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Abstract Researchers and policymakers have proposed systems to detect novel pathogens earlier than existing surveillance systems by monitoring samples from hospital patients, wastewater, and air travel, in order to mitigate future pandemics. How much benefit would such systems offer? We developed, empirically validated, and mathematically characterized a quantitative model that simulates disease spread and detection time for any given disease and detection system. We find that hospital monitoring could have detected COVID-19 in Wuhan 0.4 weeks earlier than it was actually discovered, at 2,300 cases (standard error: 76 cases) compared to 3,400 (standard error: 161 cases). Wastewater monitoring would not have accelerated COVID-19 detection in Wuhan, but provides benefit in smaller catchments and for asymptomatic or long-incubation diseases like polio or HIV/AIDS. Air travel monitoring does not accelerate outbreak detection in most scenarios we evaluated. In sum, early detection systems can substantially mitigate some future pandemics, but would not have changed the course of COVID-19.

The potential for accidental or deliberate misuse of biotechnology is of concern for international biosecurity. Here the authors apply machine learning to DNA sequences and associated phenotypic data to facilitate genetic engineering attribution and identify country-of-origin and ancestral lab of engineered DNA sequences.

Abstract Central nervous system germ cell tumors (CNS-GCT) are malignant neoplasms that arise predominantly during adolescence and young adulthood. These tumors are typically sensitive to treatment, but resulting long-term health deficits are common. Additional clinical challenges include surgical risks associated with tumor biopsy, and need to determine treatment response for adapting radiotherapy protocols. The aim of this study was to establish the detectability of circulating-tumor DNA (ctDNA) from cerebrospinal fluid (CSF) of children with CNS-GCT as a potential biomarker. We obtained CSF from patients with CNS-GCT by lumbar puncture or intra-operatively. Cell-free DNA (cfDNA) was extracted and subjected to low-pass whole genome sequencing (LP-WGS). Copy-number alterations (CNAs) were inferred and served as a marker of measurable residual disease (MRD). Comparisons with imaging findings and tumor marker levels were made. A total of 29 CSF samples from 21 patients (16 with germinoma, 5 with non-germinomatous GCT) were sequenced. Twenty samples from 19 patients were collected at diagnosis, and 9 samples from 7 patients were collected during or after therapy. Among the diagnostic samples, CNAs were detected in samples from 17/19 patients (89%), which included 8 with marker-negative tumors. Specific clinical scenarios suggested that serial cfDNA analysis may carry utility in tracking treatment responses as well as clarifying indeterminate imaging findings. Our results provide evidence for the high-sensitivity in detecting ctDNA from CSF of CNS-GCT patients using LP-WGS, with potential utility for non-invasive diagnosis and disease monitoring in upcoming CNS-GCT studies.

Abstract Candida auris is a globally emerged fungal pathogen causing nosocomial invasive infections. Here, we use cutting-edge genomic approaches to elucidate the temporal and geographic epidemiology of drug-resistant C. auris within the UK. We analysed a representative sample of over 200 isolates from multiple UK hospitals to assess the number and timings of C. auris introductions and infer subsequent patterns of inter- and intra-hospital transmission of azole drug-resistant isolates. We identify at least one introduction from Clade I and two from Clade III into the UK, and observe temporal and geographical evidence for multiple transmission events of antifungal drug resistant isolates between hospitals and identified local within-hospital patient-to-patient transmission events. Our study confirms outbreaks of drug-resistant C. auris are linked and that transmission amongst patients occurs, explaining local hospital outbreaks, and demonstrating a need for improved epidemiological surveillance of C. auris to protect patients and healthcare services.

Abstract Background Housing insecurity can be understood as experiencing or being at risk of multiple house moves that are not through choice and related to poverty. Many aspects of housing have all been shown to impact children/young people’s health and wellbeing. However, the pathways linking housing and childhood health and wellbeing are complex and poorly understood. Methods We undertook a systematic review synthesising qualitative data on the perspectives of children/young people and those close to them, from the United Kingdom (UK). We searched databases, reference lists, and UK grey literature. We extracted and tabulated key data from the included papers, and appraised study quality. We used best fit framework synthesis combined with thematic synthesis, and generated diagrams to illustrate hypothesised causal pathways. Results We included 59 studies and identified four populations: those experiencing housing insecurity in general (40 papers); associated with domestic violence (nine papers); associated with migration status (13 papers); and due to demolition-related forced relocation (two papers). Housing insecurity took many forms and resulted from several interrelated situations, including eviction or a forced move, temporary accommodation, exposure to problematic behaviour, overcrowded/poor-condition/unsuitable property, and making multiple moves. Impacts included school-related, psychological, financial and family wellbeing impacts, daily long-distance travel, and poor living conditions, all of which could further exacerbate housing insecurity. People perceived that these experiences led to mental and physical health problems, tiredness and delayed development. The impact of housing insecurity was lessened by friendship and support, staying at the same school, having hope for the future, and parenting practices. The negative impacts of housing insecurity on child/adolescent health and wellbeing may be compounded by specific life circumstances, such as escaping domestic violence, migration status, or demolition-related relocation. Conclusion Housing insecurity has a profound impact on children and young people. Policies should focus on reducing housing insecurity among families, particularly in relation to reducing eviction; improving, and reducing the need for, temporary accommodation; minimum requirements for property condition; and support to reduce multiple and long-distance moves. Those working with children/young people and families experiencing housing insecurity should prioritise giving them optimal choice and control over situations that affect them.

Recent explosions have prompted researchers to investigate the vulnerability of civil structures, leading to an increased demand for blast-resistant buildings. Laminated glass (LG) panels in glazed facades boost resilience, yet understanding glass fragment interaction with interlayers remains incomplete. This paper presents an integrated experimental-computational study on strain localization in LG polymeric interlayers to accurately simulate their response, addressing this gap. Uniaxial tensile tests were performed on the polymeric interlayer materials polyvinyl butyral (PVB) and SentryGlas® (SG), commonly used in the design of LG in blast-resistant glazing systems. Digital image correlation was used to characterize strain localization within the material. The experimental results were used to calibrate material model parameters to be used in the modeling of LG systems. A three-network viscoplastic (TNV) material model for SG interlayer was calibrated using PolymerFEM software. Yeoh hyperelastic material model parameters were calibrated for the quasistatic response of PVB. A finite element computational model was developed using Ansys LS-DYNA software and validated with experimental data. The study results showcase finite element modeling's ability to accurately predict both the hyperelastic response of PVB and the post-peak large strain behavior of SG interlayer materials by 8% and 3.6%, respectively.

Abstract Background Complex health interventions (CHIs) are increasingly used in public health, clinical research and education to reduce the burden of disease worldwide. Numerous theories, models and frameworks (TMFs) have been developed to support implementation of CHIs. This systematic review aims to identify and critique theoretical frameworks concerned with three features of implementation; adaptability, scalability and sustainability (ASaS). By dismantling the constituent theories, analysing their component concepts and then exploring factors that influence each theory the review team hopes to offer an enhanced understanding of considerations when implementing CHIs. Methods This review searched PubMed MEDLINE, CINAHL, Web of Science, and Google Scholar for research investigating the TMFs of complex health interventions. Narrative synthesis was employed to examine factors that may influence the adaptability, scalability and sustainability of complex health interventions. Results A total of 9763 studies were retrieved from the five databases (PubMed, MEDLINE, CINAHL, Web of Science, and Google Scholar). Following removal of duplicates and application of the eligibility criteria, 35 papers were eligible for inclusion. Influencing factors can be grouped within outer context (socio-political context; leadership funding, inter-organisational networks), inner context; (client advocacy; organisational characteristics), intervention characteristics (supervision, monitoring and evaluation), and bridging factors (individual adopter or provider characteristics). Conclusion This review confirms that identified TMFS do not typically include the three components of adaptability, scalability, and sustainability. Current approaches focus on high income countries or generic “whole world” approaches with few frameworks specific to low- and middle-income countries. The review offers a starting point for further exploration of adaptability, scalability and sustainability, within a low- and middle-income context. Trial registration Not registered.

Objectives The COVID-19 pandemic has led to increased use of digital clinical consultations (phone or video calls) within UK maternity services. This project aimed to review the evidence on digital clinical consultations in maternity systems to illuminate how, for whom and in what contexts, they can be used to support safe, personalised and equitable care.Design A realist synthesis, drawing on diverse sources of evidence (2010–present) from OECD countries, alongside insights from knowledge user groups (representing healthcare providers and service users).Methods The review used three analytical processes (induction, abduction and retroduction) within three iterative stages (development of initial programme theories; evidence retrieval and synthesis; validation and refinement of the programme theories).Results Ninety-three evidence sources were included in the final synthesis. Fifteen programme theories were developed showing that digital clinical consultations involve different mechanisms operating across five key contexts: the organisation, healthcare providers, the clinical relationship, the reason for consultation and women. The review suggests that digital clinical consultations can be effective and acceptable to stakeholders if there is access to appropriate infrastructure/digital resources and if implementation is able to ensure personalisation, informed choice, professional autonomy and relationship-focused connections. The review found relatively less evidence in relation to safety and equity.Conclusions Due to the complexity of maternity systems, there can be ‘no one-size fits all’ approach to digital clinical consultations. Nonetheless, the review distills four ‘CORE’ implementation principles: C—creating the right environment, infrastructure and support for staff; O—optimising consultations to be responsive, flexible and personalised to different needs and preferences; R—recognising the importance of access and inclusion; and E—enabling quality and safety through relationship-focused connections. Service innovation and research are needed to operationalise, explore and evaluate these principles, particularly in relation to safety and equity.PROSPERO registration number CRD42021288702.

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality and residing in a rural and remote region is associated with an increased risk. The impact of rurality on CVD outcomes needs to be fully elucidated. Objectives: The purpose of this study was to assess the difference in mortality, readmission within 30 days, total readmissions, survival, and total emergency department (ED) presentations following an index CVD admission among patients from rural or remote areas as compared to metropolitan areas. Methods: This retrospective observational study included all index hospitalizations with heart failure (HF), atrial fibrillation (AF), or acute coronary syndrome (ACS) within the Hunter New England region of Australia, between January 1, 2008, and December 31, 2021. Results: There were 27,995 ACS admissions, 15,586 HF admissions, and 16,935 AF admissions. Patients from a rural or remote area presenting with CVD presentations had increased 30-day readmission (OR: 1.19; P

В секвенаторе ДНК «Нанофор СПС», разработанном в Институте аналитического приборостроения РАН, реализован метод массового параллельного секвенирования для расшифровки последовательности нуклеиновых кислот. Этот метод позволяет определять последовательность нуклеотидов в ДНК или РНК, содержащих от нескольких сотен до сотен миллионов звеньев мономеров. Таким образом, имеется возможность получения подробной информации о геноме различных биологических объектов, в том числе человека, животных и растений. Важнейшей частью этого прибора является программное обеспечение, без которого невозможно решение задач по расшифровке генома. Выходными данными оптической детекции в секвенаторе являются набор изображений по четырем каналам, соответствующим типам нуклеотидов: A, C, G, T. С помощью специального программного обеспечения определяется положение молекулярных кластеров и их интенсивностные характеристики вместе с параметрами окружающего фона. В ходе создания программного обеспечения прибора были разработаны алгоритмы и программы обработки сигналов флуоресценции, рассмотренные в работе. Также, для отладки и тестирования рабочих программ созданы модели построения изображений, аналогичных реальным данным, получаемым в ходе работы секвенатора. Данные модели позволили получить значительный массив информации без запуска дорогостоящих экспериментов. За последние годы достигнуты значительные успехи в области машинного обучения, в том числе и в области биоинформатики, что привело к реализации наиболее распространенных моделей и возможности их применения для практических задач. Однако, если на этапе вторичного анализа биоинформационных данных эти методы широко зарекомендовали себя, то их потенциал для первичного анализа остается недостаточно раскрытым. В данной работе особое внимание уделяется разработке и внедрению методов машинного обучения для первичного анализа оптических изображений сигналов флуоресценции в реакционных ячейках. Описаны методы кластеризации и их апробация на моделях и на изображениях, полученных на приборе. Цель этой статьи – продемонстрировать возможности алгоритмов первичного анализа сигналов флуоресценции, получающихся в процессе секвенирования на приборе «Нанофор СПС». В работе описаны основные задачи анализа сигналов флуоресценции и сравниваются традиционные методы их решения с использованием технологий машинного обучения.

