Predicting patients with dementia most at risk of needing psychiatric in-patient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study.

BACKGROUND: Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death. AIMS: To test whether individuals who are most likely to need enhanced care later in the disease course can be identified at the point of diagnosis, thus allowing the targeted intervention. METHOD: We used clinical information collected routinely in de-identified electronic patient records from two UK National Health Service (NHS) trusts to identify at diagnosis which individuals were at increased risk of needing enhanced care (psychiatric in-patient or intensive (crisis) community care). RESULTS: We examined the records of a total of 25 326 patients with dementia. A minority (16% in the Cambridgeshire trust and 2.4% in the London trust) needed enhanced care. Patients who needed enhanced care differed from those who did not in age, cognitive test scores and Health of the Nation Outcome Scale scores. Logistic regression discriminated risk, with an area under the receiver operating characteristic curve (AUROC) of up to 0.78 after 1 year and 0.74 after 4 years. We were able to confirm the validity of the approach in two trusts that differed widely in the populations they serve. CONCLUSIONS: It is possible to identify, at the time of diagnosis of dementia, individuals most likely to need enhanced care later in the disease course. This permits the development of targeted clinical interventions for this high-risk group.

Estimating demand for potential disease-modifying therapies for Alzheimer's disease in the UK.

BACKGROUND: Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring. AIMS: To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK. METHOD: We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment. RESULTS: We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally. CONCLUSIONS: Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.

Associations between rural/urban status, duration of untreated psychosis and mode of onset of psychosis: a mental health electronic clinical records analysis in the East of England, UK.

PURPOSE: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis. METHODS: We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015. We performed descriptive statistics and multivariable linear and multinomial regression to assess the relationships between the study outcomes and the independent variables. RESULTS: One hundred and fifty-five FEP patients were identified, with a mean age of 23.4 (SD, 5.3) years. The median DUP was 129.0 (IQR: 27.5-524.0) days. In rural areas, FEP patients were more likely to be employed and live with family than those in urban areas. A longer DUP was observed among patients with an insidious onset of psychosis compared with an acute onset (619.5 (IQR: 333.5-945.0)) vs. (17.0 (IQR: 8.0-30.5)) days respectively, p < 0.0001. We found evidence that the mode of onset of psychosis differed by employment status and living circumstances. There was insufficient evidence of rural/urban differences in DUP and mode of onset of psychosis. CONCLUSIONS: Our results suggest that the mode of onset of psychosis is an important indicator of treatment delay and could provide vital information for service planning and delivery. Sociodemographic variations in FEP exist in rural populations, and our findings are similar to those observed in urban settings.

The patient journeys of children and adolescents with depression: a study of electronic health records.

In England, children and adolescents with depression can seek treatment from specialist mental health services. We know little about how they journey through these services, or whether healthcare providers collect sufficient data to accurately appraise this. We aimed to summarise the child and adolescent depression pathway for two healthcare providers. This cohort study used de-identified electronic health records extracted from Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) and South London and Maudsley NHS Foundation Trust (SLaM). We identified referrals between 2015 and 2019 during which the referred patient received their first depression diagnosis aged < 18 years. We described patient demographic and clinical characteristics, and features of the referral. In total, n = 296 (CPFT) and n = 2502 (SLaM) patients had a referral which met eligibility criteria. In both sites, patients were more frequently female (CPFT 79.3%; SLaM 69.3%) and White ethnicity (CPFT 88.9%; SLaM 57.9%) as compared to respective population estimates for the Trusts' catchment areas. Patients typically received their first depression diagnosis during adolescence (median ages 16 in CPFT and 15 in SLaM). The most common comorbidity was anxiety disorder. Referrals were usually routine, to community teams specialising in the child age group. Commonly mentioned interventions included antidepressant medication, cognitive behavioural therapy, and dialectical behaviour therapy. However, pathways varied within and between sites, and the quality and consistency of some data was poor. These findings provide an overview of service pathways experienced by children and adolescents with depression, but also highlight that pathways can vary according to individual need and healthcare provider. More systematic collection of some data, and standardisation in record systems used by different providers, would be beneficial.

