Recognizing animal personhood in compassionate conservation

Compassionate conservation is based on the ethical position that actions taken to protect biodiversity should be guided by compassion for all sentient beings. Critics argue that there are 3 core reasons harming animals is acceptable in conservation programs: the primary purpose of conservation is biodiversity protection; conservation is already compassionate to animals; and conservation should prioritize compassion to humans. We used argument analysis to clarify the values and logics underlying the debate around compassionate conservation. We found that objections to compassionate conservation are expressions of human exceptionalism, the view that humans are of a categorically separate and higher moral status than all other species. In contrast, compassionate conservationists believe that conservation should expand its moral community by recognizing all sentient beings as persons. Personhood, in an ethical sense, implies the individual is owed respect and should not be treated merely as a means to other ends. On scientific and ethical grounds, there are good reasons to extend personhood to sentient animals, particularly in conservation. The moral exclusion or subordination of members of other species legitimates the ongoing manipulation and exploitation of the living worlds, the very reason conservation was needed in the first place. Embracing compassion can help dismantle human exceptionalism, recognize nonhuman personhood, and navigate a more expansive moral space

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

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 study of the clinical impact and outcomes of pharmacist-led interventions in the outpatient model of care for Hepatitis C patients in Ireland and their development into a novel complex intervention toolkit.

Given the high rates of sustained virological response and good tolerability of direct-acting antiviral regimens, international guidelines now recommend that all Hepatitis C infected patients be considered for access to therapy. Hepatitis C infection presents specific challenges that requires having diversity in the available models of Hepatitis C patient care, regardless of who prescribes the DAA therapy. Non-specialist healthcare professionals treating patients with Hepatitis C infection, as part of a broader community-based model of care, require the right tools to enable them to successfully engage in treating patients. The aim of this research project was to develop, evaluate and implement a complex intervention toolkit, based on pharmacist-led interventions in Hepatitis C patients care, to ensure optimum pharmacotherapy decision making at the initial prescribing step, and to increase training and prescribing rates among community treatment providers, who can reach the hard to treat populations whom are key if Hepatitis C elimination targets are to be achieved. Analysis of pharmacist-led interventions in Hepatitis C patient care, completed as part of this research identified a significant number of medication reconciliation variances and clinically significant drug-drug interactions which put patients at potential risk of Hepatitis C treatment failure, inappropriate co-morbidity management and patient morbidity. These study findings provided justification for both medication reconciliation and drug-drug interaction analysis to form the basis of the novel complex intervention toolkit. A key guiding resource identified in complex intervention toolkit development was the UK Medical Research Council framework, for the development and evaluation of complex interventions. The toolkit moved from initial design, based on the outcomes of primary research conducted, and progressed through stakeholder review, feasibility testing, a pilot study and then on to an evaluation study. The findings of the evaluation study confirmed the effectiveness of the PTPA toolkit in aiding pharmacists and doctors in selecting the optimum HCV treatment for patients (p <0.05) and in improving DDI detections rates among pharmacist, doctors and nurses (P< 0.05). The pre-treatment patient assessment (PTPA) complex intervention toolkit is a novel intervention incorporating all aspects of the PTPA process, to ensure optimum pharmacotherapy for all Hepatitis C patients in Ireland, across the continually expanding model of care, which strives to achieve Hepatitis C eradication. The potential for healthcare professionals working in all practice environments, including community, to safely assess and manage Hepatitis C treatment outside of specialist centres, can be supported using this toolkit. This type of capacity building within our limited healthcare resources is key to up-scaling the model of care in Ireland and internationally to achieve World Health Organisation elimination targets

A study of the clinical impact and outcomes of pharmacist-led interventions in the outpatient model of care for Hepatitis C patients in Ireland and their development into a novel complex intervention toolkit

