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Summary: Background: Integration of paediatric health services across primary and secondary care holds great promise for the management of chronic conditions, yet limited evidence exists on its cost-effectiveness. This paper reports the results of the economic evaluation of the Children and Young People's Health Partnership (CYPHP) aimed at integrating care for children with common chronic conditions (asthma, eczema, and constipation). Methods: Cost-effectiveness, cost-utility and cost-benefit analyses were conducted alongside a pragmatic cluster randomised controlled trial involving 97,970 children in 70 general practices in South London, including 1,731 participants with asthma, eczema and or constipation with self-reported health-related quality of life measures. Analyses considered the National Health Service (NHS)/Personal Social Service (PSS) and societal perspectives, and time horizons of 6 and 12-months. Costs included intervention delivery, health service use (primary and secondary care), referrals to social services, and time lost from work and school. Health outcomes were measured through the Paediatric Quality of Life Inventory, the Child Health Utility 9-Dimensions, and monetarised benefit combining Quality-Adjusted Life Years (QALYs) for children and parental mental well-being. Results present incremental cost-effectiveness ratios (ICERs), compared to a willingness to pay threshold (WTP) of £20,000–30,000/QALY, and net monetary benefit (NMB), with deterministic sensitivity analyses. Findings: At 6 months, from the NHS/PSS perspective, CYPHP is not cost-effective (ICER = £721,000/QALY), and this result holds at 12 months (ICER = £45,586/QALY). However, under the societal perspective CYPHP falls within WTP thresholds (ICER = £22,966/QALY), with a probability of being cost-effective between 0.4 and 0.6 at £20,000/QALY and £30,000/QALY, respectively. The cost-benefit analysis yields a positive NMB of CYPHP at 12 months £109 under the societal perspective, with similar probabilistic results. Interpretation: CYPHP was not cost-effective at 6 months or under the NHS/PSS perspective. Trends towards cost-effectiveness are observed once a longer time horizon and a more inclusive perspective on effects is considered. Further research beyond 12 months is needed as the model becomes firmly embedded into the paediatric healthcare delivery system. Funding: This research was funded by Guy's and St Thomas' Charity, Lambeth and Southwark Clinical Commissioning Groups. The funders had no role in the writing of the manuscript, decision to submit it for publication, or any other process involved in the research.

Point- and non-point source nutrients are likely to have different ecological impacts in receiving waters, due to differences in the concentration and proportions of nutrient fractions. However, the direct comparison of their ecological impacts in receiving waters has barely been quantified. We undertook algal bioassays with algal communities from river sites and showed that there was a photosynthetic yield (Fv/Fm) response to nutrient enrichment when river nutrient concentrations were relatively low, but not at higher nutrient concentrations. To combat this variability in the photosynthetic state of algae, we developed a standardized algal bioassay (3-day), using a cultured species of algae which was starved of nitrogen, to compare the photosynthetic response to three nitrogen sources: treated wastewater, aquaculture farm discharges, and soil erosion-derived nutrient sources. This study showed that the nutrient parameter that had the highest correlation with algal photosynthetic response was total dissolved nitrogen (TDN), i.e., the sum of dissolved inorganic and organic nitrogen, rather than dissolved inorganic nitrogen alone. This was true across all three nutrient sources (R2 = 0.58–0.78). Additionally, the same concentrations of TDN from soil erosion-derived and aquaculture samples resulted in a significantly higher algal photosynthetic response, compared to the treated wastewater. This indicates that TDN from soils and aquaculture farms was significantly more bioavailable to the cultured algae than treated wastewater. When a range of parameters were correlated with algal responses, organic and inorganic nutrients, and organic carbon were the parameters that had the highest explanatory power for soil erosion-derived and aquaculture samples (R2 = 0.75–0.87). The importance of organic compounds in these equations points to the potential of microbial transformation of organic nutrients into more bioavailable forms during the 3-day bioassay. This highlights the need to understand the relationship between algal and microbial communities in natural systems for nutrient source impact assessment. This study provides an improved understanding and metrics for comparing the algal growth response to different nutrient sources.

Pressurized metered-dose inhalers (pMDIs) deliver life-saving medications to patients with respiratory conditions and are the most used inhaler delivery device globally. pMDIs utilize a hydrofluoroalkane (HFA), also known as an F-gas, as a propellant to facilitate the delivery of medication into the lungs. Although HFAs have minimal impact on ozone depletion, their global warming potential (GWP) is more than 1,000 times higher than CO2, bringing them in scope of the F-Gas Regulation in the European Union (EU). The pharmaceutical industry is developing solutions, including a near-zero GWP “next-generation propellant,” HFO-1234ze(E). At the same time, the EU is also evaluating a restriction on per-and polyfluoroalkyl substances (PFAS) under the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation. Trifluoroacetic acid (TFA) is a persistent PFAS and a potential degradation product of HFO-1234ze(E). We quantified yield of TFA from HFO-1234ze(E) using a computational model under Europe-relevant atmospheric conditions. The modeling suggests that most HFO-1234ze(E) degrades into formyl fluoride within 20 days (≥85%) even at the highest examined altitude. These results suggest that TFA yield from HFO-1234ze(E) varies between 0%–4% under different atmospheric conditions. In 2022, France represented the highest numbers of pMDI units sold within the EU, assuming these pMDIs had HFO-1234ze(E) as propellant, we estimate an annual rainwater TFA deposition of ∼0.025 μg/L. These results demonstrate negligible formation of TFA as a degradation product of HFO-1234ze(E), further supporting its suitability as a non-persistent, non-bioaccumulative, and non-toxic future propellant for pMDI devices to safeguard access for patients to these essential medicines.

