The increase in eating disorder (ED) presentations among children and young people (CYP) during the Covid-19 pandemic represents a global health concern, given the associated morbidity and mortality associated with these conditions. We conducted a meta-analysis to estimate the worldwide pooled prevalence of EDs in CYP at a population level. We searched MEDLINE, EMBASE, PsycINFO and LILACS for all English-language studies reporting population level ED prevalence data between January 2013 to February 27th, 2024. The primary outcome was overall prevalence of EDs. We used a random-effects model for the meta-analysis, I 2 statistics to assess heterogeneity, and the Hoy scale for quality assessment. This study is registered with PROSPERO, number CRD42022333223. Sixteen studies including 77,714 children and young people from 12 countries met eligibility criteria and were included in the systematic review, whilst twelve studies with 56,758 participants provided data suitable for inclusion in the meta-analysis. Study quality was moderate; ten studies were classified with a low risk of bias, one with moderate and five with high. The global point prevalence for any ED was 5.23% (95% confidence interval (CI) 0.41 to 10.05, I 2 = 99.95%). The commonest type was Other Specified Feeding or ED (point prevalence of 4.88%, 95% CI 1.46 to 8.30, I 2 = 99.42%), which, like all types of ED was more common among girls (5.25%, 95% CI 0.32 to 10.18, I 2 = 99.69%) than boys (3.97%, 95% CI 0.45 to 7.49, I 2 = 97.77%), although confidence intervals overlapped. Our findings illustrate the urgent need to expand service provision as well as to evaluate and develop strategies for early ED identification in children and young people, given a global prevalence of 1 in 20.

OBJECTIVE:Children and young people (CYP) with special educational needs (SENs) have an increased risk of psychopathology and long-term physical conditions (LTCs) compared with their peers. Yet, exploring the overlap between SEN, psychopathology and physical health using population-based data is lacking. We explored this association in a large, nationally representative survey of school-age children aged 5-16 in England. DESIGN:A secondary analysis of the Mental Health of Children and Young People 2017 survey, applying multiple imputation and logistic regression models. SETTING:A nationally representative community-based sample of children in England. PATIENTS:6673 children aged 5-16 years, with parent-reported data on SEN status, Education, Health and Care Plan (EHCP) status and LTCs, and clinically rated Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) psychiatric diagnoses (via the Development and Well-being Assessment). INTERVENTIONS:None. MAIN OUTCOME MEASURES:Parent-reported SEN status; EHCP status RESULTS: Among CYPs with SEN (n=559), 73% (n=409) had a DSM-5 disorder and/or at least one LTC. CYP with psychiatric disorders or LTCs showed substantially higher odds of having SEN (adjusted OR (AOR) DSM-5=7.76, 95% CI 6.41 to 9.39; AOR LTC=2.76, 95% CI 2.31 to 3.29) compared with non-affected peers. The interaction between psychiatric disorder and male gender was significant, indicating stronger associations with SEN and EHCP for boys than for girls, whereas disorder-specific interactions were not significant. CONCLUSIONS:For CYPs with SEN, comorbidity with psychopathology and LTC is common, which underscores the need for effective liaison between education, healthcare and social services to ensure comprehensive support for CYPs with complex needs.

