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Factors influencing use and choice of Core Outcome Sets and Outcome Measurement Instruments in trials of interventions to prevent childhood obesity: a mixed-methods survey
Full text linkBackground and Objective: Heterogeneity in what and how outcomes are measured in childhood obesity prevention trials limits evidence synthesis and evaluation of intervention effectiveness. Core Outcome Sets (COS) and Core Outcome Measurement Sets (COMS) can standardize measurement and reporting across trials, but only if they are used by trialists. This study examined trialists’ awareness and attitudes toward two childhood obesity–related COS and factors influencing their use; characteristics of Outcome Measurement Instruments (OMIs) used in childhood obesity prevention trials; and how trialists choose these OMIs. Methods: An online, international, cross-sectional survey was conducted including trialists engaged in designing and/or conducting childhood obesity prevention trials in children aged 0–5 years. Trialists were recruited via peer-reviewed publications, the Transforming Obesity Prevention for CHILDren Collaboration and professional contacts. The survey examined trialist characteristics, awareness, and use of existing COS, OMI characteristics, and factors influencing trialist selection of OMIs. Quantitative data were analyzed descriptively; qualitative data were analyzed using content analysis. Results: The majority of the 46 trialists who completed the survey were senior-career researchers (61%; n = 28), with 1 to 38 years' experience in childhood obesity prevention trials. Seventy percent (n = 32) were familiar with COS in general; 84% (n = 26) of these were familiar with one or both childhood obesity–related COS. These trialists' COS use was limited by perceived participant burden, cost, and lack of knowledge; availability of guidelines, and resources facilitated COS use. Trialists favored measuring outcomes using existing (83%; n = 38) and adapted (80%; n = 37) questionnaires, and anthropometric measures (80%; n = 37). Quantitative and qualitative data indicated that measurement properties (eg, reliability, validity), cost, perceived burden, ease of use, and feasibility were the most important factors influencing trialists’ OMI choice. Conclusion: Trialists’ awareness and use of childhood obesity–related COS is positive, and may be enhanced through provision of guidance and resources to support COS and COMS use. Development of COMS should consider trialist-reported factors related to feasibility and measurement properties. Such considerations can enhance COS and COMS use in trials, reducing outcome heterogeneity, and improving evaluation of intervention effectiveness to prevent childhood obesity
Anti-tumour and associated metabolic effects of repurposed afuresertib and taxifolin for glioblastoma treatment
Full text linkIsocitrate dehydrogenase wild-type glioblastoma (GBM) is a particularly devastating central nervous system tumour with limited treatments. Taking advantage of computational strategies, drug repurposing has been regarded as an alternative and effective tool in GBM drug development, especially models targeting altered metabolic pathways and genomic alterations. In previous work, afuresertib and taxifolin were selected as repurposed candidates after the application of Transcriptomics-informed Stoichiometric Modelling and Network analysis. Although these two candidates have been studied in other types of cancers, they have not been tested against GBM. This study explored the in vitro anti-tumour effect of afuresertib and taxifolin using the PrestoBlue metabolic viability assay and Transwell collagen barrier assay on patient-derived glioblastoma cell lines. Their associated metabolic impact was revealed by the application of an untargeted metabolomics method. The results showed that afuresertib exhibited stronger inhibition of GBM cell proliferation and invasion than taxifolin. Glycerophospholipid metabolism was more active in cells derived from the invasion margin than in cells from the tumour core, indicating the possibility of varying underlining genetic mutations between GIN and GCE cell lines. Afuresertib could affect amino acid metabolism and glycerophospholipid metabolism, exerting the function of anti-proliferation and anti-invasion. Taxifolin could damage nicotinate and nicotinamide metabolism, leading to the death of tumour cells
Role of stability and triangulation-based methods to improve identification of risk factors for lameness in ewes
Full text linkLameness has serious impact on sheep health and profitability. In the UK, the largest-scale questionnaire investigating risk factors for lameness (107 questions and 1260 respondents) identified 20 significant variables using stepwise Poisson regression. It is now known that stepwise procedures with wide data can result in overfit models. This research reanalysed these data, using methods that minimise the likelihood of overfitting and therefore reduce the probability of identifying false positive variables. Poisson and log-normal regression models were built with six different variable selection methods, stability selection and triangulation. Six variables were selected in the final triangulated models associated with a reduced prevalence of lameness, fewer than the 20 variables selected in the original analysis. These six variables covered early treatment of individual sheep, treating sheep with any severity of lameness, avoiding routine foot trimming and avoiding footbathing to treat underrunning footrot. Early treatment of individual lame sheep had the highest population attributable fraction for reduction of lameness. Our results highlight the importance of addressing overfitting when fitting models to wide data and the usefulness of triangulating results across different model types. The results strengthen the evidence that the greatest reduction in lameness nationwide would be achieved if farmers treated the first lame sheep in a group rather than waiting until more become lame