Abstract Background Scales are mineralised exoskeletal structures that are part of the dermal skeleton. Scales have been mostly lost during evolution of terrestrial vertebrates whilst bony fish have retained a mineralised dermal skeleton in the form of fin rays and scales. Each scale is a mineralised collagen plate that is decorated with both matrix-building and resorbing cells. When removed, an ontogenetic scale is quickly replaced following differentiation of the scale pocket-lining cells that regenerate a scale. Processes promoting de novo matrix formation and mineralisation initiated during scale regeneration are poorly understood. Therefore, we performed transcriptomic analysis to determine gene networks and their pathways involved in dermal scale regeneration. Results We defined the transcriptomic profiles of ontogenetic and regenerating scales of zebrafish and identified 604 differentially expressed genes (DEGs). These were enriched for extracellular matrix, ossification, and cell adhesion pathways, but not in enamel or dentin formation processes indicating that scales are reminiscent to bone. Hypergeometric tests involving monogenetic skeletal disorders showed that DEGs were strongly enriched for human orthologues that are mutated in low bone mass and abnormal bone mineralisation diseases (P

Osmotic compensation by electroneutral ion transport buffers TORC1-mediated changes in the cytosolic proteome, and maintains intracellular homeostasis and cell volume over the circadian cycle. Here, the authors find such ion content changes drive daily rhythms in cardiomyocyte electrical activity.

Modern mammals are endothermic, but it has not been clear when this type of metabolism evolved. Here, Newham et al. analyse tooth and bone structure in Early Jurassic stem-mammal fossils to estimate lifespan and blood flow rates, which inform about basal and maximum metabolic rates, respectively, and show these stem-mammals had metabolic rates closer to modern ectothermic reptiles than to endothermic mammals.

Abstract Background International data suggest that living in a rural area is associated with an increased risk of perinatal mental illness. This study tested the association between rurality and risk for two mental illnesses prevalent in perinatal women - depression and anxiety. Methods Using a cross-sectional design, antenatal and postnatal women were approached by healthcare professionals and through other networks in a county in Northern England (UK). After providing informed consent, women completed a questionnaire where they indicated their postcode (used to determine rural-urban status) and completed three outcome measures: the Edinburgh Postnatal Depression Scale (EPDS), the Whooley questions (depression measure), and the Generalised Anxiety Disorder 2-item (GAD-2). Logistic regression models were developed, both unadjusted and adjusted for potential confounders, including socioeconomic status, social support and perinatal stage. Results Two hundred ninety-five participants provided valid data. Women in rural areas (n = 130) were mostly comparable to their urban counterparts (n = 165). Risk for depression and/or anxiety was found to be higher in the rural group across all models: unadjusted OR 1.67 (0.42) 95% CI 1.03 to 2.72, p = .038. This difference though indicative did not reach statistical significance after adjusting for socioeconomic status and perinatal stage (OR 1.57 (0.40), 95% CI 0.95 to 2.58, p = .078), and for social support (OR 1.65 (0.46), 95% CI 0.96 to 2.84, p = .070). Conclusions Data suggested that women in rural areas were at higher risk of depression and anxiety than their urban counterparts. Further work should be undertaken to corroborate these findings and investigate the underlying factors. This will help inform future interventions and the allocation of perinatal services to where they are most needed.

Abstract Background Universal child health services (UCHS) provide an important pragmatic platform for the delivery of universal and targeted interventions to support families and optimize child health outcomes. We aimed to identify brief, evidence-based interventions for common health and developmental problems that could be potentially implemented in UCHS. Methods A restricted evidence assessment (REA) of electronic databases and grey literature was undertaken covering January 2006 to August 2019. Studies were eligible if (i) outcomes related to one or more of four areas: child social and emotional wellbeing (SEWB), infant sleep, home learning environment or parent mental health, (ii) a comparison group was used, (iii) universal or targeted intervention were delivered in non-tertiary settings, (iv) interventions did not last more than 4 sessions, and (v) children were aged between 2 weeks postpartum and 5 years at baseline. Results Seventeen studies met the eligibility criteria. Of these, three interventions could possibly be implemented at scale within UCHS platforms: (1) a universal child behavioural intervention which did not affect its primary outcome of infant sleep but improved parental mental health, (2) a universal screening programme which improved maternal mental health, and (3) a targeted child behavioural intervention which improved parent-reported infant sleep problems and parental mental health. Key lessons learnt include: (1) Interventions should impart the maximal amount of information within an initial session with future sessions reinforcing key messages, (2) Interventions should see the family as a holistic unit by considering the needs of parents with an emphasis on identification, triage and referral, and (3) Brief interventions may be more acceptable for stigmatized topics, but still entail considerable barriers that deter the most vulnerable. Conclusions Delivery and evaluation of brief evidence-based interventions from a UCHS could lead to improved maternal and child health outcomes through a more responsive and equitable service. We recommend three interventions that meet our criteria of “best bet” interventions.

Evidence suggests that mental health interventions are more effective when they consider the whole context of schools; addressing the needs of all students, their families, and staff; otherwise known as a whole-school approach (WSA). The UK Government is piloting WSAs to transform mental health and wellbeing by locating educational mental health practitioners in educational settings across England. This study aims to develop a ‘bottom-up’ understanding of the contextual factors and mechanisms that underlie WSAs in Trailblazer schools in the North East and North Cumbria, to gain insight into the facilitators and barriers of delivering a WSA, and optimal evaluation methods. To undertake a realist evaluation, we included the generation of initial programme theories from existing academic literature and policy documents; ‘theory gleaning’ interviews with NHS/local authority stakeholders, Trailblazer staff and school senior leaders; refining and development of theories; and individual interviews and focus groups with pupils, parent/carers and school staff. The findings will enable Trailblazer partners to better understand how their WSAs to mental health contain the essential components for transformation in schools in the region. This will contribute to the embedding of continuous evaluation into regional Trailblazers’ practice for participating schools, for subsequent annual waves and producing relevant findings for non-Trailblazer schools. Complementing the national evaluation of all 25 Wave 1 Trailblazer pilot sites, this study will generate an explanatory theoretical account of how to optimally design, implement and evaluate WSAs by exploring the contextual factors associated with implementation of WSAs.

