Characteristics of service users and provider organisations associated with experience of out of hours general practitioner care in England: population based cross sectional postal questionnaire survey.

OBJECTIVE: To investigate the experience of users of out of hours general practitioner services in England, UK. DESIGN: Population based cross sectional postal questionnaire survey. SETTING: General Practice Patient Survey 2012-13. MAIN OUTCOME MEASURES: Potential associations between sociodemographic factors (including ethnicity and ability to take time away from work during working hours to attend a healthcare consultation) and provider organisation type (not for profit, NHS, or commercial) and service users' experience of out of hours care (timeliness, confidence and trust in the out of hours clinician, and overall experience of the service), rated on a scale of 0-100. Which sociodemographic/provider characteristics were associated with service users' experience, the extent to which any observed differences could be because of clustering of service users of a particular sociodemographic group within poorer scoring providers, and the extent to which observed differences in experience varied across types of provider. RESULTS: The overall response rate was 35%; 971,232/2,750,000 patients returned surveys. Data from 902,170 individual service users were mapped through their registered practice to one of 86 providers of out of hours GP care with known organisation type. Commercial providers of out of hours GP care were associated with poorer reports of overall experience of care, with a mean difference of -3.13 (95% confidence interval -4.96 to -1.30) compared with not for profit providers. Asian service users reported lower scores for all three experience outcomes than white service users (mean difference for overall experience of care -3.62, -4.36 to -2.89), as did service users who were unable to take time away from work compared with service users who did not work (mean difference for overall experience of care -4.73, -5.29 to -4.17). CONCLUSIONS: Commercial providers of out of hours GP care were associated with poorer experience of care. Targeted interventions aimed at improving experience for patients from ethnic minorities and patients who are unable to take time away from work might be warranted

Singing for people with aphasia (SPA): a protocol for a pilot randomised controlled trial of a group singing intervention to improve well-being

Introduction: The singing for people with aphasia (SPA) intervention aims to improve quality of life and well-being for people with poststroke aphasia. A definitive randomised controlled trial (RCT) is required to assess the clinical and cost effectiveness of SPA. The purpose of this pilot study is to assess the feasibility of such a definitive trial and inform its design. Methods and analysis: A two-group, assessor-blinded, randomised controlled external pilot trial with parallel mixed methods process evaluation and economic evaluation. Forty-eight participants discharged from clinical speech and language therapy will be individually randomised 1:1 to SPA (10 group sessions plus a resource booklet) or control (resource booklet only). Outcome assessment at baseline, 3 and 6 months postrandomisation include: ICEpop CAPability measure for adults, Stroke and Aphasia Quality of Life, EQ-5D-5L, modified Reintegration into Normal Living Index, Communication Outcome After Stroke, Very Short Version of the Minnesota Aphasia Test, Service Receipt Inventory and Care Related Quality of Life. Feasibility, acceptability and process outcomes include recruitment and retention rates, with measurement burden and trial experiences being explored in qualitative interviews (15 participants, 2 music facilitators and 2 music champions). Analyses include: descriptive statistics, with 95% CIs where appropriate; qualitative themes; intervention fidelity from videos and session checklists; rehearsal of health economic analysis. Ethics and dissemination: NHS National Research Ethics Service and the Health Research Authority confirmed approval in April 2017; recruitment commenced in June 2017. Outputs will include: pilot data to inform whether to proceed to a definitive RCT and support a funding application; finalised intervention manual for multicentre replication of SPA; presentations at conferences, public involvement events; internationally recognised peer reviewed journal publications, open access sources and media releases

Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy.

Autophagy is an important degradation pathway, which is induced after starvation, where it buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. While the classical pathway mediating this response is via mTOR inhibition, there are likely to be additional pathways that support the process. Here, we identify Annexin A2 as an autophagy modulator that regulates autophagosome formation by enabling appropriate ATG9A trafficking from endosomes to autophagosomes via actin. This process is dependent on the Annexin A2 effectors ARP2 and Spire1. Annexin A2 expression increases after starvation in cells in an mTOR-independent fashion. This is mediated via Jun N-terminal kinase activation of c-Jun, which, in turn, enhances the trans-activation of the Annexin A2 promoter. Annexin A2 knockdown abrogates starvation-induced autophagy, while its overexpression induces autophagy. Hence, c-Jun-mediated transcriptional responses support starvation-induced autophagy by regulating Annexin A2 expression levels.Openheimer Memorial TrustThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms904

Iterative focused screening with biological fingerprints identifies selective Asc-1 inhibitors distinct from traditional high throughput screening

N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer’s disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine–serine–cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs. To identify novel Asc-1 inhibitors, two different screening approaches were performed with whole-cell amino acid uptake in heterologous cells stably expressing human Asc-1: (1) a high-throughput screen (HTS) of 3 M compounds measuring 35S l-cysteine uptake into cells attached to scintillation proximity assay beads in a 1536 well format and (2) an iterative focused screen (IFS) of a 45 000 compound diversity set using a 3H d-serine uptake assay with a liquid scintillation plate reader in a 384 well format. Critically important for both screening approaches was the implementation of counter screens to remove nonspecific inhibitors of radioactive amino acid uptake. Furthermore, a 15 000 compound expansion step incorporating both on- and off-target data into chemical and biological fingerprint-based models for selection of additional hits enabled the identification of novel Asc-1-selective chemical matter from the IFS that was not identified in the full-collection HTS