The hippocampus is a key site of atrophy in Alzheimer’s disease (AD) and MRI derived estimates of hippocampal volume have been shown to be a robust biomarker of AD-related neurodegeneration. However, its application at the individual level is limited by the lack of reference standards from large normative datasets that can be applied across a wide range of settings. We aimed to investigate the utility of hippocampal volume centile scores adjusted for age, sex and total intracranial volume (TIV) derived from a normative data from 101,457 participants across the life course, as a biomarker of neurodegeneration in AD. BrainChart calculates age and sex adjusted centile scores for structural MRI metrics using a GAMLSS (Generalised Additive Models for Location Scale and Shape) approach and can be applied to individual datasets using an out-of-sample centile scoring approach that calculates study-specific offsets (Bethlehem, Seidlitz, White et al. Nature 2022). Using this approach, we developed models for Freesurfer derived estimates of hippocampal volume additionally incorporating TIV as a co-variate. This was then applied to 351 individuals with pathologically confirmed AD (median scan time prior to death 5.9 years) from the NACC dataset, as well as 110 amyloid-PET positive patients from the ADNI-3 cohort (MCI n=71, AD dementia n=39). Wilcoxon rank-sum tests were used to assess differences between patient groups and cognitively normal controls from the relevant datasets. Spearman’s rank correlations were used to assess relationships with cognition (MMSE score). Median centile scores were reduced in all patient groups (pathologically confirmed AD cases left = 0.13, right =0.13; amyloid-PET positive MCI cases left=0.12, right=0.16; and amyloid-PET positive AD dementia left=0.01, right=0.02). This was significantly different to cognitively normal controls from both the NACC dataset (n=1400, cases left=0.52, right=0.52) and ADNI-3 dataset (n=247, cases left=0.50, right=0.50), all to a significance level of p<0.0001. Hippocampal centile scores strongly predicted MMSE score in both cohorts (Spearmans’ Rho range 0.37-0.41, p<0.001). BrainChart age, sex and TIV adjusted hippocampal volume centile scores, derived from an extensive normative dataset, represent a method for objectively identifying neurodegeneration in AD that is interpretable at the individual level.

Lateralization is a fundamental principle of structural brain organization. In vivo imaging of brain asymmetry is essential for deciphering lateralized brain functions and their disruption in neurodevelopmental and neurodegenerative disorders. Here, we present a normative framework for benchmarking brain asymmetry across the lifespan, developed from an aggregated sample of 128 primary neuroimaging studies, including 177,701 scans from 138,231 individuals, jointly spanning the age range from 20 post menstrual weeks to 102 years. This resource includes comprehensive, hemisphere-specific brain growth charts for multiple neuroimaging phenotypes: regional cortical grey matter volume, thickness, surface area, and subcortical volumes. Our findings reveal distinct spatial patterns of asymmetry, with early leftward asymmetry observed in association cortices and late rightward asymmetry in sensory regions. These trajectories support theories of the neuroplasticity of asymmetry and the role of both genetic and environmental factors in shaping brain lateralization. Additionally, we provide tools to generate asymmetry centile scores, which allow the quantification of individual deviations from typical asymmetry throughout the lifespan and can be applied to unseen data or clinical populations. We demonstrate the utility of these models by highlighting group-level differences in asymmetry in autism spectrum disorder, schizophrenia, and Alzheimer's disease, and exploring genetic correlations with hemispheric specialization. To facilitate further research, we have made this normative framework freely available as an interactive open-access resource (upon publication), offering an essential tool to advance both basic and clinical neuroscience.

Given the poor long-term effectiveness of opioids for persistent non-cancer pain, and their potential for harm, evidence-based interventions to address opioid overprescribing for persistent pain are needed. This study aimed to explore the acceptability and feasibility of a primary care practice pharmacist-led intervention (PROMPPT review) for patients prescribed opioids for persistent pain and the feasibility of evaluating PROMPPT in a definitive trial. A single-arm study, with mixed methods process evaluation, was conducted in four English primary care practices. Adults prescribed opioids for ≥ 6 months were invited to participate in the Management of Opioids and Persistent Pain (MOPP) study by completing baseline and 3-month follow-up questionnaires. Practices invited a representative sample of MOPP participants to schedule a PROMPPT review, eight of which were audio-recorded. Following the review, pharmacists completed intervention delivery templates, and participants were sent an Acceptability Questionnaire and invited to consent to an interview. Between November 2020 and May 2021, 148 participants were recruited to the MOPP study. Of these, 123 (83 ISRCTN87628403 , registered 31 July 2020