The bone-cartilage unit (BCU) is a universal feature in diarthrodial joints, which is mechanically-graded and subjected to shear and compressive strains. Changes in the BCU have been linked to osteoarthritis (OA) progression. Here we report existence of a physiological internal strain gradient (pre-strain) across the BCU at the ultrastructural scale of the extracellular matrix (ECM) constituents, specifically the collagen fibril. We use X-ray scattering that probes changes in the axial periodicity of fibril-level D-stagger of tropocollagen molecules in the matrix fibrils, as a measure of microscopic pre-strain. We find that mineralized collagen nanofibrils in the calcified plate are in tensile pre-strain relative to the underlying trabecular bone. This behaviour contrasts with the previously accepted notion that fibrillar pre-strain (or D-stagger) in collagenous tissues always reduces with mineralization, via reduced hydration and associated swelling pressure. Within the calcified part of the BCU, a finer-scale gradient in pre-strain (0.6% increase over ~50μm) is observed. The increased fibrillar pre-strain is linked to prior research reporting large tissue-level residual strains under compression. The findings may have biomechanical adaptative significance: higher in-built molecular level resilience/damage resistance to physiological compression, and disruption of the molecular-level pre-strains during remodelling of the bone-cartilage interface may be potential factors in osteoarthritis-based degeneration.

Inorganic nanoparticles have long been applied as catalysts and nanozymes with exceptional rate constants arising from their large surface areas. While it is understood that high surface area-to-volume ratios and low average atomic coordination are responsible for their exceptional catalytic properties, these facets remain under exploited in the design of gold nanoparticle catalysts and nanozymes. Here we have developed 3D, 2D, and quasi-1D gold nanoparticles for use as catalysts in reducing 4-nitrophenol by sodium borohydride. Each morphology was characterised with transmission electron microscopy and UV–vis absorption spectroscopy, while the highest catalytic activity was achieved when the perimeter-to-surface area, or amount of ‘edge’, was maximised. The particles were then applied as nanozymes in modular nano-composite hydrogels. Independent hydrogel tiles containing either the substrate or catalyst were bonded in stacks, which allowed reagent transport across their interface for the colourimetric detection of hydrogen peroxide. This work presents novel insight into the catalytic activity of low-dimension nanoparticles and their potential application in nanozyme-based diagnostic devices.

Abstract Background To meet emergent healthcare needs, innovations need to be implemented into routine clinical practice. Community pharmacy is increasingly considered a setting through which innovations can be implemented to achieve positive service and clinical outcomes. Small-scale pilot programmes often need scaled up nation-wide to affect population level change. This systematic review aims to identify facilitators and barriers to the national implementation of community pharmacy innovations. Methods A systematic review exploring pharmacy staff perspectives of the barriers and facilitators to implementing innovations at a national level was conducted. The databases Medline, EMBASE, PsycINFO, CINAHL, and Open Grey were searched and supplemented with additional search mechanisms such as Zetoc alerts. Eligible studies underwent quality assessment, and a directed content analysis approach to data extraction was conducted and aligned to the Consolidated Framework for Implementation Research (CFIR) to facilitate narrative synthesis. Results Thirty-nine studies were included: 16 were qualitative, 21 applied a questionnaire design, and 2 were mixed methods. Overarching thematic areas spanning across the CFIR domains were pharmacy staff engagement (e.g. their positive and negative perceptions), operationalisation of innovations (e.g. insufficient resources and training), and external engagement (e.g. the perceptions of patients and other healthcare professionals, and their relationship with the community pharmacy). Study participants commonly suggested improvements in the training offered, in the engagement strategies adopted, and in the design and quality of innovations. Conclusions This study’s focus on national innovations resulted in high-level recommendations to facilitate the development of successful national implementation strategies. These include (1) more robust piloting of innovations, (2) improved engagement strategies to increase awareness and acceptance of innovations, (3) promoting whole-team involvement within pharmacies to overcome time constraints, and (4) sufficient pre-implementation evaluation to gauge acceptance and appropriateness of innovations within real-world settings. The findings highlight the international challenge of balancing the professional, clinical, and commercial obligations within community pharmacy practice. A preliminary theory of how salient factors influence national implementation in the community pharmacy setting has been developed, with further research necessary to understand how the influence of these factors may differ within varying contexts. Trial registration A protocol for this systematic review was developed and uploaded onto the PROSPERO international prospective register of systematic reviews database (Registration number: CRD42016038876).