Abstract We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92–0.94) and the Lung Cancer Symptom Scale-Mesothelioma (0.79–0.87) at each co-administration of the scales. The CSS also had good sensitivity to worsening disease and global quality-of-life ratings. The MDASI-MPM CSS can be used as an outcome in MPM clinical trials, including in responder analyses and at the individual patient level. It is brief enough to administer frequently, including electronically, to better capture symptom trajectories during and after a trial and in clinical practice. As a single score, the CSS addresses multiplicity issues that can arise when several symptoms increase due to worsening disease. Our process can be adapted to produce a CSS for other advanced-cancer trials.

Abstract Background Societal changes have led to greater isolation and higher levels of loneliness particularly for older generations. Loneliness is a significant public health challenge leading to increased levels of poor mental health. Depression and anxiety are also increasing in prevalence amongst children and young people. Intergenerational activities are interventions designed to bring together older and younger generations with the purpose of allowing participants to utilise their experiences and skills, and to give participants a chance to experience the pleasure and excitement that occurs with the transmission of knowledge and skills from one generation to another. Intergenerational activities are therefore potential interventions that can address the growing problems associated with loneliness and lack of wellbeing. Objectives This systematic review aims to examine the impact of intergenerational interventions on the wellbeing and mental health in children and adolescents, and potential harmful effects. It also aims to identify areas for future research as well as key messages for service commissioners. Search Methods We searched an evidence and gap map published in 2022 (comprehensive searches conducted July 2021 and updated June 2023) to identify randomised controlled trials of intergenerational interventions that report mental health and wellbeing outcomes for children and young people. Selection Criteria Randomised controlled trials of intergenerational interventions that involved unrelated younger and older people with at least one skipped generation between them and reported mental health or wellbeing outcomes for children and young people were included in this review. Data Collection and Analysis We used standard methodological procedures expected by The Campbell Collaboration. We conducted data extraction and Cochrane risk of bias assessments in EPPI reviewer. Main Results While we identified 500 evaluations of intergenerational interventions, where the impact on participating children and/or young people was evaluated this was most often limited to assessing their impact on attitudes to aging. We identified five studies evaluating five different types of intergenerational interventions which included one‐off sessions to ones that spanned a year measuring their impact on the mental health and wellbeing of children and/or young people. The purposes of the interventions differed, which included promoting social skills, preventing harmful behaviour and promoting learning. The ages of children also varied across the five studies, with one targeting younger children, two targeting younger teenagers and two targeting older teenagers. One study included socioeconomically disadvantaged children, and in the other studies the socioeconomic backgrounds of the children and young people were not described. The outcome measures used to evaluate the interventions varied with none of the studies measuring the same outcomes. One study showed improvements in wellbeing measures, and this was an intervention delivered to children in deprived neighbourhoods, where the intervention duration was for a year allowing the development of a greater depth of relationship between the younger and older participants. Four studies found no……. The included studies were at high risk of bias therefore raising uncertainty in the reliability of the findings. Underpinning theories that supported the development of the interventions and explained the mechanisms of effect were poorly described. Authors' Conclusions The evidence for the effectiveness of intergenerational interventions on the mental health and wellbeing of children and young people is limited and inconclusive. Few evaluations have sought to measure how intergenerational interventions impact children and young people and where this impact is measured the focus is usually limited to attitudes to aging. The evidence that has been collected is too heterogenous to allow synthesis of the findings. The underpinning theories to support their development are poorly described with no follow‐up data to ascertain if benefits are maintained. Intergenerational interventions show promise but researchers have failed to measure how they impact on the mental health and wellbeing of children and young people. This is a serious limitation of the evidence base that needs to be addressed in robust and rigorous evaluations.

Introduction Prolonged ambulance response times and unacceptable emergency department (ED) wait times are significant challenges in urgent and emergency care systems associated with patient harm. This scoping review aimed to evaluate the evidence base for 10 urgent and emergency care high-impact initiatives identified by the National Health Service (NHS) England.Methods A two-stage approach was employed. First, a comprehensive search for reviews (2018–2023) was conducted across PubMed, Epistemonikos and Google Scholar. Additionally, full-text searches using Google Scholar were performed for studies related to the key outcomes. In the absence of sufficient review-level evidence, relevant available primary research studies were identified through targeted MEDLINE and HMIC searches. Relevant reviews and studies were mapped to the 10 high-impact initiatives. Reviewers worked in pairs or singly to identify studies, extract, tabulate and summarise data.Results The search yielded 20 771 citations, with 48 reviews meeting the inclusion criteria across 10 sections. In the absence of substantive review-level evidence for the key outcomes, primary research studies were also sought for seven of the 10 initiatives. Evidence for interventions improving ambulance response times was generally scarce. ED wait times were commonly studied using ED length of stay, with some evidence that same day emergency care, acute frailty units, care transfer hubs and some in-patient flow interventions might reduce direct and indirect measures of wait times. Proximal evidence existed for initiatives such as urgent community response, virtual hospitals/hospital at home and inpatient flow interventions (involving flow coordinators), which did not typically evaluate the NHS England outcomes of interest.Conclusions Effective interventions were often only identifiable as components within the NHS England 10 high-impact initiative groupings. The evidence base remains limited, with substantial heterogeneity in urgent and emergency care initiatives, metrics and reporting across different studies and settings. Future research should focus on well-defined interventions while remaining sensitive to local context.

Background Winter pressures are a familiar phenomenon within the National Health Service and represent the most extreme of many regular demands placed on health and social care service provision. This review focuses on a part of the pathway that is particularly problematic: the discharge process from hospital to social care and the community. Although studies of discharge are plentiful, we identified a need to focus on identifying interventions and initiatives that are a specific response to ‘winter pressures’. This mapping review focuses on interventions or initiatives in relation to hospital winter pressures in the United Kingdom with either discharge planning to increase smart discharge (both a reduction in patients waiting to be discharged and patients being discharged to the most appropriate place) and/or integrated care. Methods We conducted a mapping review of United Kingdom evidence published 2018–22. Initially, we searched MEDLINE, Health Management Information Consortium, Social Care Online, Social Sciences Citation Index and the King’s Fund Library to find relevant interventions in conjunction with winter pressures. From these interventions we created a taxonomy of intervention types and a draft map. A second broader stage of searching was then undertaken for named candidate interventions on Google Scholar (Google Inc., Mountain View, CA, USA). For each taxonomy heading, we produced a table with definitions, findings from research studies, local initiatives and systematic reviews and evidence gaps. Results The taxonomy developed was split into structural, changing staff behaviour, changing community provision, integrated care, targeting carers, modelling and workforce planning. The last two categories were excluded from the scope. Within the different taxonomy sections we generated a total of 41 headings. These headings were further organised into the different stages of the patient pathway: hospital avoidance, alternative delivery site, facilitated discharge and cross-cutting. The evidence for each heading was summarised in tables and evidence gaps were identified. Conclusions Few initiatives identified were specifically identified as a response to winter pressures. Discharge to assess and hospital at home interventions are heavily used and well supported by the evidence but other responses, while also heavily used, were based on limited evidence. There is a lack of studies considering patient, family and provider needs when developing interventions aimed at improving delayed discharge. Additionally, there is a shortage of studies that measure the longer-term impact of interventions. Hospital avoidance and discharge planning are whole-system approaches. Considering the whole health and social care system is imperative to ensure that implementing an initiative in one setting does not just move the problem to another setting. Limitations Time limitations for completing the review constrained the period available for additional searches. This may carry implications for the completeness of the evidence base identified. Future work Further research to consider a realist review that views approaches across the different sectors within a whole system evaluation frame. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR130588) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 31. See the NIHR Funding and Awards website for further award information. Plain language summary Every year, the National Health Service struggles with huge care demands from people with heart and lung problems. This ‘mapping review’ aimed to chart the evidence around what has been done to minimise winter pressures related to discharge planning, by helping people leaving hospital sooner, and by optimising integrated care (also known as ‘collaborative care’) and to make suggestions for future research. Good research evidence was identified for three specific approaches: Acute medical units: these units provide rapid assessment, diagnosis and treatment for adults referred by their general practitioner or the emergency department. Discharge to assess: this involves discharging patients who need care services but not an acute hospital bed. Patients are either discharged home or are transferred to an appropriate community setting with short-term funded support while their future care needs are assessed. Hospital at home: this approach provides patients with the care they need at home instead of in hospital (also known as virtual wards). The evidence for many other activities to reduce winter pressures was weaker, coming from case studies, conference presentations or small, low methodological quality (poorly designed or executed) research studies. The review identified many different initiatives with diverse names or labels and it is also important to consider how implementing an initiative in one setting might affect another setting. Further research is recommended around what works best for which patient groups, under what circumstances and why, based on common processes within the different initiatives and across the whole health and social care system. Scientific summary Introduction The term ‘winter pressures’ refers to ‘how hospitals cope with the challenges of maintaining regular service over the winter period’. Attention often focuses on additional demands on accident and emergency services but pressures are exerted in terms of increased demand across the entire health and social care system. Increased prevalence of respiratory and cardiovascular illnesses during the winter places severe demands upon systems that already face difficulties in matching service provision to demand. Better or earlier planning and/or increasing service provision across integrated care systems and related sectors, such as housing, constitute just two of the possible responses to increased demand. Winter pressures are a familiar phenomenon within the National Health Service and represent the most extreme of many regular demands placed on health service provision. The impact of winter pressures is pervasive and operates along a continuum from public health, in mitigation via immunisation campaigns, through to discharge into social care and the community. Interventions target multiple points along this continuum, as well as whole-system approaches. This mapping review focuses on one stage of the pathway, considered particularly problematic, namely the discharge process from hospital. Studies of discharge interventions and transfers of care are plentiful and international initiatives have been reviewed in a recent scoping review. However, a considerable challenge lies in identifying interventions that specifically are articulated as an explicit response to ‘winter pressures’. There is strong rationale for focusing on the subgroup of ‘winter pressure’ interventions as specific interventions implemented in response to acute and severe system pressure. This contrasts with interventions that seek to improve discharge within a system in ‘steady state’. While commentators on the current context articulate that the system experiences ‘winter pressures’ all year round, until recently, responses have targeted the context of winter pressures. Potentially, this set of studies therefore represents a highly relevant evidence base on discharge related interventions to inform current National Health Service (NHS) planning. This mapping review aims to chart and document the evidence in relation to winter pressures in the United Kingdom, together with either discharge planning to increase discharge (both a reduction in patients waiting to be discharged and patients being discharged to the most appropriate place) and/or integrated care. For the purposes of this review, ‘integrated care’ involves partnerships of organisations that come together to plan and deliver joined-up health and care services within NHS England. The primary objective of the mapping review is to address the question: Which interventions in relation to discharge planning/integrated care have been suggested, tried or evaluated in seeking to address winter pressures in the United Kingdom? The secondary review question is: Which research or evaluation gaps exist in relation to service- or system-level interventions as a response to discharge planning/integrated care in the context of winter pressures? In addressing this question the mapping review will seek: To identify a potential winter pressures research agenda in relation to discharge planning/integrated care to inform commissioning of future research. Methods We conducted a mapping review of UK evidence published 2018–22. For the mapping review, we used a two-stage search process to search for the evidence. Initially, we searched MEDLINE, Health Management Information Consortium, Social Care Online, Social Sciences Citation Index and the King’s Fund Library to find relevant interventions. The search was broad for terms for winter pressures. Searches on Google Scholar (Google Inc., Mountain View, CA, USA), which searches the full text instead of just title and abstract, included terms for discharge and integrated care. Study screening and selection was undertaken in Microsoft Excel® (Microsoft Corporation, Redmond, WA, USA) by three reviewers who independently screened the title and abstracts of the 723 references that were retrieved by the search. Study eligibility was based on following aspects – population, exposure, comparative, outcome(s), study types: users of UK health and/or social care systems (population) winter pressures impacting on discharge, to social care and the community, and integrated care (exposure) other foreseeable, unusual or exceptional periods of demand (if appropriate) (comparison – may or may not be present) increased smart discharge (both a reduction in patients waiting to be discharged and patients being discharged to the most appropriate place), system effects, health and health service outcomes, effects on patients, carers and staff (outcomes) eligible types of study design (primary research study, evidence synthesis or research report) (study types). To classify within the broader thematic groups of interventions, we developed a taxonomy documenting the candidate interventions together with other relevant supporting literature. Our team started from categories developed by the Cochrane Effective Practice and Organisation of Care Group for their systematic reviews of discharge planning. These were further expanded using categories from a rapid review produced by the Centre for Clinical Effectiveness, Monash University. This process resulted in the following broad groupings: structural, changing staff behaviour, changing community provision, integrated care and targeting carers. The draft taxonomy was reviewed for parsimony (to minimise duplication of concepts) and comprehensiveness (to include all named interventions identified to date). However, published commentary has documented the non-exclusivity and lack of precision of existing labels. Following the production of the draft map using the taxonomy, we decided to further split the taxonomy headings to represent contributions to the patient pathway: hospital avoidance, alternate delivery site, facilitated discharge and cross-cutting. The modelling and workforce planning groupings were not considered as within scope because of their limited relevance to short-term alleviation of winter pressures and were therefore discarded. The second stage of searching consisted of searches for named candidate interventions from the literature and current practice on Google Scholar. The second stage was to identify where possible reviews, ideally systematic reviews, and these searches were broader than winter pressures but were limited to research published from 2012 to 2022. The second-stage searches helped in completing the intervention tables and identifying the evidence gaps. Research priorities were classified as high, moderate or low and further classified by the nature of the evidence gap(s) identified (research gap, synthesis gap and/or implementation gap). Results The taxonomy consists of a total of 41 headings. These headings were further organised into the different contributions to the patient pathway: hospital avoidance, alternative delivery site, facilitated discharge and cross-cutting. The evidence for each heading was provided and this helped with identification of the evidence gaps. Within structural interventions for the hospital avoidance part of the patient pathway research gap were identified for same-day emergency care and research and implementation gaps for surgical hubs. The alternative delivery sites subsection is populated by systematic review evidence for the effectiveness of acute medical units, other specialist units developing using winter funding need to be fully evaluated. Models based on ‘discharge to assess’ (also ‘home first’ and others) within facilitated discharge are relatively well researched. Some taxonomy headings (e.g. ‘bed management’ and ‘discharge co-ordinators’) were often evaluated within a broader process of ‘discharge planning’. ‘Patient flow’ is another broad heading with some overlap with both bed management and discharge planning. The concept of patient flow is also broader than facilitated discharge, although its ultimate goal is ensuring safe discharge as soon as is clinically appropriate. The evidence base for initiatives defined as ‘cross-cutting’ varied widely and was characterised by case studies with a lack of research studies. Community provision initiatives and integrated care were heterogeneous and characterised by multiple diverse initiatives, largely unevaluated, and by involvement of multiple contributors and sectors. Overall, the evidence base is characterised by large numbers of case studies, often published online or presented at conferences, and relatively few peer-reviewed journal articles. Case studies are often accompanied by guidance to support implementation of changes to services. This distribution of evidence probably reflects the urgent need to develop and implement solutions to the ever increasing winter (and increasingly year round) pressures on the health and care system. The majority of evaluations report positive effects on important outcomes such as length of hospital stay but many are uncontrolled or based on small samples, meaning that they need to be interpreted with caution. Conclusions Few initiatives identified were specifically implemented as a response to winter pressures. Hospital at home, as a heavily used intervention, was well-supported by the evidence but other responses, while also heavily used, were based on limited evidence. There is a lack of studies considering patient, family and provider needs when developing interventions aimed at improving delayed discharge. Additionally, few studies measure the impact of interventions over a long time; short-term results can appear promising but evidence for longer-term sustainability is notably absent. Hospital avoidance and delayed discharge requires a whole-system approach. It is imperative to consider the whole system to ensure that implementing an initiative in one setting does not just move the problem to another setting. Limitations Time limitations for completing the review constrained the period available for additional searches with a focus on systematic reviews and high-profile studies. This carries implications for the variability of coverage and completeness of the evidence base identified. Implications for service delivery Effective interventions to avoid hospital admission, deliver services in different settings and facilitate discharge are key to reducing short-term acute pressures on health and social care. These pressures are generally associated with the winter period but have increasingly been experienced throughout the year and are particularly acute at the time of writing (January 2023). Longer-term improvements to service delivery may require policy changes related to investment and workforce planning that are outside the scope of this review. Implications for research We identified high priority topics for primary research and evaluation in all the broad groupings of taxonomy headings as follows: Changing community provision: private sector, step-up facilities. Changing staff behaviour: clinical audit, quality improvement programmes, protocols/guidelines, quality management systems. Integrated care: integrated care discharge huddle. Structural (S): bed management, extra service delivery, governance, monitoring and review, same-day services, specialist units, volunteers. In terms of evidence synthesis, our detailed exploration further supports the need for a realist review that views approaches across the different sectors within a whole-system evaluation frame. Further evidence synthesis should consider identified synthesis gaps in research within the aforementioned areas. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR130588) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 31. See the NIHR Funding and Awards website for further award information.

