Progressing the understanding of chronic illness and its treatment: A post-human, ethological understanding of haemodialysis.

Haemodialysis is a common treatment option offered internationally for people requiring kidney replacement therapy. Research exploring haemodialysis is predominantly clinical and quantitative, and improvements to its provision and receipt tends also to be clinically focused. In recent years, however, a number of studies have sought to explore the lived experience of haemodialysis. These studies tend to use semi-structured interviews and present descriptive findings. Such findings serve to raise the profile of patient perspectives and encourage thinking beyond the clinical gaze. To progress this, we apply a post-humanism approach to the understanding of the receipt of haemodialysis. Drawing on findings from a study to explore the experience and impact of in-centre, daytime, haemodialysis we follow Fox and Alldred's ethological toolkit to provide a post-human analysis of haemodialysis. In doing so we argue that haemodialysis exists as a heterogenous and changeable assemblage of multiple and fluid, human and non-human factors that has the capacity to affect. Here we outline this post-human approach and the impact it has for understanding not just haemodialysis but also the receipt of treatment for other chronic illnesses.

The NightLife study - the clinical and cost-effectiveness of thrice-weekly, extended, in-centre nocturnal haemodialysis versus daytime haemodialysis using a mixed methods approach: study protocol for a randomised controlled trial.

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Reducing the carbon footprint of research: experience from the NightLife study.

BACKGROUND: As set out in the Climate Change Act (2008), the UK National Health Service (NHS) has made a commitment to halve greenhouse gas emissions by 2025 and reach net zero by 2050. Research forms a core part of NHS activity and reducing the carbon footprint of clinical trials is a core element of the National Institute for Health and Care Research Carbon Reduction Strategy (2019). KEY ARGUMENTS: However, support from funding organisations on how to achieve these targets is lacking. This brief communication article reports the reduction in the carbon footprint of the NightLife study, an ongoing multicentre randomised controlled trial assessing the impact of in-centre nocturnal haemodialysis on quality of life. CONCLUSION: By using remote conferencing software and innovative data collection methods, we demonstrated a total saving of 136 tonnes of carbon dioxide equivalent over three workstreams during the first 18 months of the study, following grant activation on 1 January 2020. In addition to the environmental impact, there were additional benefits seen to cost as well as increased participant diversity and inclusion. This work highlights ways in which trials could be made less carbon intensive, more environmentally sustainable and better value for money.

Biographical dialectics: The ongoing and creative problem solving required to negotiate the biographical disruption of chronic illness.

Here we propose the term 'biographical dialectics' as a sister term to 'biographical disruption' to capture the ongoing problem solving that characterises the lives of many people living with life limiting chronic illnesses. The paper is based on the experiences of 35 adults with end-stage kidney disease (ESKD) in receipt of haemodialysis. Photovoice and semi-structured interviews showed that ESKD and the use of haemodialysis was widely agreed to be biographically disruptive. In talking about and showing disruption through photographs the participants' ongoing problem solving was universal across their diverse experiences. 'Biographical disruption' and Hegalian dialectical logic, are drawn on to make sense of these actions and to further understand the personal and disruptive experience of chronic illness. Based on this, 'biographical dialectics' captures the work that is required to account for and manage the enduring and biographical impact of chronic illness that follows the initial disruption of diagnosis and continues as life progresses.

Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): a phase 2a, placebo-controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory airway disease. The epithelial-derived IL-33 and its receptor ST2 have been implicated in airway inflammation and infection. We aimed to determine whether astegolimab, a selective ST2 IgG2 monoclonal antibody, reduces exacerbations in COPD. METHODS: COPD-ST2OP was a single-centre, randomised, double-blinded, placebo-controlled phase 2a trial in moderate-to-very severe COPD. Participants were randomly assigned (1:1) with a web-based system to received 490 mg subcutaneous astegolimab or subcutaneous placebo, every 4 weeks for 44 weeks. The primary endpoint was exacerbation rate assessed for 48 weeks assessed with a negative binomial count model in the intention-to-treat population, with prespecified subgroup analysis by baseline blood eosinophil count. The model was the number of exacerbations over the 48-week treatment period, with treatment group as a covariate. Safety was assessed in the whole study population until week 60. Secondary endpoints included Saint George's Respiratory Questionnaire for COPD (SGRQ-C), FEV1, and blood and sputum cell counts. The trial was registered with ClinicalTrials.gov, NCT03615040. FINDINGS: The exacerbation rate at 48 weeks in the intention-to-treat analysis was not significantly different between the astegolimab group (2·18 [95% CI 1·59 to 2·78]) and the placebo group (2·81 [2·05 to 3·58]; rate ratio 0·78 [95% CI 0·53 to 1·14]; p=0·19]). In the prespecified analysis stratifying patients by blood eosinophil count, patients with 170 or fewer cells per µL had 0·69 exacerbations (0·39 to 1·21), whereas those with more than 170 cells per µL had 0·83 exacerbations (0·49 to 1·40). For the secondary outcomes, the mean difference between the SGRQ-C in the astegolimab group versus placebo group was -3·3 (95% CI -6·4 to -0·2; p=0·039), and mean difference in FEV1 between the two groups was 40 mL (-10 to 90; p=0·094). The difference in geometric mean ratios between the two groups for blood eosinophil counts was 0·59 (95% CI 0·51 to 0·69; p<0·001) and 0·25 (0·19 to 0·33; p<0·001) for sputum eosinophil counts. Incidence of treatment-emergent adverse events was similar between groups. INTERPRETATION: In patients with moderate-to-very severe COPD, astegolimab did not significantly reduce exacerbation rate, but did improve health status compared with placebo. FUNDING: Funded by Genentech and National Institute for Health Research Biomedical Research Centres.