ABSTRACT Bone homeostasis is a dynamic, multicellular process that is required throughout life to maintain bone integrity, prevent fracture, and respond to skeletal damage. WNT16 has been linked to bone fragility and osteoporosis in human genome wide‐association studies, as well as the functional hematopoiesis of leukocytes in vivo. However, the mechanisms by which WNT16 promotes bone health and repair are not fully understood. In this study, CRISPR‐Cas9 was used to generate mutant zebrafish lacking Wnt16 (wnt16−/−) to study its effect on bone dynamically. The wnt16 mutants displayed variable tissue mineral density (TMD) and were susceptible to spontaneous fractures and the accumulation of bone calluses at an early age. Fractures were induced in the lepidotrichia of the caudal fins of wnt16−/− and WT zebrafish; this model was used to probe the mechanisms by which Wnt16 regulates skeletal and immune cell dynamics in vivo. In WT fins, wnt16 expression increased significantly during the early stages for bone repair. Mineralization of bone during fracture repair was significantly delayed in wnt16 mutants compared with WT zebrafish. Surprisingly, there was no evidence that the recruitment of innate immune cells to fractures or soft callus formation was altered in wnt16 mutants. However, osteoblast recruitment was significantly delayed in wnt16 mutants postfracture, coinciding with precocious activation of the canonical Wnt signaling pathway. In situ hybridization suggests that canonical Wnt‐responsive cells within fractures are osteoblast progenitors, and that osteoblast differentiation during bone repair is coordinated by the dynamic expression of runx2a and wnt16. This study highlights zebrafish as an emerging model for functionally validating osteoporosis–associated genes and investigating fracture repair dynamically in vivo. Using this model, it was found that Wnt16 protects against fracture and supports bone repair, likely by modulating canonical Wnt activity via runx2a to facilitate osteoblast differentiation and bone matrix deposition. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Cementum, the tissue attaching mammal tooth roots to the periodontal ligament, grows appositionally throughout life, displaying a series of circum-annual incremental features. These have been studied for decades as a direct record of chronological lifespan. The majority of previous studies on cementum have used traditional thin-section histological methods to image and analyse increments. However, several caveats have been raised in terms of studying cementum increments in thin-sections. Firstly, the limited number of thin-sections and the two-dimensional perspective they impart provide an incomplete interpretation of cementum structure, and studies often struggle or fail to overcome complications in increment patterns that complicate or inhibit increment counting. Increments have been repeatedly shown to both split and coalesce, creating accessory increments that can bias increment counts. Secondly, identification and counting of cementum increments using human vision is subjective, and it has led to inaccurate readings in several experiments studying individuals of known age. Here, we have attempted to optimise a recently introduced imaging modality for cementum imaging; X-ray propagation-based phase-contrast imaging (PPCI). X-ray PPCI was performed for a sample of rhesus macaque (Macaca mulatta) lower first molars (n = 10) from a laboratory population of known age. PPCI allowed the qualitative identification of primary/annual versus intermittent secondary increments formed by splitting/coalescence. A new method for semi-automatic increment counting was then integrated into a purpose-built software package for studying cementum increments, to count increments in regions with minimal complications. Qualitative comparison with data from conventional cementochronology, based on histological examination of tissue thin-sections, confirmed that X-ray PPCI reliably and non-destructively records cementum increments (given the appropriate preparation of specimens prior to X-ray imaging). Validation of the increment counting algorithm suggests that it is robust and provides accurate estimates of increment counts. In summary, we show that our new increment counting method has the potential to overcome caveats of conventional cementochronology approaches, when used to analyse three-dimensional images provided by X-ray PPCI.

BackgroundPregnancy is a teachable moment for behaviour change. Multiple guidelines target pregnant women for behavioural intervention. This systematic review of systematic reviews reports the effectiveness of interventions delivered during pregnancy on changing women's behaviour across multiple behavioural domains.MethodsFourteen databases were searched for systematic reviews published from 2008, reporting interventions delivered during pregnancy targeting smoking, alcohol, diet or physical activity as outcomes. Data on behaviour change related to these behaviours are reported here. Quality was assessed using the JBI critical appraisal tool for umbrella reviews. Consistency in intervention effectiveness and gaps in the evidence-base are described.ResultsSearches identified 24,388 results; 109 were systematic reviews of behaviour change interventions delivered in pregnancy, and 36 reported behavioural outcomes. All smoking and alcohol reviews identified reported maternal behaviours as outcomes (n = 16 and 4 respectively), whereas only 16 out of 89 diet and/or physical activity reviews reported these behaviours. Most reviews were high quality (67%) and interventions were predominantly set in high-income countries. Overall, there was consistent evidence for improving healthy diet behaviours related to increasing fruit and vegetable consumption and decreasing carbohydrate intake, and fairly consistent evidence for increase in some measures of physical activity (METs and VO2 max) and for reductions in fat intake and smoking during pregnancy. There was a lack of consistent evidence across reviews reporting energy, protein, fibre, or micronutrient intakes; smoking cessation, abstinence or relapse; any alcohol behaviours.ConclusionsThe most consistent review evidence is for interventions improving dietary behaviours during pregnancy compared with other behaviours, although the majority of diet reviews prioritised reporting health-related outcomes over behavioural outcomes. Heterogeneity between reported behaviour outcomes limits ability to pool data in meta-analysis and more consistent reporting is needed. Limited data are available for alcohol interventions in pregnancy or interventions in low- or middle-income-countries, which are priority areas for future research.