The ability to collate data of healthcare clients from disparate health information systems in the public health system in the Western Cape province of South Africa presents opportunities for improved healthcare outcomes, but it also necessitates the development of systems to address risks related to the potential for data breach and privacy violations. Here, we describe the data governance infrastructure for the Provincial Health Data Centre (PHDC) in the Western Cape Province of South Africa, which consolidates person-level health data from various sources to support healthcare management and research. We describe how PHDC data governance protects sensitive health data by ensuring compliance with privacy regulations and legislation, and demonstrate the adoption of key pillars of data governance in order to implement policies and procedures that safeguard patient privacy and promote responsible data use. We review downstream impacts of data collation including improved continuity of care, outbreak detection and research support, and how these may be facilitated within the data governance infrastructure. The presentation highlights the need to balance the potential benefits of routine health data collation and secondary use with managing the risks to privacy and security for healthcare clients, and describes how this is addressed by the PHDC. Future areas to be considered include adoption of Trusted Research Environments (TRE) and the use of synthetic data, as well as identifying effective ways of enforcing data governance policies and monitoring compliance levels.

Family with sequence similarity 161 (Fam161) is an ancient family of microtubule-binding proteins located at the centriole and cilium transition zone (TZ) lumen that exhibit rapid evolution in mice. However, their adaptive role is unclear. Here, we used flies to gain insight into their cell type-specific adaptations. Fam161 is the sole orthologue of FAM161A and FAM161B found in flies. Mutating Fam161 results in reduced male reproduction and abnormal geotaxis behaviour. Fam161 localizes to sensory neuron centrioles and their specialized TZ (the connecting cilium) in a cell type-specific manner, sometimes labelling only the centrioles, sometimes labelling the centrioles and cilium TZ and sometimes labelling the TZ with varying lengths that are longer than other TZ proteins, defining a new ciliary compartment, the extra distal TZ. These findings suggest that Fam161 is an essential centriole and TZ protein with a unique cell type-specific localization in fruit flies that can produce cell type-specific adaptations.

