Donating a kidney to a stranger : a review of the benefits and controversies of unspecified kidney donation

Summary of Background Data: Unspecified kidney donation (UKD) describes living donation of a kidney to a stranger. The practice is playing an increasingly important role within the transplant programme in the United Kingdom, where these donors are commonly used to trigger a chain of transplants; thereby amplifying the benefit derived from their donation. The initial reluctance to accept UKD was in part due to uncertainty about donor motivations and whether the practice was morally and ethically acceptable. Objectives: This article provides an overview of UKD and answers common questions regarding the ethical considerations, clinical assessment, and how UKD kidneys are used to maximize utility. Existing literature on outcomes after UKD is also discussed, along with current controversies. Conclusions: We believe UKD is an ethically acceptable practice which should continue to grow, despite its controversies. In our experience, these donors are primarily motivated by a desire to help others and utilization of their kidney as part of a sharing scheme means that many more people seek to benefit from their very generous donation

Experiences of completed and withdrawn unspecified kidney donor candidates in the UK : an inductive thematic analysis from the BOUnD study

Objectives: This study sheds light on some controversial aspects of unspecified kidney donation (UKD) as well as the ways in which potential donors are screened and prepared for the donation experience and its aftermath. The aim of this study was to qualitatively investigate the experiences of individuals involved in the United Kingdom (UK) UKD scheme, including those who complete the donation, are eventually medically withdrawn, or self-withdraw. Better insight into the different experiences of these groups will provide useful guidance to clinical teams on how to better address the differing psychological needs of completed donors as well as those who do not proceed to donation. Methods: A purposive sample was recruited through the Barriers and Outcomes in Unspecified Donation (BOUnD) study covering twenty-three transplant centres in the UK. Semi-structured interviews were audio-recorded and transcribed verbatim and subjected to inductive thematic analysis. Results: Participants consisted of 15 individuals who had donated, 11 who had been withdrawn by the transplant team and 9 who had self-withdrawn. The analysis resulted in 6 themes and 14 subthemes. The major themes were maximising and sharing benefits; risk-to-motivation analysis; support; self-actualisation / finding meaning; the donor as patient; and relationship with the transplant team. Conclusions: The data demonstrates that, although all donors enter the process with a similar level of commitment, those who did not proceed to donation expressed dissatisfaction and lingering emotional consequences linked to lack of follow-up from transplant teams. The implication for the UKD programme is that from the beginning there needs to be a strategic and consistent approach to managing expectations in order to prepare those who embark on the donation process for all possible outcomes and their associated emotional consequences

The Effect of Pre-Analytical Conditions on Blood Metabolomics in Epidemiological Studies

Serum and plasma are commonly used in metabolomic-epidemiology studies. Their metabolome is susceptible to differences in pre-analytical conditions and the impact of this is unclear. Participant-matched EDTA-plasma and serum samples were collected from 37 non-fasting volunteers and profiled using a targeted nuclear magnetic resonance (NMR) metabolomics platform (n = 151 traits). Correlations and differences in mean of metabolite concentrations were compared between reference (pre-storage: 4 °C, 1.5 h; post-storage: no buffer addition delay or NMR analysis delay) and four pre-storage blood processing conditions, where samples were incubated at (i) 4 °C, 24 h; (ii) 4 °C, 48 h; (iii) 21 °C, 24 h; and (iv) 21 °C, 48 h, before centrifugation; and two post-storage sample processing conditions in which samples thawed overnight (i) then left for 24 h before addition of sodium buffer followed by immediate NMR analysis; and (ii) addition of sodium buffer, then left for 24 h before NMR profiling. We used multilevel linear regression models and Spearman’s rank correlation coefficients to analyse the data. Most metabolic traits had high rank correlation and minimal differences in mean concentrations between samples subjected to reference and the different conditions tested, that may commonly occur in studies. However, glycolysis metabolites, histidine, acetate and diacylglycerol concentrations may be compromised and this could bias results in association/causal analyses

Study protocol for a mixed methods prospective cohort study to explore experiences of care following a suicidal crisis in the Australian healthcare system

