Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline

Background: While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and healthy immune system to re-establish immune tolerance for a long period of time. A number of mostly open-label, uncontrolled studies conducted over the past 20 years collected about 4000 cases. They uniformly reported high efficacy of AHSCT in controlling MS inflammatory disease activity, more markedly beneficial in relapsing-remitting MS. Immunological studies provided evidence for qualitative immune resetting following AHSCT. These data and improved safety profiles of transplantation procedures spurred interest in using AHSCT as a treatment option for MS. Objective: To develop expert consensus recommendations on AHSCT in Germany and outline a registry study project. Methods: An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of virtual meetings. Results: We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS based on the Swiss criteria. Current data indicate that patients who are most likely to benefit from AHSCT have relapsing-remitting MS and are young, ambulatory and have high disease activity. Treatment data with AHSCT will be collected within the German REgistry Cohort of autologous haematopoietic stem CeLl trAnsplantation In MS (RECLAIM). Conclusion: Further clinical trials, including registry-based analyses, are urgently needed to better define the patient characteristics, efficacy and safety profile of AHSCT compared with other high-efficacy therapies and to optimally position it as a treatment option in different MS disease stages. Keywords: Autologous haematopoietic stem cell transplantation (AHSCT), multiple sclerosis, registry study, treatment recommendation

1. Netzwerktreffen Ethikberatung in der Psychiatrie

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Definition</jats:title> <jats:p>The routinization of prenatal diagnosis is the source of bioethical and policy debates regarding choice, autonomy, access, and protection. To understand these debates in the context of cultural diversity and moral pluralism, we compare Israel and Germany, focusing on two recent repro-genetic “hot spots” of such policy-making at the beginning of life: pre-implantation genetic diagnosis (PGD) and non-invasive prenatal genetic testing (NIPT), two cutting-edge repro-genetic technologies that are regulated and viewed very differently in Germany and Israel, reflecting different medicolegal policies as well as public and bioethical considerations.</jats:p> </jats:sec><jats:sec> <jats:title>Arguments</jats:title> <jats:p>First, we compare policy-making in the context of PGD for HLA (human leukocyte antigen) typing, used to create sibling donors, approved in Israel under specific conditions while prohibited in Germany. Second, we compare policy-making in the context of NIPT, which came under fire in Germany, while in Israel there has been little public debate about it.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Both countries justify their contrasting policies as reflecting a concern for the well-being and care of the embryo/child, thus highlighting different concepts of embryo/child protection, (relational) autonomy, family relations, and the impact of religion and history on the promotion/protection of life. We use the juxtaposition of PGD and NIPT to highlight some inconsistencies in policies concerning the protection of extra- and intra-corporeal embryos. We conclude by drawing on the comparison to show how national variations exist alongside co-evolution.</jats:p> </jats:sec&gt

Testimoniale Ungerechtigkeit gegenüber Menschen mit psychischer Erkrankung in der Gesundheitsversorgung. Eine konzeptionelle und ethische Analyse

Definition of the problem!#!Statistically, people with mental disorders die prematurely due to preventable and treatable somatic illness. We analyze testimonial injustice as one mechanism which contributes to poor quality of health care for people with mental disorders.!##!Argument!#!Practices in somatic health care are structured by ableist networks of social meaning. This leads to a systemic downgrading of the epistemic capacities of people with mental disorders and to a disproportionate focus on psychic disability and mental disorder in diagnostic processes. As a consequence, people with mental disorders are at high risk of suffering testimonial injustice in somatic health care. Testimonial injustice refers to the unjustified downgrading of a speaker's credibility based on a prejudice against their social identity. Testimonial injustice has important epistemic and ethical implications. It can lead to medical errors with serious health consequences for those affected. It can also lead to a loss of trust in the health system by people with mental disorders.!##!Conclusion!#!Testimonial injustice against people with mental disorders reproduces structural discrimination and is ethically problematic. Practices of somatic health care need to be improved to reduce discrimination

Epistemic appropriation and the ethics of engaging with trans community knowledge in the context of mental healthcare research

Mental healthcare research increasingly focuses the needs of trans people and, in doing so, acknowledges knowledge and epistemic resources developed in trans communities. In this article, we aim to raise awareness of an ethical issue described by Emmalon Davis that may arise in the context of engaging with community knowledge and epistemic resources: the risk of epistemic appropriation. It is composed of two harms (1) a detachment of epistemic resources developed in the originating community and (2) a misdirection of these epistemic resources for epistemic goals of a dominant community. In this article, we map and discuss the ethical concerns in using knowledge originating in trans communities in terms of epistemic appropriation in the context of mental healthcare research. We first argue that misgendering, failing to reference non-academic sources and a lack of attribution in community authorship are forms of epistemic detachment. Second, we problematize cases of epistemic misdirection of trans epistemic resources, focusing on the examples of detransition and transition regret. We discuss harms related to epistemic appropriation in relationship to risks to safety. The article aims to raise awareness about the risk of epistemic appropriation both in researchers engaging with trans knowledge as well as in mental healthcare workers who seek information on trans

Situational vulnerability within mental healthcare – a qualitative analysis of ethical challenges during the COVID-19 pandemic

Abstract Background Mental healthcare users and patients were described as a particularly vulnerable group in the debate on the burdens of the COVID-19 pandemic. Just what this means and what normative conclusions can be derived from it depend to a large extent on the underlying concept of vulnerability. While a traditional understanding locates vulnerability in the characteristics of social groups, a situational and dynamic approach considers how social structures produce vulnerable social positions. The situation of users and patients in different psychosocial settings during the COVID-19 pandemic has not yet been comprehensively considered and ethically analyzed under the aspect of situational vulnerability. Methods We present the results of a retrospective qualitative analysis of a survey of ethical challenges in different mental healthcare facilities of a large regional mental healthcare provider in Germany. We evaluate them ethically using a dynamic and situational understanding of vulnerability. Results Difficulties in implementing infection prevention measures, restrictions of mental health services in favor of infection prevention, social isolation, negative health effects on mental healthcare users and patients, and challenges in implementing regulations on state and provider levels within the local specificities emerged across different mental healthcare settings as ethically salient topics. Conclusions Applying a situational and dynamic understanding of vulnerability allows the identification of specific factors and conditions that have contributed to an increased context-dependent vulnerability for mental healthcare users and patients. These factors and conditions should be considered on the level of state and local regulations to reduce and address vulnerability