Helping people with dementia to eat well at home: An investigation to understand and enhance nutritional care

There are three studies in this thesis which have been published. The substantial contribution to co-authored papers was made by the candidate. Chapters 3, 4 and 5 contain the manuscripts, and are presented in the format requested by the respective journal.In this thesis I developed a complex intervention to help people living at home with dementia to eat well, and improve nutritional care. This was achieved through four studies conducted using multiple methods. A scoping review found 61 studies reported in 63 articles after searching six databases from inception to July 2016. Content analysis was used, and the overarching categories were: ‘timely identification of nutritional risk and subsequent regular monitoring of nutritional status’, ‘multi-component tailored interventions’, and the ‘influence of the caregiving dyad on nutritional status’. Most studies were cross-sectional (n=24), cohort (n=15) or qualitative (n=9). Only three were randomised controlled trials. People living at home with dementia are identified as a vulnerable group (n=35), however only four studies tested interventions to improve nutritional care. In two qualitative studies, semi-structured interviews were used (alongside diaries and a vignette) to explore the experiences of the nutritional care of people living with dementia at home from the perspectives of family members, healthcare professionals and homecare workers. Eight family carers (mean age of 69.6 years) and seven healthcare professionals and homecare workers (mean time spent in profession = 8.9 years) were purposively recruited and interviewed between October 2017 and March 2018. An Interpretative phenomenological analysis approach was used. Three superordinate themes were identified for family carers: ‘becoming carer and cook’, ‘changing role and relationships’, and ‘emotional eating’. Four superordinate themes were identified for healthcare professionals and homecare workers: ‘responsibility to care’, ‘practice restrained by policy’, ‘in it together’, and ‘improving nutritional care’. Family carers, healthcare professionals and homecare workers feel that they do not have adequate knowledge to support someone if they are nutritionally compromised. They are conscious about ‘doing the right thing’ when it comes to providing nutritional care. The acceptability and feasibility of three podcasts designed for homecare workers about providing nutritional care to someone with dementia were trialled. Six homecare workers took part between October and December 2019, attending a focus group, and completing a quiz. Normalisation process theory underpinned the thematic analysis of qualitative data. Knowledge improved from a score of 5.5 (median) before listening to 7.5 (median) after listening. Eight themes represented the views of the participants. Podcasts about nutritional care and dementia are acceptable to homecare workers, and knowledge of the nutritional concerns associated with dementia improved. Family carers and people living at home with dementia should be supported when making appropriate food and drink choices, preventing the risk of malnutrition. It is anticipated that the findings of the studies included in this thesis, will encourage healthcare professionals and researchers to place more focus on the nutritional needs of people with dementia living at home. Further development is required for podcasts, and evaluation of their impact in terms of practice and clinical outcomes are required.This study was financed with the aid of a studentship from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South West Peninsula, now recommissioned as NIHR Applied Research Collaboration (ARC) South West Peninsul

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

The HIF complex recruits the histone methyltransferase SET1B to activate specific hypoxia-inducible genes.

Hypoxia-inducible transcription factors (HIFs) are fundamental to cellular adaptation to low oxygen levels, but it is unclear how they interact with chromatin and activate their target genes. Here, we use genome-wide mutagenesis to identify genes involved in HIF transcriptional activity, and define a requirement for the histone H3 lysine 4 (H3K4) methyltransferase SET1B. SET1B loss leads to a selective reduction in transcriptional activation of HIF target genes, resulting in impaired cell growth, angiogenesis and tumor establishment in SET1B-deficient xenografts. Mechanistically, we show that SET1B accumulates on chromatin in hypoxia, and is recruited to HIF target genes by the HIF complex. The selective induction of H3K4 trimethylation at HIF target loci is both HIF- and SET1B-dependent and, when impaired, correlates with decreased promoter acetylation and gene expression. Together, these findings show SET1B as a determinant of site-specific histone methylation and provide insight into how HIF target genes are differentially regulated.Lister Institute NIHR Addenbrooke's Charitable Trus