Background Signposting typically refers to an informal process that involves giving information to patients to enable them to access external services and support. It is perceived to reduce demand on primary care and other urgent care services. Methods This focused realist review was conducted rapidly within time constraints. Searches to identify theory were undertaken on MEDLINE, Cumulative Index to Nursing and Allied Health Literature and Social Sciences Citation Index in June 2022 for research published in English from 2016. We selected 22 publications and extracted programme theories from these to develop three priority questions: Question 1: What do people with health and social care needs require from a signposting service to believe it is valuable? Question 2: What resources do providers require to confidently deliver an effective signposting service? Question 3: Under what circumstances should commissioners commission generic or specialist signposting services? Purposive searching was conducted to find a rich sample of studies. UK studies were prioritised to optimise the applicability of synthesis findings. Results The review included 27 items, 4 reviews and 23 studies, a mix of qualitative, evaluations and case studies. Service users value a joined-up response that helps them to navigate the available resources. Key features include an understanding of their needs, suggestion of different options and a summary of recommended actions. Only a small number of service user needs are met by signposting services alone; people with complex health and social care needs often require extended input and time. Front-line providers of signposting services require appropriate training, ongoing support and supervision, good knowledge of relevant and available activities and an ability to match service users to appropriate resources. Front-line providers need to offer a flexible response targeted at user needs. Commissioned signposting services in England (no studies from Scotland, Wales and Northern Ireland) are highly diverse in terms of client groups, staff delivering the service, referral routes and role descriptions. A lack of service evaluation poses a potential barrier to effective commissioning. A shortage of available services in the voluntary and community sector may limit the effectiveness of signposting services. Commissioners should ensure that referrals target intensive support at patients most likely to benefit in the longer term. Conclusions Signposting services need greater clarity of roles and service expectations to facilitate evaluation. Users with complex health and social care needs require intensive, repeat support from specialist services equipped with specific knowledge and situational understanding. A tension persists between efficient (transactional) service provision with brief referral and effective (relational) service provision, underpinned by competing narratives. Do signposting services represent ‘diversion of unwanted demand from primary care/urgent care services’ or ‘improved quality of care through a joined-up response by health, social care and community/voluntary services’? Limitations This realist review was conducted within a tight time frame with a potential impact on methodology; for example, the use of purposive searching may have resulted in omission of relevant evidence. Future work Signposting services require service evaluation and consideration of the issue of diversity. Study registration This study is registered as PROSPERO CRD42022348200. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR130588) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 26. See the NIHR Funding and Awards website for further award information. Plain language summary Signposting points people to information, help or advice that they should find useful. Signposting can be delivered face to face, by phone, or virtually, by technology. This review of research brings together what is already known. We have not collected any data ourselves. The review uses realist synthesis. This method tries to understand the whys and ways (the mechanisms and theories) of how things work (or do not work!). It goes beyond whether something works (is effective). It tries to explain why something might work for some people but not others. For example, why an approach may not be helpful for people with disabilities, why it might work in some places but not others and exactly what leads to what effects (what are the ‘key ingredients’). The report answers the following three questions: What do people with health and social care needs require from a signposting service to enable them to believe it is a valuable and useful service? What resources do people providing signposting services require to ensure that they can confidently provide effective signposting services? How can commissioners/funders specify, monitor and evaluate signposting services (generic or specific) to optimise value for money and outcomes for service users? Specifically, do any factors favour funding general over specialist services and vice versa? The diversity of signposting services within health or across social and community services, including voluntary services, makes them difficult to evaluate and compare. Within each service, different people undertake signposting roles: from general practitioners, practice nurses or receptionist to a standalone signposting role, each for a different purpose and intensity. Only a small number of service users potentially benefit from signposting-only services. Many service users have complex health and social care needs and, therefore, need different support extended over a longer time. Scientific summary Introduction Signposting is an informal process that involves giving information to patients to enable them to access external, usually non-clinical, services and support (Harris E, Barker C, Burton K, Lucock M, Astin F. Self-management support activities in primary care: a qualitative study to compare provision across common health problems. Patient Educ Couns 2020;103:2532–9. https://doi.org/10.1016/j.pec.2020.07.003). Signposting also includes self-referral, which often requires patients to contact health and support services by telephone or the internet. Signposting may also take place within clinical interactions or within more extensive social prescribing. Methods A protocol was developed that received input from commissioning and patient and public involvement representatives. This study used realist synthesis to answer three key questions. Information about each is provided below. Initial searches to identify theory were conducted on MEDLINE, Cumulative Index to Nursing and Allied Health Literature and the Social Sciences Citation Index for research published in English from 2016 to current in June 2022. The broad search retrieved 716 unique references and the focused search retrieved 31 references. One reviewer (AB) reviewed the results of the focused and then the broader search and selected 22 studies to use for theory identification. The three reviewers divided these studies between them and extracted initial programme theories in the form of context–mechanism–outcome (CMO) configurations: IF (context) – THEN (mechanism) – LEADING TO (outcome) statements. Extracted data related to IF (WHO? DO WHAT? FOR WHOM?) THEN (THE RESPONSE IS) LEADING TO (WHAT OUTCOMES? FOR WHOM?) followed by the reference source. The team prioritised complete (i.e. three-element) CMO configurations, whenever possible. A limited number of two-element CMO configurations were included when they provided unique insights, for completeness. The signposting programme theories identified are provided in the report. All CMO configurations were checked by a single reviewer experienced in realist synthesis to ensure that they were complete, in a common format, and that the agency (i.e. who was the agent for action) could be identified. The review team then met to discuss the initial programme theories and identified a need to address three complementary perspectives: those of the service user, service provider and commissioner. Identification of programme theory led to the development of a priority question constructed to match each perspective. Question 1 (value and usefulness of signposting) considers the service user perspective: What do people with health and social care needs require from a signposting service to believe it is a valuable and useful service? Question 2 (required resources) considers the perspective of the front-line provider of the signposting service: What resources (training, directories/databases, credible and high-quality services for referral) do providers of front-line signposting services require to confidently deliver effective signposting services? Question 3 (specification, monitoring and evaluation) considers the viewpoint of the commissioner/funder: Under what circumstances should commissioners commission generic or specialist signposting services? Purposive searching was undertaken for each question to find a sample of rich relevant studies. The searching included forward and backward citation searching of relevant studies from the theories searches, focused searches and searching for UK initiatives. Where possible, we predominantly included UK studies to optimise the usefulness of the synthesis findings with a UK context and included studies based on richness, rigour and relevance. All documents with signposting in the title were included along with any qualitative studies of social prescribing and care navigation with multiple occurrences of ‘signposting’ in the full text. Studies from other comparable countries were included where relevant. Several studies supplied data to address more than one question and were therefore included in multiple sections. Formal quality appraisal was not undertaken. An online meeting of the Health Service and Delivery Research Sheffield Evidence Synthesis Centre Public Advisory Group met to provide input into the review. The group were asked about their understanding of the term signposting and their experiences of accessing signposting services. Question 1: What do people with health and social care needs require from a signposting service to believe it is a valuable and useful service? (Service user perspective) Findings for Question 1 are organised under the four identified subquestions. A total of 19 items of evidence were reviewed including 4 reviews and 15 individual items reporting UK studies or service evaluations. The nature of the question meant that studies were mainly qualitative or mixed-methods studies with one quantitative study in the included evidence. Summary of findings for Question 1 (value and usefulness: service user perspective) Service users value a ‘linking’ or ‘joined-up’ response that helps them to navigate resources offered by different organisations and/or by different sectors and helps them to reach an appropriate destination. Key features from a service user viewpoint are an understanding of their needs, presentation of options (together with alternatives if required) and a summary of the recommended action to be taken. This needs to be supported by appropriate matching of opportunities to their needs and resourced provision and capacity so that they can pursue these opportunities. Above all, a signposting service must reduce the ‘patient burden’ encountered in contacts with formal health services when trying to pursue options and alternatives. A key consideration is whether signposting services are conceived to operate in isolation or whether they form the front end of an integrated pathway of care with multiple routes and outcomes. The needs of only a small proportion of those targeted by signposting services are met by signposting services alone. Where people with complex needs interact with signposting services, interaction may require extended time or multiple episodes. Alternatively, they may perceive that their needs were imperfectly or incompletely met by a brief intervention. Effective use of signposting, which requires a clear, and often detailed, understanding of service user needs, may operate against a programme theory that conceives them as an efficient brief intervention to divert service users away from formal health services towards wider resources in the community. Question 2: What resources (training, directories/databases, credible and high-quality services for referral) do providers of front-line signposting services require to confidently deliver effective signposting services? (Service provider perspective) For Question 2, a total of 14 items of evidence were reviewed including 1 review and 13 individual items reporting UK, USA or Canadian studies or service evaluations. The findings from the included studies are discussed within themes. Summary of findings for Question 2 (required resources: service provider perspective) Front-line providers of signposting services require appropriate training, ongoing support and supervision. Front-line providers of signposting services require good knowledge of relevant health, social care, community, voluntary or other agency activities and opportunities to which they feel empowered to refer. Front-line providers of signposting services need be able to match appropriate services or resources to the needs of a service user – this may take time, extensive interaction and the creation of trust over time. Front-line providers of signposting services need to provide a flexible response in order to meet very diverse levels and types of individual needs. Requirements may also differ according to differing levels of availability of complementary services (e.g. where separate health and social care signposting services coexist or not). For a signposting service to be considered useful, those providing signposting services must be confident that, even in times of resource constraint, sufficient appropriate, high-quality resources exist to which they can refer. Question 3: How can commissioners/funders specify, monitor and evaluate signposting services (generic or specific) to optimise value for money and outcomes for service users? Specifically, are there factors that favour funding of generic versus specialist services or vice versa? (Service commissioner/funder perspective) For Question 3, a total of four items of evidence were reviewed; data were extracted from a survey of Clinical Commissioning Groups in England; evaluations of a social prescribing service and a primary care diabetes care navigation service; and a qualitative study of a new care model in Child and Adolescent Mental Health Services. Commissioned signposting services in England (no studies from Wales and Northern Ireland) are highly diverse in terms of client groups, staff delivering the service, referral routes and how the role is described. Evaluation of services is uncommon and is a potential barrier to effective commissioning. Lack of availability of services in the voluntary and community sector may limit the effectiveness of signposting/care navigation in both primary and secondary care and their potential to reduce urgent care use and improve well-being in service users. Brief signposting interventions are sufficient for some service users. Others require intensive support to overcome barriers to engagement with either the care signposting/care navigation process or, subsequently, services to which they are referred. From the commissioner perspective, it is important that referral processes provide intensive support to those most likely to benefit in the longer term. Summary of integrated findings across the three perspectives (service user, service provider and service commissioner/funder) Clarity of roles and expectations is required within signposting services. Signposting services may operate within health or across social and community services including voluntary service provision. Those signposting may include this role within wider clinical [general practitioner (GP) or practice nurse] or administrative roles (receptionists), as one of many functions within tailored social prescribing or care navigation roles, or as a standalone signposting role. This makes evaluation and comparison challenging. Only a small number of service users potentially benefit from signposting-only services. Many users have complex health and social care needs that require intensive and repeated support. Specialist services demand greater empathy, knowledge and situational understanding and so are likely to extend beyond signposting. Service users and service providers need to develop a shared confidence in the signposting role. This requires good communication skills and training, backed up with resources, to firstly identify activities and opportunities and then for adequate levels of resource provision to enable them to be accessed and used. The tension between (1) efficient (transactional) service provision with brief referral and (2) effective (relational) service provision, requiring detailed understanding of individual service user needs, remains unreconciled. This tension is underpinned by competing narratives of ‘diversion of unwanted demand from primary care and other urgent care services’ and of ‘improved quality of care through a joined-up response that encompasses health, social care and community/voluntary services’. Conclusion Signposting services need to achieve greater clarity around roles and the expectations of the service to enable thorough evaluation. Evaluation and comparisons are challenging; signposting services which operate within health or across social and community services, including voluntary service provision, are diverse. The diversity of signposting roles and services makes evaluation and comparisons challenging. Within each service, roles may vary in function and intensity from a recognisable signposting function within a wider clinical (GP or practice nurse) or administrative role (receptionists) through one of many components within tailored social prescribing or care navigation roles to a standalone signposting role. Commissioners of services need to recognise that the complex health and social care needs of many service users require intensive and repeated support. Specialist services demand greater empathy, knowledge and situational understanding, and thus contact is likely to extend in time and scope beyond straightforward signposting. Service users and service providers need to develop a shared confidence in the signposting role. This requires good communication skills and training together with resources; first, to identify relevant activities and opportunities and then to enable service users to access them. The tension between efficient (transactional) service provision with brief referral and effective (relational) service provision, which requires a detailed understanding of individual service user needs, remains unreconciled. This tension is underpinned by competing narratives of whether signposting represents ‘diversion of unwanted demand from primary care and other urgent care services’ or ‘improved quality of care through a joined-up response that encompasses health, social care and community/voluntary services’. Research gaps and priorities The review identified the following research gaps and priorities: There is a need to evaluate different levels of intensity of service provision and their differential benefits and value for money. Productive comparison and evaluation (through benchmarking and audit) of similar services is required (i.e. signposting services to be compared with similar brief services and services providing more intensive and sustained to be compared with similar). Further comparison and evaluation of signposting services could explore levels of service provided by different staff roles. Specialist services may particularly benefit from evaluation tailored to the needs and objectives of each specific service. Issues of cultural diversity are absent from the literature particularly, as they relate to setting up a service; thus, we have identified a need for research around setting up and providing services for diverse populations. Research examining the impact of economic constraints on informal social provision would be potentially informative. Further consideration of the extent to which each service developed should prioritise and manage brief interactions with large numbers of generic users or sustained, and even prolonged, support to a targeted user group with complex health and social needs. Study registration This study is registered as PROSPERO CRD42022348200. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR130588) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 26. See the NIHR Funding and Awards website for further award information.

# Background Perinatal depression is a common mental health disorder which spans during and after pregnancy. Unfortunately, there is poor healthcare-seeking behaviour for this treatable condition. Additionally, maternal healthcare workers sometimes overlook the signs and symptoms, failing to diagnose it adequately. This review aims to provide a framework for understanding the in-depth perceptions and implementation gaps surrounding perinatal depression in Nigeria. # Methods This study employed a rigorous qualitative evidence synthesis methodology to gather and analyse both published and unpublished qualitative research on the lived experiences and perceptions of perinatal depression in Nigeria. The research was conducted by searching multiple electronic databases, citation chaining, and checking reference lists. The studies were then screened by title, abstract, and full text, and the quality of the included studies was evaluated using the Critical Appraisal Skills Programme (CASP) checklist for appraising a qualitative study. The data extracted from these studies were then synthesized using the ‘best-fit’ framework method, which combines deductive and inductive approaches to analysis. # Results 10 eligible papers were identified. Data were organised into themes eight themes mapped to an already existing framework: Recognitions of perinatal mental distress, labelling of mental distress, symptom patterns, social norms, roles and expectations, supernatural factors, physical/bodily issues, coping strategies, help-seeking from professionals/medical institutions. No study was excluded as a result of methodological limitations. # Conclusions The review highlights the significance of integrating mental health services into routine perinatal care and the need for comprehensive interventions that consider sociocultural factors. The findings emphasize the importance of increasing awareness and education among women and healthcare providers to improve early detection and intervention. Healthcare professionals play a crucial role in identifying and managing perinatal depression; therefore, it is essential to provide them with comprehensive and regular training.

BackgroundHuman CD16+ monocytes (hCD16+ Ms) have proangiogenic properties. We assessed the feasibility, safety and efficacy of hCD16+ Ms in a porcine model of myocardial infarction (MI).Methods and resultsA total of 27 female Large White pigs underwent MI with reperfusion and cardiac magnetic resonance (CMR). Five days later, animals received intramyocardial injections of hCD16+ Ms in saline (n = 13) or saline only (n = 14). hCD16+ Ms were selected from leucocyte cones. Feasibility/safety endpoints included injury at injected sites, malignant arrhythmias, cancer, haematoma, left ventricular (LV) dilatation, troponin release and downstream organ injury. Co-primary efficacy outcome included LV scar and ejection fraction (LVEF) at 30-day post-injections by CMR. Immunohistochemistry included neo-angiogenesis, fibrosis, markers of myofibroblast and inflammation. Four animals were excluded before injections due to untreatable malignant arrhythmias or lung injury. Median cell number and viability were 48.75 million and 87%, respectively. No feasibility/safety concerns were associated with the use of hCD16+ Ms. The LV scar dropped by 14.5gr (from 25.45 ± 8.24 to 10.8 ± 3.4 gr; −55%) and 6.4gr (from 18.83 ± 5.06 to 12.4 ± 3.9gr; −30%) in the hCD16+ Ms and control groups, respectively (p = 0.015). The 30-day LVEF did not differ between groups, but a prespecified sub-analysis within the hCD16+ Ms group showed that LVEF was 2.8% higher and LV scar 1.9gr lower in the subgroup receiving a higher cell dose. Higher tissue levels of neo-angiogenesis, myofibroblast and IL-6 and lower levels of TGF-β were observed in the hCD16+ Ms group.ConclusionsThe use of hCD16+ Ms in acute MI is feasible, safe and associated with reduced LV scar size, increased tissue levels of neo-angiogenesis, myofibroblasts and IL-6 and reduced pro-fibrotic TGF-β at 30-day post-injections. A higher cell dose might increase the LVEF effect while reducing scar size, but this warrants validation in future studies.