The Species Effect: Differential Sphingosine-1-Phosphate Responses in the Bone in Human Versus Mouse.

The deterioration of osteoblast-led bone formation and the upregulation of osteoclast-regulated bone resorption are the primary causes of bone diseases, including osteoporosis. Numerous circulating factors play a role in bone homeostasis by regulating osteoblast and osteoclast activity, including the sphingolipid-sphingosine-1-phosphate (S1P). However, to date no comprehensive studies have investigated the impact of S1P activity on human and murine osteoblasts and osteoclasts. We observed species-specific responses to S1P in both osteoblasts and osteoclasts, where S1P stimulated human osteoblast mineralisation and reduced human pre-osteoclast differentiation and mineral resorption, thereby favouring bone formation. The opposite was true for murine osteoblasts and osteoclasts, resulting in more mineral resorption and less mineral deposition. Species-specific differences in osteoblast responses to S1P were potentially explained by differential expression of S1P receptor 1. By contrast, human and murine osteoclasts expressed comparable levels of S1P receptors but showed differential expression patterns of the two sphingosine kinase enzymes responsible for S1P production. Ultimately, we reveal that murine models may not accurately represent how human bone cells will respond to S1P, and thus are not a suitable model for exploring S1P physiology or potential therapeutic agents.

Perceived Health Needs of Church Leaders and Members: A Secondary Data Analysis of the Mid-South Congregational Health Survey.

Needs assessments have been successful in helping communities and congregations focus their health ministry efforts; however, most have used leader perceptions of congregational health needs. The purpose of this study was to examine and compare the self-reported needs of both church leaders and members to be addressed by their congregation. Church leaders (n = 369) and members (n = 459) from 92 congregations completed the 2019 Mid-South Congregational Health Survey. Frequencies and generalized linear mixed models (GLMM) were performed to examine the top 10 self-reported needs and associations by church role, respectively. Of the top 10 congregational needs, anxiety or depression, high blood pressure, stress, and healthy foods were ranked identically regardless of church role. Church leaders perceived obesity and diabetes to be important congregational health needs, whereas members perceived affordable health care and heart disease to be important congregational health needs. GLMM, controlling for within-church clustering and covariates, revealed church leaders were more likely than members to report obesity (odds ratio [OR]: 1.93, 95% confidence interval [CI] = [1.39, 2.67], p < .0001) and diabetes (OR: 1.73, 95% CI = [1.24, 2.41], p = .001) as congregational needs. Findings display similarities and differences in needs reported by church role. Including many perspectives when conducting congregational health needs assessments will assist the development of effective faith-based health promotion programs.

Radiation Therapy for Primary Cutaneous Gamma Delta Lymphoma Prior to Stem Cell Transplantation.

We present a patient with widespread PCGD-TCL of the bilateral arms and legs, who underwent radiotherapy with 34 Gy in 17 fractions using circumferential VMAT and 3-D printed bolus to the four extremities prior to planned stem cell transplant, who was then found to have progression in the liver, lung, and skin, followed by drastic regression of all in and out-of-field lesions on imaging 1.5 months later. The cause of regression may be related to a radiation-induced abscopal effect from the immunomodulatory effects of radiation, or related to immune reactivation in the setting of cessation of systemic immunosuppressive agents.

Organoids in the Clinic: A Systematic Review of Outcomes.

Research on organoids has undergone significant advances during the last decade. However, outcomes from the use of organoids in clinical trials have not yet been documented. Therefore, there is an urgent need to assess the reporting of clinically relevant outcomes from organoid research in the scientific literature. This article presents a systematic review and appraisal of the published literature in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, together with a synopsis of recent relevant reviews. Surprisingly, no randomized controlled trials have reported clinical outcomes with any types of organoids. We found very few ongoing and registered studies that may provide clinically relevant results within this decade. Our screening and interpretation of the literature, including review articles, indicate a focus on technical and preclinical aspects of organoid research. This is the first systematic review of clinical trials involving organoids. Few clinical studies are planned or already underway, and, so far, no high-quality evidence relating to the clinical outcomes of organoid research has been published. The many promises of organoid research still need to be translated from bench to bed.

