Strategic vision for improving human health at The Forefront of Genomics.

Starting with the launch of the Human Genome Project three decades ago, and continuing after its completion in 2003, genomics has progressively come to have a central and catalytic role in basic and translational research. In addition, studies increasingly demonstrate how genomic information can be effectively used in clinical care. In the future, the anticipated advances in technology development, biological insights, and clinical applications (among others) will lead to more widespread integration of genomics into almost all areas of biomedical research, the adoption of genomics into mainstream medical and public-health practices, and an increasing relevance of genomics for everyday life. On behalf of the research community, the National Human Genome Research Institute recently completed a multi-year process of strategic engagement to identify future research priorities and opportunities in human genomics, with an emphasis on health applications. Here we describe the highest-priority elements envisioned for the cutting-edge of human genomics going forward-that is, at 'The Forefront of Genomics'.

Estimating the Lifetime Costs and Benefits of the Incredible Years Teacher Classroom Management Intervention Using Data From 30 Months Follow-Up of the Supporting Teachers and childRen in Schools Trial.

OBJECTIVES: The Incredible Years Teacher® Classroom Management (IY-TCM) intervention is associated with short-term improvements in mental health difficulties in young people. The aim was to estimate the long-term impact and cost-effectiveness of the IY-TCM intervention compared with no intervention. METHODS: An existing health economic model (LifeSim 1.0) was used to translate short-term changes in the Strength and Difficulties Questionnaire (SDQ), based on the Supporting Teachers and childRen in Schools cluster randomized controlled trial of the IY-TCM intervention in schools, into estimated medium- and long-term effects using multiple longitudinal data sets. LifeSim 1.0 was adapted to incorporate teacher-reported SDQ and account for individual heterogeneity. Cost-effectiveness analyses were conducted using the trial-based intervention cost with subgroup analyses on deprivation, conduct scores and parental depression in the simulated baseline population. RESULTS: Regression analyses show significant predictor variables for intervention effectiveness, including deprivation and baseline SDQ. LifeSim results indicate small gains in long-term outcomes, and cost-effective analyses estimated that the IY-TCM intervention could be cost-effective, but there was a large amount of uncertainty (net monetary benefit = £10, Estimated CI = -£134, £156). Benefits and certainty of cost-effectiveness were greater for some subgroups, such as those with high conduct scores at baseline (net monetary benefit = £206, Estimated CI = £26, £318). CONCLUSIONS: IY-TCM could be cost-effective, but there was a large amount of uncertainty around costs and benefits. Greater benefits for pupils with difficulties at baseline suggest that the intervention may be more cost-effective for schools in more deprived areas with high levels of conduct problems.

Cross-model validation of public health microsimulation models; comparing two models on estimated effects of a weight management intervention.

BACKGROUND: Health economic modelling indicates that referral to a behavioural weight management programme is cost saving and generates QALY gains compared with a brief intervention. The aim of this study was to conduct a cross-model validation comparing outcomes from this cost-effectiveness analysis to those of a comparator model, to understand how differences in model structure contribute to outcomes. METHODS: The outcomes produced by two models, the School for Public Health Research diabetes prevention (SPHR) and Health Checks (HC) models, were compared for three weight-management programme strategies; Weight Watchers (WW) for 12 weeks, WW for 52 weeks, and a brief intervention, and a simulated no intervention scenario. Model inputs were standardised, and iterative adjustments were made to each model to identify drivers of differences in key outcomes. RESULTS: The total QALYs estimated by the HC model were higher in all treatment groups than those estimated by the SPHR model, and there was a large difference in incremental QALYs between the models. SPHR simulated greater QALY gains for 12-week WW and 52-week WW relative to the Brief Intervention. Comparisons across socioeconomic groups found a stronger socioeconomic gradient in the SPHR model. Removing the impact of treatment on HbA1c from the SPHR model, running both models only with the conditions that the models have in common and, to a lesser extent, changing the data used to estimate risk factor trajectories, resulted in more consistent model outcomes. CONCLUSIONS: The key driver of difference between the models was the inclusion of extra evidence-based detail in SPHR on the impacts of treatments on HbA1c. The conclusions were less sensitive to the dataset used to inform the risk factor trajectories. These findings strengthen the original cost-effectiveness analyses of the weight management interventions and provide an increased understanding of what is structurally important in the models.