Background: To help alleviate the global pressure on primary care, there has been an increase in the number of clinical pharmacists within primary care. Educational resources are necessary to support this workforce and their development within this role. An educational resource package was developed in Scotland to support the General Practice Clinical Pharmacists (GPCPs), containing a hard copy Competency and Capability Framework (CCF), an online platform (TURAS) and both clinical and educational supervisors in 2016. Objective: To examine the implementation of a competency-based educational resource package through the exploration of pharmacists’ perceptions of its adoption, acceptability, appropriateness, and feasibility. Methods: Participants were GPCPs who had been part of a national training event between 2016 and 2018. The participants were given the opportunity to complete an online questionnaire or a semi-structured telephone interview. Both data collection tools were based on Proctor’s model of implementation outcomes: adoption, acceptability, appropriateness and feasibility. Areas covered included GPCPs’ perceptions and level of adoption of the educational resource package developed to support them in their role. Results: Of a potential 164 participants, 52 (31.7%) completed the questionnaire and 12 (7.3%) completed the interview. GPCPs indicated widespread adoption and were accepting of the resources; however, it was suggested that its value was undermined, as it was not associated with a qualification. The appropriateness and feasibility of the resources depended on GPCPs’ individual situation (including current role, previous job experience, time available, support received from peers and supervisors, and perceptions of resources available). Conclusions: The suitability of the CCF was evidenced by participants’ adoption and acceptance of the resource, indicating the necessity of a competence-based framework to support the GPCPs’ role. However, its suitability was hindered in terms of varied perceptions of appropriateness and feasibility. Despite the limited sample size, the results indicate that the value of these resources should be promoted across primary care; nevertheless further facilitation is required to allow GPCPs to fully engage with the resources.

Abstract The discovery of large, complex, internal canals within the rostra of fossil reptiles has been linked with an enhanced tactile function utilised in an aquatic context, so far in pliosaurids, the Cretaceous theropod Spinosaurus, and the related spinosaurid Baryonyx. Here, we report the presence of a complex network of large, laterally situated, anastomosing channels, discovered via micro-focus computed tomography (μCT), in the premaxilla and maxilla of Neovenator, a mid-sized allosauroid theropod from the Early Cretaceous of the UK. We identify these channels as neurovascular canals, that include parts of the trigeminal nerve; many branches of this complex terminate on the external surfaces of the premaxilla and maxilla where they are associated with foramina. Neovenator is universally regarded as a ‘typical’ terrestrial, predatory theropod, and there are no indications that it was aquatic, amphibious, or unusual with respect to the ecology or behaviour predicted for allosauroids. Accordingly, we propose that enlarged neurovascular facial canals shouldn’t be used to exclusively support a model of aquatic foraging in theropods and argue instead that an enhanced degree of facial sensitivity may have been linked with any number of alternative behavioural adaptations, among them defleshing behaviour, nest selection/maintenance or social interaction.

James J Newham,1 Justin Presseau,2 Karen Heslop-Marshall,1 Sian Russell,1 Oladapo J Ogunbayo,1 Paul Netts,3 Barbara Hanratty,1 Eileen Kaner1 1Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK; 2Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, Ottawa, ON, Canada; 3NHS Newcastle Gateshead Clinical Commissioning Group, Newcastle upon Tyne, UK Background: Self-management interventions (SMIs) are recommended for individuals with COPD to help monitor symptoms and optimize health-related quality of life (HRQOL). However, SMIs vary widely in content, delivery, and intensity, making it unclear which methods and techniques are associated with improved outcomes. This systematic review aimed to summarize the current evidence base surrounding the effectiveness of SMIs for improving HRQOL in people with COPD.Methods: Systematic reviews that focused upon SMIs were eligible for inclusion. Intervention descriptions were coded for behavior change techniques (BCTs) that targeted self-management behaviors to address 1) symptoms, 2) physical activity, and 3) mental health. Meta-analyses and meta-regression were used to explore the association between health behaviors targeted by SMIs, the BCTs used, patient illness severity, and modes of delivery, with the impact on HRQOL and emergency department (ED) visits.Results: Data related to SMI content were extracted from 26 randomized controlled trials identified from 11 systematic reviews. Patients receiving SMIs reported improved HRQOL (standardized mean difference =−0.16; 95% confidence interval [CI] =−0.25, −0.07; P=0.001) and made fewer ED visits (standardized mean difference =−0.13; 95% CI =−0.23, −0.03; P=0.02) compared to patients who received usual care. Patients receiving SMIs targeting mental health alongside symptom management had greater improvement of HRQOL (Q=4.37; P=0.04) and fewer ED visits (Q=5.95; P=0.02) than patients receiving SMIs focused on symptom management alone. Within-group analyses showed that HRQOL was significantly improved in 1) studies with COPD patients with severe symptoms, 2) single-practitioner based SMIs but not SMIs delivered by a multidisciplinary team, 3) SMIs with multiple sessions but not single session SMIs, and 4) both individual- and group-based SMIs.Conclusion: SMIs can be effective at improving HRQOL and reducing ED visits, with those targeting mental health being significantly more effective than those targeting symptom management alone. Keywords: self-management, emergency department visits, behavior change techniques, COPD, mental health, meta-analysis

Introduction Children and young people (CYP) in many high-income settings have poor healthcare outcomes, especially those with long-term conditions (LTCs). Emergency and outpatient hospital service use is increasing unsustainably. To address these problems, the Children and Young People’s Health Partnership (CYPHP) has developed and is evaluating an integrated model of care as part of a health systems strengthening programme across two boroughs of London, UK that are characterised by mixed ethnic populations and varying levels of deprivation. The CYPHP Evelina London model of care comprises proactive case-finding and triage, specialist clinics and transformative education and training for professionals working with CYP. Services are delivered by multidisciplinary health teams with an emphasis on increased coordination across primary, community and hospital settings and integration of physical and mental healthcare that accounts for the CYP’s social context.Methods and analysis The phased roll out of the CYPHP Evelina London model allows an opportunistic population-based evaluation using a cluster randomised controlled trial design. Seventy general practices across two London boroughs, grouped into 23 clusters, were randomised to provide either the CYPHP model of care (n=11) or enhanced usual care (n=12).The evaluation will measure the impact of the CYPHP Evelina London model of care on child and parent health and well-being, healthcare quality and health service use up to 2 years postimplementation. A population-level evaluation will use routinely collected pseudonymised healthcare data to conduct a service-use analysis for all CYP registered with a participating general practice (n=~90 000) with the rate of non-elective admissions as the primary outcome. We will seek consent from a subset of this population, with specific conditions (target n=2138) to assess the impact on patient-reported outcomes using the Paediatric Quality of Life Inventory (PedsQL) and Warwick-Edinburgh Mental Well-Being Scale (WEBWMS) as, respectively, the child- and parent-related primary outcomes.Ethics and dissemination Ethics approval obtained from South West-Cornwall & Plymouth Research Ethics Committee. Results will be submitted for publication in peer-reviewed journals. Findings will be generalisable to community-based models of care, especially in urban settings. Our process evaluation will identify barriers and enablers of implementation and delivery of care salient to the context and condition.Trial registration number NCT03461848; Pre-results.

