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Background: The European Association for Palliative Care (EAPC) acknowledges palliative sedation as an important, broadly accepted intervention for patients with life-limiting disease experiencing refractory symptoms. The EAPC therefore developed 2009 a framework on palliative sedation. A revision was needed due to new evidence from literature, ongoing debate and criticism of methodology, terminology and applicability., Aim: To provide evidence- and consensus-based guidance on palliative sedation for healthcare professionals involved in end-of-life care, for medical associations and health policy decision-makers., Design: Revision between June 2020 and September 2022 of the 2009 framework using a literature update and a Delphi procedure., Setting: European., Participants: International experts on palliative sedation (identified through literature search and nomination by national palliative care associations) and a European patient organisation., Results: A framework with 42 statements for which high or very high level of consensus was reached. Terminology is defined more precisely with the terms suffering used to encompass distressing physical and psychological symptoms as well as existential suffering and refractory to describe the untreatable (healthcare professionals) and intolerable (patient) nature of the suffering. The principle of proportionality is introduced in the definition of palliative sedation. No specific period of remaining life expectancy is defined, based on the principles of refractoriness of suffering, proportionality and independent decision-making for hydration. Patient autonomy is emphasised. A stepwise pharmacological approach and a guidance on hydration decision-making are provided., Conclusions: This is the first framework on palliative sedation using a strict consensus methodology. It should serve as comprehensive and soundly developed information for healthcare professionals., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that there is no conflict of interest. The authors (apart from HB and SMS) participated in the Delphi process. However, the two researchers coordinating the consensus process and the evaluation (HB and SMS) did not participate, thus preventing any bias in the evaluation.

In 2009, the European Association for Palliative Care (EAPC) developed a framework on palliative sedation, acknowledging this practice as an important and ethically acceptable intervention of last resort for terminally ill patients experiencing refractory symptoms. Before and after that, other guidelines on palliative sedation have been developed in Europe with variations in terminology and concepts. As part of the Palliative Sedation project (Horizon 2020 Funding No. 825700), a revision of the EAPC framework is planned. The aim of this article is to analyze the most frequently used palliative sedation guidelines as reported by experts from eight European countries to inform the discussion of the new framework. The three most reported documents per country were identified through an online survey among 124 clinical experts in December 2019. Those meeting guideline criteria were selected. Their content was assessed against the EAPC framework on palliative sedation. The quality of their methodology was evaluated with the Appraisal Guideline Research and Evaluation (AGREE) II instrument. Nine guidelines were included. All recognize palliative sedation as a last-resort treatment for refractory symptoms, but the criterion of refractoriness remains a matter of debate. Most guidelines recognize psychological or existential distress as (part of) an indication and some make specific recommendations for such cases. All agree that the assessment should be multiprofessional, but they diverge on the expertise required by the attending physician/team. Regarding decisions on hydration and nutrition, it is proposed that these should be independent of those for palliative sedation, but there is no clear consensus on the decision-making process. Several weaknesses were highlighted, particularly in areas of rigor of development and applicability. The identified points of debate and methodological weaknesses should be considered in any update or revision of the guidelines analyzed to improve the quality of their content and the applicability of their recommendations.

Transitions at the End of Life Abstract. Transitions in places of care are often associated with a high symptom burden, a constantly growing care network and / or frequent changes between ambulatory and inpatient care. Interface problems occur at the organizational, communication, information, and knowledge levels, as well as in the networking of care facilities and services. Indications of care deficits at the end of life and the extent to which unsuccessful symptom relief or frequent changes between ambulatory and inpatient care can be cushioned are discussed on the basis of study results. At the end of life, open empathic conversations, symptom relief, psycho-social support, and, if necessary, the addressing of spiritual questions with needs-based availability of facilities and services are important cornerstones for the dying and the bereaved. An overview of the various kinds of hospice and palliative care services in the ambulatory and inpatient sector, including those for the bereaved, will also be presented.

Objective : The present study aimed to investigate the correlation between moral distress and mental health symptoms, socio-demographic, occupational, and COVID-19-related variables, and to determine differences in healthcare workers' (HCW) moral distress during the first wave of the COVID-19 pandemic. Method : Data from 3,293 HCW from a web-based survey conducted between the 20th of April and the 5th of July 2020 were analyzed. We focused on moral distress (Moral Distress Thermometer, MDT), depressive symptoms (Patient Health Questionnaire-2, PHQ-2), anxiety symptoms (Generalized Anxiety Disorder-2, GAD-2), and increased general distress of nurses, physicians, medical-technical assistants (MTA), psychologists/psychotherapists, and pastoral counselors working in German hospitals. Results : The strongest correlations for moral distress were found with depressive symptoms, anxiety symptoms, occupancy rate at current work section, and contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nurses and MTA experienced significantly higher moral distress than physicians, psychologists/psychotherapists, and pastoral counselors. The average level of moral distress reported by nurses from all work areas was similar to levels which before the pandemic were only experienced by nurses in intensive or critical care units. Conclusion : Results indicate that moral distress is a relevant phenomenon among HCW in hospitals during the COVID-19 pandemic, regardless of whether they work at the frontline or not and requires urgent attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schneider, Hiebel, Kriegsmann-Rabe, Schmuck, Erim, Morawa, Jerg-Bretzke, Beschoner, Albus, Hannemann, Weidner, Steudte-Schmiedgen, Radbruch, Brunsch and Geiser.)