Objective: Africa contributes significantly to the increasing global prevalence (>37 %), unmet need and treatment burden for people with osteoarthritis. Despite this, little research has examined the expressed needs of patients with osteoarthritis (OA) and joint pain in West-Africa. This study aimed to explore lived experiences, expressed needs and current care gaps for people living with osteoarthritis in low-health resource contexts using Nigeria as a case study. Design: Qualitative study using Focus Groups. People aged 45 years and over living with osteoarthritis and joint pain were recruited at local health services or via wide advertisements in the community. Discussions were recorded and transcribed verbatim. Data were analyzed using thematic analysis (inductive approach). Results: Three focus groups were conducted with people living with osteoarthritis (n 1/4 30, age range 45-90 years) across socio-demographic strata. Participants described their experiences of living with osteoarthritis as emotionally, physically, and socio-economically challenging. Four main themes (and 14 sub-themes) were identified. Participants expressed the need for an information and health education campaign and access to appropriate health professionals (especially physiotherapists) for providing support, guidance, and assistance with self-management. Conclusions: The provision of an accessible, and contextually appropriate patient education package, in line with evidence-based recommendations is a critical need for people living with osteoarthritis in Nigeria. This will promote evidence-based care for OA in low-resource settings, empowering patients to self-manage and reducing confusion related to inconsistent advice and mixed messages about cause, healthcare access and OA care.

Background Although dementia is a terminal condition, palliation can be a challenge for clinical services. As dementia progresses, people frequently develop behavioural and psychological symptoms, sometimes so severe they require care in specialist dementia mental health wards. Although these are often a marker of late disease, there has been little research on the mortality of people admitted to these wards. Aims We sought to describe the mortality of this group, both on-ward and after discharge, and to investigate clinical features predicting 1-year mortality. Method First, we conducted a retrospective analysis of 576 people with dementia admitted to the Cambridgeshire and Peterborough National Health Service (NHS) Foundation Trust dementia wards over an 8-year period. We attempted to identify predictors of mortality and build predictive machine learning models. To investigate deaths occurring during admission, we conducted a second analysis as a retrospective service evaluation involving mental health wards for people with dementia at four NHS trusts, including 1976 admissions over 7 years. Results Survival following admission showed high variability, with a median of 1201 days (3.3 years). We were not able to accurately predict those at high risk of death from clinical data. We found that on-ward mortality remains rare but had increased from 3 deaths per year in 2013 to 13 in 2019. Conclusions We suggest that arrangements to ensure effective palliation are available on all such wards. It is not clear where discussions around end-of-life care are best placed in the dementia pathway, but we suggest it should be considered at admission.

Tailed bacteriophages are one of the most numerous and diverse group of viruses. They store their genome at quasi-crystalline densities in capsids built from multiple copies of proteins adopting the HK97-fold. The high density of the genome exerts an internal pressure, requiring a maturation process that reinforces their capsids. However, it is unclear how capsid stabilization strategies have adapted to accommodate the evolution of larger genomes in this virus group. Here we characterize a capsid reinforcement mechanism in two evolutionary-related actinobacteriophages that modifies the length of a stabilization protein to accommodate a larger genome while maintaining the same capsid size. We use cryo-EM to reveal that capsids contain split hexamers of HK97-fold proteins with a stabilization protein in the chasm. The observation of split hexamers in mature capsids is unprecedented, so we rationalize this result mathematically, discovering that icosahedral capsids can be formed by all split or skewed hexamers as long as their T-number is not a multiple of three. Our results suggest that analogous stabilization mechanisms can be present in other icosahedral capsids, and they provide a strategy for engineering capsids accommodating larger DNA cargoes as gene delivery systems.

Nationally representative mental health data in adolescents from low- and middle-income countries (LMICs) are scarce. This study aimed to examine mental health and wellbeing indicators amongst adolescents in 12 LMICs across Eastern and Southern Africa and Southeast Asia. We conducted a secondary analysis of data involving 12,169 internet-using adolescents, aged 12–17 years, from Ethiopia, Kenya, Mozambique, Namibia, Tanzania, Uganda, Cambodia, Indonesia, Malaysia, Philippines, Thailand, and Vietnam. We explored cross-country measurement invariance of the multi-item mental health scales, computed country-level estimates for life satisfaction, psychological wellbeing, anxiety, depression, loneliness, self-harm and suicidal ideation/attempts, and examined socio-demographic variations (across age, gender and food insecurity). Measurement invariance was not established, limiting cross-country comparisons. No consistent patterns of mental health estimates emerged across countries. The greatest variation was observed for loneliness (ranging from 18.3% in Vietnam to 71.3% in the Philippines) and for suicidal ideation/attempts (ranging from 7% in Vietnam to 52.7% in Uganda). Gender and age disparities were present, but their magnitude and direction varied by country. The experience of food insecurity was the most consistent correlate of mental health outcomes, with significant associations with life satisfaction and psychological wellbeing in seven countries each, with anxiety in six, and with depression and loneliness in four. Overall, our findings provide key insights into the validity and use of a range of mental health measures among adolescents across 12 LMICs, as well as valuable within-country observations that may help inform and tailor interventions, policies and future research on adolescent mental health to local contexts.