Mortality rates and proximal causes of death in patients with Lewy body dementia versus Alzheimer's disease: A longitudinal study using secondary care mental health records.

BACKGROUND: Previous studies have shown reduced survival in Lewy body dementia (LBD) compared to Alzheimer's disease (AD), but the reasons for this are not known. We identified cause of death categories accounting for the reduced survival in LBD. METHODS: We linked cohorts of patients with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and AD, with proximal cause of death data. We examined mortality by dementia group and hazard ratios for each death category by dementia group in males and females separately. In a specific focus on the dementia group with the highest mortality rate versus reference, we examined cumulative incidence to identify the main causes of death accounting for the excess deaths. RESULTS: Hazard ratios for death were higher in PDD and DLB compared to AD, for both males and females. PDD males had the highest hazard ratio for death across the dementia comparison groups (HR 2.7, 95% CI 2.2-3.3). Compared with AD, hazard ratios for "nervous system" causes of death were significantly elevated in all LBD groups. Additional significant cause-of-death categories included aspiration pneumonia, genitourinary causes, other respiratory causes, circulatory and a "symptoms and signs" category in PDD males; other respiratory causes in DLB males; mental disorders in PDD females; and aspiration pneumonia, genitourinary and other respiratory causes in DLB females. CONCLUSION: Further research and cohort development is required to investigate differences by age group, to extend cohort follow-up to the whole population and to investigate the risk-balance of interventions which may differ by dementia group.

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

Equipoise, standard of care and consent: responding to the authorisation of new COVID-19 treatments in randomised controlled trials.

In response to the COVID-19 pandemic, large-scale research and pharmaceutical regulatory processes have proceeded at a dramatically increased pace with new and effective, evidence-based COVID-19 interventions rapidly making their way into the clinic. However, the swift generation of high-quality evidence and the efficient processing of regulatory authorisation have given rise to more specific and complex versions of well-known research ethics issues. In this paper, we identify three such issues by focusing on the authorisation of molnupiravir, a novel antiviral medicine aimed at reducing the ability of SARS-CoV-2 to multiply in the body, for clinical use by the National Health Service in England and the concomitant testing of molnupiravir through the large-scale Platform Adaptive trial of Novel antiviRals for eArly treatMent of COVID-19 In the Community randomised control trial. By analysing the ways in which the authorisation and clinical use of molnupiravir complicate standard approaches to clinical equipoise, standard of care and participant consent in the PANORAMIC randomised control trial, we will explain some of ethical implications for clinical trials that aim to study the efficacy and safety of new COVID-19 and other therapeutics when conditional authorisation has already been granted and when such treatments have already been made available to patients by national health providers.

De-identified Bayesian personal identity matching for privacy-preserving record linkage despite errors: development and validation.

BACKGROUND: Epidemiological research may require linkage of information from multiple organizations. This can bring two problems: (1) the information governance desirability of linkage without sharing direct identifiers, and (2) a requirement to link databases without a common person-unique identifier. METHODS: We develop a Bayesian matching technique to solve both. We provide an open-source software implementation capable of de-identified probabilistic matching despite discrepancies, via fuzzy representations and complete mismatches, plus de-identified deterministic matching if required. We validate the technique by testing linkage between multiple medical records systems in a UK National Health Service Trust, examining the effects of decision thresholds on linkage accuracy. We report demographic factors associated with correct linkage. RESULTS: The system supports dates of birth (DOBs), forenames, surnames, three-state gender, and UK postcodes. Fuzzy representations are supported for all except gender, and there is support for additional transformations, such as accent misrepresentation, variation for multi-part surnames, and name re-ordering. Calculated log odds predicted a proband's presence in the sample database with an area under the receiver operating curve of 0.997-0.999 for non-self database comparisons. Log odds were converted to a decision via a consideration threshold θ and a leader advantage threshold δ. Defaults were chosen to penalize misidentification 20-fold versus linkage failure. By default, complete DOB mismatches were disallowed for computational efficiency. At these settings, for non-self database comparisons, the mean probability of a proband being correctly declared to be in the sample was 0.965 (range 0.931-0.994), and the misidentification rate was 0.00249 (range 0.00123-0.00429). Correct linkage was positively associated with male gender, Black or mixed ethnicity, and the presence of diagnostic codes for severe mental illnesses or other mental disorders, and negatively associated with birth year, unknown ethnicity, residential area deprivation, and presence of a pseudopostcode (e.g. indicating homelessness). Accuracy rates would be improved further if person-unique identifiers were also used, as supported by the software. Our two largest databases were linked in 44 min via an interpreted programming language. CONCLUSIONS: Fully de-identified matching with high accuracy is feasible without a person-unique identifier and appropriate software is freely available.

