance directive, (2) oral treatment preferences and substituted judgement, and (3) the patient's best interest. Thereby, (1) has priority over (2) and (2) has priority over (3). In addition, the article discusses conflicts between autonomy and well-being of the patient.

[Extent and impact of bedside rationing in German hospitals: results of a representative survey among physicians]. / Ausmass und Auswirkungen von Rationierung in deutschen Krankenhäusern. Arztliche Einschätzungen aus einer repräsentativen Umfrage.

BACKGROUND: Healthcare rationing is increasingly discussed among German physicians. However, in contrast to the relatively intense debates on how to prioritize and ration on the macro level of the health system, there is hardly any discussion on how doctors can make the unavoidable rationing decisions on the micro level in a medically and ethically appropriate manner. The development of both accountable and feasible guidance requires empirical evidence about the prevalence of bedside rationing and a more in-depth understanding of the practical challenges. METHODS: Based on the official German hospital registry a national survey was performed nationwide among 1,137 randomly selected physicians working in cardiology or critical care medicine. RESULTS: 68% of the respondents stated that they had already withheld from patients medical services with a potential benefit for the patient because of cost considerations. However, only few of them indicated that this happens often. The frequency of bedside rationing differed, in some cases significantly, in relation to specialty, professional status and hospital funding. The majority of clinicians describes a negative impact of cost pressure on their work satisfaction and on the patient-doctor relationship. German clinicians have become aware of only a few opportunities that would allow them to increase their efficiency with a view to avoiding healthcare rationing. Instead, more then 50 % of the doctors considered additional funding for the health care system, through higher contributions to the statutory health insurance or higher out-of-pocket spending by patients, to be an acceptable approach to dealing with scarce resources. CONCLUSION: There is a need to develop explicit methods that support physicians in making inevitable rationing decisions at the bedside. Such methods must be accompanied by consultation procedures so that a rational and fair use of scarce health care resources is achieved.

The ethics of mandatory vaccination against influenza for health care workers.

Vaccination of health care workers (HCW) in long-term care results in indirect protection of patients who are at high-risk for influenza. The voluntary uptake of influenza vaccination among HCW is generally low. We argue that institutions caring for frail elderly have the responsibility to implement voluntary programmes for vaccination against influenza of HCW. When uptake falls short a mandatory programme may be justified. The main justification stems from the duty of care givers not to harm one's patient when one knows there is a significant risk of harm and the intervention to reduce this chance has a favourable balance of benefit over burdens and risks.