Introduction Children and young people (CYP) in the UK have poor health outcomes, and there is increasing emergency department and hospital outpatient use. To address these problems in Lambeth and Southwark (two boroughs of London, UK), the local Clinical Commissioning Groups, Local Authorities and Healthcare Providers formed The Children and Young People’s Health Partnership (CYPHP), a clinical-academic programme for improving child health. The Partnership has developed the CYPHP Evelina London model, an integrated healthcare model that aims to deliver effective, coordinated care in primary and community settings and promote better self-management to over approximately 90 000 CYP in Lambeth and Southwark. This protocol is for the process evaluation of this model of care.Methods and analysis Alongside an impact evaluation, an in-depth, mixed-methods process evaluation will be used to understand the barriers and facilitators to implementing the model of care. The data collected mapped onto a logic model of how CYPHP is expected to improve child health outcomes. Data collection and analysis include qualitative interviews and focus groups with stakeholders, a policy review and a quantitative analysis of routine clinical and administrative data and questionnaire data. Information relating to the context of the trial that may affect implementation and/or outcomes of the CYPHP model of care will be documented.Ethics and dissemination The study has been reviewed by NHS REC Cornwall & Plymouth (17/SW/0275). The findings of this process evaluation will guide the scaling up and implementation of the CYPHP Evelina London Model of Care across the UK. Findings will be disseminated through publications and conferences, and implementation manuals and guidance for others working to improve child health through strengthening health systems.Trial registration number NCT03461848

Introduction: Children with critical or chronic physical illness and their families report high levels of psychological distress alongside, or as a result of, demanding treatment protocols. Calls for accessible, evidence-based and cost-effective mental health care to be integrated in routine physical health care are not new, but the content, format and efficacy of these services are largely unknown. Our aim was to identify, synthesise and critically evaluate the evidence on integrated mental health care in paediatric hospitals, and provide a set of evidence-based recommendations for successful integration. Methods: Six electronic databases were systematically searched for English language studies involving children with medical illness aged 0-18 years. Studies were eligible for inclusion if they reported on a psychosocial screening, assessment and/or intervention provided within an existing paediatric hospital service. No restrictions were made on trial design. Data was extracted following eight implementation outcomes: acceptability (satisfaction with the service), adoption (service utilization), appropriateness (patients’ perceived suitability of the service), feasibility (providers’ perception of utility), fidelity (service is delivered as intended), cost (cost-effectiveness of service), penetration (embedding into practice), and sustainability (continuation of service within hospital system). Results: A total of 10 studies were identified as eligible for review.Of these, five studies described psychosocial care provided within specialty clinics (2 cardiology, 2 epilepsy, 1 dermatology), three studies reported on psychological screening practices in hospital wards (2 general wards, 1 oncology), and two studies evaluated delivery of a manualised psychological intervention for hospital inpatients (2 oncology). Psychological services provided in paediatric hospitals were most commonly identified as both acceptable and feasible. Utilization of services varied according to the overall engagement of medical practitioners and hospital staff. Data on overall efficacy, cost-effectiveness, and service sustainability was under-reported across studies. Discussion & Conclusion: The importance of integrated psychological care as part of holistic paediatric care is well-established; yet as this review demonstrates, there is a striking lack of evidence on the efficacy of implementing these models for children with chronic illness and their families. Integration of mental health care into paediatric hospitals is significantly influenced by individual, organisational and system level factors. Integrated service implementation requires strong provider commitment and yet limited evidence on the markers of service efficacy is a significant barrier to widespread adoption. Our review provides a platform for establishing co-ordinated, collaborative mental health care for this highly vulnerable population of children and families. Lessons learned: Evidence-based, conceptually driven implementation frameworks are vital for integrating psychological care into paediatric health care. Clear, universally used measures of efficacy are required to improve service uptake and outcomes. Our findings provide vital guidance for systemic and organisational change. Limitations: Studies reporting on implementation, efficacy and cost-effectiveness of integrated mental health services within paediatric hospitals are scarce. Our review is limited by the inclusion of only English language, peer-reviewed articles. Suggestions for future research: Methodologically rigorous research, including longitudinal assessment of health outcomes and costs is needed to truly assess the impact of these services for children and their families.