Towards a concept of embodied autonomy: In what ways can a patient's body contribute to the autonomy of medical decisions?

"Bodily autonomy" has received significant attention in bioethics, medical ethics, and medical law in terms of the general inviolability of a patient's bodily sovereignty and the rights of patients to make choices (e.g., reproductive choices) that concern their own body. However, the role of the body in terms of how it can or does contribute to a patient's capacity for, or exercises of their autonomy in clinical decision-making situations has not been explicitly addressed. The approach to autonomy in this paper is aligned with traditional theories that conceive autonomy in terms of an individual's capacities for, and exercises of rational reflection. However, at the same time, this paper extends these accounts by arguing that autonomy is, in part, embodied. Specifically, by drawing on phenomenological conceptions of the experience of autonomy, we argue that, in principle, the body is a necessary component of the capacity for autonomy. Secondly, through the presentation of two different cases, we highlight ways in which a patient's body can contribute to the autonomy of treatment choices. Ultimately, we hope to encourage others to explore additional conditions under which a concept of embodied autonomy should be employed in medical decision making, how its underlying principles might be operationalised in clinical situations, and its consequences for approaches to patient autonomy in healthcare practice, policy, and law.

Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study.

BACKGROUND: Dementia is the leading cause of death in elderly Western populations. Preventative interventions that could delay dementia onset even modestly would provide a major public health impact. There are no disease-modifying treatments currently available. Lithium has been proposed as a potential treatment. We assessed the association between lithium use and the incidence of dementia and its subtypes. METHODS AND FINDINGS: We conducted a retrospective cohort study comparing patients treated between January 1, 2005 and December 31, 2019, using data from electronic clinical records of secondary care mental health (MH) services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million). Eligible patients were those aged 50 years or over at baseline and who had at least 1 year follow-up, excluding patients with a diagnosis of mild cognitive impairment (MCI) or dementia before, or less than 1 year after, their start date. The intervention was the use of lithium. The main outcomes were dementia and its subtypes, diagnosed and classified according to the International Classification of Diseases-10th Revision (ICD-10). In this cohort, 29,618 patients (of whom 548 were exposed to lithium) were included. Their mean age was 73.9 years. A total of 40.2% were male, 33.3% were married or in a civil partnership, and 71.0% were of white ethnicity. Lithium-exposed patients were more likely to be married, cohabiting or in a civil partnership, to be a current/former smoker, to have used antipsychotics, and to have comorbid depression, mania/bipolar affective disorder (BPAD), hypertension, central vascular disease, diabetes mellitus, or hyperlipidemias. No significant difference between the 2 groups was observed for other characteristics, including age, sex, and alcohol-related disorders. In the exposed cohort, 53 (9.7%) patients were diagnosed with dementia, including 36 (6.8%) with Alzheimer disease (AD) and 13 (2.6%) with vascular dementia (VD). In the unexposed cohort, corresponding numbers were the following: dementia 3,244 (11.2%), AD 2,276 (8.1%), and VD 698 (2.6%). After controlling for sociodemographic factors, smoking status, other medications, other mental comorbidities, and physical comorbidities, lithium use was associated with a lower risk of dementia (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.40 to 0.78), including AD (HR 0.55, 95% CI 0.37 to 0.82) and VD (HR 0.36, 95% CI 0.19 to 0.69). Lithium appeared protective in short-term (≤1-year exposure) and long-term lithium users (>5-year exposure); a lack of difference for intermediate durations was likely due to lack of power, but there was some evidence for additional benefit with longer exposure durations. The main limitation was the handling of BPAD, the most common reason for lithium prescription but also a risk factor for dementia. This potential confounder would most likely cause an increase in dementia in the exposed group, whereas we found the opposite, and the sensitivity analysis confirmed the primary results. However, the specific nature of the group of patients exposed to lithium means that caution is needed in extending these findings to the general population. Another limitation is that our sample size of patients using lithium was small, reflected in the wide CIs for results relating to some durations of lithium exposure, although again sensitivity analyses remained consistent with our primary findings. CONCLUSIONS: We observed an association between lithium use and a decreased risk of developing dementia. This lends further support to the idea that lithium may be a disease-modifying treatment for dementia and that this is a promising treatment to take forwards to larger randomised controlled trials (RCTs) for this indication.

