Realist synthesis protocol for understanding which strategies are effective to prevent urinary tract infection in older people in care homes.

AIM: To identify and characterize strategies, which contribute to the prevention of urinary tract infection (UTI) in older people living in care homes. DESIGN: The realist synthesis has four iterative stages to (1) develop initial programme theory; (2) search for evidence; (3) test and refine theory supported by relevant evidence and (4) formulate recommendations. Data from research articles and other sources will be used to explore the connection between interventions and the context in which they are applied in order to understand the mechanisms, which influence the outcomes to prevent UTI. METHODS: A scoping search of the literature and workshops with stakeholders will identify initial programme theories. These theories will be tested and refined through a systematic search for evidence relating to mechanisms that trigger prevention and recognition of UTI in older people in care homes. Interviews with key stakeholders will establish practical relevance of the theories and their potential for implementation. DISCUSSION: UTI is the most commonly diagnosed infection in care home residents. Evidence on the effectiveness of strategies to prevent UTI in long-term care facilities does not address the practicality of implementing these approaches in UK care homes. The realist synthesis is designed to examine this important gap in evidence. IMPACT: Our evidence-informed programme theory will help inform programmes to improve practice to reduce the incidence of UTI in older people living in care homes and related research. Patient and public involvement will be crucial to ensuring that our findings reach carers and the public. PATIENT AND PUBLIC CONTRIBUTION: Involvement of patient and public representatives is embedded throughout the study to ensure it is underpinned by multiple perspectives of importance to care home residents. Our co-investigator representing patient and public involvement is a lay member of the team and will chair the Project Advisory Group, which has two additional lay members. This will help to ensure that our findings and resources reach carers and the public and represent their voice in our publications and presentations to professional and lay audiences.

Percutaneous Transcatheter Closure of Post-infarction Ventricular Septal Defect: An Alternative to Surgical Intervention.

Post-infarction ventricular septal defect is a mechanical complication of acute MI. The incidence of this complication is low in the primary percutaneous coronary intervention era. However, the associated mortality is very high at 94% with medical management alone. Open surgical repair or percutaneous transcatheter closure still has an in-hospital mortality >40%. Retrospective comparisons between both closure methods are limited by observation and selection bias. This review addresses the assessment and optimisation of patients prior to repair, the optimal timing of repair, and the limitations in current data. The review considers techniques for percutaneous closure, and finally considers the path that future research should take to improve outcomes for patients.

Using arts-based research in applied health care: An example from an evaluation of NHS dental contract reform in Wales.

OBJECTIVE: Arts-based research (ABR) refers to the use of art in the research process to help generate, interpret and/or communicate knowledge. We used ABR principles to adapt a centre-staging method to complement a more traditional qualitative approach to evaluate participants' views on dental service reform. METHODS: We asked five individuals in the dental health sector in the National Health Service in Wales to select objects to depict their views on the current reform process and their ideal reform process. This process took place alongside traditional semi-structured interviews with the participants. RESULTS: There were three marked differences in the centre-staging process as compared to the interviews: (1) there was a greater use of symbolism by the participants, (2) the participants put a greater focus on the process of change and (3) the participants were more likely to reveal the emotions underlying their assessments of the reform process. CONCLUSIONS: The arts-based approach adopted appeared to be highly accessible and has the potential to be used in a wide range of applications.

Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy and the impact of mavacamten.

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder characterised by unexplained left ventricular hypertrophy. Left ventricular outflow tract obstruction is an integral component of the disease, often resulting in significant symptoms, but also carrying a risk of progression to heart failure and death. Advancements in our understanding of the pathophysiology of HCM have led to the development of new therapies targeting the molecular basis of the disease at the level of the cardiac sarcomere, the basic contractile apparatus of the myocardium. Myosin modulators are a novel class of small molecules which target cardiac myosins directly to modulate cardiac contractility. The myosin inhibitors present the first advancement in pharmacological management of obstructive HCM in almost 35 years, with a growing body of evidence for the safety, tolerability and efficacy of mavacamten, and to a lesser extent aficamten. The aim of this review is to summarise the current management of patients with obstructive HCM and review the most recent available data from clinical trials pertaining to myosin inhibition.

uSing rolE-substitutioN In care homes to improve ORal health (SENIOR): a study protocol.

