93 research outputs found

    Dataset for "What Should Inpatient Psychological Therapies be for? Qualitative Views of Service Users on Outcomes"

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    This data outlines the views of 14 participants who had an inpatient admission within the last year, on what outcomes they think are important to measure in psychological therapy trials in acute mental health inpatient wards. This data includes the 14 transcripts of the qualitative semi-structured interviews.The interview schedule was piloted with a Person with Personal Experience Researcher (LC) and included questions adapted from a previous Core Outcome Set study (Tyler et al., 2020). The semi-structured interviews were conducted remotely by either video call or telephone and audio-recorded for transcription.The transcripts were anonymised and demographic details were removed. The data includes the transcription from the first question to the final question.The transcripts are in Microsoft Word format.Transcription was completed following the Transcription Notation System for Orthographic Transcription (revised from Braun & Clarke, 2013)

    A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-Ī±

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    <p>Abstract</p> <p>Background</p> <p>Long-term depression (LTD) in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs) and muscarinic acethycholine receptors (mAChRs). Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC), it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-Ī±.</p> <p>Results</p> <p>Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-Ī±. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms.</p> <p>Conclusion</p> <p>Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-Ī±. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-Ī±.</p

    Neurological updates: neurological complications of CAR-T therapy

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    Chimeric antigen receptor (CAR) expressing T-cells now offer an effective treatment option for people with previously refractory B-cell malignancies and are under development for a wide range of other tumours. However, neurological toxicity is a common complication of CAR T-cell therapy, seen in over 50% of recipients in some cohorts. Since 2018, the term immune effector cell-associated neurotoxicity syndrome (ICANS) has been used to describe and grade neurotoxicity seen after CAR T-cells and other similar therapies. ICANS following CAR-T therapy is usually self-limiting but can necessitate admission to the intensive care unit and is rarely fatal. As CAR-T therapies enter routine clinical practice, it is important for neurologists to be aware of the nature of neurological complications. Here we summarise the clinical manifestations, mechanisms, investigations and recommended treatment of CAR-T related neurotoxicity, focusing on the licensed CD19 products

    Protocol for 'Seal or Varnish' (SoV) trial: A randomised controlled trial to measure the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay

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    Background Dental caries remains a significant public health problem, prevalence being linked to social and economic deprivation. Occlusal surfaces of first permanent molars are the most susceptible site in the developing permanent dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and fluoride varnish (FV) to be effective over no intervention in preventing caries. However, the comparative cost and effectiveness of these treatments is uncertain. The primary aim of the trial described in this protocol is to compare the clinical effectiveness of PFS and FV in preventing dental caries in first permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs and the relative cost-effectiveness of PFS and FV delivered in a community/school setting; examining the impact of PFS and FV on children and their parents/carers in terms of quality of life/treatment acceptability measures; and examining the implementation of treatment in a community setting. Methods/design The trial design comprises a randomised, assessor-blinded, two-arm, parallel group trial in 6ā€“7 year old schoolchildren. Clinical procedures and assessments will be performed at 66 primary schools, in deprived areas in South Wales. Treatments will be delivered via a mobile dental clinic. In total, 920 children will be recruited (460 per trial arm). At baseline and annually for 36 months dental caries will be recorded using the International Caries Detection and Assessment System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and 30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24, and 30 months, and will be re-applied if the existing sealant has become detached/is insufficient. The economic analysis will estimate the costs of providing the PFS versus FV. The process evaluation will assess implementation and acceptability through acceptability scales, a schools questionnaire and interviews with children, parents, dentists, dental nurses and school staff. The primary outcome measure will be the proportion of children developing new caries on any one of up to four treated first permanent molars. Discussion The objectives of this study have been identified by the National Institute for Health Research as one of importance to the National Health Service in the UK. The results of this trial will provide guidance on which of these technologies should be adopted for the prevention of dental decay in the most susceptible tooth-surface in the most at risk children

    Healthcare Staff Perceptions and Misconceptions regarding Antibody Testing in the United Kingdom: Implications for the next steps for antibody screening

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    Background Healthcare workers have been at increased risk of exposure, infection and serious complications from COVID-19. Antibody testing has been used to identify staff members who have been previously infected by SARS-CoV-2, and has been rolled out rapidly in the United Kingdom. a number of published comment and editorial articles raising concerns about antibody testing in this context. We present perceptions of NHS healthcare workers in relation to SARS-CoV-2 antibody testing. Methods Electronic survey regarding perceptions towards SARS-CoV-2 antibody testing which was distributed to all healthcare workers at a major NHS tertiary hospital following implementation of antibody testing. Results In total, 560 healthcare workers completed the survey (80% female; 25% of BAME background; 58% from frontline clinical staff). Exploring whether they previously had COVID-19 was the primary reported reason for choosing to undergo antibody testing (85.2%). In case of a positive antibody test, 72% reported that they would feel relieved, whilst 48% felt that they would be happier to work in a patient-facing area. Moreover, 12% responded that a positive test would mean ā€œsocial distancing is less importantā€, with 34% of the responders indicating that in this case they would be both less likely to catch COVID-19 and happier to visit friends/relatives. Conclusions NHS staff members primarily seek out SARS-CoV-2 antibody testing for an appropriate reason. Based on our findings and given the lack of definite data regarding the extent of immunity protection from a positive SARS-CoV-2 antibody test, significant concerns may be raised regarding the reported interpretation by healthcare workers of positive antibody test results. This needs to be further explored and addressed to protect NHS staff and patients

    Recommendations for accurate CT diagnosis of suspected acute aortic syndrome (AAS)-on behalf of the British Society of Cardiovascular Imaging (BSCI)/British Society of Cardiovascular CT (BSCCT)

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    Accurate and timely assessment of suspected acute aortic syndrome is crucial in this life-threatening condition. Imaging with CT plays a central role in the diagnosis to allow expedited management. Diagnosis can be made using locally available expertise with optimized scanning parameters, making full use of recent advances in CT technology. Each imaging centre must optimize their protocols to allow accurate diagnosis, to optimize radiation dose and in particular to reduce the risk of false-positive diagnosis that may simulate disease. This document outlines the principles for the acquisition of motion-free imaging of the aorta in this context.published_or_final_versio

    Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk.

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    BACKGROUND: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. METHODS: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. RESULTS: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). CONCLUSIONS: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer

    Site use andĀ connectivity ofĀ female grey seals (Halichoerus grypus) aroundĀ Wales

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    The UK Natural Environment Research Council (NERC) provided core funding to the Sea Mammal Research Unit during this work and NERC Grant No. NE/G008930/1 to PP and LH to develop photo-ID use for grey seals. The EsmĆ©e Fairbairn Foundation provided additional funding to PP and LH for photo-ID work with grey seals. NRW funded survey work by MB, LM, SW and PS; contracted LH for survey design, software development and data management; IL and PP for work related to the production of this manuscript.Grey seals (Halichoerus grypus) are a qualifying feature of three special areas of conservation (SACs) in Wales, yet relatively little is known of their site use along this coastline. Since 1992, many individuals and organisations have contributed to a grey seal photographic identification database held by Natural Resources Wales, which is one of the largest and oldest of its kind, providing key information from grey seal haul-out sites around the Celtic and Irish Seas. Here, we investigated spatial connectivity of haul-out sites and fidelity of adult females to breeding sites. The minimum number of adult female grey seals using the area between 1992 and 2016 was 2688. Individual capture histories and relative spatial transition probabilities (Pij) between pairs of location groups were calculated. Adjacent locations were highly connected (e.g. Lleyn Peninsula and Bardsey, Pijā€‰=ā€‰0.7) but connections spanned the entire region, up to 230Ā km apart (e.g. Skomer and Dee Estuary, Pijā€‰=ā€‰0.004). Resights were recorded within SACs (e.g. Lleyn Peninsula and Bardsey [Lleyn Peninsula and the Sarnau SAC], Pijā€‰=ā€‰0.7), between SACs (e.g. Bardsey and Skomer [Pembrokeshire Marine], Pijā€‰=ā€‰0.03), between SACs and non-designated areas (e.g. Skerries and Bardsey, Pijā€‰=ā€‰0.09) and between sites outside any protected area (e.g. Dee Estuary and Anglesey, Pijā€‰=ā€‰0.5). While inter-annual fidelity to breeding sites was high (Pijā€‰=ā€‰0.82ā€“1), individual female grey seals moved throughout the region. This evidence of extensive site use beyond protected areas is important for the management and conservation of grey seals around Wales.Publisher PDFPeer reviewe
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