Patient and public involvement (PPI) in delirium research

Poster presented at: Clinical School conference - RD&E (1st June 2016), #icanpreventdelirium conference - Newcastle (14th June 2016) and Postgraduate Society Conference - Plymouth University (20th June 2016). Work done in collaboration with NIHR PenCLAHRC

Activity interventions to improve the experience of care in hospital for people living with dementia: a systematic review

Background: An increasingly high number of patients admitted to hospital have dementia. Hospital environments can be particularly confusing and challenging for people living with dementia (Plwd) impacting their wellbeing and the ability to optimize their care. Improving the experience of care in hospital has been recognized as a priority, and non-pharmacological interventions including activity interventions have been associated with improved wellbeing and behavioral outcomes for Plwd in other settings. This systematic review aimed at evaluating the effectiveness of activity interventions to improve experience of care for Plwd in hospital. Methods: Systematic searches were conducted in 16 electronic databases up to October 2019. Reference lists of included studies and forward citation searching were also conducted. Quantitative studies reporting comparative data for activity interventions delivered to Plwd aiming to improve their experience of care in hospital were included. Screening for inclusion, data extraction and quality appraisal were performed independently by two reviewers with discrepancies resolved by discussion with a third where necessary. Standardized mean differences (SMDs) were calculated where possible to support narrative statements and aid interpretation. Results: Six studies met the inclusion criteria (one randomized and five non-randomized uncontrolled studies) including 216 Plwd. Activity interventions evaluated music, art, social, psychotherapeutic, and combinations of tailored activities in relation to wellbeing outcomes. Although studies were generally underpowered, findings indicated beneficial effects of activity interventions with improved mood and engagement of Plwd while in hospital, and reduced levels of responsive behaviors. Calculated SMDs ranged from very small to large but were mostly statistically non-significant. Conclusions: The small number of identified studies indicate that activity-based interventions implemented in hospitals may be effective in improving aspects of the care experience for Plwd. Larger well-conducted studies are needed to fully evaluate the potential of this type of non-pharmacological intervention to improve experience of care in hospital settings, and whether any benefits extend to staff wellbeing and the wider ward environment.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Funding was provided by the Health Services and Delivery Research programme of the National Institute for Health Research, and 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 Peninsula. The funding body had no role in design of the study, analysis and interpretation of the data or writing of the manuscript.published version, accepted version, submitted versio

The experiences of hospital staff who provide care for people living with dementia: A systematic review and synthesis of qualitative studies

Aims and objectives: To systematically review and synthesise qualitative data from studies exploring the experiences of hospital staff who care for people living with dementia (Plwd). Background: In hospital, the number of Plwd continues to rise; however, their experiences of care remain problematic. Negative experiences of care are likely to contribute to poorer mental and physical health outcomes for Plwd while in hospital and after discharge. Experiences of the hospital staff who care for Plwd can also be poor or unrewarding. It is important to understand the experiences of staff in order to improve staff well-being and ultimately the experience of care for Plwd while in hospital. Design: Systematic review and evidence synthesis of qualitative research. Data sources: We searched 16 electronic databases in March 2018 and completed forward and backward citation chasing. Methods: Eligible studies explored the experiences of paid and unpaid staff providing care in hospital for Plwd. Study selection was undertaken independently by two reviewers, and quality appraisal was conducted. We prioritised included studies according to richness of text, methodological rigour and conceptual contribution. We adopted approaches of meta-ethnography to analyse study findings, creating a conceptual model to represent the line of argument. Findings: Forty-five studies reported in 58 papers met the inclusion criteria, and of these, we prioritised 19 studies reported in 24 papers. The line of argument was that Institutions can improve staff experiences of care for Plwd by fostering person-centred care (PCC). PCC aligned with staff perceptions of 'good care'; however, staff often felt prevented from providing PCC because of care cultures that prioritised tasks, routines and physical health. Staff experienced conflict over the care they wanted to give versus the care they were able to give, and this caused moral distress. When staff were able to provide PCC, this increased experiences of job satisfaction and emotional well-being. Conclusions: Person-centred care not only has the potential to improve the experience of care for Plwd and their carers, but can also improve the experiences of hospital staff caring for Plwd. However, without institutional-level changes, hospital staff are often unable to provide PCC even when they have the experience and knowledge to do so. Implications for practice: Institutional-level areas for change include the following: training; performance indicators and ward cultures that prioritise psychological needs alongside physical needs; adequate staffing levels; inclusive approaches to carers; physical environments that promote familiarisation, social interaction and occupation; systems of documentation about individual needs of Plwd; and cultures of sharing knowledge across hierarchies.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.HS&DR 14/19/16/Health Services and Delivery Research Programmepublished version, accepted version (12 month embargo), submitted versio