People with dementia frequently develop behavioural and psychological symptoms, sometimes necessitating care in specialist dementia mental health wards. There has been little research on their life expectancy following admission or need for palliative care. The work presented here explores the mortality of these patients and whether this can be predicted at their time of admission to the ward. We conducted a retrospective analysis of 576 patients admitted to the Cambridgeshire and Peterborough NHS Foundation Trust dementia mental health wards in the United Kingdom, and built a Kaplan-Meier survival curve as well as machine learning models. Next, to examine changes in deaths occurring over time, a retrospective service evaluation was conducted involving four mental health wards for people with dementia in the United Kingdom, encompassing a further 1,976 patients. The median survival length post-admission was 1201 days. Clinical data collected on admission did not predict mortality in machine learning models at a level of accuracy likely to have clinical utility. Data from four different wards show that the number of patients dying in dementia mental health wards has increased over time. Our cohort had a high mortality, although with a wide range of survival times. We suggest all people admitted to these units should have discussions and access to high-quality end-of-life care.

Lipoprotein(a) (Lp[a]) is a genetic and often unmeasured contributor to atherosclerotic cardiovascular disease (ASCVD) risk. In this study, Lp(a) was estimated from exome data by quantifying Kringle IV subtype 2 repeats alongside a single-nucleotide variant-based genetic risk score. This method was applied to a diverse cohort (N = 76,147) from the Helix Research Network. The method better identified individuals with high Lp(a) levels, especially among individuals not genetically similar to Europeans. High genetic risk for high Lp(a) level was correlated with earlier and more frequent ASCVD diagnoses. Those with high genetic Lp(a) were more likely to have ASCVD without traditional risk factors present.

Educational attainment is a key social determinant of health; however, there is a paucity of research worldwide on the educational attainment of autistic people. Leveraging data from a large, anonymous online survey, the study matched 14,519 autistic adults and 37,458 non-autistic adults with high autistic traits (henceforth high AQ) 1:5 on age, gender, and UK region to non-autistic adults. Autistic and high AQ people had lower levels of educational attainment than others, on average; however, autistic people achieved postgraduate qualifications at similar levels to matched peers. This suggests that most autistic and high AQ people experience significant barriers to educational attainment, but some autistic people achieve advanced educational qualifications. In addition, it provides evidence that educational systems may fail to effectively support a wider range of learners than those with formally recognized special educational needs. As educational attainment predicts long-term health and financial stability, timely autism diagnosis and adaptations to national and international educational policies are urgently needed.

PURPOSE:We quantitively explored adolescents' concerns about privacy, confidentiality, and data use in health research and their potential impact on the accuracy of self-report data. METHODS:We analyzed data from 17,729 secondary school students who participated in the 2023 OxWell Student Survey. The survey assessed 5 concerns about privacy, confidentiality, and data use and asked students whether these concerns impacted the accuracy of their answers. We calculated the proportions who (a) endorsed each concern and (b) reported inaccuracies associated with their concern(s). We then examined associations of concerns and self-reported inaccuracies with nonresponse and score distributions on sensitive measures of mental illness (depression/anxiety and disordered eating) and adversity (child maltreatment) using logistic regression. RESULTS:46.0% (8,160/17,729) of students endorsed ≥1 concern, and of these, 29.2% (2,379/8,160) reported associated inaccuracies. Relative to boys, concerns were more common amongst gender diverse adolescents (adjusted odds ratio [aOR] = 5.71, 95% confidence interval [CI] 4.40-7.48), gender nondisclosing adolescents (aOR = 4.36, 95% CI 3.62-5.26), and girls (aOR = 2.52, 95% CI 2.36-2.69), with smaller differences in self-reported inaccuracies. Students with self-reported inaccuracies were significantly more likely to have nonresponse on the 3 measures of mental illness and adversity (aORs = 1.53-3.38), whilst score distributions on those measures varied substantially according to whether students reported concerns. DISCUSSION:Concerns about privacy, confidentiality, and data use were common amongst student participants, as were self-reported inaccuracies. Substantial differences in nonresponse and score distributions on sensitive measures highlight potential impacts of these concerns. Co-designing and implementing strategies to address these concerns might help to support evidence-based decision-making by improving representativeness and data quality in adolescent health research.

