Protocol for a hybrid effectiveness-implementation clinical trial evaluating video-assisted electronic consent vs standard consent for patients initiating and continuing haemodialysis in Australia (eConsent HD).

INTRODUCTION: Communicating complex information about haemodialysis (HD) and ensuring it is well understood remains a challenge for clinicians. Informed consent is a high-impact checkpoint in augmenting patients' decision awareness and engagement prior to HD. The aims of this study are to (1) develop a digital information interface to better equip patients in the decision-making process to undergo HD; (2) evaluate the effectiveness of the co-designed digital information interface to improve patient outcomes; and (3) evaluate an implementation strategy. METHODS AND ANALYSIS: First, a co-design process involving consumers and clinicians to develop audio-visual content for an innovative digital platform. Next a two-armed, open-label, multicentre, randomised controlled trial will compare the digital interface to the current informed consent practice among adult HD patients (n=244). Participants will be randomly assigned to either the intervention or control group. Intervention group: Participants will be coached to an online platform that delivers a simple-to-understand animation and knowledge test questions prior to signing an electronic consent form. CONTROL GROUP: Participants will be consented conventionally by a clinician and sign a paper consent form. Primary outcome is decision regret, with secondary outcomes including patient-reported experience, comprehension, anxiety, satisfaction, adherence to renal care, dialysis withdrawal, consent time and qualitative feedback. Implementation of eConsent for HD will be evaluated concurrently using the Consolidation Framework for Implementation Research (CFIR) methodology. ANALYSIS: For the randomised controlled trial, data will be analysed using intention-to-treat statistical methods. Descriptive statistics and CFIR-based analyses will inform implementation evaluation. ETHICS AND DISSEMINATION: Human Research Ethics approval has been secured (Metro North Health Human Research Ethics Committee B, HREC/2022/MNHB/86890), and Dissemination will occur through partnerships with stakeholder and consumer groups, scientific meetings, publications and social media releases. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ACTRN12622001354774).

Measuring practice preference variation for quality improvement in neonatal respiratory care.

OBJECTIVES: The authors sought to measure and compare practice preference variation in neonatal respiratory care within and between neonatal intensive care units (NICUs) using the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT). STUDY DESIGN: Eleven NICUs completed the NSIGHT between 2019 and 2021. Net preference was measured by mean response; agreement was ranked by standard distribution of response values. Heat maps showed comparisons between NICUs and disciplines. RESULTS: NICUs and individuals agreed most often on use of pressure support with mandatory ventilation and on use of non-invasive positive pressure ventilation for apnea. High preference variation surrounded decisions for invasive ventilation versus continuous positive airway pressure for extremely low birth weight infants. Preference difference was most frequent between neonatologists and nurses. CONCLUSIONS: Patterns of practice preference variation in neonatal respiratory care are specific to clinical scenario. Measuring preference variation may inform psychology of change and strengthen quality improvement efforts.

Neonatal respiratory care practice among level III and IV NICUs in New England.

OBJECTIVES: To assess respiratory care guidelines and explore variations in management of very low birth weight (VLBW) infants within a collaborative care framework. Additionally, to gather clinical leaders' perspectives on guidelines and preferences for ventilation modalities. STUDY DESIGN: Leaders from each NICU participated in a practice survey regarding the prevalence of unit clinical guidelines, and management, at many stages of care. RESULTS: Units have an average of 4.3 (±2.1) guidelines, of 9 topics queried. Guideline prevalence was not associated with practice or outcomes. An FiO2 requirement of 0.3-0.4 and a CPAP of 6-7 cmH2O, are the most common thresholds for surfactant administration, which is most often done after intubation, and followed by weaning from ventilatory support. Volume targeted ventilation is commonly used. Extubation criteria vary widely. CONCLUSIONS: Results identify trends and areas of variation and suggest that the presence of guidelines alone is not predictive of outcome.

Human proximal tubular epithelial cell-derived small extracellular vesicles mediate synchronized tubular ferroptosis in hypoxic kidney injury.

Hypoxia is the key pathobiological trigger of tubular oxidative stress and cell death that drives the transition of acute kidney injury (AKI) to chronic kidney disease (CKD). The mitochondrial-rich proximal tubular epithelial cells (PTEC) are uniquely sensitive to hypoxia and thus, are pivotal in propagating the sustained tubular loss of AKI-to-CKD transition. Here, we examined the role of PTEC-derived small extracellular vesicles (sEV) in propagating the 'wave of tubular death'. Ex vivo patient-derived PTEC were cultured under normoxia (21 % O2) and hypoxia (1 % O2) on Transwell inserts for isolation and analysis of sEV secreted from apical versus basolateral PTEC surfaces. Increased numbers of sEV were secreted from the apical surface of hypoxic PTEC compared with normoxic PTEC. No differences in basolateral sEV numbers were observed between culture conditions. Biological pathway analysis of hypoxic-apical sEV cargo identified distinct miRNAs linked with cellular injury pathways. In functional assays, hypoxic-apical sEV selectively induced ferroptotic cell death (↓glutathione peroxidase-4, ↑lipid peroxidation) in autologous PTEC compared with normoxic-apical sEV. The addition of ferroptosis inhibitors, ferrostatin-1 and baicalein, attenuated PTEC ferroptosis. RNAse A pretreatment of hypoxic-apical sEV also abrogated PTEC ferroptosis, demonstrating a role for sEV RNA in ferroptotic 'wave of death' signalling. In line with these in vitro findings, in situ immunolabelling of diagnostic kidney biopsies from AKI patients with clinical progression to CKD (AKI-to-CKD transition) showed evidence of ferroptosis propagation (increased numbers of ACSL4+ PTEC), while urine-derived sEV (usEV) from these 'AKI-to-CKD transition' patients triggered PTEC ferroptosis (↑lipid peroxidation) in functional studies. Our data establish PTEC-derived apical sEV and their intravesicular RNA as mediators of tubular lipid peroxidation and ferroptosis in hypoxic kidney injury. This concept of how tubular pathology is propagated from the initiating insult into a 'wave of death' provides novel therapeutic check-points for targeting AKI-to-CKD transition.

Measuring practice preference variation for quality improvement: development of the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT).

BACKGROUND: Understanding behavioural psychology and the human side of change are guiding principles for quality improvement (QI). Tools to measure these to guide improvement efforts are lacking. METHODS: We created a clinical vignette-based survey to measure provider preferences for respiratory care in the neonatal intensive care unit. Fourteen vignettes were included, each vignette offering two reasonable practice choices. Responses were based on a 5-point Likert scale, ranging from neutral to strong preference for either choice. The survey was completed by physicians, nurses, advanced practice providers and respiratory therapists in 2017 and again in 2019. Net preference was measured as the median value of responses, and agreement was measured as the SD of responses. Net preference and agreement were assessed for all responses, by discipline, and by year. RESULTS: Response rates were 51% of all staff in 2017 and 57% in 2019. Vignettes asking about non-invasive respiratory support showed more defined net preferences and higher agreement between years, coinciding with QI efforts and guideline implementation in this area during the interval time. Results on other areas of practice were consistent between years. Discipline comparisons showed nurses and physicians agreed the least often. Six response patterns were identified, ranging from net preference and high agreement to no net preference and low agreement. CONCLUSION: We propose this survey, called the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool, is a novel method for measurement of hospital unit psychology and culture. Demonstrated improvement where QI efforts were focused and consistency in results in other areas support the validity of this tool. Measuring the human side of change may impact QI efforts.