BACKGROUND: Dental service provision in the care home sector is poor, with little emphasis on prevention. Emerging evidence suggests that the use of Dental Care Professionals (dental therapists and dental nurses) as an alternative to dentists has the potential to improve preventive advice, the provision of care and access to services within care homes. However, robust empirical evidence from definitive trials on how to successfully implement and sustain these interventions within care homes is currently lacking. The aim of the study is to determine whether Dental Care Professionals could reduce plaque levels of dentate older adults (65 + years) residing in care homes. METHODS: This protocol describes a two-arm cluster-randomised controlled trial that will be undertaken in care homes across Wales, Northern Ireland and England. In the intervention arm, the dental therapists will visit the care homes every 6 months to assess and then treat eligible residents, where necessary. All treatment will be conducted within their Scope of Practice. Dental nurses will visit the care homes every month for the first 3 months and then three-monthly afterwards to promulgate advice to improve the day-to-day prevention offered to residents by carers. The control arm will be 'treatment as usual'. Eligible care homes (n = 40) will be randomised based on a 1:1 ratio (20 intervention and 20 control), with an average of seven residents recruited in each home resulting in an estimated sample of 280. Assessments will be undertaken at baseline, 6 months and 12 months and will include a dental examination and quality of life questionnaires. Care home staff will collect weekly information on the residents' oral health (e.g. episodes of pain and unscheduled care). The primary outcome will be a binary classification of the mean reduction in Silness-Löe Plaque Index at 6 months. A parallel process evaluation will be undertaken to explore the intervention's acceptability and how it could be embedded in standard practice (described in a separate paper), whilst a cost-effectiveness analysis will examine the potential long-term costs and benefits of the intervention. DISCUSSION: This trial will provide evidence on how to successfully implement and sustain a Dental Care Professional-led intervention within care homes to promote access and prevention. TRIAL REGISTRATION: ISRCTN16332897 . Registered on 3 December 2021.

The in-practice prevention programme: an example of flexible commissioning from Yorkshire and the Humber.

Introduction An In-Practice Prevention (IPP) programme was developed by the Local Dental Network in the North Yorkshire and the Humber area in England in response to an oral health needs assessment. The underpinning logic model drew on a flexible commissioning approach and aimed to incentivise dental teams with NHS contracts to promote the delivery of prevention. This used care pathways that involved the whole dental team and was cost-neutral.Aim The programme was evaluated using realist methodology to identify 'what works, in which circumstances, how and for who?'.Design Realist evaluations are explanatory in nature and attempt to understand the factors that appear to influence the success (or not) of an intervention, rather than demonstrating causality.Methods and results Following a review of the pertinent literature, semi-structured interviews and focus groups, five theory areas were considered to be critical to the delivery of IPP. In order of stated priority, these were: 1) clinical leadership; 2) 'skill mix'; 3) financial incentives; 4) institutional logic/practice culture; and 5) behaviour change.Conclusion The results appear to show that clinically-led programmes could offer value to dental commissioners within a flexible commissioning model, although this would need to be further tested using an experiment design.

Comparison of CPU and GPU bayesian estimates of fibre orientations from diffusion MRI.

BACKGROUND: The correct estimation of fibre orientations is a crucial step for reconstructing human brain tracts. Bayesian Estimation of Diffusion Parameters Obtained using Sampling Techniques (bedpostx) is able to estimate several fibre orientations and their diffusion parameters per voxel using Markov Chain Monte Carlo (MCMC) in a whole brain diffusion MRI data, and it is capable of running on GPUs, achieving speed-up of over 100 times compared to CPUs. However, few studies have looked at whether the results from the CPU and GPU algorithms differ. In this study, we compared CPU and GPU bedpostx outputs by running multiple trials of both algorithms on the same whole brain diffusion data and compared each distribution of output using Kolmogorov-Smirnov tests. RESULTS: We show that distributions of fibre fraction parameters and principal diffusion direction angles from bedpostx and bedpostx_gpu display few statistically significant differences in shape and are localized sparsely throughout the whole brain. Average output differences are small in magnitude compared to underlying uncertainty. CONCLUSIONS: Despite small amount of differences in output between CPU and GPU bedpostx algorithms, results are comparable given the difference in operation order and library usage between CPU and GPU bedpostx.