Background: Chronic, non-communicable disease, accounts for the vast majority of all disability adjusted life years lost (DALYS), among children and young people in high income countries. Our current model of hospital‐centred paediatric care was developed to deliver acute inpatient and high intensity specialist services rather than high quality care for children and young people (CYP) with long-term conditions. The CYPHP Evelina London model was developed with key stakeholders including CYP, carers, front line practitioners and health service commissioners in response to these evolving health care needs. The CYPHP Evelina London model is an innovative approach to reshaping everyday healthcare services, expanding on the principles of integrated care. CYPHP brings together physical and mental healthcare, addresses the social context of families, integrates primary and secondary healthcare, and links healthcare with local government efforts to improve the wider determinants of health. A major focus of the CYPHP Evelina London model is improving front line care for all CYP. Methods: The CYPHP model will be rolled out in phases, allowing an opportunistic evaluation using a cluster Randomised Controlled Trial (cRCT) design involving 90,000 children and young people in 23 clusters. The evaluation has four component parts: 1- Pseudonymised population-based evaluation for all children and young people in participating GP practices to assess health service use; 2- An evaluation of consented children with asthma, eczema, and constipation to assess impact on health-related quality of life, parental-reported disease severity, prevalence and severity of mental health difficulties, and mental wellbeing among parents, using validated questionnaires. 3- A mixed-methods process evaluation to understand the barriers and facilitators to implementing the model of care; 4- Economic evaluation. Results: Initial baseline results from the first 219 Health Checks showed poorly controlled symptoms for asthma, eczema and constipation in between 60 and 76% of young people. In total, 28% of CYP scored ‘High’/’Very High’ on Strengths & Difficulties Questionnaire for mental health difficulties. Over a quarter of families reported problems paying bills and 12% of parents expressed concerns regarding their own mental health. Discussion: The ongoing CYPHP evaluation is the largest population based evaluation of a pediatrics integrated care model to date in the UK. We will discuss the need for robust evaluation in the space of health transformation using CYPHP as an exemplar. Conclusions: Initial results show high levels of unmet physical, psychological and social needs in children and young people with common and chronic illness. Clinical academic partnerships are key to robust evaluation of health service models at scale. Lessons learned: The difficulties, of carrying out a large randomised controlled trial of a health systems transformation programme across two London Boroughs including partnership working, funding models, ethics approval and recruitment will be discussed. Limitations: Though final results are not available, initial results show high levels of unmet need in our population which the CYPHP model of care is meeting. Suggestions for future research: Robust evaluation using experimental designs is possible and needed in the health systems space. These evaluations at scale will inform new health system design.

Background: Children and young people’s (CYP) health and healthcare outcomes are often poor. Demand for urgent healthcare is rising. The current model of care is primarily reactive and acute rather than proactive and preventative; leading to increased use and reliance on secondary healthcare services. Over the past 5 years there has been increases in non-elective admissions and attendances and outpatient appointments (1.7%, 3% and 3.2%). At a population level, these small increases incur increasing financial cost and burden on services already at capacity. The clinical-academic Children and Young People’s Health Partnership (CYPHP) is delivers new care models to improve CYP health; with evaluation using robust designs to determine the extent the new model of care is curbing rising healthcare use. Methods: CYPHP is a partnership between 3 large NHS Trusts, including mental health and children’s, 2 Clinical Commissioning Groups and Local Authorities, and a University. Model design included analysis of segmented population need, systematic literature reviews, and extensive engagement with CYP, parents, health professionals, providers, and commissioners. An evidence-based implementation plan was agreed to roll out services to a child population of 120,000. We are opportunistically evaluating the service using a cluster randomised control trial (cRCT) design. Results: We are implementing and evaluating an evidence-based comprehensive new child and family-centred integrated cycle of care including individual and population health promotion; proactive case-finding and triage for ongoing conditions at a population-level; biopsychosocial assessment and self-referral via a patient portal; holistic tailored care, specialist clinics and increased education and training for professionals working with CYP. Services are delivered by multidisciplinary health teams to increase coordination across primary, community, and hospital settings and to better integrate physical and mental healthcare for CYP’s social context. The cRCT evaluation design, with nested process evaluation and qualitative studies, will provide high quality evidence of the impact of the CYPHP model on outcomes including CYP health and wellbeing, healthcare quality, and health service and system measures. Implications: CYPHP is implementing and evaluating a new model of care to improve health, heathcare quality, and outcomes for local CYP, contribute generalizable evidence about children’s health services and systems, and shape child health policy.

Introduction: New models of healthcare have largely focussed on adults, with increasing policy and practice interest in integrated care across many high-income countries. Integrated care models have been identified as a promising solution by children and young people (CYP), and by policy-makers, to target the gaps in healthcare delivery for CYP with on-going conditions. However, there has been limited work on developing and evaluating integrated models of child healthcare, so there is an evidence gap in this important area of policy. This systematic review and meta-analysis assessed the effects of integrated care interventions on child health, health service use, and healthcare quality for CYP with on-going conditions. Methods: Articles were eligible for the review if they 1) reported randomised controlled trials (RCTs), published between 1996 and September 2018; 2) evaluated an integrated healthcare intervention designed to improve child health; 3) included CYP (0-18 years) with an on-going health condition; 4) included at least one health-related outcome. Descriptive data on a range of outcomes was synthesised for all included papers, and data homogeneity allowed further meta-analyses to explore the effects of integrated care interventions compared with usual care, on health-related quality of life (QOL) and number of emergency department visits. Results: Twenty-three randomised controlled trials were identified, describing 18 interventions. Studies had medium risk of bias, as assessed by the Cochrane Risk of Bias tool. Improvements were found for quality of care (87% of interventions found a positive effect for intervention) and child health (39% found a positive effect for intervention). The meta-analyses found that integrated care interventions have a positive effect in improving QOL over usual care (n=5 trials; SMD = 0.24; 95% CI = 0.03, 0.44; P=0.02), but no significant difference across groups for emergency department contacts (n=5 trials; OR=0.82; 95% CI = 0.53, 1.26; p=0.37). Conclusion and Discussion: Integrated care interventions for CYP with on-going conditions may deliver improved quality of life for children, health, and quality of care. However, no conclusions can be made about the direction or magnitude of the effect for integrated care interventions on emergency department contacts in CYP with on-going conditions. However, only 23 RCTs were included in this review, which were of moderate quality, highlighting the need for more robust trials to inform current health service delivery in this area and fully establish the effectiveness of integrated healthcare interventions on CYP outcomes. In collaboration with NHS Trusts, local councils, CYP and families, the findings from this review have been used to inform a fully integrated healthcare model for CYP that will be implemented at scale, and rigorously evaluated using an RCT design.