Untargeted analysis of plasma samples from pre-eclamptic women reveals polar and apolar changes in the metabolome

IntroductionPre-eclampsia is a hypertensive gestational disorder that affects approximately 5% of all pregnancies.ObjectivesAs the pathophysiological processes of pre-eclampsia are still uncertain, the present case–control study explored underlying metabolic processes characterising this disease.MethodsMaternal peripheral plasma samples were collected from pre-eclamptic (n = 32) and healthy pregnant women (n = 35) in the third trimester. After extraction, high-resolution mass spectrometry-based untargeted metabolomics was used to profile polar and apolar metabolites and the resulting data were analysed via uni- and multivariate statistical approaches.ResultsThe study demonstrated that the metabolome undergoes substantial changes in pre-eclamptic women. Amongst the most discriminative metabolites were hydroxyhexacosanoic acid, diacylglycerols, glycerophosphoinositols, nicotinamide adenine dinucleotide metabolites, bile acids and products of amino acid metabolism.ConclusionsThe putatively identified compounds provide sources for novel hypotheses to help understanding of the underlying biochemical pathology of pre-eclampsia

A Randomised Controlled Trial of a Facilitated Home-Based Rehabilitation Intervention in Patients with Heart Failure with Preserved Ejection Fraction and their Caregivers:The REACH-HFpEF Pilot Study

Abstract Introduction Home-based cardiac rehabilitation may overcome suboptimal rates of participation. The overarching aim of this study was to assess the feasibility and acceptability of the novel Rehabilitation EnAblement in CHronic Hear Failure (REACH-HF) rehabilitation intervention for patients with heart failure with preserved ejection fraction (HFpEF) and their caregivers. Methods and results Patients were randomised 1:1 to REACH-HF intervention plus usual care (intervention group) or usual care alone (control group). REACH-HF is a home-based comprehensive self-management rehabilitation programme that comprises patient and carer manuals with supplementary tools, delivered by trained healthcare facilitators over a 12 week period. Patient outcomes were collected by blinded assessors at baseline, 3 months and 6 months postrandomisation and included health-related quality of life (primary) and psychological well-being, exercise capacity, physical activity and HF-related hospitalisation (secondary). Outcomes were also collected in caregivers. We enrolled 50 symptomatic patients with HF from Tayside, Scotland with a left ventricular ejection fraction ≥45% (mean age 73.9 years, 54% female, 100% white British) and 21 caregivers. Study retention (90%) and intervention uptake (92%) were excellent. At 6 months, data from 45 patients showed a potential direction of effect in favour of the intervention group, including the primary outcome of Minnesota Living with Heart Failure Questionnaire total score (between-group mean difference −11.5, 95% CI −22.8 to 0.3). A total of 11 (4 intervention, 7 control) patients experienced a hospital admission over the 6 months of follow-up with 4 (control patients) of these admissions being HF-related. Improvements were seen in a number intervention caregivers' mental health and burden compared with control. Conclusions Our findings support the feasibility and rationale for delivering the REACH-HF facilitated home-based rehabilitation intervention for patients with HFpEF and their caregivers and progression to a full multicentre randomised clinical trial to test its clinical effectiveness and cost-effectiveness

'Digital by Default' and the 'hard to reach': Exploring solutions to digital exclusion in remote rural areas

Williams, F., Philip, L., Fairhurst, G., & Farrington, J. (2016). ‘Digital by Default’ and ‘the hard to reach’: exploring solutions to digital exclusion in remote rural areas. Local Economy, 31(7), 757-777. DOI: 10.1177/0269094216670938. Copyright © 2016 SAGE. Reprinted by permission of SAGE Publications.In the UK, the geography of Information and Communication Technology (ICT) infrastructure required for Internet connectivity is such that high speed broadband and mobile phone networks are generally less available in rural areas compared with urban areas or, in other words, as remoteness and population sparsity increase so too does the likelihood of an area having no or very poor broadband connectivity. Against a policy backdrop of UK Government efforts to bring forward network infrastructure upgrades and to improve the accessibility of broadband services in locations where there is a weak commercial investment case, this paper considers the options for the ‘final few’ in the prevailing ‘Digital by Default’ public services context. The paper outlines the Rural Public Access WiFi Services project, a study focused upon enabling Internet connectivity for commercially ‘hard to reach’ rural areas in the UK. The Rural Public Access WiFi Services concept and the experiment are introduced before findings from a pilot deployment of a broadband service to households in a remote rural area, who may be classified as ‘digitally excluded’, are presented. The paper then reflects on our field experiment and the potential of the Rural Public Access WiFi Services model as a solution to overcoming some of the digital participation barriers manifest in the urban–rural divide. Early indications show that the Rural Public Access WiFi Services model has the potential to encourage participation in the Digital Economy and could aid the UK Government’s Digital by Default agenda, although adoption of the model is not without its challenges

Telephone triage for management of same-day consultation requests in general practice (the ESTEEM trial): A cluster-randomised controlled trial and cost-consequence analysis

Telephone triage is increasingly used to manage workload in primary care; however, supporting evidence for this approach is scarce. We aimed to assess the effectiveness and cost consequences of general practitioner-(GP)-led and nurse-led telephone triage compared with usual care for patients seeking same-day consultations in primary care