Percutaneous management of paravalvular leaks.

Paravalvular leak (PVL) is a challenging complication of valve replacement surgery that can cause heart failure and haemolysis. Surgical repair is the traditional treatment for severe, symptomatic PVL, but many patients with PVL fall into high-risk categories for redo surgery. Percutaneous techniques for closure of PVL have been increasingly refined over the last decade with availability of approved purpose-specific devices for closure. Percutaneous closure requires a heart team approach, with attention paid to appropriate preprocedural and periprocedural imaging to ensure a successful closure with minimal residual leak or complication. There are limited studies addressing the selection of a percutaneous approach to PVL. No randomised trials comparing surgical and percutaneous repair have been conducted. Large national registries from the UK and Ireland and from Spain have demonstrated that high rates of technical success can be achieved, with mortality comparable with surgical repair. Six retrospective studies comparing surgical and percutaneous approaches have been published. These broadly show comparable technical success between the interventions, with reduced short-term mortality among patients treated percutaneously. Long-term outcomes were similar between both treatment options. Percutaneous repair is an attractive treatment option in many patients due to its reduced invasiveness and quicker recovery period. However, more prospective studies are needed to validate its place in the armamentarium of the heart team.

Left atrial function analysis in patients in sinus rhythm, normal left ventricular function and indeterminate diastolic function.

Assessment of diastolic function by echocardiography may be indeterminate as demonstrated in previous studies where diastolic measurement is a discrepant. We aimed to assess whether left atrial (LA) function may contribute to left ventricle filling evaluation in patients with indeterminate diastolic function (IndtDFx). This retrospective study included 3 groups of patients based on diastolic function: normal diastolic function (NDFx), definite diastolic dysfunction (DDFx) and IndtDFx. All patients had sinus rhythm with left ventricular ejection fraction ≥ 45%. Diastolic function was determined according to the following echocardiographic parameters: mitral E', mitral E/E' ratio, LA maximal volume index, and pulmonary pressure. NDFx was defined as having less than 2 abnormal parameters, DDFx as more than 2 abnormal parameters, and IndtDFx as 2 abnormal parameters. LA function analysis was performed in all patients using echocardiographic 2D speckle tracking. Sixty seven patients were included in strain analysis. The DDFx group (n = 21) and IndtDFx (n = 19) were significantly different from NDFx (27) in some demographics, cardiovascular risk factors, presentation and echocardiographic parameters. Some of the phasic LA function (phasic LA volumes and strains) parameters in the IndtDFx group were similar to DDFx and significantly different from the NDFx group, while other parameters fell in between the two groups. Phasic LA minimal volume index was found to be associated with heart failure symptoms. The IndtDFx group is a heterogeneous group demonstrating clinical and echocardiographic profiles that closely resemble that of DDFx group. LA phasic function analysis may help in re-classification of patients with IndtDFx as actual DDFx or as NDFx.

'Function First': how to promote physical activity and physical function in people with long-term conditions managed in primary care? A study combining realist and co-design methods.