Background: Children and young people’s (CYP) health outcomes in England are variable and often poor. Health systems throughout high income countries are struggling to adapt to epidemiological transitions, social change, rising demand, and budget cuts. There was a 58% rise in CYP attending EDs between 2007 and 2016, projected to rise 50-60% more by 2030. CYP from the most deprived backgrounds are 60-70% more likely to go to A&E than the least deprived. The majority of ED attendances by CYP are manageable in primary care or integrated models, yet 85% of ED attendances are for minor illnesses, increasing 5% annually. The Children and Young People’s Health Partnership (CYPHP) is a health system strengthening initiative implementing and evaluating a new model of care. Methods: Health system strengthening using the WHO building blocks model included service design by analysis of population need, systematic literature reviews, and extensive patient and public involvement. An evidence-based implementation plan was agreed for a child population of 90,000 in London, and we are evaluating using a cluster randomised control trial (cRCT) design with nested process evaluation and qualitative studies to assess CYP health and wellbeing, healthcare quality, patterns of healthcare use, and cost effectiveness. Results: CYPHP’s comprehensive care includes health promotion and supported self-management, proactive case-finding, biopsychosocial assessment and self-referral via a patient portal, with care delivered by a multidisciplinary team. Services are integrated vertically and horizontally incorporating physical and mental healthcare. Implementation has taken two years longer than anticipated due to technical and cultural challenges of health system strengthening. Early results indicate a reduction of 72 ED contacts per 100 children with asthma, 30 for children with epilepsy, and 15 for children with constipation. We estimate cost savings per 100 asthma patients to be over £15,000, for epilepsy over £6,000, and for constipation over £3,000. Of the first 200 patients, most were from socially deprived areas and 68% were from black and minority ethnic groups. Families report more confidence in managing their child’s condition. Discussion: As a clinical academic partnership, CYPHP combines pragmatic quality improvement and rigorous health services research. CYPHP demonstrates that health system strengthening in high income countries is feasible and effective for implementing and testing new models of care to improve child health. Conclusions: Early results suggest encouraging impact on patterns of healthcare use and potential cost savings. CYPHP’s population health approach provides care for those with greatest health and social need. Lessons learned: Rigorous health services and systems research is feasible in large scale system change in the NHS. Health system strengthening is a new concept in high income countries. It is slow and difficult, but important for effective implementation of new models of care. Fully integrated comprehensive models of care for children may improve health and healthcare outcomes. Limitations: Results are preliminary and reflect early implementation. Suggestions for future research: Rigorously designed health services research for ongoing large-scale health systems changes are an important source of new knowledge. There are few examples of such opportunistic research, representing new avenues for opportunity.

Aim: The aim of this study was to characterize acceleration transmission and neuromuscular responses to rotational vibration (RV) and vertical vibration (VV) at different frequencies and amplitudes. Methods: Twelve healthy males completed 2 experimental trials (RV vs VV) during which vibration was delivered during either squatting (30°; RV vs VV) or standing (RV only) with 20, 25, and 30 Hz, at 1.5 and 3.0 mm peak-to-peak amplitude. Vibration-induced accelerations were assessed with triaxial accelerometers mounted on the platform and bony landmarks at ankle, knee, and lumbar spine. Results: At all frequency/amplitude combinations, accelerations at the ankle were greater during RV (all P < .03) with the greatest difference observed at 30 Hz, 1.5 mm. Transmission of RV was also influenced by body posture (standing vs squatting, P < .03). Irrespective of vibration type, vibration transmission to all skeletal sites was generally greater at higher amplitudes but not at higher frequencies, especially above the ankle joint. Acceleration at the lumbar spine increased with greater vibration amplitude but not frequency and was highest with RV during standing. Conclusions/Implications: The transmission of vibration during whole-body vibration (WBV) is dependent on intensity and direction of vibration as well as body posture. For targeted mechanical loading at the lumbar spine, RV of higher amplitude and lower frequency vibration while standing is recommended. These results will assist with the prescription of WBV to achieve desired levels of mechanical loading at specific sites in the human body.

Addressing environmental management problems at catchment scales requires an integrated modelling approach, in which key bio-physical and socio-economic drivers, processes and impacts are all considered. Development of Decision Support Systems (DSSs) for environmental management is rapidly progressing. This paper describes the integration of physical, ecological, and socio-economic components in a Bayesian Decision Network (BDN) and its implementation in the Interactive Component Modelling System (ICMS) software to build a prototype DSS for salinity management in the Little River catchment in the upper Macquarie River basin, NSW Australia. Salinity is a major environmental problem in the country. This integrated model implemented in a DSS has been developed to co-ordinate the various disciplines involved in salinity problems, integrate data and information available, and allow the investigation of the potential outcomes arising from implementing salinity management options at the catchment scale. The analysis of the trade-offs presented in this study shows that there is no single or ultimate solution to salinity management problems for the catchment, but the Little River catchment BDN decision support system, as a decision toolbox, does clarify the impacts of management options. It assists users to reach their own conclusions on the basis of their improved understanding of the system and of the trade-offs among various outcomes arising from implementing salinity management scenarios