A narrative review of online food delivery in Australia: challenges and opportunities for public health nutrition policy.

OBJECTIVE: Online food delivery (OFD) platforms offer consumers a convenient and fast delivery service of foods and drinks sourced from foodservice partners (e.g. restaurants, quick service restaurants). There is a need to assess the impact of this emergent segment of the foodservice sector on diet and diet-related health. The aim of this narrative review was to describe the OFD sector in Australia, its use and identify potential ways to include OFD platforms in existing public health nutrition policy. DESIGN: A search was conducted in peer-reviewed and grey literature. Sources were analysed and synthesised to report the characteristics of OFD platforms, delivery process, users and potential drivers of usage. The aim and scope of public health nutrition policies were analysed to identify ways of including OFD platforms. SETTING: Australia. PARTICIPANTS: General population. RESULTS: There are three main operators with 9000-16 000 foodservice partners based predominantly in the main cities of Australia. OFD revenue has grown by 72 % in the last 5 years and is predicted to increase driven by usage by working adults with high disposable income who demand convenience. Current policies and initiatives aimed at manufacturers, retailers and foodservice outlets do not specifically regulate OFD platforms, although there is scope for these to be extended to such platforms. CONCLUSIONS: OFD platforms are disruptors of the foodservice sector. Innovative and consistent health policy options that target the unique challenges and opportunities posed by OFD platforms are required to limit the potentially negative impact of OFD platforms on diet and diet-related health.

Mechanisms of Action in a Behavioral Weight-Management Program: Latent Growth Curve Analysis.

BACKGROUND: A greater understanding of the mechanisms of action of weight-management interventions is needed to inform the design of effective interventions. PURPOSE: To investigate whether dietary restraint, habit strength, or diet self-regulation mediated the impact of a behavioral weight-management intervention on weight loss and weight loss maintenance. METHODS: Latent growth curve analysis (LGCA) was conducted on trial data in which adults (N = 1,267) with a body mass index (BMI) ≥28 kg/m2 were randomized to either a brief intervention (booklet on losing weight), a 12 week weight-management program or the same program for 52 weeks. LGCA estimated the trajectory of the variables over four time points (baseline and 3, 12 and 24 months) to assess whether potential mechanisms of action mediated the impact of the weight-management program on BMI. RESULTS: Participants randomized to the 12 and 52 week programs had a significantly greater decrease in BMI than the brief intervention. This direct effect became nonsignificant when dietary restraint, habit strength, and autonomous diet self-regulation were controlled for. The total indirect effect was significant for both the 12 (estimate = -1.33, standard error [SE] = 0.41, p = .001) and 52 week (estimate = -2.13, SE = 0.52, p < .001) program. Only the individual indirect effect for dietary restraint was significant for the 12 week intervention, whereas all three indirect effects were significant for the 52 week intervention. CONCLUSIONS: Behavior change techniques that target dietary restraint, habit strength, and autonomous diet self-regulation should be considered when designing weight loss and weight loss maintenance interventions. Longer interventions may need to target both deliberative and automatic control processes to support successful weight management.

Estimating the impact of changes in weight and BMI on EQ-5D-3L: a longitudinal analysis of a behavioural group-based weight loss intervention.

