Quality care close to home: Objectives and early outcomes of a second paediatric heart transplant service in Australia.

AIM: We describe the experience of a new paediatric heart transplant (HT) centre in Australia. New South Wales offers quaternary paediatric cardiac services including comprehensive care pre- and post-HT; however, perioperative HT care has previously occurred at the national paediatric centre or in adult centres. Internationally, perioperative HT care is highly protocol-driven and a majority of HT occurs in low volume centres. Establishing a low volume paediatric HT centre in New South Wales offers potential for quality HT care close to home. METHODS: Retrospective review of programme data for the first 12 months was undertaken. Patient selection was audited against the programme's intended initiation criteria. Longitudinal patient data on outcomes and complications were obtained from patient medical records. RESULTS: The programme's initial phase offered HT to children with non-congenital heart disease and no requirement for durable mechanical circulatory support. Eight patients met criteria for HT referral. Three underwent interstate transfer to the national paediatric centre. Five children (13-15 years, weight 36-85 kg) underwent HT in the new programme. Individual predicted 90-day mortality was 1.3-11.6%, with increased risk for recipients transplanted from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and with restrictive/hypertrophic cardiomyopathies. Survival at 90 days and for duration of follow-up is 100%. Observed programme benefits include mitigation of family dislocation and improved continuity of care within a family-centred programme. CONCLUSION: Audit of the first 12 months' activity of a second paediatric HT centre in Australia demonstrates adherence to proposed patient selection criteria and excellent 90-day patient outcomes. The programme demonstrates feasibility of care close to home, providing continuity for all patients including those requiring increased rehabilitation and psychosocial support post-transplantation.

Rationing in the Pediatric Intensive Care Unit-ethical or unethical?

Rationing in health care is controversial, and even more so in pediatrics. Children are an inherently vulnerable group because they are reliant on their parents and caregivers to make decisions in their best interests and have no political voice. Historically, there has been general acceptance of the need to ration healthcare at a systems level, however there is controversy over whether healthcare professionals should be involved in rationing at the bedside. The COVID-19 pandemic has highlighted that bedside rationing is unavoidable, at least in times of extreme resource scarcity. Internationally, there has been significant ethical analysis and guideline development to guide intensive care rationing decisions in the event that resources are overwhelmed. This paper explores the principles underlying distributive justice in healthcare rationing and discusses how these were operationalized in ethical guidelines for the COVID-19 pandemic. In fact, rationing is unavoidable and occurs constantly in everyday nursing and medical ICU practice, often in mundane and uncontroversial ways. Some argue that these everyday decisions are not true rationing decisions, but resource allocation, or stewardship decisions. We argue there are no clear lines between resource allocation and rationing decisions, rather that they occur on a spectrum. These everyday rationing decisions are particularly susceptible to personal biases that are often implicit. Due to the subtle and constant nature of most everyday rationing decisions, specific guideline development will rarely be practical or appropriate. However, it is possible to develop other processes to improve decision making. There are a variety of strategies we recommend for this including, encouraging reflective practice; developing explicit frameworks that promote collaborative decision making; being transparent about resource allocation and rationing decisions with colleagues, patients, and families; and promoting a workplace culture of speaking up and accessing support in identifying and managing everyday rationing decisions.

Diagnosis and incidence of acute kidney injury in a mixed paediatric intensive care unit: Retrospective analysis, 2005 and 2015.

Acute kidney injury (AKI) is common in intensive care patients. While creatinine definitions for AKI have been validated, oliguria criteria are less well evaluated in children. Our study compared the validity and agreement of creatinine and oliguria criteria for diagnosing AKI in a large mixed medical, surgical and cardiac paediatric intensive care unit (PICU), and assessed the significance of their independent and combined effects on predicted mortality relative to paediatric index of mortality (PIM risk of death) on admission. Creatinine measurements during PICU admissions in 2005 and 2015 were obtained from the electronic medical record. Urine output was reviewed to identify periods of oliguria of more than eight hours. We used the PIM3 model for predicted risk of death. AKI based on creatinine rise occurred in 23.6% of the total 2203 admissions (10.0%, 8.2% and 5.6% for mild, moderate and severe categories, respectively). Oliguria occurred in 11.4% (8.4%, 1.8% and 1.2% for mild, moderate and severe categories, respectively) and overlapped only partially with creatinine criteria. Mortality relative to predicted mortality increased with increasing creatinine and oliguria severity, but was lower than predicted where oliguria occurred without creatinine rise. AKI by creatinine criteria and/or oliguria are common in the PICU, but criteria overlap only partially. Increasing severity of creatinine rise and oliguria confers increasing risk-adjusted mortality, especially for admissions with low PIM3 risk of death. The mortality of patients with AKI defined by oliguria alone is low. Defining AKI by oliguria alone has less clinical utility and may not represent true AKI.

Paediatric advance care planning: Physician experience and education in initiating difficult discussions.

AIM: Our study aimed to assess physicians' experiences and education regarding advance care planning (ACP) in paediatrics. We aimed to assess barriers to ACP initiation, including the adequacy of exposure and education regarding ACP and whether practitioners would deem improved education and resource provision useful. METHODS: A 25-question survey was designed following literature review. Paediatricians, intensivists and advanced trainees at Sydney Children's Hospital were invited to complete the online survey. Ninety-two responses were obtained over a 10-week period. RESULTS: Patients with life-limiting conditions are encountered frequently, with 57% of respondents caring for at least 10 such patients during the last 2 years. In total, 64% of respondents felt that ACP discussions should occur early around the time of diagnosis or during a period of stability; however, 57% observed discussions occurring late in illness after multiple acute, severe deteriorations. In total, 46% felt that multidisciplinary teams were the most appropriate to initiate ACP discussions. Prognostic uncertainty was the most common barrier to ACP initiation. Lack of experience and education were identified as barriers by 43 and 32%, respectively. The majority of respondents regarded exposure to ACP and education during training as inadequate. CONCLUSIONS: ACP discussions are being initiated later than physicians deem optimal. Of concern, clinicians prefer ACP discussions to be initiated by multidisciplinary teams, which may create a barrier to timely initiation. Barriers due to lack of education and experience could be overcome with improvements in training. Provision of education and resources would be welcomed and improve clinician skills in this area.

siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth.

Interferon regulatory factor (IRF) 1 and its functional antagonist IRF2 were originally discovered as transcription factors that regulate the interferon-beta gene. Control of cell growth has led to the definition of IRF1 as a tumour suppressor gene and IRF2 as an oncogene. Clinically, approximately 70% of cases of acute myeloid leukaemia demonstrate dysregulated expression of IRF1 and/or IRF2. Our previous studies have shown that human leukaemic TF-1 cells exhibit abnormally high expression of both IRF1 and IRF2, the latter acting to abrogate IRF1 tumour suppression, making these cells ideal for analysis of down-regulation of IRF2 expression. A novel G418 screening protocol was developed and used for identifying effective siRNA that targets IRF2 (siIRF2). Using optimized siIRF2 in leukaemic TF-1 cells, IRF2 was down-regulated by approximately 70% at both mRNA and protein levels. Phenotypically, this resulted in growth inhibition associated with G2/M arrest as well as induction of polyploidy, differentiation and apoptosis. In contrast to these results, siIRF2 targeting did not affect normal haematopoietic stem/progenitor cell growth. These results indicate the potential utility of IRF2 inhibition as a therapeutic approach to cancer.