Evaluating dosimetric parameters predictive of hematologic toxicity in cervical cancer patients undergoing definitive pelvic chemoradiotherapy.

PURPOSE: We performed a retrospective study of cervical cancer pelvic radiotherapy plans to explore dosimetric parameters predictive of hematologic toxicity (HT), with specific interest in evaluating metabolic parameters and identifying the best predictive model. METHODS: Active marrow was retroactively contoured as pelvic bone with SUV > mean on 18F-FDG-PET. "Highly active" marrow was contoured as the hottest 10-14% volume of active marrow. Pelvic bone contour was segmented into lumbosacral, iliac crest, and lower pelvis. Predictors of HT were evaluated using logistic regression and repeated measures modeling. RESULTS: One hundred women were evaluated from 2009 to 2020. The plurality/majority had stage IIIC1 disease (38%) and underwent IMRT (88%) with pelvic field alone (72%). The majority received weekly cisplatin (78%), and 82% completed at least five cycles. The most common HT was leukopenia (grade 2+: 68%). Predictors of grade 2+ and 3+ HT were baseline WBC (p < 0.001), and 10- and 20-Gy dosimetric parameters to the active marrow, highly active marrow, and pelvic bone. The best predictive model of leukocyte trajectory included baseline WBC (p < 0.001), highly active marrow V20 (p < 0.001), and interactions of baseline WBC with time (p < 0.001) and highly active marrow V20 (p < 0.001), such that those with low baseline WBC experienced the greatest impact of highly active marrow V20. CONCLUSION: Baseline WBC was highly predictive of HT; dosimetric predictors included dose to the active marrow, highly active marrow, and pelvic bone, with the greatest impact from V20 to the highly active marrow, particularly in women with low baseline WBC. Future studies should consider incorporating baseline WBC and limiting dose to the most highly active marrow.

The epidemiology and clinical features of personality disorders in later life; a study of secondary care data.

OBJECTIVES: Personality disorders (PDs) are often conceptualised as impacting individuals throughout their life. However, there has been limited study of the disorders in those over the age of 65. We have used the psychiatric secondary care medical records of 21,971 individuals over the age of 65 from Cambridgeshire, UK, who received care between 2014 and 2021 to characterise older patients with a PD diagnosis. METHODS: The data from all patients >65 with a diagnosis of personality disorder (PD) was extracted (n = 217) along with two comparison groups (n = 2170); patients <65 with a diagnosis of PD and patients >65 with a psychiatric diagnosis other than PD or dementia. RESULTS: Compared to younger patients with PD, older patients were more likely to be male, married, suffering from a mixed PD and live in less deprived areas. Compared to patients >65 with diagnoses other than PD, older patients were more likely to be female, single or divorced and had a higher level of social deprivation. Our most striking finding was that older patients with PDs were more likely to experience polypharmacy. A mean of 18.48 different drugs had been prescribed over their lifetime, compared to 9.51 for patients >65 with other mental health diagnoses. CONCLUSION: Here we present the largest ever description of this group of patients and provide insights that could inform clinical practice and future research.