Intraoperative drug delivery to hindbrain tumours via an injectable hydrogel is well tolerated and confers survival benefit against atypical teratoid/rhabdoid xenografts
No full textIntraoperatively applied local drug delivery systems (LDDS) offer a means of overcoming blood–brain barrier (BBB) impermeability. However, there is a paucity of LDDS development for paediatric tumours arising in the posterior fossa. Here we demonstrate applicability of an LDDS against medulloblastoma group 3 (G3 MB) and atypical teratoid/rhabdoid tumours (AT/RT), neoplasms associated with poor prognoses. A poly(ethyleneglycol)-poly(caprolactone)-poly(ethyleneglycol) (PECE) hydrogel loaded with chemotherapeutics identified as effective against primary G3 MB and AT/RTin vitro, was prepared as an injectable, biodegradable formulation. CHIR99021 (glycogen synthase kinase-3 inhibitor), ribavirin (guanosine analogue) and PG545 (heparanase inhibitor) were chosen based upon an inability to traverse the BBB. The hydrogel alone was well-tolerated, and drug-loaded hydrogel achieved > 1-month therapeutic release.Orthotopic xenograft studies against G3 MB and AT/RT indicated good tolerability to combined CHIR99021 and PG545 or combined CHIR99021 and ribavirin loaded loaded LDDS respectively. Median survival of AT/RT arms receiving XRT alone was comparable to CHIR99021- and ribavirin-loaded LDDS, with long-term survivors observed only in the latter arm, demonstrating a significant survival benefit. LDDS against cerebellar tumours using PECE offers a promising therapeutic alternative and the possibility of circumventing radiation-induced adverse effects for children impacted by these diseases
Online Remote Behavioural Intervention for Tics (ORBIT-UK): protocol of a single cohort usability study
No full textIntroduction Tourette syndrome is a common, disabling childhood-onset condition. Exposure and response prevention (ERP) is an effective treatment for tics, yet access remains limited due to a shortage of trained therapists and uneven geographical distribution of services. The ORBIT trial demonstrated that internet-delivered ERP is both clinically and cost-effective, but was developed on a university research platform, not suitable for widescale roll-out. To enable adoption by the National Health Service (NHS) in England, ORBIT has been redeveloped on an NHS compliant platform. This study will evaluate the usability, acceptability and preliminary outcomes of ORBIT on the new platform within an NHS tic disorder service.Methods and analysis This single-cohort usability study will recruit 20 children and young people (aged 9–17) with tics and their chosen supporters (parents/carers). Participants will receive a 10-week online ERP intervention supported by trained coaches. Outcomes include uptake, adherence, system usability, satisfaction and clinical measures such as the Yale Global Tic Severity Scale, Parent Tic Questionnaire and Goal-Based Outcomes. Qualitative feedback will be collected via semi-structured exit interviews. Usability metrics and adverse events will be monitored throughout.Ethics and dissemination The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref: 25/NW/0107). The findings from the study will inform future NHS adoption. The results will be submitted for publication in peer-reviewed journals.Trial registration number ISRCTN82718960. Registered 10 July 2025. https://doi.org/10.1186/ISRCTN8271896
Validation and Preference-Based Scoring of the York Binaural Hearing-Related Quality of Life Questionnaire for Young People
Full text linkObjectives: The York Binaural Hearing-Related Quality of Life questionnaire for Young People (YBHRQL-Y) is a 3-item measure of hearing-related quality of life devised specifically for use with young people (children aged 8 to 16 years old) with hearing loss. This research had three objectives: (1) to assign numerical values where a higher value corresponds to better perceived overall health status (“health utility weights”) to each of 27 unique combinations of difficulties with speech understanding, sound localization, and listening effort (“hearing health states”); (2) to assess its validity and reproducibility when used with young people with hearing loss; (3) to assess the feasibility of a proxy version designed to be completed by the parents/guardians of young people with hearing loss.Design: Health utility weights were obtained by conducting time trade-off interviews with a cross-sectional sample of 155 young adults, aged 18 to 24 years old, recruited from social media and UK universities. To assess validity and reproducibility, the YBHRQL-Y and other established instruments measuring functional hearing and hearing-related quality of life in children were administered to young people with hearing loss at two time points, 2 wk apart. In total, 71 children aged 8 to 16 yr old with at least a severe hearing loss took part and were recruited from social media, relevant charities, and support groups in the United Kingdom. The feasibility of obtaining information about the binaural hearing-related quality of life of young people with hearing loss indirectly was assessed by administering a proxy version of the YBHRQL-Y to the parents or guardians of the young people who participated in the research. A