Total uncertainty: a systematic review and thematic synthesis of experiences of uncertainty in older people with advanced multimorbidity, their informal carers and health professionals.

OBJECTIVES: uncertainty pervades the complex illness trajectories experienced by older adults with multimorbidity. Uncertainty is experienced by older people, their informal carers and professionals providing care, yet is incompletely understood. We aimed to identify and synthesise systematically the experience of uncertainty in advanced multimorbidity from patient, carer and professional perspectives. DESIGN: systematic literature review of published and grey qualitative literature from 9 databases (Prospero CRD 42021227480). PARTICIPANTS: older people with advanced multimorbidity, and informal carers/professionals providing care to this group. Exclusion criteria: early multimorbidity, insufficient focus on uncertainty. ANALYSIS: weight-of-evidence assessment was used to appraise included articles. We undertook thematic synthesis of multi-perspective experiences and response to uncertainty. RESULTS: from 4,738 unique search results, we included 44 articles relating to 40 studies. 22 focused on patient experiences of uncertainty (n = 460), 15 on carer experiences (n = 197), and 19 on health professional experiences (n = 490), with 10 exploring multiple perspectives. We identified a shared experience of 'Total Uncertainty' across five domains: 'appraising and managing multiple illnesses'; 'fragmented care and communication'; 'feeling overwhelmed'; 'uncertainty of others' and 'continual change'. Participants responded to uncertainty by either active (addressing, avoiding) or passive (accepting) means. CONCLUSIONS: the novel concept of 'Total Uncertainty' represents a step change in our understanding of illness experience in advanced multimorbidity. Patients, carers and health professionals experienced uncertainty in similar domains, suggesting a shared understanding is feasible. The domains of total uncertainty form a useful organising framework for health professionals caring for older adults with multimorbidity.

Getting out of the box: the future of the UK donation after circulatory determination of death heart programme.

Heart failure imposes a significant burden on all health care systems and has a 5-year mortality of 50%. Heart transplantation and ventricular assist device (VAD) implantation are the definitive therapies for end stage heart disease, although transplantation appears to offer superior long-term survival and quality of life over VAD implantation. Transplantation is limited by a shortage in donor hearts, resulting in considerable waiting list mortality. Donation after circulatory determination of death (DCD) offers a significant uplift in the number of donors for heart transplantation. The outcomes both from the UK and internationally have been exciting, with outcomes at least as good as conventional donation after brain death (DBD) transplantation. Currently, DCD hearts are reperfused using ex-situ machine perfusion (ESMP). Whilst ESMP has enabled the development of DCD transplantation, it comes at significant cost, with the per run cost of approximately GBP £90,000. In-situ perfusion of the heart, otherwise known as thoraco-abdominal normothermic regional perfusion (taNRP) is cheaper, but there are ethical concerns regarding the potential to restore cerebral perfusion in the donor. We must determine whether there is any cerebral circulation during in-situ perfusion of the heart to ensure that it does not invalidate the diagnosis of death and potentially violate the dead donor rule. Besides this, there is a need for a randomised controlled trial to definitively determine whether taNRP offers any clinical advantages over ex-situ machine perfusion. This viewpoint article explores these issues in more detail.

The international experience of in-situ recovery of the DCD heart: a multicentre retrospective observational study.

Background: Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP. Method: This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival. Findings: taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n = 156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n = 72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n = 13). Interpretation: Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use. Funding: None of the authors have a financial relationship with a commercial entity that has an interest in the subject.