PURPOSE: To estimate the association between changes in BMI and changes in Health-Related Quality of Life (EQ-5D-3L). METHODS: The WRAP trial was a multicentre, randomised controlled trial with parallel design and recruited 1267 adults (BMI ≥ 28 kg/m2). Participants were allocated to Brief Intervention, a Commercial weight management Programme (WW, formerly Weight Watchers) for 12 weeks, or the same Programme for 52 weeks. Participants were assessed at 0, 3, 12, 24, and 60 months. We analysed the relationship between BMI and EQ-5D-3L, adjusting for age and comorbidities, using a fixed effects model. Test for attrition, model specification and missing data were conducted. Secondary analyses investigated a non-symmetric gradient for weight loss vs. regain. RESULTS: A unit increase in BMI was associated with a - 0.011 (95% CI - 0.01546, - 0.00877) change in EQ-5D-3L. A unit change in BMI between periods of observation was associated with - 0.016 017 (95% CI - 0.0077009, - 0.025086) change in EQ-5D-3L. The negative association was reduced during weight loss, as opposed to weight gain, but the difference was not statistically significant. CONCLUSIONS: We have identified a strong and statistically significant negative relationship between BMI changes and HRQoL. These estimates could be used in economic evaluations of weight loss interventions to inform policymaking. CLINICAL TRIAL REGISTRATION: This trial was registered with Current Controlled Trials, number ISRCTN82857232.

Using health economic modelling to inform the design and development of an intervention: estimating the justifiable cost of weight loss maintenance in the UK.

BACKGROUND: There is a need to develop cost-effective weight loss maintenance interventions to prolong the positive impact of weight loss on health outcomes. Conducting pre-trial health economic modelling is recommended to inform the design and development of behavioural interventions. We aimed to use health economic modelling to estimate the maximum cost per-person (justifiable cost) of a cost-effective behavioural weight loss maintenance intervention, given an estimated intervention effect for individuals with: i) a Body Mass Index (BMI) of 28 kg/m2 or above without diabetes and ii) a diagnosis of type 2 diabetes prescribed a single non-insulin diabetes medication. METHODS: The School for Public Health Research Diabetes prevention model was used to estimate the lifetime Quality-adjusted life year (QALY) gains, healthcare costs, and maximum justifiable cost associated with a weight loss maintenance intervention. Based on a meta-analysis, the estimated effect of a weight loss maintenance intervention following a 9 kg weight loss, was a regain of 1.33 kg and 4.38 kg in years one and two respectively compared to greater regain of 2.84 kg and 5.6 kg in the control group. Sensitivity analysis was conducted around the rate of regain, duration of effect and initial weight loss. RESULTS: The justifiable cost for a weight loss maintenance intervention at an ICER of £20,000 per QALY was £104.64 for an individual with a BMI of 28 or over and £88.14 for an individual with type 2 diabetes. Within sensitivity analysis, this varied from £36.42 to £203.77 for the former, and between £29.98 and £173.05 for the latter. CONCLUSIONS: Researchers developing a weight loss maintenance intervention should consider these maximum justifiable cost estimates and the potential impact of the duration of effect and initial weight loss when designing intervention content and deciding target populations. Future research should consider using the methods demonstrated in this study to use health economic modelling to inform the design and budgetary decisions in the development of a behavioural interventions.

Phylogenetic signals and predictability in plant-soil feedbacks.

There is strong evidence for a phylogenetic signal in the degree to which species share co-evolved biotic partners and in the outcomes of biotic interactions. This implies there should be a phylogenetic signal in the outcome of feedbacks between plants and the soil microbiota they cultivate. However, attempts to identify a phylogenetic signal in plant-soil feedbacks have produced mixed results. Here we clarify how phylogenetic signals could arise in plant-soil feedbacks and use a recent compilation of data from feedback experiments to identify: whether there is a phylogenetic signal in the outcome of plant-soil feedbacks; and whether any signal arises through directional or divergent changes in feedback outcomes with evolutionary time. We find strong evidence for a divergent phylogenetic signal in feedback outcomes. Distantly related plant species show more divergent responses to each other's soil microbiota compared with closely related plant species. The pattern of divergence implies occasional co-evolutionary shifts in how plants interact with soil microbiota, with strongly contrasting feedback responses among some plant lineages. Our results highlight that it is difficult to predict feedback outcomes from phylogeny alone, other than to say that more closely related species tend to have more similar responses.

Elevated International Normalized Ratio (INR) is Associated With an Increased Risk of Intraventricular Hemorrhage in Extremely Preterm Infants.