A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy

Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease

HIF–VEGF Pathways Are Critical for Chronic Otitis Media in Junbo and Jeff Mouse Mutants

Otitis media with effusion (OME) is the commonest cause of hearing loss in children, yet the underlying genetic pathways and mechanisms involved are incompletely understood. Ventilation of the middle ear with tympanostomy tubes is the commonest surgical procedure in children and the best treatment for chronic OME, but the mechanism by which they work remains uncertain. As hypoxia is a common feature of inflamed microenvironments, moderation of hypoxia may be a significant contributory mechanism. We have investigated the occurrence of hypoxia and hypoxia-inducible factor (HIF) mediated responses in Junbo and Jeff mouse mutant models, which develop spontaneous chronic otitis media. We found that Jeff and Junbo mice labeled in vivo with pimonidazole showed cellular hypoxia in inflammatory cells in the bulla lumen, and in Junbo the middle ear mucosa was also hypoxic. The bulla fluid inflammatory cell numbers were greater and the upregulation of inflammatory gene networks were more pronounced in Junbo than Jeff. Hif-1a gene expression was elevated in bulla fluid inflammatory cells, and there was upregulation of its target genes including Vegfa in Junbo and Jeff. We therefore investigated the effects in Junbo of small-molecule inhibitors of VEGFR signaling (PTK787, SU-11248, and BAY 43-9006) and destabilizing HIF by inhibiting its chaperone HSP90 with 17-DMAG. We found that both classes of inhibitor significantly reduced hearing loss and the occurrence of bulla fluid and that VEGFR inhibitors moderated angiogenesis and lymphangiogenesis in the inflamed middle ear mucosa. The effectiveness of HSP90 and VEGFR signaling inhibitors in suppressing OM in the Junbo model implicates HIF–mediated VEGF as playing a pivotal role in OM pathogenesis. Our analysis of the Junbo and Jeff mutants highlights the role of hypoxia and HIF–mediated pathways, and we conclude that targeting molecules in HIF–VEGF signaling pathways has therapeutic potential in the treatment of chronic OM

Loss of Mitogen-Activated Protein Kinase Kinase Kinase 4 (MAP3K4) Reveals a Requirement for MAPK Signalling in Mouse Sex Determination

The boygirl (byg) mouse mutant reveals that MAP3K4-mediated signaling is necessary for normal SRY expression and testis specification in the developing mouse gonad

A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways

Otitis media (OM), inflammation of the middle ear (ME), is a common cause of conductive hearing impairment. Despite the importance of the disease, the aetiology of chronic and recurrent forms of middle ear inflammatory disease remains poorly understood. Studies of the human population suggest that there is a significant genetic component predisposing to the development of chronic OM, although the underlying genes are largely unknown. Using N-ethyl-N-nitrosourea mutagenesis we identified a recessive mouse mutant, edison, that spontaneously develops a conductive hearing loss due to chronic OM. The causal mutation was identified as a missense change, L972P, in the Nischarin (NISCH) gene. edison mice develop a serous or granulocytic effusion, increasingly macrophage and neutrophil rich with age, along with a thickened, inflamed mucoperiosteum. We also identified a second hypomorphic allele, V33A, with only modest increases in auditory thresholds and reduced incidence of OM. NISCH interacts with several proteins, including ITGA5 that is thought to have a role in modulating VEGF-induced angiogenesis and vascularization. We identified a significant genetic interaction between Nisch and Itga5; mice heterozygous for Itga5-null and homozygous for edison mutations display a significantly increased penetrance and severity of chronic OM. In order to understand the pathological mechanisms underlying the OM phenotype, we studied interacting partners to NISCH along with downstream signalling molecules in the middle ear epithelia of edison mouse. Our analysis implicates PAK1 and RAC1, and downstream signalling in LIMK1 and NF-κB pathways in the development of chronic OM

Practice question

What are twiddlemuffs is a question I have been asked many times in the months since we introduced these handmade knitted items in Exeter

Can person-centred care for people living with dementia be delivered in the acute care setting?

The need to improve care for people living with dementia in the hospital setting has long been recognised. Person-centred care has the potential to improve the experience of care for persons living with dementia and their carers, and has been shown to improve the experiences of hospital staff caring for the persons living with dementia, however it remains challenging to deliver in a time- and task-focussed acute care setting. This commentary suggests that to embed person-centred care across the hospital environment, cultural changes are needed at organisational and ward levels. In particular there needs to be: leadership that supports and advocates for workforce capacity to recognise and meet both psychological and physical needs of people living with dementia, promotion of physical environments that support familiarisation and social interactions, an inclusive approach to carers and the development of a culture of sharing knowledge and information across hierarchies and roles. An evidence-based set of pointers for service change are described which highlight institutional and environmental practices and processes that need to be addressed in order for person-centred care to become part of routine care.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted version (12 month embargo), submitted versio