Intentional sedation as a means to ease suffering: a systematically constructed terminology for sedation in palliative care

BACKGROUND: Terminology concerning sedation in palliative care is heterogeneous, vague, and difficult to apply with negative impact on the reliability of quantitative data, practice, and ethical discourse. DESIGN: To clarify the concept, we systematically developed definitions of core terms in an interdisciplinary research group comprising palliative care, ethics, law, and philosophy, integrating feedback from external experts. RESULTS: We define terms stepwise, separating matters of terminology (What is the practice?) from matters of good practice (How to use it?). We start with an operational definition of “reduced level of consciousness” (score < 0 on the Richmond Agitation-Sedation Scale modified for palliative care inpatients (RASS-PAL), followed by defining “sedating,” “sedation,” and “intentional sedation” as the result or process of sedating a patient as a means of achieving a previously defined treatment goal and the terms “light,” “deep,” “temporary,” and “sedation until death.” CONCLUSION: The terminology facilitates the precise phrasing of aims, indications, and rules for good practice. Empirical research on acceptance and feasibility is needed

Optimization in computational systems biology

Optimization aims to make a system or design as effective or functional as possible. Mathematical optimization methods are widely used in engineering, economics and science. This commentary is focused on applications of mathematical optimization in computational systems biology. Examples are given where optimization methods are used for topics ranging from model building and optimal experimental design to metabolic engineering and synthetic biology. Finally, several perspectives for future research are outlined

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A New Argument Scheme for Causal Explanations by Analogy? The Case of Galileo’s Explanation of the Tides

This paper is a case study. After formulating three norms for critical assessment of argumentation (section 1), I give a brief overview of Galileo’s argumentative strategy in his Dialogue and present his argument for the cause of the tides, which appears as an argument by analogy (section 2). I then discuss possible reconstructions of this argumentation, with one particular suggestion in detail. These arguments seem to fall short, given the aforementioned set of norms (section 3). This leads to my own proposal of Galileo’s argument. I defend this proposal and it’s general idea - that is, the argument’s pattern. It will be classified as ‘interventionist’ and useful regarding the goals of critical assessment (section 4). Finally, I suggest that the pattern of argument is applicable to other cases and useful for applied theory of science (section 5)

Expert-approved best practice recommendations on the use of sedative drugs and intentional sedation in specialist palliative care (SedPall)

Abstract Background The use of sedative drugs and intentional sedation in end-of-life care is associated with clinical, ethical and legal challenges. In view of these and of the issue’s great importance to patients undergoing intolerable suffering, we conducted a project titled SedPall (“From anxiolysis to deep continuous sedation – Development of recommendations for sedation in palliative care“) with the purpose of developing best practice recommendations on the use of sedative drugs and intentional sedation in specialist palliative care and obtaining feedback and approval from experts in this area. Design Our stepwise approach entailed drafting the recommendations, obtaining expert feedback, conducting a single-round Delphi study, and convening a consensus conference. As an interdisciplinary group, we created a set of best practice recommendations based on previously published guidance and empirical and normative analysis, and drawing on feedback from experts, including patient representatives and of public involvement participants. We set the required agreement rate for approval at the single-round Delphi and the consensus conference at ≥80%. Results Ten experts commented on the recommendations’ first draft. The Delphi panel comprised 50 experts and patient and public involvement participants, while 46 participants attended the consensus conference. In total, the participants in these stages of the process approved 66 recommendations, covering the topics “indications”, “intent/purpose [of sedation]”, “decision-making”, “information and consent”, “medication and type of sedation”, “monitoring”, “management of fluids and nutrition”, “continuing other measures”, “support for relatives”, and “team support”. The recommendations include suggestions on terminology and comments on legal issues. Conclusion Further research will be required for evaluating the feasibility of the recommendations’ implementation and their effectiveness. The recommendations and the suggested terminology may serve as a resource for healthcare professionals in Germany on the use of sedative drugs and intentional sedation in specialist palliative care and may contribute to discussion on the topic at an international level. Trial Registration DRKS00015047 (German Clinical Trials Register