Trazodone and patient outcomes in dementia-Limitations of naturalistic cohort data.

The unfolded protein response has been increasingly implicated as an important pathological pathway and target for therapeutic intervention in neurodegeneration. The licensed antidepressant trazodone is one drug which has been proposed to act on this pathway and may therefore be a potential therapy. Previous examination of existing data for patients with dementia prescribed trazodone did not find a signal suggesting a disease modifying effect. Here we add to that literature by examining the electronic patient record of patients with dementia in Cambridgeshire UK. We found that trazodone is rarely prescribed and where it is used it is at a dose less than half that predicted to be disease modifying. We also found that patients prescribed trazodone had higher levels of neuropsychiatric symptoms and were relatively late in the disease course, likely beyond the optimal point for therapeutic intervention. We suggest it is therefore premature to discard potential therapies based on observational data alone, particularly when experimental medicine approaches to examine the effects of trazodone are feasible.

Organoid biobanking, autonomy and the limits of consent.

In the debates regarding the ethics of human organoid biobanking, the locus of donor autonomy has been identified in processes of consent. The problem is that, by focusing on consent, biobanking processes preclude adequate engagement with donor autonomy because they are unable to adequately recognize or respond to factors that determine authentic choice. This is particularly problematic in biobanking contexts associated with organoid research or the clinical application of organoids because, given the probability of unforeseen and varying purposes for which a donor's organoids could be employed and given the different ways in which a donor can relate to her biospecimens, a donor can value her organoids differently in different contexts, and her reasons for autonomously permitting use of her cells and tissues in one case may not support an autonomous decision in another. In response, this paper has three aims: first, to make the case for why organoid biobanks ought to respect donor autonomy conceived as authentic choice; second, to explore the autonomy-respecting limits of established and widely prevalent models of biobank consent; and third, to propose certain conditions that organoid biobanks ought to support or facilitate in order to respect donor autonomy.

An Ethical Exploration of Increased Average Number of Authors Per Publication.

This article explores the impact of an Increase in the average Number of Authors per Publication (INAP) on known ethical issues of authorship. For this purpose, the ten most common ethical issues associated with scholarly authorship are used to set up a taxonomy of existing issues and raise awareness among the community to take precautionary measures and adopt best practices to minimize the negative impact of INAP. We confirm that intense international, interdisciplinary and complex collaborations are necessary, and INAP is an expression of this trend. However, perverse incentives aimed to increase institutional and personal publication counts and egregious instances of guest or honorary authorship are problematic. We argue that whether INAP is due to increased complexity and scale of science, perverse incentives or undeserved authorship, it could negatively affect known ethical issues of authorship at some level. In the long run, INAP depreciates the value of authorship status and may disproportionately impact junior researchers and those who contribute to technical and routine tasks. We provide two suggestions that could reduce the long-term impact of INAP on the reward system of science. First, we suggest further refinement of the CRediT taxonomy including better integration into current systems of attribution and acknowledgement, and better harmony with major authorship guidelines such as those suggested by the ICMJE. Second, we propose adjustments to the academic recognition and promotion systems at an institutional level as well as the introduction of best practices.

Patient autonomy, clinical decision making, and the Phenomenological reduction.

Phenomenology gives rise to certain ontological considerations that have far-reaching implications for standard conceptions of patient autonomy in medical ethics, and, as a result, the obligations of and to patients in clinical decision-making contexts. One such consideration is the phenomenological reduction in classical phenomenology, a core feature of which is the characterisation of our primary experiences as immediately and inherently meaningful. This paper builds on and extends the analyses of the phenomenological reduction in the works of Husserl, Heidegger, and Merleau-Ponty in order to identify and explain its implications for our current understanding of the principle of respect for patient autonomy and the norms of clinical decision making.