Introduction For individuals presenting to the emergency department (ED) for a suicide attempt, the period after discharge from hospital is marked by heightened vulnerability for further suicide attempts. Effective care following a suicidal crisis has the potential to significantly decrease this risk. The current study aims to examine the impact of the LifeSpan multilevel suicide prevention model on experiences of care following a suicidal crisis. Perspectives from healthcare consumers (individuals who have presented to the ED following a suicidal crisis), carers, and health professionals will be explored. The LifeSpan model is currently being evaluated as a high-fidelity trial in four geographically defined regions in New South Wales, Australia. Methods and analysis This study will use a mixed methods prospective cohort design. Quantitative data collection includes a structured survey, administered to healthcare consumers from LifeSpan sites and control sites. Two cohorts of healthcare consumers will be recruited 12 months apart with baseline assessment occurring within 18 months of the ED presentation, and follow-up 12 months after the initial assessment. Survey participants will be recruited online and through participating EDs, mental health organisations and aftercare services. Qualitative interview data from healthcare consumers, carers who have accompanied a loved one to the ED following a suicidal crisis and health professionals who provide care to people at risk of suicide will be collected concurrently with the recruitment of the first cohort of survey participants. Purposive and convenience sampling techniques will be used for recruitment of interview participants. The primary outcome for this study will be healthcare consumers' experiences of service provided at the ED. Analysis will be undertaken of the change over time within LifeSpan sites, as well as between LifeSpan sites and control sites, using mixed effects repeated measures models as principal means of data analysis.This work is supported by a $14.76 million grant from the Paul Ramsay Foundation for the period of 1 January 2016 until 31 December 202

Donor autonomy and self-sacrifice in living organ donation : an ethical legal and psychological aspects of transplantation (ELPAT) view

Clinical teams understandably wish to minimise risks to living kidney donors undergoing surgery, but are often faced with uncertainty about the extent of risk, or donors who wish to proceed despite those risks. Here we explore how these difficult decisions may be approached and consider the conflicts between autonomy and paternalism, the place of self-sacrifice and consideration of risks and benefits. Donor autonomy should be considered as in the context of the depth and strength of feeling, understanding risk and competing influences. Discussion of risks could be improved by using absolute risk, supra-regional MDMs and including the risks to the clinical team as well as the donor. The psychological effects on the donor of poor outcomes for the untransplanted recipient should also be taken into account. There is a lack of detailed data on the risks to the donor who has significant co-morbidities

Scale-up and optimization of the synthesis of dual CBP/BRD4 inhibitor ISOX-DUAL

ISOX-DUAL is a dual inhibitor of CBP/p300 (IC50 = 0.65 μM) and BRD4 (IC50 = 1.5 μM) bromodomains, and a useful chemical probe for epigenetic research. Aspects of the published synthetic route to this compound and its analogues are small-scale, poor-yielding or simply unamenable to scale-up without optimization. Herein we describe the development of a refined synthesis that circumvents the challenges of the original report, with notable improvements to several of the key synthetic transformations. Moreover, a general Suzuki Miyaura protocol for the late stage installation of alternative dimethyl-isoxazole acetyl-lysine (KAc) binding motifs is presented

Probing BRD inhibition substituent effects in bulky analogues of (+)-JQ1

A series of bulky organometallic and organic analogues of the bromodomain (BRD) inhibitor (+)-JQ1 have been prepared. The most potent, N-[(adamantan-1-yl)methyl]-2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide, 2e, showed excellent potency with an KD=ca. 130 nm vs. BRD4(1) and a ca. 2-fold selectivity over BRD4(2) (KD=ca. 260 nm). Its binding to the first bromodomain of BRD4 was determined by a protein cocrystal structure

Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor

(+)-JD1, a rationally designed ferrocene analogue of the BET bromodomain (BRD) probe molecule (+)-JQ1, has been synthesized and evaluated in biophysical, cell-based assays as well as in pharmacokinetic studies. It displays nanomolar activity against BRD isoforms, and its cocrystal structure was determined in complex with the first bromodomain of BRD4 and compared with that of (+)-JQ1, a known BRD4 small-molecule probe. At 1 μM concentration, (+)-JD1 was able to inhibit c-Myc, a key driver in cancer and an indirect target of BRD4

The 24/7 approach to promoting optimal welfare for captive wild animals

We have an ethical responsibility to provide captive animals with environments that allow them to experience good welfare. Husbandry activities are often scheduled for the convenience of care staff working within the constraints of the facility, rather than considering the biological and psychological requirements of the animals themselves. The animal welfare 24/7 across the lifespan concept provides a holistic framework to map features of the animal’s life cycle, taking into account their natural history, in relation to variations in the captive environment, across day and night, weekdays, weekends, and seasons. In order for animals to have the opportunity to thrive, we argue the need to consider their lifetime experience, integrated into the environments we provide, and with their perspective in mind. Here, we propose a welfare assessment tool based upon 14 criteria, to allow care staff to determine if their animals’ welfare needs are met. We conclude that animal habitat management will be enhanced with the use of integrated technologies that provide the animals with more opportunities to engineer their own environments, providing them with complexity, choice and control