Abstract Introduction Persistent low back pain (LBP) is the leading cause of disability worldwide, and therapeutic exercise is recommended as a first-line treatment in international guidelines. The effects of exercise on clinical outcomes of pain and physical function are small to moderate, despite broader impacts on cardiovascular systems, biological health, mood, and emotional well-being. Therapeutic exercise prescription is defined as exercise that is prescribed by a clinician for a health-related treatment. It is unknown how therapeutic exercise prescription creates effects on outcomes of importance. Realist reviews explore how underlying mechanisms (M) may be active in the context (C) of certain situations, settings, or populations to create an intended or unintended outcome (O). Our objective is to explore and understand the mechanisms by which therapeutic exercise prescription changes outcomes for people with persistent LBP. Methods We will develop initial programme theories based on preliminary data from a previous systematic review and consensus workshop. These theories will be modified with input from a steering group (experts), a stakeholder group (people with lived experience of exercise for persistent LBP and clinicians), and a scoping search of the published literature. An information specialist will design and undertake an iterative search strategy. These will be used to create CMO configurations, which will be refined and tested using the literature. The realist review will be reported following RAMESES guidance. Discussion Realist reviews are uncommon in LBP research to date, yet those offer an opportunity to contrast with traditional methods of randomised controlled trials and systematic reviews and provide additional information regarding the contexts and mechanisms that may trigger certain outcomes. This can aid our understanding of the contextual features that may influence exercise prescription, such as for whom they are most effective, in what setting, how they are implemented and why. This realist synthesis will enhance our understanding of therapeutic exercise prescription to improve adherence and engagement and ultimately will provide clinically relevant recommendations regarding exercise prescription for those with persistent LBP. Systematic review registration The review has been registered with PROSPERO (CRD42017072023).

Abstract Becker muscular dystrophy (BMD) is characterised by fiber loss and expansion of fibrotic and adipose tissue. Several cells interact locally in what is known as the degenerative niche. We analysed muscle biopsies of controls and BMD patients at early, moderate and advanced stages of progression using Hyperion imaging mass cytometry (IMC) by labelling single sections with 17 markers identifying different components of the muscle. We developed a software for analysing IMC images and studied changes in the muscle composition and spatial correlations between markers across disease progression. We found a strong correlation between collagen-I and the area of stroma, collagen-VI, adipose tissue, and M2-macrophages number. There was a negative correlation between the area of collagen-I and the number of satellite cells (SCs), fibres and blood vessels. The comparison between fibrotic and non-fibrotic areas allowed to study the disease process in detail. We found structural differences among non-fibrotic areas from control and patients, being these latter characterized by increase in CTGF and in M2-macrophages and decrease in fibers and blood vessels. IMC enables to study of changes in tissue structure along disease progression, spatio-temporal correlations and opening the door to better understand new potential pathogenic pathways in human samples.

Abstract Background People who are unhoused, use substances (drugs and/or alcohol), and who have mental health conditions experience barriers to care access and are frequently confronted with discrimination and stigma in health care settings. The role of Peer Workers in addressing these gaps in a hospital-based context is not well characterized. The aim of this evaluation was to 1) outline the role of Peer Workers in the care of a marginalized populations in the emergency department; 2) characterize the impact of Peer Workers on patient care, and 3) to describe how being employed as a Peer Worker impacts the Peer. Methods Through a concurrent mixed methods evaluation, we explore the role of Peer Workers in the care of marginalized populations in the emergency department at two urban hospitals in Toronto, Ontario Canada. We describe the demographic characteristics of patients (n = 555) and the type of supports provided to patients collected through a survey between February and June 2022. Semi-structured, in-depth interviews were completed with Peer Workers (n = 7). Interviews were thematically analyzed using a deductive approach, complemented by an inductive approach to allow new themes to emerge from the data. Results Support provided to patients primarily consisted of friendly conversations (91.4%), discharge planning (59.6%), tactics to help the patient navigate their emotions/mental wellbeing (57.8%) and sharing their lived experience (50.1%). In over one third (38.9%) of all patient interactions, Peer Workers shared new information about the patient with the health care team (e.g., obtaining patient identification). Five major themes emerged from our interviews with Peer Workers which include: (1) Establishing empathy and building trust between the patient and their care team through self-disclosure; (2) Facilitating a person-centered approach to patient care through trauma-informed listening and accessible language; (3) Support for patient preferences on harm reduction; (4) Peer worker role facilitating self-acceptance and self-defined recovery; and (5) Importance of supports and resources to help Peer Workers navigate the emotional intensity of the emergency department. Conclusions The findings add to the literature on Peer Worker programs and how such interventions are designed to best meet the needs of marginalized populations.

Objectives: As development and introduction of digital self-management technologies continues to increase, the gap between those who can benefit, and those who cannot correspondingly widens. This research aimed to explore the use of digital self-management technology by older adults with three highly-prevalent long-term conditions (chronic kidney disease, diabetes and dementia), and build expert consensus across the conditions on changes needed to improve effective usage. Method: This qualitative research involved a modified e-Delphi Study. The Delphi panel was comprised of experts with personal, academic or clinical expertise related to one of the long-term conditions and/or the development and use of digital self-management technology. The e-Delphi involved a round of online semi-structured interviews followed by two rounds of a structured online survey. Results: Fourteen experts participated in the study, with eleven of the fourteen completing all three rounds. Analysis of the interviews (round 1 of the Delphi) led to 7 main themes and 29 sub-themes. These were translated into 26 statements that formed the basis of the online survey questions. In the first administration of the survey (round 2) 19 statements reached consensus. After the second administration a further 6 statements reach consensus. Conclusion: The findings reflect expert consensus on barriers to the use of digital self-management by older adults with 3 different, but inter-related conditions, and identify ways in which the design and provision of such technologies could be improved to facilitate more effective use. It is concluded that both the design and the provision of technologies should consider a combination of individual, condition-specific and age-related requirements. By building a consensus on issues and potential strategies common across the three conditions, we aim to inform future research and practice and facilitate effective self-management by older adults.

Summary: Introduction: Historically, antimicrobial stewardship (AMS) has considered the judicious use of antibiotics. AMS is widely adopted across Europe and the US; recently antifungal AMS is gaining momentum but antiviral AMS has been little described. Here we describe the introduction of AMS virology reviews at University Hospitals Birmingham (UHBFT); a novel concept and an opportunity to broaden the beneficial aspects of AMS to virology, termed anti-viral stewardship (AVS). Method: In June 2022, a UK supply issue with aciclovir injection (ACV IV) was announced. In order to review and preserve parenteral ACV for those in greatest need, UHBFT pharmacist and virologists implemented a specialist review for patients prescribed more than 48 hours of treatment. This review initially lasted 10 weeks and data was collected on the advice offered, whether it was accepted, and time required completing the review. Results: AVS rounds halved IV ACV consumption, compared to pre or post intervention levels, with more than half of patients advised to stop or switch to oral therapy. Diagnostics and sampling guidance was offered in one quarter of reviews, whilst the remaining interventions were more stewardship focused. In almost all cases stewardship advice was readily accepted by clinical teams. Due to positive feedback from clinicians and its effective management of supply, the anti-viral stewardship (AVS) programme was re-introduced in June 2023. Conclusions: Antiviral AMS rounds provide an opportunity to optimise sampling, diagnosis and improve patient management. Introduction of regular AVS at UHBFT are now well established and plan to be implemented in other hospitals.

BackgroundThe traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary "cyclical" cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting.Methods and findingsThis observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality.ConclusionsUsing routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades.

Introduction Decisions about nurse staffing models are a concern for health systems globally due to workforce retention and well-being challenges. Nurse staffing models range from all Registered Nurse workforce to a mix of differentially educated nurses and aides (regulated and unregulated), such as Licensed Practical or Vocational Nurses and Health Care Aides. Systematic reviews have examined relationships between specific nurse staffing models and client, staff and health system outcomes (eg, mortality, adverse events, retention, healthcare costs), with inconclusive or contradictory results. No evidence has been synthesised and consolidated on how, why and under what contexts certain staffing models produce different outcomes. We aim to describe how we will (1) conduct a realist review to determine how nurse staffing models produce different client, staff and health system outcomes, in which contexts and through what mechanisms and (2) coproduce recommendations with decision-makers to guide future research and implementation of nurse staffing models.Methods and analysis Using an integrated knowledge translation approach with researchers and decision-makers as partners, we are conducting a three-phase realist review. In this protocol, we report on the final two phases of this realist review. We will use Citation tracking, tracing Lead authors, identifying Unpublished materials, Google Scholar searching, Theory tracking, ancestry searching for Early examples, and follow-up of Related projects (CLUSTER) searching, specifically designed for realist searches as the review progresses. We will search empirical evidence to test identified programme theories and engage stakeholders to contextualise findings, finalise programme theories document our search processes as per established realist review methods.Ethics and dissemination Ethical approval for this study was provided by the Health Research Ethics Board of the University of Alberta (Study ID Pro00100425). We will disseminate the findings through peer-reviewed publications, national and international conference presentations, regional briefing sessions, webinars and lay summary.

Background: In South African antiretroviral guidelines, selected patients failing second-line protease inhibitor (PI)-based therapy qualify for genotypic resistance testing – those with PI resistance receive darunavir-based third-line regimens; those without PI resistance continue current regimen with adherence support. The Western Cape province, from September 2020, implemented a strategy of tenofovir-lamivudine-dolutegravir (TLD) for patients, provided there was no tenofovir resistance, irrespective of PI resistance. Objectives: To evaluate virologic outcomes with TLD among adults failing second-line PI regimens with no tenofovir resistance. Method: An observational cohort study comparing outcomes in patients switched to TLD with those continuing the same PI or switched to darunavir-based regimens. Follow-up was until virologic suppression (HIV-1 RNA 400 copies/mL), or at the point of censoring. Results: One hundred and thirty-three patients switched to TLD, 101 to darunavir-based regimens, and 121 continued with the same PI. By 12 months, among patients with PI resistance, 42/47 (89%) in the TLD group had HIV-1 RNA 400 copies/mL compared to 91/99 (92%) in the darunavir group (hazard ratio, 1.11; 95% confidence interval, 0.77–1.60). In patients without PI resistance, 66/86 (77%) in the TLD group had HIV-1 RNA 400 copies/mL compared to 42/120 (35%) in those continuing with the same PI (hazard ratio, 4.03; 95% confidence interval, 2.71–5.98). Two patients receiving TLD developed virologic failure with high-level dolutegravir resistance. Conclusion: Amongst patients failing second-line PI with no PI resistance, switching to TLD was associated with higher virologic suppression, likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to darunavir-based regimens or TLD.

Abstract Introduction In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. Methods We analysed data from people living with HIV (aged 15–49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan–Meier curves and proportional‐hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. Results Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25–27%) had disengaged from care by 1 year and 34% (95% CI 33–36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70–2.60), restarted (C: aHR 3.32, 95% CI 2.70–4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12–2.74) had increased hazards of postpartum disengagement compared to those on ART (A). Conclusions There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care.

Background: Increasing evidence suggests that air pollution exposure contributes to the development of mental health problems, including psychosis and depression. However, little is known about the importance of early-life exposure, nor the potential role of noise pollution, a correlate of air pollution. We examined the association of exposure to air and noise pollution from pregnancy to age 12 years with three mental health problems assessed at ages 12, 18, and 24 years. Methods: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), which tracks the development of about 14 000 babies who had expected delivery dates between April 1, 1991, and Dec 31, 1992, in Avon, UK. This was linked with novel data on nitrogen dioxide, PM2·5, and noise pollution in pregnancy, childhood (ages 1–9 years), and adolescence (ages 10–12 years). Psychotic experiences, depression, and anxiety were measured at ages 12, 18, and 24 years. Logistic regression models were controlled for individual-level, family-level, and area-level confounders, and e-values were calculated to estimate residual confounding. Findings: Participants exposed to higher PM2.5, particularly during pregnancy, had greater odds for psychotic experiences (adjusted odds ratio 1·17 [95% CI 1·05–1·30]) and depression (1·11 [1·01–1·22]). There was little evidence associating nitrogen dioxide or noise pollution with psychotic experiences or depression. Conversely, higher nitrogen dioxide (but not PM2·5) exposure in pregnancy (1·16 [1·01–1·33]), and higher noise pollution in childhood (1·20 [1·06-1·37]) and adolescence (1·17 [1·02-1·35]), were associated with greater odds for anxiety. Interpretation: Our study builds on evidence linking air pollution to psychosis and depression and provides rare longitudinal evidence linking noise pollution to anxiety. Our findings indicate that air pollution exposure earlier in development (eg, during pregnancy) might be particularly important, and suggest a degree of specificity in terms of pollutant-outcome associations. If causal, our findings suggest that interventions to reduce air pollution would improve global mental health. Funding: Wellcome Trust, UK Medical Research Council–Wellcome, and University of Bristol.

