Engagement in research during specialist geriatric medicine training: results of a national trainee survey.

INTRODUCTION: Meaningful ageing research across the UK is dependent on a network of engaged geriatricians. The research in geriatric specialty training (RGST) survey aimed to establish current research opportunities available to geriatric medicine specialty trainees in the UK. METHODS: The RGST survey was disseminated to UK higher specialist trainees in geriatric medicine in 2019 via the Geriatric Medicine Research Collaborative network. RESULTS: Among the 36.9% (192/521) of respondents, 44% (83/188) reported previous research involvement and 7% (n=8) held a PhD or MD. Of the respondents with no research experience to date, 59.0% (n=49) reported a desire to undertake a period of research. One-third (31%) of geriatric registrars surveyed felt that they had gained sufficient research experience during their training. Perceived encouragement and support to undertake research was low (30.7%). Enablers and barriers to research engagement were identified. CONCLUSION: Research opportunity and engagement in geriatric medicine training is lacking. This could jeopardise the future workforce of research-active geriatricians in the UK and limit patient access to emerging research and innovation. Interventions to promote research engagement among geriatric medicine trainees are needed to facilitate integration of research into routine clinical practice to improve the health and care of older people

HeAlth System StrEngThening in four sub-Saharan African countries (ASSET) to achieve high-quality, evidence-informed surgical, maternal and newborn, and primary care: protocol for pre-implementation phase studies

To achieve universal health coverage, health system strengthening (HSS) is required to support the of delivery of high-quality care. The aim of the National Institute for Health Research Global Research Unit on HeAlth System StrEngThening in Sub-Saharan Africa (ASSET) is to address this need in a four-year programme, with three healthcare platforms involving eight work-packages. Key to effective health system strengthening (HSS) is the pre-implementation phase of research where efforts focus on applying participatory methods to embed the research programme within the existing health system. To conceptualise the approach, we provide an overview of the key methods applied across work-package to address this important phase of research conducted between 2017 and 2021. Work-packages are being undertaken in publicly funded health systems in rural and urban areas in Ethiopia, Sierra Leone, South Africa, and Zimbabwe. Stakeholders including patients and their caregivers, community representatives, clinicians, managers, administrators, and policymakers are the main research participants. In each work-package, initial activities engage stakeholders and build relationships to ensure co-production and ownership of HSSIs. A mixed-methods approach is then applied to understand and address determinants of high-quality care delivery. Methods such as situation analysis, cross-sectional surveys, interviews and focus group discussions are adopted to each work-package aim and context. At the end of the pre-implementation phase, findings are disseminated using focus group discussions and participatory Theory of Change workshops where stakeholders from each work package use findings to select HSSIs and develop a programme theory. ASSET places a strong emphasis of the pre-implementation phase in order to provide an in-depth and systematic diagnosis of the existing heath system functioning, needs for strengthening and stakeholder engagement. This common approach will inform the design and evaluation of the HSSIs to increase effectiveness across work packages and contexts, to better understand what works, for whom, and how

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Functional analyses of cardiomyopathic contractile proteins : mutations in troponin that cause familial hypertrophic cardiomyopathy and familial dilated cardiomyopathy

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Novel model for the in vivo study of central nervous system infection due to Acanthamoeba spp. (T4 genotype)

In this study it was shown for what is believed to be the first time that the African migratory locust can be used as a model for the study of Acanthamoeba pathogenesis. Mature adult locusts were injected intra-abdominally with 10 µl suspension of 106 Acanthamoeba (a clinical isolate of the T4 genotype) in culture medium, or with the same volume of sterile culture medium. Locusts injected with Acanthamoeba showed significant weight loss and reduced production of faeces compared with control locusts. Furthermore, injection of amoebae killed all of the locusts within 17 days at room temperature, although the speed of kill was temperature and dose dependent. When samples of faecal pellets and various tissues of infected locusts were cultured on non-nutrient agar plates containing bacterial lawns, live amoebae were recovered from haemolymph, flight muscle and fat body samples, but not from faeces. When brains dissected from locusts were incubated with an anti-amoebic drug (100 µM chlorhexidine) to kill extracellular amoebae, and then washed, homogenized and cultured on bacteria-seeded non-nutrient agar plates, only lysates from amoebae-infected locusts were positive for Acanthamoeba. This strongly suggests that amoebae invade the locust brain and, indeed, trophozoites of Acanthamoeba could be identified within the brain in histological sections of brains from infected locusts, but not from uninfected locusts. These findings support the view that locusts can be used as a model for the study of Acanthamoeba pathogenesis in vivo

Establishing disease causality for a novel gene variant in familial dilated cardiomyopathy using a functional in-vitro assay of regulated thin filaments and human cardiac myosin

BACKGROUND: As next generation sequencing for the genetic diagnosis of cardiovascular disorders becomes more widely used, establishing causality for putative disease causing variants becomes increasingly relevant. Diseases of the cardiac sarcomere provide a particular challenge in this regard because of the complexity of assaying the effect of genetic variants in human cardiac contractile proteins. RESULTS: In this study we identified a novel variant R205Q in the cardiac troponin T gene (TNNT2). Carriers of the variant allele exhibited increased chamber volumes associated with decreased left ventricular ejection fraction. To clarify the causal role of this variant, we generated recombinant variant human protein and examined its calcium kinetics as well as the maximally activated ADP release of human β-cardiac myosin with regulated thin filaments containing the mutant troponin T. We found that the R205Q mutation significantly decreased the calcium sensitivity of the thin filament by altering the effective calcium dissociation kinetics. CONCLUSIONS: The development of moderate throughput post-genomic assays is an essential step in the realization of the potential of next generation sequencing. Although technically challenging, biochemical and functional assays of human cardiac contractile proteins of the thin filament can be achieved and provide an orthogonal source of information to inform the question of causality for individual variants