Issues of collaboration, representation, meaning and emotions: Utilising participant-led visual diaries to capture the everyday lives of people in mid to later life

In recent years there has been an increasing use of visual methods in ageing research. There are, however, limited reflections and critical explorations of the implications of using visual methods in research with people in mid to later life. This paper examines key methodological complexities when researching the daily lives of people as they grow older and the possibilities and limitations of using participant-generated visual diaries. The paper will draw on our experiences of an empirical study, which included a sample of 62 women and men aged 50 years and over with different daily routines. Participant-led photography was drawn upon as a means to create visual diaries, followed by in-depth, photo-elicitation interviews. The paper will critically reflect on the use of visual methods for researching the daily lives of people in mid to later life, as well as suggesting some wider tensions within visual methods that warrant attention. First, we explore the extent to which photography facilitates a ‘collaborative’ research process; second, complexities around capturing the ‘everydayness’ of daily routines are explored; third, the representation and presentation of ‘self’ by participants within their images and interview narratives is examined; and, finally, we highlight particular emotional considerations in visualising daily life

A revision of the early neotheropod genus <i>Sarcosaurus</i> from the Early Jurassic (Hettangian–Sinemurian) of central England

Neotheropoda represents the main evolutionary radiation of predatory dinosaurs and its oldest records come from Upper Triassic rocks (c. 219 Mya). The Early Jurassic record of Neotheropoda is taxonomically richer and geographically more widespread than that of the Late Triassic. The Lower Jurassic (upper Hettangian-lower Sinemurian) rocks of central England have yielded three neotheropod specimens that have been assigned to two species within the genus Sarcosaurus, S. woodi (type species) and S. andrewsi. These species have received little attention in discussions of the early evolution of Neotheropoda and recently have been considered as nomina dubia. Here, we provide a detailed redescription of one of these specimens (WARMS G667-690) and reassess the taxonomy and phylogenetic relationships of the genus Sarcosaurus. We propose that the three neotheropod specimens from the Early Jurassic of central England represent a single valid species, S. woodi. The second species of the genus, 'S. andrewsi', is a subjective junior synonym of the former. A quantitative phylogenetic analysis of early theropods recovered S. woodi as one of the closest sister-taxa to Averostra and provides new information on the sequence of character state transformations in the lead up to the phylogenetic split between Ceratosauria and Tetanurae.Fil: Ezcurra, Martin Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Butler, Richard J.. University of Birmingham; Reino UnidoFil: Maidment, Susannah C. R.. University of Birmingham; Reino Unido. Natural History Museum; Reino UnidoFil: Sansom, Ivan J.. University of Birmingham; Reino UnidoFil: Meade, Luke E.. University of Birmingham; Reino UnidoFil: Radley, Jonathan D.. University of Birmingham; Reino Unid

Preclinical evidence implicating corticotropin-releasing factor signaling in ethanol consumption and neuroadaptation

The results of many studies support the influence of the corticotropin-releasing factor (CRF) system on ethanol (EtOH) consumption and EtOH-induced neuroadaptations that are critical in the addiction process. This review summarizes the preclinical data in this area after first providing an overview of the components of the CRF system. This complex system involves hypothalamic and extra-hypothalamic mechanisms that play a role in the central and peripheral consequences of stressors, including EtOH and other drugs of abuse. In addition, several endogenous ligands and targets make up this system and show differences in their involvement in EtOH drinking and in the effects of chronic or repeated EtOH treatment. In general, genetic and pharmacological approaches paint a consistent picture of the importance of CRF signaling via type 1 CRF receptors (CRF1) in EtOH-induced neuroadaptations that result in higher levels of intake, encourage alcohol seeking during abstinence and alter EtOH sensitivity. Furthermore, genetic findings in rodents, non-human primates and humans have provided some evidence of associations of genetic polymorphisms in CRF-related genes with EtOH drinking, although additional data are needed. These results suggest that CRF1 antagonists have potential as pharmacotherapeutics for alcohol use disorders. However, given the broad and important role of these receptors in adaptation to environmental and other challenges, full antagonist effects may be too profound and consideration should be given to treatments with modulatory effects.The authors were supported by the Department of Veterans Affairs; NIH NIAAA grants P60AA010760, R24AA020245 and U01AA013519 and NIH NIDA grant P50DA018165, during the writing of this manuscript. The authors have no financial conflict of interest to disclose

CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity

Although immunodominance of CD8+ T-cell responses is a well-recognised feature of viral infections, its role in responses to more antigenically complex pathogens is less clear. In previous studies we have observed that CD8+ T-cell responses to Theileria parva exhibit different patterns of parasite strain specificity in cattle of different MHC genotypes. In the current study, we demonstrated that animals homozygous for the A10 and A18 MHC haplotypes have detectable responses to only one of 5 T. parva antigens. Over 60% of the responding T cells from the A18+ and A10+ animals recognised defined epitopes in the Tp1 and Tp2 antigens, respectively. Comparison of T-cell receptor β chain expression profiles of CD8+ T-cell lines and CD8+ T cells harvested ex vivo confirmed that the composition of the T-cell lines was representative of the in vivo memory CD8+ T-cell populations. Analysis of the Tp1 and Tp2 antigens revealed sequence polymorphism, which was reflected by differential recognition by T-cell lines. In conclusion, we have demonstrated a profound immunodominance in the CD8+ T-cell response to T. parva, which we propose is a major determinant of the parasite strain specificity of the response and hence immune protection

Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (IDrug) – study protocol for a pragmatic randomized controlled trial

Background Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident. Purpose of this randomized controlled trial is to compare the effect of a concise individual risk information leaflet with standard information on risk factors for side effects. Methods/Design The trial was designed as a prospective, two-arm, randomized, controlled, multicenter, pragmatic study. 960 elderly, multimorbid outpatients in general medicine are included if they take at least one high risk and one other long-term drug (polymedication). As high risk “index drugs” oral anticoagulants and antiplatelets were chosen because of their specific, objectively assessable side effects. Following randomization, test group patients receive an individualized risk assessment leaflet evaluating their personal data concerning bleeding- and thromboembolic-risk-scores, potential drug-drug-interactions, age, renal function and pharmacogenetic factors. Control group patients obtain a standardized leaflet only containing general information on these criteria. Follow-up period is 9 months for each patient. Primary endpoint is the occurrence of a thromboembolic/bleeding event or death. Secondary endpoints are other adverse drug reactions, hospital admissions, specialist referrals and medication changes due to adverse drug reactions, the patients’ adherence to medication regimen as well as health related quality of life, mortality and resulting costs. Discussion Despite extensive evidence of risk factors for adverse drug reactions, there are few prospective trial data about an individualized risk assessment including pharmacogenetic information to increase patient safety. By conducting a health economic analysis, we will evaluate if the application of an individualized drug therapy in daily routine is cost-effective. Trial registration German Clinical Trials Register: DRKS00006256, date of registration 09/01/15

REPAIRS Delphi: A UK and Ireland Consensus Statement on the Management of Infected Arterial Pseudoaneurysms Secondary to Groin Injecting Drug Use

\ua9 2024 The Author(s)Objective: Consensus guidelines on the optimal management of infected arterial pseudoaneurysms secondary to groin injecting drug use are lacking. This pathology is a problem in the UK and globally, yet operative management options remain contentious. This study was designed to establish consensus to promote better management of these patients, drawing on the expert experience of those in a location with a high prevalence of illicit drug use. Methods: A three round modified Delphi was undertaken, systematically surveying consultant vascular surgeons in the UK and Ireland using an online platform. Seventy five vascular surgery units were invited to participate, with one consultant providing the unit consensus practice. Round one responses were thematically analysed to generate statements for round two. These statements were evaluated by participants using a five point Likert scale. Consensus was achieved at a threshold of 70% or more agreement or disagreement. Those statements not reaching consensus were assessed and modified for round three. The results of the Delphi process constituted the consensus statement. Results: Round one received 64 (86%) responses, round two 59 (79%) responses, and round three 62 (83%) responses; 73 (97%) of 75 units contributed. Round two comprised 150 statements and round three 24 statements. Ninety one statements achieved consensus agreement and 15 consensus disagreement. The Delphi statements covered sequential management of these patients from diagnosis and imaging, antibiotics and microbiology, surgical approach, wound management, follow up, and additional considerations. Pre-operative imaging achieved consensus agreement (97%), with computerised tomography angiography being the modality of choice (97%). Ligation and debridement without arterial reconstruction was the preferred approach at initial surgical intervention (89%). Multidisciplinary management, ensuring holistic care and access to substance use services, also gained consensus agreement. Conclusion: This comprehensive consensus statement provides a strong insight into the standard of care for these patients

Evaluation of the NHS England Low-Calorie Diet implementation pilot: a coproduced mixed-method study