Abstract Background There is a need for scalable clinician education in rational medication prescribing and rational ordering of pathology and imaging to help improve patient safety and enable more efficient utilisation of healthcare resources. Our wider study evaluated the effectiveness of a multifaceted education intervention for general practitioners (GPs) in rational prescribing and ordering of pathology and imaging tests, in the context of Australia’s online patient-controlled health record system, My Health Record (MHR), and found evidence for measurable behaviour change in pathology ordering among participants who completed the educational activities. This current study explored the mechanisms of behaviour change brought about by the intervention, with a view to informing the development of similar interventions in the future. Methods This mixed methods investigation used self-reported questionnaires at baseline and post-education on MHR use and rational prescribing and test ordering. These were analysed using multi-level ordinal logistic regression models. Semi-structured interviews pre- and post-intervention were also conducted and were analysed thematically using the COM-B framework. Results Of the 106 GPs recruited into the study, 60 completed baseline and 37 completed post-education questionnaires. Nineteen participants were interviewed at baseline and completion. Analysis of questionnaires demonstrated a significant increase in confidence using MHR and in self-reported frequency of MHR use, post-education compared with baseline. There were also similar improvements in confidence across the cohort pre-post education in deprescribing, frequency of review of pathology ordering regimens and evidence-based imaging. The qualitative findings showed an increase in GPs’ perceived capability with, and the use of MHR, at post-education compared with baseline. Participants saw the education as an opportunity for learning, for reinforcing what they already knew, and for motivating change of behaviour in increasing their utilisation of MHR, and ordering fewer unnecessary tests and prescriptions. Conclusions Our education intervention appeared to provide its effects through providing opportunity, increasing capability and enhancing motivation to increase MHR knowledge and usage, as well as rational prescribing and test ordering behaviour. There were overlapping effects of skills acquisition and confidence across intervention arms, which may have contributed to wider changes in behaviour than the specific topic area addressed in the education. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12620000010998) (09/01/2020).

Abstract African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.

Abstract Background With millions of unscheduled patient contacts every year and increasing call outs clustered around the most deprived communities, it is clear the ambulance sector could have a role to play in improving population health. However, the application and value of a public health approach within the ambulance sector has not been comprehensively explored. A scoping review was undertaken to explore the role of the ambulance sector in the delivery of public health interventions and what impact this has on population health and ambulance sector outcomes. Methods A search strategy was developed on MEDLINE and translated to other major medical and health related bibliographic databases (Embase; CINAHL; HMIC; Science and Social Sciences Citation Index; Cochrane Library) to identify literature published since 2000 in OECD countries. Targeted grey literature, reference list, and citation searching was also carried out. Search results were downloaded to Microsoft Excel and screened by three reviewers according to pre-determined inclusion / exclusion criteria. Data from included studies, such as the type of activity noted within the paper, the population involved and the public health approach that was utilised, was extracted from within the paper using a data extraction form and narratively synthesised. Results Fifty-two references were included in the final review (37 database searching; 9 reference list searching; 6 grey literature). Included articles were categorised according to the relevant public health domains and subdomains as articulated by the UK Faculty of Public Health: 1. Health improvement domain: Public health education and advice (Health promotion sub-domain) (n=13) Emergency Services personnel providing vaccines (Disease prevention sub-domain) (n=1) 2. Health care public health domain Paramedicine (Service delivery sub-domain) (n=30) Screening tools and referral pathways used by the ambulance sector (Service delivery sub-domain) (n=28) Health intelligence using ambulance sector data (population health management sub-domain) (n=26) Of note, some domains (e.g. health protection) returned nil results. Discussion The scoping review demonstrates the breadth of public health related activities in which the ambulance sector is involved. However, an overemphasis on demand management outcomes precludes definitive conclusions on the impact of ambulance sector-led public health initiatives on public health outcomes. Future evaluations of public health initiatives should incorporate wider health system perspectives beyond the immediately apparent remit of the ambulance sector.

Abstract Background Despite the close relationship between pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and postpartum weight (PPW), these factors are often studied separately. There are no data characterising longitudinal weight trajectories among pregnant and postpartum women in urban African populations. We examined maternal weight trajectories from pregnancy through to 12 months postpartum, factors associated with higher weight trajectory class membership and associations of weight trajectories with infant growth at 12 months. Methods Data from 989 women were examined for weight trajectories from first antenatal care visit in pregnancy to 12 months postpartum using latent-class growth models. Baseline factors associated with class membership were assessed using multinomial logistic regression. Of the enrolled women, 613 of their infants were assessed for growth at 12 months. Anthropometry measurements for mothers and infants were conducted by a trained study nurse. Associations between maternal weight trajectory class and infant weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) at 12 months of age were analysed using linear regression. Results Four distinct classes of maternal weight trajectories were identified. The classes included consistent low (29%), consistent medium (37%), medium–high (24%) and consistent high (10%) trajectories. Similar to trends observed with medium–high trajectory, baseline factors positively associated with consistent high class membership included age (OR 1.05, 95% CI 1.01–1.09), pre-pregnancy BMI (OR 2.24, 95% CI 1.97–2.56), stage 1 hypertension (OR 3.28, 95% CI 1.68–6.41), haemoglobin levels (OR 1.39, 95% CI 1.11–1.74) and parity (OR 1.39, 95% CI 1.15–1.67); living with HIV (OR 0.47, 95% CI 0.30–0.74) was inversely associated. In adjusted analyses, compared to consistent medium weight trajectory, consistent low weight trajectory (mean difference -0.41, 95% CI -0.71;-0.12) was associated with decreased, and consistent high weight trajectory (mean difference 1.21, 95% CI 0.59–1.83) with increased infant WAZ at 12 months of age. Conclusion Identification of unique longitudinal weight trajectory groupings might inform comprehensive efforts targeted at improving healthy maternal weight and infant outcomes.

Abstract Background Criminal legal system data are one source for measuring some types of firearm-related harms, including those that do not necessarily result in injury or death, but measurement can be hampered by imprecise criminal code statutes. We quantified the degree of misclassification in Washington state criminal codes for measuring firearm-related crime. Findings In this study of individuals aged 18 years and older who were convicted of a misdemeanor in Washington Superior Courts from 1/1/2015 through 12/31/2019, we compared firearm-related charges as measured with criminal codes and with manual review of probable cause documents, considered the gold standard. The sample included 5,390 criminal cases. Of these, 77 (1.4%) were firearm-related as measured with criminal codes and 437 (8.1%) were firearm-related as measured via manual record review. In the sample overall, the sensitivity of criminal codes was 17.6% (95% CI 14.2–21.5%), and negative predictive value (NPV) was 93.2% (95% CI 92.5–93.9%). Sensitivity and NPV were higher for cases with exclusively non-violent charges. For all cases and for cases with any violent crime charge, firearm-related crimes described in probable cause documents most often involved explicit verbal threats, firearm possession, and pointing a firearm at or touching a firearm to someone; almost 10% of all cases involved shooting/discharging a firearm. For cases with exclusively non-violent charges, the most common firearm-related crime was unlawful possession. Conclusions Criminal records can be used for large-scale policy-relevant studies of firearm-related harms, but this study suggests Washington state criminal codes substantially undercount firearm-related crime, especially firearm-related violent crime.

In this study, we have explored the effectiveness of two instructional approaches in the context of the motion of objects falling at terminal speed in the presence of air resistance. We ground these instructional approaches in dual-process theories of reasoning, which assert that human cognition relies on two thinking processes. Dual-process theories suggest multiple possible avenues by which instruction might impact student reasoning. In this paper, we compare two possible instructional approaches: one designed to reinforce the normative approach (improving the outputs of the intuitive process) and another that guides students to reflect on and analyze their initial ideas (supporting the analytic process). The results suggest that for students who have already demonstrated a minimum level of requisite knowledge, instruction that supports analysis of their likely intuitive mental model leads to greater learning benefits in the short term than instruction that focuses solely on providing practice with the normative mindware. These results have implications for the design of instructional materials and help to demonstrate how dual-process theories can be leveraged to explain the success of existing research-based materials.

Abstract Background Disaster medicine is a growing field within the specialty of emergency medicine, but educational training typically focuses on hospital drills or other educational strategies, such as didactics, simulation, or tabletop exercises. With the success of gamification in other medical education applications, we sought to investigate if a novel gamified curricular innovation would lead to improved test performance and confidence in the ability to manage a real mass casualty incident (MCI). Methods This was a prospective observational study of medical students and emergency medicine residents who participated in a 4-h simulation-based competition consisting of 4 unique stations. Each station had learning objectives associated with the content taught. Learners completed a pre-event survey, followed by participation in the competitive gamification event, and subsequently completed a post-event survey. Differences between pre- and post-event responses were matched and analyzed using paired and unpaired t tests for medical knowledge assessments, the Mann–Whitney U test for perceptions of confidence in the ability to manage an MCI event, and descriptive statistics provided on perceptions of the effectiveness of this educational strategy. Results We analyzed data from 49 learners with matched (and unmatched) pre- and post-event survey responses. There was a statistically significant increase in medical knowledge assessment scores in both unmatched group means and available matched data (47 to 69%, p

Abstract Background GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative Research) is a methodological approach to systematically and transparently assess how much confidence decision makers can place in individual review findings from qualitative evidence syntheses. The number of reviews applying GRADE-CERQual is rapidly expanding in guideline and other decision-making contexts. The objectives of this evaluation were, firstly, to describe the uptake of GRADE-CERQual in qualitative evidence synthesis by review authors and, secondly, to assess both reporting of and fidelity to the approach. Methods The evaluation had two parts. Part 1 was a citation analysis and descriptive overview of the literature citing GRADE-CERQual. Authors worked together to code and chart the citations, first by title and abstract and second by full text. Part 2 was an assessment and analysis of fidelity to, and reporting of, the GRADE-CERQual approach in included reviews. We developed fidelity and reporting questions and answers based on the most recent guidance for GRADE-CERQual and then used NVivo12 to document assessments in a spreadsheet and code full-text PDF articles for any concerns that had been identified. Our assessments were exported to Excel and we applied count formulae to explore patterns in the data. We employed a qualitative content analysis approach in NVivo12 to sub-coding all the data illustrating concerns for each reporting and fidelity criteria. Results 233 studies have applied the GRADE-CERQual approach, with most (n = 225, 96.5%) in the field of health research. Many studies (n = 97/233, 41.6%) were excluded from full fidelity and reporting assessment because they demonstrated a serious misapplication of GRADE-CERQual, for example interpreting it as a quality appraisal tool for primary studies or reviews. For the remaining studies that applied GRADE-CERQual to assess confidence in review findings, the main areas of reporting concern involved terminology, labelling and completeness. Fidelity concerns were identified in more than half of all studies assessed. Conclusions GRADE-CERQual is being used widely within qualitative evidence syntheses and there are common reporting and fidelity issues. Most of these are avoidable and we highlight these as gaps in knowledge and guidance for applying the GRADE-CERQual approach.

Background When the Avon Longitudinal Study of Parents and Children (ALSPAC) was planned, it was assumed that the clinical obstetric data would be easily accessible from the newly developed National Health Service computerised ‘STORK’ system. Pilot studies, however, showed that, although fairly accurate in regard to aspects of labour and delivery, it was, at the time (1990-2), inadequate for identifying the full antenatal and postnatal details of clinical complications and treatments of the women in the Study. Methods A scheme was therefore developed to train research staff to find and abstract relevant details from clinical records onto proformas designed for the purpose. Extracting such data proved very time consuming (up to six hours for complicated pregnancies) and consequently expensive. Funding for the enterprise was obtained piecemeal using specific focussed grants to extract data for subsamples of the Study, including a random sample to serve as controls. Results To date, detailed records have been completed for 8369 pregnancies, and a further 5336 (13,705 in total) have complete details on specific prenatal areas, including serial measures of maternal blood pressure, proteinuria and weight. In this Data Note we describe the information abstracted from the obstetric medical records concerning the mother during pregnancy, labour, delivery and the first two weeks of the puerperium. Information abstracted relating to the fetus (including fetal monitoring, presentation, method of delivery) and neonate (signs of asphyxia, resuscitation, treatment and well-being) have been described in a further Data Note. Conclusions These data add depth to ALSPAC concerning ways in which the signs and symptoms, procedures and treatments of the mother prenatally, intrapartum and postnatally, may impact on the long-term health and development of both mother and child. They augment the data collected from the mothers’ questionnaires (described elsewhere) and the ‘STORK’ digital hospital data.

