Coventry (United Kingdom)

Direct-to-consumer neuromodulation technologies are transforming how sleep and mood disorders are self-managed outside clinical settings. Cranial electrotherapy stimulation (CES) is a low-intensity, portable intervention with growing accessibility but limited evidence in non-clinical populations and real-life contexts. This naturalistic cohort study investigated the effects of CES on sleep, anxiety, depression, stress, quality of life, and self-efficacy in a real-world, community-based setting. Sixty adults agreed to use the Alpha-Stim AID CES device daily for 21 days (40-60 min/day). Validated self-report measures were completed at baseline, day 21 (end-of-treatment), and day 42 (follow-up). A subsample (n = 27) wore actigraphy devices to monitor objective sleep changes. By day 21, sleep quality significantly improved, with 48 % achieving insomnia remission and 50 % a reduction in daytime sleepiness. Actigraphy data corroborated subjective sleep improvements. Anxiety and depression remission rates were 72.3 % and 71.2 %, with improvements maintained three weeks post-intervention. Stress levels decreased, while self-efficacy, wellbeing, and quality of life improved, with moderate to large effect sizes. CES was rated as safe, acceptable, and easy to use: 48 % of participants preferred it over psychotherapy or medication. CES is a safe, self-administered intervention that benefits sleep, mental health, and quality of life. This study presents the first actigraphy evidence of CES effects on sleep in a diverse, non-clinical population. Findings support a novel framework for accessible, non-pharmacological interventions for sleep and wellbeing with sustained impact at three-week follow-up. Results have significant implications for sleep quality and mental health, especially for populations underserved by traditional healthcare.

In England, care homes are the primary providers of long-term care for older adults. The increasing recognition of the importance of social care underscores the importance of collaboration between the National Health Service and care homes. The lack of data sharing among stakeholders limits opportunities for co-ordinated care, service development and research. Identify how to support research, service development and innovation in care homes. Combine existing evidence with care home-generated resident data to create a minimum data set that is relevant and usable for stakeholders, including residents, relatives, practitioners, researchers, regulators and commissioners. The study used a mixed-methods approach, structured into five work packages, supported by patient and public involvement and engagement with residents, carers and staff: Work package 1: Conducted two evidence reviews on outcome measures and factors enhancing research productivity in care homes. Work package 2: Created a trial archive for secondary data analysis. Work package 3: Conducted a scoping review, a realist review and a national survey to define minimum data set content and assess implementation challenges in English care homes. Work package 4: Linked residents' data from National Health Service and social care data sets with data from study care homes, deriving useful minimum data set variables and assessing data quality. Work package 5: Piloted the minimum data set at two points in care homes within three integrated care systems, conducted focus groups and interviews with care home and integrated care system staff. Three national consultations explored how stakeholders use resident information, measure quality of life and minimum data set usefulness. Additionally, subprojects examined data availability in domiciliary settings, staff reasoning when assessing resident well-being and completing research during rapid policy changes. The reviews revealed significant heterogeneity in outcome measurement and questioned the appropriateness of some methods and measures used for care home research. The Virtual International Care Home Trials Archive merged data from 6 United Kingdom randomised controlled trials with 5674 residents across 308 care homes. International minimum data set studies are a valuable resource for international comparative research. The wide range of measures used are mostly clinical with under-representation of measures important to care homes (e.g. quality of life). A national survey of care homes demonstrated the range of information, including clinical measures being routinely collected. The realist review identified motivation, front-line staff monitoring and embedded recording systems as important for minimum data set implementation. The pilot study recruited 996 residents from 45 care homes, with 727 residents' data included in the minimum data set. Residents' digital care records were linked to statutory health and social care data sets, creating a viable minimum data set prototype with metadata as resource. The study provided an evidence-based critique of care home research and a resource for secondary data analysis for future research. It developed a prototype minimum data set linking National Health Service, social care and care home data, demonstrating its importance as a basis for discussions between health and care staff. The COVID-19 pandemic disrupted relationships and recruitment. Governance challenges prevented linking residents' data to general practitioner records. Future research should assess whether the care home minimum data set improves resident outcomes, service delivery, staff experience, cross-sector collaboration, resource use and digital technology implementation. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR127234.