INTRODUCTION: The international normalized ratio (INR), a standardized method of reporting the prothrombin time, can be a surrogate marker of the vitamin K-dependent coagulation pathways. OBJECTIVE: To evaluate the relationship between INR measurements in the first 48 hours of life and subsequent development of intraventricular hemorrhage (IVH) in extremely preterm infants. MATERIALS AND METHODS: A single-center retrospective, observational cohort study of infants born at <28 weeks gestation. The main outcome measure was defined as the degree of IVH seen on cranial ultrasound examinations at day 7 postnatal age. RESULTS: Of 200 infants, 109 (mean gestational age, 25.2 wk [SD, 1.27]) had coagulation results available. Of 109, 26 developed IVH. Elevated INR was associated with increased risk of a severe IVH (odds ratio [OR] 6.50; 95% confidence interval [CI], 1.65-25.62; P=0.008) adjusted for gestation, birth weight, and sex. INR was significantly associated with severe IVH in infants who did not receive blood products (OR, 64.60; 95% CI, 1.35-3081.25; P=0.035), but not in those who did (OR, 2.93; 95% CI, 0.67-12.71; P=0.151) (Pinteraction=0.086). CONCLUSION: An elevated INR in the first 48 hours of life may be useful to identify preterm infants at risk of severe IVH and may guide strategies to prevent the development, or limit the extension, of IVH.

Awareness of alcohol as a risk factor for cancer is associated with public support for alcohol policies.

BACKGROUND: Globally, alcohol is causally related to 2.5 million deaths per year and 12.5% of these are due to cancer. Previous research has indicated that public awareness of alcohol as a risk factor for cancer is low and this may contribute to a lack of public support for alcohol policies. The aim of this study was to investigate the relationship between awareness of the alcohol-cancer link and support for a range of alcohol policies in an English sample and policy context. METHODS: A cross-sectional survey of 2100 adult residents in England was conducted in which respondents answered questions regarding awareness of the link between alcohol and cancer and support for 21 policy proposals. Principal component analysis (PCA) was used to reduce the 21 policy proposals down to a set of underlying factors. Multiple regression analyses were conducted to estimate the relationship between awareness of the alcohol-cancer link and each of these policy factors. RESULTS: Thirteen per cent of the sample were aware of the alcohol-cancer link unprompted, a further 34% were aware when prompted and 53% were not aware of the link. PCA reduced the policy items to four policy factors, which were named price and availability, marketing and information, harm reduction and drink driving. Awareness of the alcohol-cancer link unprompted was associated with increased support for each of four underlying policy factors: price and availability (Beta: 0.06, 95% CI: 0.01, 0.10), marketing and information (Beta: 0.05, 95% CI: 0.00, 0.09), harm reduction (Beta: 0.09, 95% CI: 0.05, 0.14), and drink driving (Beta: 0.16, 95% CI: 0.11, 0.20). CONCLUSIONS: Support for alcohol policies is greater among individuals who are aware of the link between alcohol and cancer. At the same time, a large proportion of people are unaware of the alcohol-cancer link and so increasing awareness may be an effective approach to increasing support for alcohol policies.

The Ethics Liaison Program: building a moral community.

Ethicists often struggle to maintain institution-wide awareness of and commitment to medical ethics. At Beth Israel Deaconess Medical Center (BIDMC), we created the Ethics Liaison Program to address that challenge by making ethics part of the moral culture of the institution. Liaisons represent clinical and non-clinical areas throughout the medical centre. The liaison has a four-part role: to spread awareness and understanding of Ethics Programs among their coworkers; share information regarding ethical dilemmas in their work area with the members of the Ethics Support Service; review ethics activities and needs within their area; and undertake ethics-related projects. This paper lists the notable attributes of the Ethics Liaison Program, and describes the purpose and structure of the programme, its advantages and the challenges to implementing it. The Ethics Liaison Program has helped to make ethics part of the everyday culture at BIDMC, and other medical centres might benefit from the establishment of similar programmes.

Correction to: Psychosocial and Clinical Correlates of Fatigue in Haemodialysis Patients: the Importance of Patients' Illness Cognitions and Behaviours.