BACKGROUND:People with dementia frequently develop behavioural and psychological symptoms, sometimes necessitating care in specialist dementia mental health wards. There has been little research on their life expectancy following admission or need for palliative care. The work presented here explores the mortality of these patients and whether this can be predicted at their time of admission to the ward. METHOD:We conducted a retrospective analysis of 576 patients admitted to the Cambridgeshire and Peterborough NHS Foundation Trust dementia mental health wards in the United Kingdom, and built a Kaplan-Meier survival curve as well as machine learning models. Next, to examine changes in deaths occurring over time, a retrospective service evaluation was conducted involving four mental health wards for people with dementia in the United Kingdom, encompassing a further 1,976 patients. RESULT:The median survival length post-admission was 1201 days. Clinical data collected on admission did not predict mortality in machine learning models at a level of accuracy likely to have clinical utility. Data from four different wards show that the number of patients dying in dementia mental health wards has increased over time. CONCLUSION:Our cohort had a high mortality, although with a wide range of survival times. We suggest all people admitted to these units should have discussions and access to high-quality end-of-life care.

Actinobacteriophage NapoleonB is a lytic double-stranded(ds) DNA phage of the Caudovirales order with a prolate capsid head. High resolution structures of elongated capsid heads are scarce and present challenges in characterization at atomic resolution. Here we investigated phage NapoleonB using cryo-EM, conducted extensive atomic model building, and complemented our study with molecular dynamics (MD) simulations. Our comprehensive analysis revealed the structural intricacies of the NapoleonB capsid, portal complex and its long,flexible tail.

Neuro-imaging data can often be represented as statistical networks, especially for functional magnetic resonance imaging (fMRI) data, where brain regions are defined as nodes and the functional interactions between those regions are taken as edges. Such networks are commonly divided into classes depending on the type of edges, namely binary or weighted. A binary network means edges can either be present or absent. Whereas the edges of a weighted network are associated with weight values, and fMRI networks belong to weighted networks. Statistical methods are often adopted to analyse such networks, among which, the exponential random graph model (ERGM) is an important network analysis approach. Typically ERGMs are applied to binary networks, and weighted networks often need to be binarised by arbitrarily selecting a threshold value to define the presence of the edges, which can lead to non-robustness and loss of valuable edge weight information representing the strength of fMRI interaction in fMRI networks. While it is therefore important to gain deeper insight in adopting ERGM on weighted networks, there only exists a few different ERGM frameworks for weighted networks; some of these are not directly implementable on fMRI networks based on their original proposal. We systematically review, implement, analyse and compare five such frameworks via a simulation study and provide guidelines on each modelling framework as well as conclude the suitability of them on fMRI networks based on a range of criteria. We concluded that Multi-Layered ERGM is currently the most suitable framework.