OBJECTIVES: To develop a taxonomy of interventions and a programme theory explaining how interventions improve physical activity and function in people with long-term conditions managed in primary care. To co-design a prototype intervention informed by the programme theory. DESIGN: Realist synthesis combining evidence from a wide range of rich and relevant literature with stakeholder views. Resulting context, mechanism and outcome statements informed co-design and knowledge mobilisation workshops with stakeholders to develop a primary care service innovation. RESULTS: A taxonomy was produced, including 13 categories of physical activity interventions for people with long-term conditions. ABRIDGED REALIST PROGRAMME THEORY: Routinely addressing physical activity within consultations is dependent on a reinforcing practice culture, and targeted resources, with better coordination, will generate more opportunities to address low physical activity. The adaptation of physical activity promotion to individual needs and preferences of people with long-term conditions helps affect positive patient behaviour change. Training can improve knowledge, confidence and capability of practice staff to better promote physical activity. Engagement in any physical activity promotion programme will depend on the degree to which it makes sense to patients and professions, and is seen as trustworthy. CO-DESIGN: The programme theory informed the co-design of a prototype intervention to: improve physical literacy among practice staff; describe/develop the role of a physical activity advisor who can encourage the use of local opportunities to be more active; and provide materials to support behaviour change. CONCLUSIONS: Previous physical activity interventions in primary care have had limited effect. This may be because they have only partially addressed factors emerging in our programme theory. The co-designed prototype intervention aims to address all elements of this emergent theory, but needs further development and consideration alongside current schemes and contexts (including implications relevant to COVID-19), and testing in a future study. The integration of realist and co-design methods strengthened this study.

Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure.

Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may influence white matter (WM) development, as previous studies report widespread microstructural alterations and reduced interhemispheric connectivity in SSRI-exposed infants. In rodents, perinatal SSRIs had sex-specific disruptions in corpus callosum (CC) axon architecture and connectivity; yet it is unknown whether SSRI-related brain outcomes in humans are sex specific. In this study, the neonate CC was selected as a region-of-interest to investigate whether prenatal SSRI exposure has sex-specific effects on early WM microstructure. On postnatal day 7, diffusion tensor imaging was used to assess WM microstructure in SSRI-exposed (n = 24; 12 male) and nonexposed (n = 48; 28 male) term-born neonates. Fractional anisotropy was extracted from CC voxels and a multivariate discriminant analysis was used to identify latent patterns differing between neonates grouped by SSRI-exposure and sex. Analysis revealed localized variations in CC fractional anisotropy that significantly discriminated neonate groups and correctly predicted group membership with an 82% accuracy. Such effects were identified across three dimensions, representing sex differences in SSRI-exposed neonates (genu, splenium), SSRI-related effects independent of sex (genu-to-rostral body), and sex differences in nonexposed neonates (isthmus-splenium, posterior midbody). Our findings suggest that CC microstructure may have a sex-specific, localized, developmental sensitivity to prenatal SSRI exposure.

Transthoracic echocardiography of hypertrophic cardiomyopathy in adults: a practical guideline from the British Society of Echocardiography.

Hypertrophic cardiomyopathy (HCM) is common, inherited and characterised by unexplained thickening of the myocardium. The British Society of Echocardiography (BSE) has recently published a minimum dataset for transthoracic echocardiography detailing the core views needed for a standard echocardiogram. For patients with confirmed or suspected HCM, additional views and measurements are necessary. This guideline, therefore, supplements the minimum dataset and describes a tailored, stepwise approach to the echocardiographic examination, and echocardiography's position in the diagnostic pathway, before advising on the imaging of disease complications and invasive treatments.

Warped rhythms: Epileptic activity during critical periods disrupts the development of neural networks for human communication.

It is well established that temporal lobe epilepsy-the most common and well-studied form of epilepsy-can impair communication by disrupting social-emotional and language functions. In pediatric epilepsy, where seizures co-occur with the development of critical brain networks, age of onset matters: The earlier in life seizures begin, the worse the disruption in network establishment, resulting in academic hardship and social isolation. Yet, little is known about the processes by which epileptic activity disrupts developing human brain networks. Here we take a synthetic perspective-reviewing a range of research spanning studies on molecular and oscillatory processes to those on the development of large-scale functional networks-in support of a novel model of how such networks can be disrupted by epilepsy. We seek to bridge the gap between research on molecular processes, on the development of human brain circuitry, and on clinical outcomes to propose a model of how epileptic activity disrupts brain development.

Patent Foramen Ovale Closure: State of the Art.