We wish to highlight a discrepancy with regards to the reported mean fatigue severity score (mean = 28.3, standard deviation = 6.5). Since publication we have followed this sample up over time and are currently evaluating the longitudinal trajectories of fatigue severity.

Psychosocial and Clinical Correlates of Fatigue in Haemodialysis Patients: the Importance of Patients' Illness Cognitions and Behaviours.

PURPOSE: Fatigue is commonly experienced in end-stage kidney disease (ESKD) and is associated with poor outcomes. Currently, little research has examined the psychosocial correlates of fatigue severity and its impact on renal disease patients. We predicted that psychological factors (distress, cognitions and behaviours) would be associated with fatigue severity and impairment in ESKD patients even when controlling for clinical and disease factors. METHOD: One hundred seventy-four haemodialysis patients completed the Chalder Fatigue Questionnaire (fatigue severity) and the Work and Social Adjustment Scale (fatigue-related impairment) in addition to measures evaluating distress, fatigue perceptions, symptom beliefs and behaviours. Demographic and clinical data were also collected. RESULTS: Fatigue severity was not related to haemoglobin levels, serum albumin or dialysis vintage. In hierarchical regression models, demographic and clinical factors explained 20 % of the variance in fatigue (ethnicity, body mass index, exercise, log C-reactive protein and multimorbidity). Psychological distress (beta = 0.21, p < 0.01), negative beliefs about fatigue (beta = 0.10, p = 0.01) and unhelpful behaviours (all-or-nothing behaviour [beta = 0.28, p < 0.01] and avoidance [beta = 0.16, p < 0.01]) explained an additional 36.4 % of the variance. Fatigue-related impairment was associated with psychological distress, perceptions that symptoms indicate damage, avoidance behaviour and the level of fatigue severity. CONCLUSION: Patients' mood, beliefs and behaviours are associated with fatigue in dialysis patients. Psychological interventions to alter these factors may reduce fatigue severity and fatigue-related disability in ESKD patients.

Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits.

Circulating hormones influence multiple aspects of hypothalamic development and play a role in directing formation of neural circuits. Leptin is secreted by adipocytes and functions as a key developmental signal that promotes axon outgrowth from the arcuate nucleus (ARH) during a discrete developmental critical period. To determine the cellular mechanisms by which leptin impacts development of hypothalamic circuits, we examined roles for leptin receptor (LepRb) signals in neonatal mice. LepRb, ERK, and STAT3 signaling were required for leptin-stimulated neurite outgrowth from ARH explants in vitro. Neonatal mice with disrupted LepRb→ERK signaling displayed impaired ARH projections but were able to compensate by adulthood. LepRb→STAT3 signaling also plays a role in early circuit formation and controls the ultimate architecture of POMC, but not AgRP, projections. Thus, the developmental actions of leptin on feeding circuits are dependent on LepRb, and distinct signaling pathways are responsible for directing formation of NPY and POMC projections.

Perinatal excellence to reduce injury in preterm birth (PERIPrem) through quality improvement.

Perinatal Excellence to Reduce Injury in Premature Birth (PERIPrem) is an 11-element perinatal care bundle designed to improve outcomes for preterm babies, in line with the National Health Service (NHS) Long Term plan. Designed in collaboration with 12 NHS Trusts (secondary care hospitals), South West and West of England Academic Health Science Networks, South West Neonatal Operational Delivery Network, parent partners and clinical experts, implementation was via bespoke quality improvement (QI) methodology. Before project initiation, there was regional variation in uptake of elements, evidenced by baseline audit. Optimisation of the preterm infant is complex; eligibility for treatments is dependent on gestation and local policies. Preterm infants experience variability in care dependent on the place of birth, and there remains an implementation gap for several effective, evidence-based treatments.The PERIPrem ambition is to reduce severe brain injury and death caused by prematurity by at least 50% through the delivery of a perinatal care bundle. The PERIPrem approach resulted in improved element implementation by 26% (from 3% to 29%) between 2019 and 2021, with dyads significantly more likely to receive the full bundle in 2021 compared with 2019 (probability=0.96 (95% CI 0.87 to 0.99), p<0.001). When examining the impact on psychological safety and team-working of PERIPrem, linear mixed models indicated an improvement in team function (p=0.021), situation monitoring (p=0.029) and communication within teams (p=0.002). Central to success was the development of a committed multiorganisational collaborative that continues to drive perinatal improvement using a common language and streamlining processes. In addition to saving the lives of the most vulnerable babies, PERIPrem aims to improve the chances of disability-free lives and is successfully nurturing high-functioning perinatal teams with enhanced QI skills.