Given the high rates of sustained virological response and good tolerability of direct-acting antiviral regimens, international guidelines now recommend that all Hepatitis C infected patients be considered for access to therapy. Hepatitis C infection presents specific challenges that requires having diversity in the available models of Hepatitis C patient care, regardless of who prescribes the DAA therapy. Non-specialist healthcare professionals treating patients with Hepatitis C infection, as part of a broader community-based model of care, require the right tools to enable them to successfully engage in treating patients. The aim of this research project was to develop, evaluate and implement a complex intervention toolkit, based on pharmacist-led interventions in Hepatitis C patients care, to ensure optimum pharmacotherapy decision making at the initial prescribing step, and to increase training and prescribing rates among community treatment providers, who can reach the hard to treat populations whom are key if Hepatitis C elimination targets are to be achieved. Analysis of pharmacist-led interventions in Hepatitis C patient care, completed as part of this research identified a significant number of medication reconciliation variances and clinically significant drug-drug interactions which put patients at potential risk of Hepatitis C treatment failure, inappropriate co-morbidity management and patient morbidity. These study findings provided justification for both medication reconciliation and drug-drug interaction analysis to form the basis of the novel complex intervention toolkit. A key guiding resource identified in complex intervention toolkit development was the UK Medical Research Council framework, for the development and evaluation of complex interventions. The toolkit moved from initial design, based on the outcomes of primary research conducted, and progressed through stakeholder review, feasibility testing, a pilot study and then on to an evaluation study. The findings of the evaluation study confirmed the effectiveness of the PTPA toolkit in aiding pharmacists and doctors in selecting the optimum HCV treatment for patients (p <0.05) and in improving DDI detections rates among pharmacist, doctors and nurses (P< 0.05). The pre-treatment patient assessment (PTPA) complex intervention toolkit is a novel intervention incorporating all aspects of the PTPA process, to ensure optimum pharmacotherapy for all Hepatitis C patients in Ireland, across the continually expanding model of care, which strives to achieve Hepatitis C eradication. The potential for healthcare professionals working in all practice environments, including community, to safely assess and manage Hepatitis C treatment outside of specialist centres, can be supported using this toolkit. This type of capacity building within our limited healthcare resources is key to up-scaling the model of care in Ireland and internationally to achieve World Health Organisation elimination targets

Theorie und Praxis verzahnen. Lebenslanges Lernen an Hochschulen

Ein zentrales Ziel des Bund-Länder-Wettbewerbs Aufstieg durch Bildung: offene Hochschulen ist es, den Ansatz des Lebenslangen Lernens im deutschen Hochschulsystem stärker zu verankern. Die Arbeit mit heterogenen, zum Teil für die Hochschulen neuen Zielgruppen hat vielfältige Implikationen - auch in Bezug auf die Gestaltung der Lehr-Lern-Formate. Diese stehen im Mittelpunkt des Teilprojektes Zielgruppengemäße Studienformate der Deutschen Universität für Weiterbildung (DUW). In diesem Band wird die zugrunde liegende Vorstellung einer Theorie-Praxis-Verzahnung an den Hochschulen auf ihre Eignung für das 21. Jahrhundert diskutiert. Dreh- und Angelpunkt ist dabei aus didaktisch-inhaltlicher Sicht vor allem die Orientierung an Kompetenzen und Lernergebnissen sowie die zentrale Rolle von Lehrenden. Der Band schließt mit einem international inspirierten Ausblick auf eine mögliche Zukunft der Hochschulen als Hochschulen des Lebenslangen Lernens. (Verlag

Recognizing animal personhood in compassionate conservation

Compassionate conservation is based on the ethical position that actions taken to protect biodiversity should be guided by compassion for all sentient beings. Critics argue that there are 3 core reasons harming animals is acceptable in conservation programs: the primary purpose of conservation is biodiversity protection; conservation is already compassionate to animals; and conservation should prioritize compassion to humans. We used argument analysis to clarify the values and logics underlying the debate around compassionate conservation. We found that objections to compassionate conservation are expressions of human exceptionalism, the view that humans are of a categorically separate and higher moral status than all other species. In contrast, compassionate conservationists believe that conservation should expand its moral community by recognizing all sentient beings as persons. Personhood, in an ethical sense, implies the individual is owed respect and should not be treated merely as a means to other ends. On scientific and ethical grounds, there are good reasons to extend personhood to sentient animals, particularly in conservation. The moral exclusion or subordination of members of other species legitimates the ongoing manipulation and exploitation of the living worlds, the very reason conservation was needed in the first place. Embracing compassion can help dismantle human exceptionalism, recognize nonhuman personhood, and navigate a more expansive moral space. https://doi.org/10.1111/cobi.13494 LinkedIn: https://www.linkedin.com/in/helenkopnina

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc