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Health utilities and quality-adjusted life years for patients with amyotrophic lateral sclerosis receiving reldesemtiv or placebo in FORTITUDE-ALS
Get PDFAimsTo estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving reldesemtiv versus placebo in FORTITUDE-ALS.Materials and methodsWe performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated reldesemtiv in patients with ALS. Health utilities from the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L) were estimated using ALS Functional Rating Scale-Revised (ALSFRS-R) scores collected during the trial. QALYs were estimated using the area under the curve method.ResultsThe full analysis set consisted of 456 patients (reldesemtiv n = 342, placebo n = 114), who received at least one dose of the double-blind study drug, and had ALSFRS-R assessed at baseline and at least one post-baseline assessment. The difference in EQ-5D-5L utility least-squares (LS) mean change from baseline to week 12 for reldesemtiv versus placebo, adjusted for baseline values, was statistically significant (0.03, 95% confidence interval [CI]: 0.01, 0.05; p = .0008). The incremental QALY of reldesemtiv versus placebo adjusted for baseline utility values showed a modest, but statistically significant, difference (0.004, 95% CI: 0.001, 0.007; p = .0058).ConclusionsThis post hoc analysis of FORTITUDE-ALS suggests that reldesemtiv showed a modest but significant benefit in health utilities and QALYs compared with placebo. Future long-term studies that include direct collection of EQ-5D-5L data will be needed to confirm our findings.ClinicalTrials.gov identifierNCT0316089
A Comprehensive Policy Review of Evidence-Based Practices in Autism Policy across the United Kingdom’s Four Nations.
Get PDFThis review provides an overview of how the four nations construct policy around supporting autistic people and identifies supports which are considered evidence‐based practice (EBP). Video‐based interventions are a recommended EBP for supporting autistic people and are recommended specifically within the National Institute for Health and Care Excellence autism guidelines. We highlight that EBP's can be difficult to identify and conclude with the recommendation that evidence and gap maps are a valuable tool that should be used to present evidence in an accessible way to policy makers, autistic people and their families and carers
Self-Help Plus for refugees and asylum seekers: an individual participant data meta-analysis
Get PDFQUESTION: Refugees and asylum seekers are at high risk of mental disorders due to various stressors before, during and after forceful displacement. The WHO Self-Help Plus (SH+) intervention was developed to manage psychological distress and a broad range of mental health symptoms in vulnerable populations. This study aimed to examine the effects and moderators of SH+ compared with Enhanced Care as Usual (ECAU) in reducing depressive symptoms among refugees and asylum seekers.STUDY SELECTION AND ANALYSIS: Three randomised trials were identified with 1795 individual participant data (IPD). We performed an IPD meta-analysis to estimate the effects of SH+, primarily on depressive symptoms and second on post-traumatic stress, well-being, self-identified problems and functioning. Effects were also estimated at 5-6 months postrandomisation (midterm).FINDINGS: There was no evidence of a difference between SH+ and ECAU+ in reducing depressive symptoms at postintervention. However, SH+ had significantly larger effects among participants who were not employed (β=1.60, 95% CI 0.20 to 3.00) and had lower mental well-being levels (β=0.02, 95% CI 0.001 to 0.05). At midterm, SH+ was significantly more effective than ECAU in improving depressive symptoms (β=-1.13, 95% CI -1.99 to -0.26), self-identified problems (β=-1.56, 95% CI -2.54 to -0.59) and well-being (β=6.22, 95% CI 1.60 to 10.90).CONCLUSIONS: Although SH+ did not differ significantly from ECAU in reducing symptoms of depression at postintervention, it did present benefits for particularly vulnerable participants (ie, unemployed and with lower mental well-being levels), and benefits were also evident at midterm follow-up. These results are promising for the use of SH+ in the management of depressive symptoms and improvement of well-being and self-identified problems among refugees and asylum seekers.</p
Testing cognitive theories with multivariate pattern analysis of neuroimaging data
Get PDFThe development of non-invasive neuroimaging techniques to measure brain activity while human participants engage in cognitive tasks has driven thousands of investigations over recent decades. This has been paralleled by advances in experimental design and analysis, including the family of approaches known as multivariate pattern analysis (MVPA). For many researchers, the increased sensitivity provided by applying MVPA to functional MRI, EEG or MEG data made it possible to address theories that describe cognition at the functional level. Here, we review a selection of studies that used MVPA to test cognitive theories from a range of domains, including perception, attention, memory, navigation, emotion, social cognition, and motor control. This broad view reveals properties of MVPA that make it suitable for understanding the ‘how’ of human cognition, such as the ability to test predictions expressed at the item or event level. It also reveals limitations and points to future directions
The Development of King Arthur’s Heroic Virtue in Geoffrey of Monmouth’s Historia Regum Britanniae and Wace’s Roman de Brut
Get PDFCRISPR-induced DNA reorganization for multiplexed nucleic acid detection
Get PDFNucleic acid sensing powered by the sequence recognition of CRIPSR technologies has enabled major advancement toward rapid, accurate and deployable diagnostics. While exciting, there are still many challenges facing their practical implementation, such as the widespread need for a PAM sequence in the targeted nucleic acid, labile RNA inputs, and limited multiplexing. Here we report FACT (Functionalized Amplification CRISPR Tracing), a CRISPR-based nucleic acid barcoding technology compatible with Cas12a and Cas13a, enabling diagnostic outputs based on cis- and trans-cleavage from any sequence. Furthermore, we link the activation of CRISPR-Cas12a to the expression of proteins through a Reprogrammable PAIRing system (RePAIR). We then combine FACT and RePAIR to create FACTOR (FACT on RePAIR), a CRISPR-based diagnostic, that we use to detect infectious disease in an agricultural use case: honey bee viral infection. With high specificity and accuracy, we demonstrate the potential of FACTOR to be applied to the sensing of any nucleic acid of interest.</p
A review of reviews exploring patient and public involvement in population health research and development of tools containing best practice guidance
Get PDFINTRODUCTION: Patient and public involvement (PPI) is increasingly seen as something that is integral to research and of importance to research funders. There is general recognition that PPI is the right thing to do for both moral and practical reasons. The aim of this review of reviews is to examine how PPI can be done 'properly' by looking at the evidence that exists from published reviews and assessing it against the UK Standards for Public Involvement in Research, as well as examining the specific features of population health research that can make PPI more challenging.METHODS: A review of reviews and development of best practice guidance was carried out following the 5-stage Framework Synthesis method.RESULTS: In total 31 reviews were included. There is a lack of current research or clarity around Governance and Impact when findings are mapped against UK Standards for Public Involvement in Research. It was also clear that there is little knowledge around PPI with under-represented groups. There are gaps in knowledge about how to ensure key specific attributes of population health research are addressed for PPI team members - particularly around how to deal with complexity and the data-driven nature of the research. Four tools were produced for researchers and PPI members to further improve their PPI activity within population health research and health research more generally, including a framework of recommended actions to address PPI in population health research, and guidance on integrating PPI based on the UK Standards for Public Involvement in Research.CONCLUSIONS: Facilitating PPI in population health research is challenging due to the nature of this type of research and there is far less evidence on how to do PPI well in this context. The tools can help researchers identify key aspects of PPI that can be integrated when designing PPI within projects. Findings also highlight specific areas where more research or discussion is needed.</p
Pupil Voice in Wales: the impact of the Covid-19 Pandemic:Part of the Collaborative Network
No full textMae’r adroddiad hwn yn ymateb i gwestiynau ymchwil am effaith pandemig Covid 19 ar lais y disgybl yng Nghymru ac yn archwilio’r gwersi y gellir eu dysgu o brofiad staff a disgyblion ysgol.This report responds to research questions about the impact on pupil voice in Walesof the Covid 19 pandemic and examines lessons that can be learned from theexperience of school staff and pupil