Individualised decision making: interpretation of risk for extremely preterm infants-a survey of UK neonatal professionals.

BACKGROUND: The British Association of Perinatal Medicine (BAPM) published a revised framework for perinatal management of extremely preterm infants (EPIs) in 2019. We aimed to assess UK neonatal professionals' interpretation of elements of this framework, as well as the consistency of their estimates of outcome for EPIs. METHODS: An online survey gave participants five cases involving anticipated extremely preterm birth with different favourable and unfavourable risk factors. Respondents were asked to assign a risk category and management option using the BAPM framework and to estimate the chance of survival if the baby received active resuscitation and the chance of severe disability if they survived. RESULTS: Respondents were consistent in interpretation of risk categories. The majority would follow parental wishes about management. Management decisions did not always correspond with risk assessment, with less inclination to recommend palliative (comfort) care. There were wide estimates of survival or severe disability (5%-90%) with consultants providing lower estimates of severe disability than other groups. CONCLUSION: UK neonatal professionals deferred to parental wishes in the cases presented, indicating an emphasis on shared decision making. However, they did not necessarily use the risk stratification approach for management decisions. Variation in estimates of outcome raises questions about the accuracy of informed decision making and suggests support is needed for UK clinicians to incorporate risk factors into individualised counselling. There may be value in validating existing online risk calculators for UK infants or in developing a UK specific risk model.

Development of a Web-Based, Guided Self-help, Acceptance and Commitment Therapy-Based Intervention for Weight Loss Maintenance: Evidence-, Theory-, and Person-Based Approach.

BACKGROUND: The long-term impact and cost-effectiveness of weight management programs depend on posttreatment weight maintenance. There is growing evidence that interventions based on third-wave cognitive behavioral therapy, particularly acceptance and commitment therapy (ACT), could improve long-term weight management; however, these interventions are typically delivered face-to-face by psychologists, which limits the scalability of these types of intervention. OBJECTIVE: The aim of this study is to use an evidence-, theory-, and person-based approach to develop an ACT-based intervention for weight loss maintenance that uses digital technology and nonspecialist guidance to minimize the resources needed for delivery at scale. METHODS: Intervention development was guided by the Medical Research Council framework for the development of complex interventions in health care, Intervention Mapping Protocol, and a person-based approach for enhancing the acceptability and feasibility of interventions. Work was conducted in two phases: phase 1 consisted of collating and analyzing existing and new primary evidence and phase 2 consisted of theoretical modeling and intervention development. Phase 1 included a synthesis of existing evidence on weight loss maintenance from previous research, a systematic review and network meta-analysis of third-wave cognitive behavioral therapy interventions for weight management, a qualitative interview study of experiences of weight loss maintenance, and the modeling of a justifiable cost for a weight loss maintenance program. Phase 2 included the iterative development of guiding principles, a logic model, and the intervention design and content. Target user and stakeholder panels were established to inform each phase of development, and user testing of successive iterations of the prototype intervention was conducted. RESULTS: This process resulted in a guided self-help ACT-based intervention called SWiM (Supporting Weight Management). SWiM is a 4-month program consisting of weekly web-based sessions for 13 consecutive weeks followed by a 4-week break for participants to reflect and practice their new skills and a final session at week 18. Each session consists of psychoeducational content, reflective exercises, and behavioral experiments. SWiM includes specific sessions on key determinants of weight loss maintenance, including developing skills to manage high-risk situations for lapses, creating new helpful habits, breaking old unhelpful habits, and learning to manage interpersonal relationships and their impact on weight management. A trained, nonspecialist coach provides guidance for the participants through the program with 4 scheduled 30-minute telephone calls and 3 further optional calls. CONCLUSIONS: This comprehensive approach facilitated the development of an intervention that is based on scientific theory and evidence for supporting people with weight loss maintenance and is grounded in the experiences of the target users and the context in which it is intended to be delivered. The intervention will be refined based on the findings of a planned pilot randomized controlled trial.