Abstract Background Defective cardiac relaxation (diastolic dysfunction) is prevalent in heart failure, particularly in the context of diabetes, obesity, hypertension, and ageing, and is associated with increased mortality. Yet no effective therapy directly targets this abnormal relaxation. Phosphorylation of troponin I by cAMP-dependent protein kinase A (PKA) promotes relaxation, but global PKA activation has widespread, undesirable effects. Here we investigated whether selectively enhancing troponin I phosphorylation could improve relaxation without engaging the broader PKA signalling network. Methods To resolve cAMP signalling at subcellular scales, we combined real-time cAMP measurements with FRET-based genetically encoded reporters targeted to defined nanodomains, alongside biochemical and genetic approaches. Protein–protein interaction surfaces were mapped using peptide-array technology, which guided the design of a disruptor peptide to displace specific interactions. The peptide’s effects on cardiomyocyte function were assessed in vitro using rodent and human cardiomyocytes with biochemical assays, real-time imaging, and work-loop analysis. In vivo effects were evaluated through echocardiography and haemodynamic measurements. Results We identified a previously unrecognized regulatory mechanism in which the cAMP-hydrolyzing enzyme PDE4D9 interacts with troponin I and restricts local cAMP levels within a nanometre-scale domain, thereby selectively controlling troponin I phosphorylation. We found that PDE4D9–troponin I association is markedly increased in cardiac disease in both rodents and humans. A peptide that displaces PDE4D9 from troponin I selectively enhances troponin I phosphorylation, accelerates cardiomyocyte relaxation, and prevents diastolic dysfunction in a mouse model of heart failure. Conclusions These findings reveal a highly specific regulatory nanodomain governing troponin I phosphorylation and points to a first-in-class, mechanism-based therapeutic strategy with the potential to address a major unmet contributor to heart failure. Clinical Perspective What Is New? We identify a previously unrecognized, nanometre-scale regulatory mechanism in which PDE4D9 binds troponin I to locally suppress cAMP and limit troponin I phosphorylation. We demonstrates that the PDE4D9–troponin I interaction is markedly upregulated in failing hearts in both rodents and humans, which can mechanistically explain the impaired cardiac relaxation. We show that this interaction is druggable: a rationally designed peptide can selectively displace PDE4D9, restore localized cAMP–PKA signalling, and normalize myocardial relaxation without global cAMP perturbation. What Are the Clinical Implications? Diastolic dysfunction, a major cause of heart failure with no targeted treatments, may be amenable to therapies that modulate cAMP signalling with subcellular precision rather than global pathway modulation. Selective disruption of PDE4D9–troponin I binding offers a mechanism-based approach with potential to restore diastolic function while minimizing off-target effects typical of GPCR-directed therapies. More broadly, this work establishes a platform for targeting localized signalling domains, a concept that may extend beyond cardiovascular disease to other pathological conditions in which dysregulated cAMP contributes to dysfunction.

(Abstracted from Lancet 2024;405:1743-1756) Shoulder dystocia is associated with several maternal and neonatal complications and is a common reason for litigation in obstetrics. Maternal complications include hemorrhage and third- and fourth-degree perineal severe tears; neonatal complications include fractures, brachial plexus injury, hypoxic ischemic encephalopathy, and neonatal death.

Enabling people to set personal carbon budgets may help them to track and reduce their carbon footprint over time. In this study, we investigated ways to encourage a representative sample of the UK population (N = 2,047) to reduce their carbon footprint by setting themselves a lower carbon budget. In an online experiment, we simulated a carbon footprint calculator based on personal spending and tested the effects of two carbon footprint anchors (low vs. high) and three social reference groups (people in the UK vs. customers at the same bank vs. people with similar expenditure) on the carbon budget set by participants. We found that providing a low anchor, independent of the corresponding social reference group, was significantly associated with setting a lower carbon budget. Setting a lower carbon budget was associated with greater motivation and self-reported willingness to change behaviour to adhere to the budget.