Adolescent development of human brain structural and functional networks is increasingly recognized as fundamental to emergence of typical and atypical adult cognitive and emotional proodal magnetic resonance imaging (MRI) data collected from N [Formula: see text] 300 healthy adolescents (51%; female; 14 to 26 y) each scanned repeatedly in an accelerated longitudinal design, to provide an analyzable dataset of 469 structural scans and 448 functional MRI scans. We estimated the morphometric similarity between each possible pair of 358 cortical areas on a feature vector comprising six macro- and microstructural MRI metrics, resulting in a morphometric similarity network (MSN) for each scan. Over the course of adolescence, we found that morphometric similarity increased in paralimbic cortical areas, e.g., insula and cingulate cortex, but generally decreased in neocortical areas, and these results were replicated in an independent developmental MRI cohort (N [Formula: see text] 304). Increasing hubness of paralimbic nodes in MSNs was associated with increased strength of coupling between their morphometric similarity and functional connectivity. Decreasing hubness of neocortical nodes in MSNs was associated with reduced strength of structure-function coupling and increasingly diverse functional connections in the corresponding fMRI networks. Neocortical areas became more structurally differentiated and more functionally integrative in a metabolically expensive process linked to cortical thinning and myelination, whereas paralimbic areas specialized for affective and interoceptive functions became less differentiated, as hypothetically predicted by a developmental transition from periallocortical to proisocortical organization of the cortex. Cytoarchitectonically distinct zones of the human cortex undergo distinct neurodevelopmental programs during typical adolescence.

IntroductionOsteoarthritis is the commonest form of chronic joint pain, which patients often self-manage before seeking healthcare advice. Patients frequently seek advice from community pharmacies, and a recent policy has recommended integrating community pharmacies into long-term condition pathways. This study explored community pharmacy teams' (CPs) and other healthcare professionals' (HCPs) views on community pharmacies providing an extended role for osteoarthritis management, identifying potential barriers and facilitators to this.MethodsA multi-methods study comprising surveys of CPs and other HCPs, followed by qualitative interviews. Descriptive statistics were used in an exploratory analysis of the survey data. Qualitative data were analysed using reflexive thematic analysis and the identified barriers and facilitators were mapped to the Theoretical Domains Framework.ResultCPs and other HCPs in the surveys and interviews reported that an extended role for osteoarthritis management could include: a subjective assessment, explaining the joint problem and its treatment, medication management and support for self-care. There was less consensus on diagnosing the problem as OA and completing an objective assessment. A key facilitator was training to deliver the role, whilst barriers were high workload and lack of access to General Practitioner medical records.DiscussionAcceptable elements of an extended community pharmacy role for osteoarthritis centre around the provision of information, advice on medication and supported self-management.ConclusionCPs are well placed to contribute towards evidenced-based osteoarthritis management. Feasibility testing of delivering the extended role is needed and future implementation requires training for CPs and raising public awareness of the extended role.

ObjectivesTo test the feasibility of a randomised controlled trial (RCT) of a novel preoperative tailored sleep intervention for patients undergoing total knee replacement.DesignFeasibility two-arm two-centre RCT using 1:1 randomisation with an embedded qualitative study.SettingTwo National Health Service (NHS) secondary care hospitals in England and Wales.ParticipantsPreoperative adult patients identified from total knee replacement waiting lists with disturbed sleep, defined as a score of 0–28 on the Sleep Condition Indicator questionnaire.InterventionThe REST intervention is a preoperative tailored sleep assessment and behavioural intervention package delivered by an Extended Scope Practitioner (ESP), with a follow-up phone call 4 weeks postintervention. All participants received usual care as provided by the participating NHS hospitals.Outcome measuresThe primary aim was to assess the feasibility of conducting a full trial. Patient-reported outcomes were assessed at baseline, 1-week presurgery, and 3 months postsurgery. Data collected to determine feasibility included the number of eligible patients, recruitment rates and intervention adherence. Qualitative work explored the acceptability of the study processes and intervention delivery through interviews with ESPs and patients.ResultsScreening packs were posted to 378 patients and 57 patients were randomised. Of those randomised, 20 had surgery within the study timelines. An appointment was attended by 25/28 (89%) of participants randomised to the intervention. Follow-up outcomes measures were completed by 40/57 (70%) of participants presurgery and 15/57 (26%) postsurgery. Where outcome measures were completed, data completion rates were 80% or higher for outcomes at all time points, apart from the painDETECT: 86% complete at baseline, 72% at presurgery and 67% postsurgery. Interviews indicated that most participants found the study processes and intervention acceptable.ConclusionsThis feasibility study has demonstrated that with some amendments to processes and design, an RCT to evaluate the clinical and cost-effectiveness of the REST intervention is feasible.Trial registration numberISRCTN14233189.