Abstract Introduction Monitoring mother‐infant pairs with HIV exposure is needed to assess the effectiveness of vertical transmission (VT) prevention programmes and progress towards VT elimination. Methods We used routinely collected data on infants with HIV exposure, born May 2018–April 2021 in the Western Cape, South Africa, with follow‐up through mid‐2022. We assessed the proportion of infants diagnosed with HIV at birth (≤7 days), 10 weeks (>1 to 14 weeks) and >14 weeks as proxies for intrauterine, intrapartum/early breastfeeding and late breastfeeding transmission, respectively. We used mixed‐effects Poisson regression to assess factors associated with VT in mothers known with HIV by delivery. Results We included 50,461 infants born to mothers known with HIV by delivery. HIV was diagnosed in 894 (1.8%) infants. Among mothers, 51% started antiretroviral treatment (ART) before and 27% during pregnancy; 17% restarted during pregnancy after ≥6 months interruption; and 6% had no recorded ART during pregnancy. Most pregnancy ART regimens included non‐nucleoside reverse transcriptase inhibitors (83%). Of mothers with available results (90% with viral load [VL]; 70% with CD4), VL nearest delivery was 14 weeks. Among these infants, 0.9%, 0.4% and 1.5% were diagnosed positive at birth, 10 weeks and >14 weeks, respectively. Among infants diagnosed with HIV, 43%, 16% and 41% were diagnosed at these respective time periods. Among mothers with VL

BackgroundOver the past decade, a growing body of scientific evidence has demonstrated that community engagement in research leads to more relevant research, enhances the uptake of research findings, and improves clinical outcomes. Despite the increasing need for the integration of community engagement methodologies into the scientific inquiry, doctoral and master's level competencies in the field of psychiatry often lack dedicated training or coursework on community engagement methodologies. ObjectiveA total of 13 service users, peer support specialists, caregivers of people with mental health challenges, and scientists (with specialties ranging from basic science to implementation science) aged 18 and older participated in remote training on community-based participatory research. Data were collected at baseline, 2 days, and 3 months. MethodsA total of 13 service users, peer support specialists, caregivers of people with mental health challenges, and scientists (with specialties ranging from basic science to implementation science) aged 18 and older participated in remote training on community-based participatory research. Data were collected at baseline, 2 days, and 3 months. ResultsThe pilot study demonstrated that a 3-month remote training on community-based participatory research (“Partnership Academy”) was deemed feasible and acceptable by service users, peer support specialists, caregivers of people with mental health challenges, and scientists. Improvements were found in research engagement and the quality of partnership. A marked increase in distrust in the medical system was also found. Groups submitted 4 grant applications and published 1 peer-reviewed journal at a 3-month follow-up. ConclusionsThis pre- and postpilot study demonstrated it is possible to train groups of service users, peer support specialists, caregivers of people with mental health challenges, and scientists in community-based participatory research. These findings provide preliminary evidence that a 3-month remote training on community-based participatory research (“Partnership Academy”) is feasible, acceptable, and potentially associated with improvements in research engagement as well as the quality of partnership and output, such as manuscripts and grant applications.

Background The development of strategies to better detect and manage patients with multiple long-term conditions requires estimates of the most prevalent condition combinations. However, standard meta-analysis tools are not well suited to synthesising heterogeneous multimorbidity data.Methods We developed a statistical model to synthesise data on associations between diseases and nationally representative prevalence estimates and applied the model to South Africa. Published and unpublished data were reviewed, and meta-regression analysis was conducted to assess pairwise associations between 10 conditions: arthritis, asthma, chronic obstructive pulmonary disease (COPD), depression, diabetes, HIV, hypertension, ischaemic heart disease (IHD), stroke and tuberculosis. The national prevalence of each condition in individuals aged 15 and older was then independently estimated, and these estimates were integrated with the ORs from the meta-regressions in a statistical model, to estimate the national prevalence of each condition combination.Results The strongest disease associations in South Africa are between COPD and asthma (OR 14.6, 95% CI 10.3 to 19.9), COPD and IHD (OR 9.2, 95% CI 8.3 to 10.2) and IHD and stroke (OR 7.2, 95% CI 5.9 to 8.4). The most prevalent condition combinations in individuals aged 15+ are hypertension and arthritis (7.6%, 95% CI 5.8% to 9.5%), hypertension and diabetes (7.5%, 95% CI 6.4% to 8.6%) and hypertension and HIV (4.8%, 95% CI 3.3% to 6.6%). The average numbers of comorbidities are greatest in the case of COPD (2.3, 95% CI 2.1 to 2.6), stroke (2.1, 95% CI 1.8 to 2.4) and IHD (1.9, 95% CI 1.6 to 2.2).Conclusion South Africa has high levels of HIV, hypertension, diabetes and arthritis, by international standards, and these are reflected in the most prevalent condition combinations. However, less prevalent conditions such as COPD, stroke and IHD contribute disproportionately to the multimorbidity burden, with high rates of comorbidity. This modelling approach can be used in other settings to characterise the most important disease combinations and levels of comorbidity.

In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe and characterise the extent of the pandemic, as well as elucidate protection conferred by prior exposure. We conducted repeated cross-sectional serosurveys (July 2020 -November 2021) using residual samples from patients from Cape Town, South Africa, sent for routine laboratory studies for non-COVID-19 conditions. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses. Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.19% (95% confidence interval [CI] 37.23-41.19) in July 2020 to 67.8% (95%CI 66.31-69.25) in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Using COVID-19 hospital admission and death data at the Provincial Health Data Centre, antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19 disease. In low-income communities, where diagnostic testing capacity is often limited, surveillance systems dependent on them will underestimate the true extent of an outbreak. Rapidly conducted seroprevalence studies can play an important role in addressing this.

Homelessness poses complex health obstacles for individuals and communities. Peer and lay health worker programs aim to increase access to health care and improve health outcomes for PEH by building trust and empowering community-based workers. The scope and breadth of peer and lay health worker programs among PEH has not been synthesized. The primary objective of this scoping review is to understand the context (setting, community, condition or disease) encompassing peer and lay health worker programs within the homelessness sector. The secondary objective is to examine the factors that either facilitate or hinder the effectiveness of peer and lay health worker programs when applied to people experiencing homelessness (PEH). We searched CINHAL, Cochrane, Web of Science Core Collection, PsycINFO, Google Scholar and MEDLINE. We conducted independent and duplicate screening of titles and abstracts, and extracted information from eligible studies including study and intervention characteristics, peer personnel characteristics, outcome measures, and the inhibitors and enablers of effective programs. We discuss how peer and lay health work programs have successfully been implemented in various contexts including substance use, chronic disease management, harm reduction, and mental health among people experiencing homelessness. These programs reported four themes of enablers (shared experiences, trust and rapport, strong knowledge base, and flexibility of role) and five themes of barriers and inhibitors (lack of support and clear scope of role, poor attendance, precarious work and high turnover, safety, and mental well-being and relational boundaries). Organizations seeking to implement these interventions should anticipate and plan around the enablers and barriers to promote program success. Further investigation is needed to understand how peer and lay health work programs are implemented, the mechanisms and processes that drive effective peer and lay health work among PEH, and to establish best practices for these programs.

BackgroundAccurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women.MethodsWe compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates.ResultsSelf-reported ART in the 2014 sentinel antenatal survey (n = 1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k = 0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data.ConclusionThis study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency.