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people, it is a benign finding; however, in some people, the PFO can open widely to enable paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of the PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised control trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this article considers the evidence for PFO closure in cryptogenic stroke. The article also addresses other potential indications for closure, including systemic arterial embolisation, decompression sickness, platypnoea-orthodeoxia syndrome and migraine with aura. The article lays out the pre-procedural investigations and preparation for the procedure. Finally, the article gives an overview of the procedure itself, including discussion of closure devices.

CASPA (CArdiac Sarcoidosis in PApworth) improving the diagnosis of cardiac involvement in patients with pulmonary sarcoidosis: protocol for a prospective observational cohort study.

INTRODUCTION: Sarcoidosis is a multisystem disease, predominantly affecting the lungs but can involve the heart, resulting in cardiac sarcoidosis (CS). Patients require MRI/Positron Emission Tomography (PET) scans for diagnosis. Echocardiography, ECG and Holter monitoring may be indicative but not diagnostic alone. Patients can present late with conduction defects, heart failure or sudden death. The CASPA (CArdiac Sarcoidosis in PApworth) study protocol aims to (1) use MRI to identify CS prevalence; (2) use speckle-tracking echocardiography, signal averaged ECG and Holter monitoring to look for diagnostic pathways; and (3) identify serum proteins which may be associated with CS. METHODS AND ANALYSIS: Participants with pulmonary sarcoidosis (and no known cardiac disease) from Royal Papworth Hospital will have the following: cardiac MRI with late gadolinium, two-dimensional transthoracic echocardiography with speckle tracking, signal averaged ECG and 24-hour Holter monitor. They will provide a serum sample for brain natriuretic peptide levels and proteomics by liquid chromatography coupled to high-resolution mass spectrometry. All data will be collected on OpenClinica platform and analysed approximately 6 months after final patient recruitment. ETHICS AND DISSEMINATION: The Camden & Kings Cross Research Ethics Committee approved the protocol (REC number: 17/LO/0667). Integrated Research Approval System (IRAS) 222 720. Dissemination of findings will be via conference presentations and submitted to peer-reviewed journals.

Pellino-1 Regulates the Responses of the Airway to Viral Infection.

Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease. Pellino-1 expression was examined in bronchial sections from patients with GOLD stage two COPD and healthy controls. Primary bronchial epithelial cells (PBECs) in which Pellino-1 expression had been knocked down were extracellularly challenged with the TLR3 agonist poly(I:C). C57BL/6 Peli1-/- mice and wild type littermates were subjected to intranasal infection with clinically-relevant respiratory viruses: rhinovirus (RV1B) and influenza A. We found that Pellino-1 is expressed in the airways of normal subjects and those with COPD, and that Pellino-1 regulates TLR3 signaling and responses to airways viruses. In particular we observed that knockout of Pellino-1 in the murine lung resulted in increased production of proinflammatory cytokines IL-6 and TNFα upon viral infection, accompanied by enhanced recruitment of immune cells to the airways, without any change in viral replication. Pellino-1 therefore regulates inflammatory airway responses without altering replication of respiratory viruses.

Advanced neuroimaging: A window into the neural correlates of fetal programming related to prenatal exposure to maternal depression and SSRIs.

Fetal programming is a conceptual framework whereby the in utero environment shapes the offspring's neurodevelopment. Maternal depression and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy are common prenatal exposures that affect critical early life developmental programming processes. Prenatal depression and SSRIs both have been reported to increase the risks for preterm birth, low birth weight, and are associated with behavioral disturbances across the early life span. However, not all exposures lead to adverse developmental outcomes and distinguishing how each exposure contributes to variations in development remains challenging. Advances in neuroimaging, using MR and EEG, offer novel insights into central processes that might reveal the neural correlates of fetal programming. This review focuses on emerging findings from neuroimaging studies reflecting early brain functional and structural development associated with prenatal exposure to maternal depression and SSRI antidepressants. Suggestions for future research directions that use neuroimaging as a tool to advancing our understanding of the early origins of developmental plasticity are offered.