total of 71 parents or guardians were recruited from social media, relevant charities, and support groups in the United Kingdom.Results: The health utility weights elicited from young adults varied monotonically with the level of hearing-related impact described on each of the three dimensions of the YBHRQL-Y, such that the greater the degree of hearing-related impact, the poorer the corresponding health state was judged to be by the respondents. Convergent validity analyses suggested that the domains of the YBHRQL-Y measure the intended constructs and the overall measure relates to the respondent’s health-related quality of life. Test-retest analyses suggested it was reliable and showed good agreement between administrations. Pairwise analysis of responses from the young person with hearing loss and those of their parent/guardian suggested that the proxy measure had poor reliability and poor agreement with the measure administered directly to the young person with hearing loss.Conclusions: The YBHRQL-Y is a valid and reliable measure of hearing-related quality of life when administered directly to a young person aged 8 to 16 with at least a severe hearing loss. An individual’s preference-based score, derived from the preferences of young adults, successfully integrates information about binaural-related hearing across the domains of speech understanding, sound localization, and listening effort. The combination of brief age-appropriate questions, good psychometric performance across time, and a preference-based scoring method makes the YBHRQL-Y a straightforward means to assess hearing-related quality of life in young people with hearing loss
Losing touch: class, social capital, and out of area housing
Full text linkWhilst the conceptualization of a housing crisis has become a common narrative within politics, research, and the media, its nebulous nature can risk failing to recognize the breadth of experiences or its exact relationship to inequality. By looking at out of area housing placements as one aspect of the ‘housing crisis’, this paper explores the way by which experiences of housing can be a disbenefit to people’s wellbeing through fracturing important social networks and connections. Using primary evidence from households placed out of area by their local authority, the paper recognizes the importance of class as a way to understood market power, which is increasingly salient as housing becomes increasingly commodified. However, in seeking to broaden this position, the concept of social capital is introduced as a way of counterbalancing economic understandings of inequality with social vulnerabilities. The paper is based on 10 households placed out of area following the use of freedom of information requests to English local authorities to ascertain the extent of the practice. The paper argues that out of area housing diminishes social capital, which as a component of total capital, can be seen as further impoverishing vulnerable households
A realist review of acute pain management in children and young people attended by ambulance
Full text linkAcute pain management in children and young people (CYP) attended by ambulance services is a significant challenge due to the complex nature of pain, the variation of approach needed across the age range, and the unpredictability of the environment. We aimed to understand how ambulance clinicians can provide improved prehospital acute pain management for CYP. A realist review was conducted and reported in accordance with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidance. We developed an initial programme theory (PT) using key stakeholder input, searched the major bibliographic databases MEDLINE, CINAHL Complete and PsycINFO, and other sources from January 2000 to February 2024, screened and assessed relevance and rigour in duplicate, and performed synthesis and programme theory refinement. We developed an initial PT that focussed on the preparedness of staff and the expectations of CYP and parents/carers, along with key outcomes such as pain score severity, fear and anxiety. The subsequent search strategy yielded 1503 documents, of which 95 were included, representing empirical research articles, reviews, theses, book chapters and clinical guidelines. The initial PT was tested and refined throughout the synthesis to produce a PT underpinned by 34 context-mechanism-outcome configurations. The PT portrayed positive (e.g. presence of parents, focussed education and training, building trust) and negative (e.g. misinformation, fear and anxiety, long-term consequences) effects on prehospital acute pain management for CYP. This PT was mapped to the Behaviour Change Wheel to provide a clinically relevant behaviour change model for improvement. This realist review has provided a clinically focussed model to guide the improvement of prehospital acute pain management in children and young people attended by ambulance. The programme theory lays a foundation on which future empirical testing can be conducted to effect behaviour change in practice
Health net-outcome objectives and approaches for spatial planning and development: a scoping review