Background National Health Service England piloted a low-calorie diet programme, delivered through total diet replacement and behaviour change support via 1 : 1, group or digital delivery, to improve type 2 diabetes in adults with excess weight. Aim To coproduce a qualitative and economic evaluation of the National Health Service low-calorie diet pilot, integrated with National Health Service data to provide an enhanced understanding of the long-term cost-effectiveness, implementation, equity and transferability across broad and diverse populations. Research questions What are the theoretical principles, behaviour change components, content and mode of delivery of the programme, and is it delivered with fidelity to National Health Service specifications? What are the service provider, user and National Health Service staff experiences of the programme? Do sociodemographics influence programme access, uptake, compliance and success? What aspects of the service work and what do not work, for whom, in what context and why? Can the programme be improved to enhance patient experience and address inequities? What are the programme delivery costs, and policy implications for wide-spread adoption? Methods A mixed-methods study underpinned by a realist-informed approach was delivered across five work packages, involving: semistructured interviews with service users (n = 67), National Health Service staff (n = 55), service providers (n = 9); 13 service provider focus groups; and service user surveys (n = 719). Findings were triangulated with clinical data from the National Health Service England’s first cohort analysis (n = 7540). Results Fifty-five per cent of service users who started total diet replacement completed the programme and lost an average of 10.3 kg; 32% of those with data available to measure remission achieved it. Examination of programme mobilisation identified barriers around referral equality and the impact of COVID-19, while effective cross-stakeholder working and communication were key facilitators. Service delivery and fidelity assessments identified a drift in implementation fidelity, alongside variation in the behaviour change content across providers. Perceived barriers to programme uptake and engagement aligned across service providers and users, resulting in key learning on: the importance of person-centred care, service user support needs, improvements to total diet replacement and the social and cultural impact of the programme. Early National Health Service quantitative analyses suggest some socioeconomic variation in programme uptake, completion and outcomes. Insights from the evaluation and National Health Service data were combined to develop the programme theory and underpinning context, mechanisms and outcomes. These were used to develop a list of recommendations to improve the cultural competency of programme delivery, total diet replacement delivery, peer support and address psychological support needs. Cost-effectiveness analyses using short-term follow-up data indicated there is potential for the programme to be cost-effective, but not cost saving. Conclusions The National Health Service low-calorie diet can provide a clinically effective and potentially cost-effective programme to support weight loss and glycaemic control in adults with type 2 diabetes. However, this evaluation identified areas for improvement in referral equity, uptake and completion, and fidelity of delivery, which have informed the development of the programme, which has now been rolled out nationally. Ongoing programme monitoring and long-term follow-up are now required. Future work and limitations The real-world setting limited some data collection and analysis. Future work will focus on the analysis of long-term clinical and cost-effectiveness, and addressing inequalities. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132075

Evaluation of the NHS England low-calorie diet implementation pilot: a coproduced mixed-method study

Background National Health Service England piloted a low-calorie diet programme, delivered through total diet replacement and behaviour change support via 1 : 1, group or digital delivery, to improve type 2 diabetes in adults with excess weight. Aim To coproduce a qualitative and economic evaluation of the National Health Service low-calorie diet pilot, integrated with National Health Service data to provide an enhanced understanding of the long-term cost-effectiveness, implementation, equity and transferability across broad and diverse populations. Research questions What are the theoretical principles, behaviour change components, content and mode of delivery of the programme, and is it delivered with fidelity to National Health Service specifications? What are the service provider, user and National Health Service staff experiences of the programme? Do sociodemographics influence programme access, uptake, compliance and success? What aspects of the service work and what do not work, for whom, in what context and why? Can the programme be improved to enhance patient experience and address inequities? What are the programme delivery costs, and policy implications for wide-spread adoption? Methods A mixed-methods study underpinned by a realist-informed approach was delivered across five work packages, involving: semistructured interviews with service users (n = 67), National Health Service staff (n = 55), service providers (n = 9); 13 service provider focus groups; and service user surveys (n = 719). Findings were triangulated with clinical data from the National Health Service England’s first cohort analysis (n = 7540). Results Fifty-five per cent of service users who started total diet replacement completed the programme and lost an average of 10.3 kg; 32% of those with data available to measure remission achieved it. Examination of programme mobilisation identified barriers around referral equality and the impact of COVID-19, while effective cross-stakeholder working and communication were key facilitators. Service delivery and fidelity assessments identified a drift in implementation fidelity, alongside variation in the behaviour change content across providers. Perceived barriers to programme uptake and engagement aligned across service providers and users, resulting in key learning on: the importance of person-centred care, service user support needs, improvements to total diet replacement and the social and cultural impact of the programme. Early National Health Service quantitative analyses suggest some socioeconomic variation in programme uptake, completion and outcomes. Insights from the evaluation and National Health Service data were combined to develop the programme theory and underpinning context, mechanisms and outcomes. These were used to develop a list of recommendations to improve the cultural competency of programme delivery, total diet replacement delivery, peer support and address psychological support needs. Cost-effectiveness analyses using short-term follow-up data indicated there is potential for the programme to be cost-effective, but not cost saving. Conclusions The National Health Service low-calorie diet can provide a clinically effective and potentially cost-effective programme to support weight loss and glycaemic control in adults with type 2 diabetes. However, this evaluation identified areas for improvement in referral equity, uptake and completion, and fidelity of delivery, which have informed the development of the programme, which has now been rolled out nationally. Ongoing programme monitoring and long-term follow-up are now required. Future work and limitations The real-world setting limited some data collection and analysis. Future work will focus on the analysis of long-term clinical and cost-effectiveness, and addressing inequalities. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132075

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)

Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies comine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV ‘Treatment as Prevention’ (TasP) in PWID