Background Risk assessment is a key process when a child or adolescent presents at risk for self-harm or suicide in a mental health crisis or emergency. Risk assessment by a healthcare professional should be included within a biopsychosocial assessment. However, the predictive value of risk-screening tools for self-harm and suicide in children and adolescents is consistently challenged. A review is needed to explore how best to undertake risk assessment and the appropriate role for tools/checklists within the assessment pathway. Aims To map research relating to risk assessment for child and adolescent mental health and to identify features that relate to a successful risk assessment. Objectives To review factors within the clinical encounter that impact upon risk assessments for self-harm and suicide in children and adolescents: to conduct a realist synthesis to understand mechanisms for risk assessment, why they occur and how they vary by context to conduct a mapping review of primary studies/reviews to describe available tools of applicability to the UK. Data sources Databases, including MEDLINE, PsycINFO®, EMBASE, CINAHL, HMIC, Science and Social Sciences Citation Index and the Cochrane Library, were searched (September 2021). Searches were also conducted for reports from websites. Review methods A resource-constrained realist synthesis was conducted exploring factors that impact upon risk assessments for self-harm and suicide. This was accompanied by a mapping review of primary studies/reviews describing risk-assessment tools and approaches used in UK child and adolescent mental health. Following piloting, four reviewers screened retrieved records. Items were coded for the mapping and/or for inclusion in the realist synthesis. The review team examined the validity and limitations of risk-screening tools. In addition, the team identified structured approaches to risk assessment. Reporting of the realist synthesis followed RAMESES guidelines. Results From 4084 unique citations, 249 papers were reviewed and 41 studies (49 tools) were included in the mapping review. Eight reviews were identified following full-text screening. Fifty-seven papers were identified for the realist review. Findings highlight 14 explanations (programme theories) for a successful risk assessment for self-harm and suicide. Forty-nine individual assessment tools/approaches were identified. Few tools were developed in the UK, specifically for children and adolescents. These lacked formal independent evaluation. No risk-screening tool is suitable for risk prediction; optimal approaches incorporate a relationship of trust, involvement of the family, where appropriate, and a patient-centred holistic approach. The objective of risk assessment should be elicitation of information to direct a risk formulation and care plan. Limitations Many identified tools are well-established but lack scientific validity, particularly predictive validity, or clinical utility. Programme theories were generated rapidly from a survey of risk assessment. Conclusions No single checklist/approach meets the needs of risk assessment for self-harm and suicide. A whole-system approach is required, informed by structured clinical judgement. Useful components include a holistic assessment within a climate of trust, facilitated by family involvement. Study registration This study is registered as PROSPERO CRD42021276671. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR135079) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary When young people up to 18 years of age present to health services, having tried to poison themselves, take an overdose or injure themselves, a health professional needs to work out whether this is likely to happen again (risk assessment). Lists of questions or things to look for (risk screening) have proved unreliable. Thorough discussion with the child or teenager may be helpful but takes much time. How can a health professional best use time spent with a young person to prevent further harm and make sure that they get the treatment that they need? This review focuses on young persons who use health services in the UK. Included studies report how health professionals work out whether young people are likely to harm themselves; either how to handle the overall discussion or to use memory aids or checklists (known as tools) to help the discussion. Tools developed in the USA many years ago have not been tested well enough with UK populations. Recent approaches within the UK are used inconsistently. Young persons do not like how they are assessed. Health professionals may use methods that have not been shown to work or use tools differently from how they were designed. This review identified 14 ways to help a young person have valued discussions with a health professional. Health professionals should not simply ‘tick boxes’; tools should help them gain a full picture, including input from other family members. Health professionals should create a trusted relationship where the young person feels respected and heard. Tools should not label someone ‘at risk’ but should support care that reduces the risk of further harm. Health professionals should gather good-quality information that includes asking about thoughts of suicide. Staff should be supported by training, guidance and feedback from experienced colleagues. Scientific summary Background Risk assessment occupies a central place in the management of children and adolescents who present to acute paediatric care settings at risk for self-harm and suicide. A risk assessment should be included within a detailed clinical assessment that includes evaluation of biological, social and psychological factors that are relevant to the child/adolescent. However, current National Institute for Health and Care Excellence (NICE) guidance cautions against using tools or checklists to predict the risk of suicide (risk screening) and against using risk-screening tools to determine subsequent clinical management. Current guidelines for self-harm (NICE. Self-harm: assessment, management and preventing recurrence NICE guideline [NG225] London: 2022) require a risk formulation as part of every psychosocial assessment, to be conducted a mental health professional who has received training in conducting psychosocial assessments and risk formulation. By gaining an accurate picture of the circumstances of a child or adolescent a mental health professional can target a future pathway to appropriate intervention and treatment. However, evidence from surveys suggests that risk assessment continues to serve its historic functions of protecting the community and avoiding claims of negligence rather than being grounded in the welfare of the child/adolescent. As a consequence risk assessment is not currently harnessing its full potential as an intervention to prevent self-harm and suicide. Numerous risk-assessment tools, including some risk-screening tools, are used across different services and information is neither gathered consistently nor completely. In some cases risk-screening tools are viewed as a tick-box exercise or even used for purposes for which the available tools or checklists are not designed. The focus of this review is on the well-being of the children or adolescents themselves and not on the actuarial function of managing risk of harm to others. Despite extensive numbers of tools and approaches, the relationship between risk assessment for self-harm and suicide and treatment intervention and outcome remains unclear. Uncertainties remain, especially around ‘what works, for whom, and why?’ Aims To map the research literature relating to risk assessment for child and adolescent mental health and then to explore published and ‘grey’ literature through a resource-constrained realist-informed review, Objectives To understand the underlying mechanisms for risk assessment for self-harm and suicide, why they occur and how they vary by context and then to review risk-screening tools currently in use in the UK and similar contexts and to explore how different approaches to using these tools impact upon risk assessment for self-harm and suicide within child and adolescent mental health services (CAMHS). Methods Two complementary reviews were conducted: (1) a realist synthesis; and (2) a mapping review of risk-screening tools and risk-assessment approaches (PROSPERO database registration number: CRD42021276671). Realist synthesis Data sources MEDLINE (including Epub Ahead of Print & In-Process), PsycINFO, EMBASE, CINAHL, HMIC, Science and Social Sciences Citation Index and the Cochrane Library. Importantly, the electronic search was complemented by innovative use of the scite tool as well as forward citation searching via Google Scholar and checking for additional relevant articles from reference lists. Screening criteria and study selection Studies that describe the procedures, format and clinical, patient and family perspectives of the risk-assessment process for self-harm and suicide within a UK setting were identified by the review team and prioritised for analysis. Following piloting of eligibility criteria within the team, titles/abstracts were initially screened by one of the review team. Articles identified as potentially relevant were obtained in full text. Attempts were made to identify unpublished literature, for example guidelines and public reports. The full-text literature was screened independently by a single reviewer. Screening was initially inclusive; to minimise threats posed by use of a single reviewer. Assessment of rigour, relevance and richness In line with realist methodology no formal attempt was made to assess the individual study quality of papers included in the synthesis. No papers were excluded on the basis of study quality. Assessment of rigour was determined by study design with weight being placed upon systematic reviews and good-quality comparative research designs. Additional quality markers comprised relevance: privileging studies conducted within child and adolescent mental health; and richness: according detail provided about the risk-assessment process. See Appendix 3 for included papers. Study characteristics The electronic search strategy identified 4084 unique references. Screening based on titles/abstracts identified 149 articles for full-text screening. Screening of full-text articles identified 29 papers to be included in the review. An additional 28 papers were identified through backwards and forwards citation searching, with 57 papers included in the final realist synthesis. Data extraction Study details (including aim, methodology, findings and implications) were extracted by a single reviewer. Details were then mapped against the 14 programme theories. Data synthesis Data were synthesised using a realist synthesis approach. One member of the review team independently generated programme theories from a survey of clinical risk assessment across the UK. Candidate programme theories were considered by the full review team before being completed and finalised. The lead reviewer then used references identified by the team, supplemented by purposive searching and follow-up of references to locate evidence to support, counter or extend the initial interpretations. The 14 programme theories were confirmed as valid propositions and combined within an overarching programme theory. Mapping review Screening criteria The mapping review used the following inclusion criteria: Population and setting: children or adolescents of 18 years of age or younger considered at risk for self-harm or suicide in the UK. Inclusion was unrestricted by setting. Index (or focal) approach or tool: either an overall approach or specific tool used to undertake a detailed clinical assessment; to include evaluation of biological, social and psychological factors relevant to the child/adolescent and relevant to future risks, limited to suicide and self-harm (risk assessment). Comparator approach or tool: any other approach or tool. Outcomes: test performance (sensitivity, specificity, positive predictive value, negative predictive value, reliability, validity), utility and acceptability. Study design: any empirical design. Reviews, systematic or quasi-systematic. Data sources A comprehensive search of MEDLINE, PsycINFO, EMBASE, CINAHL, HMIC, Science and Social Sciences Citation Index and the Cochrane Library was conducted in September 2021. Targeted ‘grey’ literature searches to identify reports/case studies in websites. Study selection Relevant empirical studies and systematic reviews were identified and screened by single review from one of the team to identify reports of approaches and tests used in a UK context for risk assessment for self-harm and suicide. Study characteristics From 4996 citations limited to the UK, 912 duplicates were removed leaving 4084 unique citations. In total, 249 papers were reviewed at full-text and 41 studies were included in the mapping review. For the mapping of reviews 1743 citations were identified; 499 duplicates were removed leaving 1244 unique review citations. Following full-text screening 8 reviews remained. Data extraction and quality assessment Secondary data were extracted on study and population characteristics, tool details and methods of evaluation. No data were available on the resource implications of use of tools or approaches. However, mention was made of the prohibitive time required to conduct a thorough biopsychosocial assessment within the context of an emergency or crisis. Quality appraisal was conducted independently using the Mixed Methods Appraisal Tool (MMAT) tool, and disagreements were resolved through discussion. Data synthesis Findings from the mapping review of tools and approaches were presented using narrative synthesis, using textual and tabular presentation. Studies were not sufficiently homogeneous to permit meta-analysis. Public and patient involvement The research team worked with the standing public and patient advisory group for the Sheffield Evidence Synthesis Centre. The group regularly feeds into the conduct and dissemination of evidence syntheses commissioned by the National Institute for Health Research, providing perspectives on contextual factors and key messages to ensure benefit and relevance for service users. Results Results from the realist synthesis Fourteen programme theories were identified and tested. These included 11 propositions relating to the conduct of risk assessment for self-harm and suicide and a further three propositions relating to what is considered unhelpful. Candidate Programme Theory Components Identified from the Literature Through this preliminary review, successful interventions are considered to require the following: IF risk-assessment approaches are simple, accessible and part of a wider assessment process THEN staff are able to generate standardised, informative and clinically useful assessments LEADING TO appropriate use of support and services. IF clinical staff focus clinical risk-assessment processes on building relationships THEN clinicians and adolescents trust each other LEADING TO frank and open communication within the clinical encounter. IF the emphasis of clinical risk-assessment processes is on gathering good-quality information on (i) the current situation, (ii) past history and (iii) social factors THEN staff use information to inform a collaborative approach to management LEADING TO coordinated and integrated care. IF staff are comfortable asking young patients about suicidal thoughts THEN young service users share relevant information concerning their circumstances LEADING TO an appropriate service response. IF risk-assessment processes are conducted consistently across mental health services THEN the quality of response to young service users does not depend upon each individual contact LEADING TO the availability of consistent information across services. IF staff are trained in how to assess, formulate and manage risk, including appropriate referral THEN staff feel equipped to manage the risks for children and adolescents who present to health services LEADING TO an emphasis on positive risk taking. IF staff are supported by on-going supervision THEN staff feel able to deliver a consistent approach to risk assessment LEADING TO a reduction in adverse events. IF families and carers are involved in the assessment process THEN families and carers are given an opportunity to express their views on potential risk LEADING TO a collaboratively developed risk-management plan. IF mental health staff communicate risk assessments with primary care THEN young people are directed to appropriate care LEADING TO successful health outcomes. IF the management of risk is personal and individualised THEN young people don’t see their care as ‘protocol driven’ and won’t feel alienated LEADING TO their engagement with care. IF organisations involved in risk assessment utilise a whole-system approach THEN this strengthens the standards of care for everyone, LEADING TO the safe management of supervision, delegation and onward referral. Three ‘counter programme theories’ relate to how risk assessment might result in unintended consequences: IF staff view risk-assessment tools as a way of predicting future suicidal behaviour THEN staff incorrectly interpret individual levels of need for care LEADING TO inappropriate use of restrictive practices, such as involuntary hospitalisation, restraint, sedation and seclusion (for the service user). IF clinicians use risk-screening tools and scales in isolation within the risk-assessment process THEN treatment decisions are determined by a score LEADING TO incorrect interpretation of individual need for care and inappropriate utilisation of CAMHS (for the service). IF staff develop tools for risk assessment locally THEN checklists and scales lack formal psychometric evaluation LEADING TO limited clinical utility of tools for risk assessment and unnecessarily restrictive treatment options. Exploring the 11 positive propositions helped in the identification of five particularly useful features include the following: (1) incorporation of tools within wider standardised and consistent assessment processes; (2) trusted relationships that encourage clear and open communication, including family involvement; (3) good-quality information within a personalised and individualised approach; (4) appropriate training and supervision; and (5) appropriate interagency communication and referral networks, within a whole-system approach. Similarly exploration of the three negative propositions helped in the identification of three negative features: (1) misuse of risk-assessment tools for prediction; (2) use of tools in isolation, typically within a ‘scoring’ approach; and (3) development of local tools with little formal validation. Results from the mapping review A total of 49 reports of tools or approaches to assessing the risk of self-harm and suicidality among children or adolescents were identified from the reviews (n = 8) or original studies (n = 41). Our analysis extended the 29 assessment tools included in a previous scoping review (Carter T, Walker GM, Aubeeluck A, Manning JC. Assessment tools of immediate risk of self-harm and suicide in children and young people: a scoping review. J Child Health Care 2019;23:178–99.); adding two recent tools (Manning JC, Walker GM, Carter T, Aubeeluck A, Witchell M, Coad J; The CYP-MH SAT study group. Children and Young People-Mental Health Safety Assessment Tool (CYP-MH SAT) study: protocol for the development and psychometric evaluation of an assessment tool to identify immediate risk of self-harm and suicide in children and young people (10-19 years) in acute paediatric hospital settings. BMJ Open 2018;8:e020964. 20180412; Vrouva I, Fonagy P, Fearon PR, Roussow T. The risk-taking and self-harm inventory for adolescents: development and psychometric evaluation. Psychol Assess 2010;22:852–65.) and expanding beyond formal tools to include overall approaches. We included tools previously included in the scoping review (Carter et al. 2019) where used in a UK context and with a primary focus on suicide. Tools varied in length, response and scoring format, age ranges and degree of psychometric testing (Carter et al. 2019). In particular, tools lacked predictive validity. Most assessments were tested across broad age ranges, and so lack sensitivity to the age groups of particular interest to this review. The relative lack of tools for children, as opposed to adolescents, is noticeable. Tools were subject to limited psychometric testing, and no single tool was valid or reliable for use with children presenting in mental health crisis to non-mental health settings (Carter et al. 2019). Implications for healthcare practice and service delivery A thorough biopsychosocial assessment offers a holistic approach to assessment across many factors including, but not focused upon, risk of self-harm and suicide. Such an assessment requires that service managers identify time for this interaction, particularly for front-line staff. Checklists may help in demonstrating compliance with national standards and protocols but, ultimately, may threaten the relationship between health professional and young person or obscure a full understanding of patient risk. Findings from these reviews confirm recommendations made by NICE guidance with regard to the misuse of risk-assessment tools for prediction of suicide risk and for determining clinical management. Variability in suicidality, even over short periods of time, make suicide risk prediction particularly problematic. Checklist approaches are static, not dynamic, and therefore unlikely to meet the needs for ongoing risk assessment. Attention should focus on improving the quality of the risk-assessment process, perhaps learning from successful training, supervision and quality improvement initiatives. Recommendations for research Further studies evaluating the utility of specific risk-screening tools and instruments are not warranted, although additional evaluations of risk-assessment processes would benefit from further qualitative insights. Such evaluations could provide an accurate picture of what assessment processes are being used and the clinical value ascribed to each component according to the principles of psychosocial assessment. Further research is required to evaluate the value to young persons, health professionals and health services of a complete and holistic assessment, not simply provision of an alternative tool. An evaluated approach to overall assessment could then be used to support safety management decisions across acute paediatric care settings. In particular, health systems and organisational leadership initiatives could benefit from further close examination of how theoretical tensions between risk minimisation and patient-centred care are enacted at a practical and operational level. Trial registration This study is registered as PROSPERO CRD42021276671. Funding This award was funded by the National Institute of Healthcare Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR135079) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.