Evaluating the clinical experience of a regional in-center nocturnal hemodialysis program: The patient and staff perspective.

INTRODUCTION: End-stage kidney disease causes significant morbidity, mortality, and reduced quality of life. Despite improvements in conventional hemodialysis, these problems persist. In-center nocturnal hemodialysis (INHD) has been shown to be beneficial in observational studies. This report outlines a 4-year renal network experience of INHD from the patient and frontline staff perspective. METHODS: Staff and patients' experiences of INHD were evaluated through two work streams. Work stream one: 12 patients who chose to stop INHD and 24 patients who chose to continue with INHD completed an anonymous survey. Work stream two: one-to-one interviews with 20 patients receiving INHD and seven staff working INHD shifts were conducted. Clinical incident reporting for conventional hemodialysis and INHD from April 2014 to December 2018 was reviewed. FINDINGS: Work stream one: Five themes were identified; facilities, time, health and well-being, sleep, and transport. A patient "starter pack" was developed and improvements to the dialysis unit were completed. Work stream two: Patient interviews demonstrated starter packs to aid sleep were well received; sleep itself was not a single reason to discontinue INHD. Staff indicated that their greatest concern was staffing levels; although staff-to-patient ratio remains unchanged, total numbers on INHD shifts were fewer, causing concern around less colleague availability for support during an emergency. SAFETY: 363 clinical incidents were reported across all dialysis shifts; for conventional hemodialysis, a larger proportion were due to medical interventions, infection control, and transport; for INHD, most incidents centered around communication with patients and relatives, delays in patient transfer, and issues with medical equipment or facilities. DISCUSSION: Patients continue with INHD due to increased social time and perceived health benefits. Patient starter packs and adjustments to the dialysis unit may enhance sleep. This experience has optimized the design of the NightLife study; a randomized controlled trial evaluated the effect of INHD on quality of life.

It is unprecedented: trial management during the COVID-19 pandemic and beyond.

The COVID-19 pandemic has presented unique challenges for the clinical trial community, both in the rapid establishment of COVID-19 clinical trials and many existing non-COVID-19 studies either being temporarily paused (whether that is a complete pause or pause in some activities) and/or adapting their processes. Trial managers have played a key role in decision-making, undertaking risk assessments and adapting trial processes, working closely with other members of the research team. This article presents some of the ways in which trial management processes have been altered and the key role that trial managers have played. It has been born out of discussions between trial managers in the UK who are members of the UK Trial Managers' Network (UKTMN), a national network of trial management professionals managing non-commercial trials.In these unprecedented times, clinical trials have faced many uncertainties and broad-ranging challenges encompassing a range of activities including prioritising patient safety amidst the pandemic, consenting and recruiting new participants into trials, data collection and management and intervention delivery. In many cases, recruitment has been paused whilst mitigations have been put in place to continue data collection. Innovative solutions have been implemented to ensure we continue, where possible, to deliver high-quality clinical trials. Technology has provided many solutions to these challenges, and trial managers have adapted to new ways of working whilst continuing to deliver their clinical trials. Trial management groups are now faced with new uncertainties around re-starting clinical trials, and it is unclear currently how this will go, though working together with sponsors, funders and site teams is clearly a priority.Clinical trial teams have worked together to ensure their trials have adapted quickly whilst ensuring participant safety is given utmost importance. There are clear examples where the trial community have come together to share experiences and expertise, and this should continue in the future to ensure the innovative practices developed become embedded in the design and conduct of clinical trials in the future.