Objective: A sense of security is important in palliative home care. Yet, knowledge about which components contribute most to feeling secure from the patients' and family caregivers' perspectives, especially since the introduction of specialist palliative home care, is sparse. The goal of the current study was to determine the key components contributing to a sense of security and how they relate to each other as experienced by patients and family caregivers in specialist and generalist palliative home care., Methods: The current sub-study, as part of a larger study, was performed in different regions in Germany. Palliative care patients and family caregivers of at least 18 years of age, being cared for at home were interviewed using semi-structured interview guides following a three-factor model and analyzed by using a combined quantitative-qualitative-content approach., Results: One hundred and ninty-seven patients and 10 carers completed interviews between December 2017 and April 2019. The majority of patients were diagnosed with an oncological disease. Sense of security was mentioned particularly often suggesting its high relevance. We identified nine subcategories that were all mentioned more frequently by specialist than generalist palliative home care recipients in the following order of priority and relation: (i) patient-centeredness: availability, provision of information/education, professional competence, patient empowerment, and trust (ii) organizational work: comprehensive responsibility, external collaboration, and internal cooperation, and (iii) direct communication., Significance of Results: The work of specialist palliative home care services in particular was perceived as very effective and beneficial. Our findings confirm a previously developed three-factor model allowing for generalizability and revealed that availability was most important for improving the sense of security for effective palliative home care.

Introduction: The COVID-19 pandemic resulted in severe detrimental effects on the mental well-being of health care workers (HCW). Consequently, there has been a need to identify health-promoting resources in order to mitigate the psychological impact of the pandemic on HCW., Objective: Our objective was to investigate the association of sense of coherence (SOC), social support and religiosity with self-reported mental symptoms and increase of subjective burden during the COVID-19 pandemic in HCW., Methods: Our sample comprised 4324 HCW of four professions (physicians, nurses, medical technical assistants (MTA) and pastoral workers) who completed an online survey from 20 April to 5 July 2020. Health-promoting resources were assessed using the Sense of Coherence Scale Short Form (SOC-3), the ENRICHD Social Support Inventory (ESSI) and one item on religiosity derived from the Scale of Transpersonal Trust (TPV). Anxiety and depression symptoms were measured with the PHQ-2 and GAD-2. The increase of subjective burden due to the pandemic was assessed as the retrospective difference between burden during the pandemic and before the pandemic., Results: In multiple regressions, higher SOC was strongly associated with fewer anxiety and depression symptoms. Higher social support was also related to less severe mental symptoms, but with a smaller effect size, while religiosity showed minimal to no correlation with anxiety or depression. In professional group analysis, SOC was negatively associated with mental symptoms in all groups, while social support only correlated significantly with mental health outcomes in physicians and MTA. In the total sample and among subgroups, an increase of subjective burden was meaningfully associated only with a weaker SOC., Conclusion: Perceived social support and especially higher SOC appeared to be beneficial for mental health of HCW during the COVID-19 pandemic. However, the different importance of the resources in the respective occupations requires further research to identify possible reasons., Competing Interests: The authors have declared that no competing interests exist.

Background: Systemic treatment with sirolimus, as used for immunosuppression in transplant patients, results in markedly low rates of in-stent restenosis. Since the underlying mechanisms remain obscure, we aimed to determine the molecular and cellular effects of systemic sirolimus treatment on vascular remodeling processes., Methods and Results: Systemic sirolimus treatment significantly reduced smooth muscle cell (SMC) proliferation 14days after wire-induced injury and neointima formation 28days after injury in C57BL/6 mice, while simultaneously impairing re-endothelialization. Interestingly, in vitro, sirolimus had no direct effect on the proliferation of SMC or endothelial cells (EC) at serum concentrations observed after systemic application. In contrast, sirolimus reduced the adhesion of leukocytes (CD45 + ) and bone marrow-derived progenitor cells (CD34 + ) to activated EC by down-regulating the adhesion molecules ICAM-1 and VCAM-1. In addition, sirolimus treatment also significantly reduced the upregulation of ICAM-1 and VCAM-1 and the recruitment of monocytic cells (MOMA-2 + ) in neointimal lesions in vivo., Conclusion: Our findings show that systemic sirolimus treatment effectively prevents SMC and EC proliferation in vivo without directly affecting these cells. Instead, sirolimus prevents neointima formation and re-endothelialization by attenuating the inflammatory response after injury with secondary effects on SMC and EC proliferation. Thus, despite a similar net effect, the mechanisms of systemic sirolimus treatment are largely different from the local effects achieved after application of sirolimus-eluting stents., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

The G534E polymorphism (Marburg I [MI]) of factor VII-activating protease (FSAP) is associated with carotid stenosis and cardiovascular disease. We have previously demonstrated that FSAP is present in atherosclerotic plaques and it is a potent inhibitor of vascular smooth muscle proliferation and migration in vitro. The effect of wild-type (WT)- and MI-FSAP on neointima formation in the mouse femoral artery after wire-induced injury was investigated. Local application of WT-FSAP led to a 70% reduction in the neointima formation, and this effect was dependent on the protease activity of FSAP. MI-FSAP did not inhibit neointima formation in vivo. This is due to a reduced proteolytic activity of MI-FSAP, compared to WT-FSAP, toward platelet-derived growth factor BB, a key mediator of neointima development. The inability of MI-FSAP to inhibit vascular smooth muscle accumulation explains the observed linkage between the MI-polymorphism and increased cardiovascular risk. Hence, FSAP has a protective function in the vasculature, and analysis of MI polymorphism is likely to be clinically relevant in restenosis.