Full text linkObjective: The objective of this scoping review was to map the body of knowledge on net gain and no-net-loss (net-outcome) objectives and approaches applicable to health in spatial planning and development policies and practice.Introduction: There is an established body of academic and gray literature addressing environmental net-outcome objectives, such as biodiversity net gain, in spatial planning policies and practice. While a health net-gain objective has been proposed as a driver for health protection and the realization of health, such an objective and approach are yet to be scoped and defined.Eligibility criteria: This review considered scientific and gray literature sources that described health net-outcome objectives and approaches that can be implemented in spatial planning and development policies and practice. Source contexts were not limited to specific countries, geographical areas, or settings. All types of evidence were considered.Methods: This review followed the JBI methodology for scoping reviews. Searches of 19 information sources were conducted in August 2023 and updated in July 2024. Key databases included Scopus, MEDLINE, and Embase. Sources of gray literature were included, and citation searching was conducted. No language or date restrictions were applied. Following a high level of agreement during piloting, titles and abstracts were screened by 1 reviewer, and 50% of full texts were screened by 2 reviewers. One reviewer extracted data describing the characteristics of evidence sources and the net-outcome objectives and approaches described within them. Data analysis included categorization, frequency counts, and a SWOT (strengths, weaknesses, opportunities, threats) analysis.Results: Of 8290 unique records identified through database and gray literature searching, 474 evidence sources were assessed for eligibility, resulting in the inclusion of 112 sources, alongside 7 others identified from citation searching, for a total of 119 sources. Included evidence sources dated from 1974 to 2024, with an increasing frequency of publication from 2008. Social objectives were found from the 1990s, and conservation policies engendered well-being objectives from 2018. Frequently encountered perspectives related to regenerative and sustainable design and development, biodiversity, and conservation. Almost all sources originated from developed Western economies. Broad objectives relevant to health (90/119) outnumbered distinct health objectives (29/119). Most sources addressed development projects, among other scales. Sources frequently described the reconceived use of development to protect and improve health and well-being, overcome sustainability challenges, and strengthen socioecological systems. Implementation often featured participatory approaches, mitigation hierarchies, and assessment, although some sources advocated positive opportunities for health creation rather than the use of contested quantitative accounting frameworks. Challenges and opportunities were predominantly associated with objective specification and assessment. Potential value conflicts were identified relating, in part, to differing anthropocentric and biocentric approaches and objections to quantification and commodification.Conclusions: This review found many socio-environmental net-outcome objectives relevant to health and emergent health objectives that were immature and less frequently reported. These present differing scopes, focuses, and implementation options that are relevant to policymakers’ specification of future objectives. Specification entails value judgments, and equity considerations are important. Knowledge gaps to address include transferability between countries, policy domains, and disciplines; multilevel evaluation; and integration within spatial planning systems and current impact assessment theory and practice
Women's Time-Thirsty Work and Time Generosity in Knowledge Production
Full text linkThe trope of the “three-legged stool” belies the imbalance and messiness of academic work as interrelated teaching, research, and academic service. A temporal lens on women academics' research work surfaces gendered discourses of time allocation and workload models, work–life, and work–work imbalance. Here, we focus on challenges women face in research work, and the resources available in research work. We report findings from two distinct but related research projects: (1) an online open-text questionnaire designed to investigate women's work and well-being at a research-intensive university; and (2) a reimagination of feminist leadership praxis in higher education. The first project was linked to activity aimed to improve research culture. The second, a Leverhulme Research Fellowship project, aimed to co-construct understandings of feminist leadership praxis with women working in UK higher education (UKHE). Feminist post-structuralist discourse analysis (FPDA) was used to analyze responses. Survey participants framed challenges in a temporal discourse of time-thirsty work marked by need, urgency, and time consumption that led to the impossibility of balancing work and life priorities satisfactorily. Resources were framed in discourses of academic and operational support and services where (un)funded time-facilitated research work. Applying a temporal lens to dialogic narrative interviews, we surfaced a feminist discourse of time generosity, associated with time spent providing support. Responding to need, mentoring, and valuing time were features of gifting time or working with a spirit of generosity with respect to the time spent. Drawing on feminist conceptualizations of time, we argue that workload planning models underestimate the time thirstiness and time generosity of women's work. Consequently, the neoliberal university system assumes the existence of funds of disposable time for research purposes and relies on unpaid overtime and goodwill to function. Thus, workload models are unfit for purpose. University leaders have a duty of care to recognize temporal rhythms of time-thirsty work beyond the commodified clock time of a capitalist economy
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