Effectiveness and cost-effectiveness of referral to a commercial open group behavioural weight management programme in adults with overweight and obesity: 5-year follow-up of the WRAP randomised controlled trial.

BACKGROUND: There is evidence that commercially available behavioural weight management programmes can lead to short-term weight loss and reductions in glycaemia. Here, we aimed to provide the 5-year impact and cost-effectiveness of these interventions compared with a brief intervention. METHODS: WRAP was a non-blinded, parallel-group randomised controlled trial (RCT). We recruited from primary care practices in England and randomly assigned participants to one of three interventions (brief intervention, 12-week open-group behavioural programme [WW, formerly Weight Watchers], or a 52-week open-group WW behavioural programme) in an uneven (2:5:5) allocation. Participants were followed up 5 years after randomisation using data from measurement visits at primary care practices or a research centre, review of primary care electronic medical notes, and self-report questionnaires. The primary outcome was change in weight at 5 years follow-up, assessed using analysis of covariance. We also estimated cost-effectiveness of the intervention. This study is registered at Current Controlled Trials, ISRCTN64986150. FINDINGS: Between Oct 18, 2012, and Feb 10, 2014, we recruited 1269 eligible participants (two participants were randomly assigned but not eligible and therefore excluded) and 1040 (82%) consented to be approached about additional follow-up and to have their medical notes reviewed at 5 years. The primary outcome (weight) was ascertained for 871 (69%) of 1267 eligible participants. Mean duration of follow-up was 5·1 (SD 0·3) years. Mean weight change from baseline to 5 years was -0·46 (SD 8·31) kg in the brief intervention group, -1·95 (9·55) kg in the 12-week programme group, and -2·67 (9·81) kg in the 52-week programme. The adjusted difference in weight change was -1·76 (95% CI -3·68 to 0·17) kg between the 52-week programme and the brief intervention; -0·80 (-2·13 to 0·54) kg between the 52-week and the 12-week programme; and -0·96 (-2·90 to 0·97) kg between the 12-week programme and the brief intervention. During the trial, the 12-week programme incurred the lowest cost and produced the highest quality-adjusted life-years (QALY). Simulations beyond 5 years suggested that the 52-week programme would deliver the highest QALYs at the lowest cost and would be the most cost-effective. No participants reported adverse events related to the intervention. INTERPRETATION: Although the difference in weight change between groups was not statistically significant, some weight loss was maintained at 5 years after an open-group behavioural weight management programme. Health economic modelling suggests that this could have important implications to reduce the incidence of weight-related disease and these interventions might be cost-saving. FUNDING: The UK National Institute for Health and Care Research Programme Grants for Applied Research and the Medical Research Council.

Systematic review and meta-analyses of the relationship between short sleep and incidence of obesity and effectiveness of sleep interventions on weight gain in preschool children.

The aim of this study is to determine (a) whether short sleep is associated with the incidence of obesity and (b) whether interventions beneficial for sleep reduce weight gain in preschool children. We systematically searched PubMed, Embase, Web of Science and Cochrane up to 12/09/2019. (a) Studies that were included were prospective, had follow-up ≥1 year, with sleep duration at baseline and required outcome measures. (b) Intervention trials with sleep intervention and measures of overweight or obesity were included. Data were extracted according to PRISMA guidelines. (a) The risk of developing overweight/obesity was greater in short sleeping children (13 studies, 42 878 participants, RR: 1.54; 95% CI, 1.33 to 1.77; p < 0.001). Sleep duration was associated with a significant change in BMI z-score (10 studies, 11 cohorts and 29 553 participants) (mean difference: -0.02 unit per hour sleep; -0.03 to -0.01; p < 0.001). (b) Four of the five intervention studies reported improved outcomes: for BMI (-0.27 kg/m2 ; -0.50 to -0.03; p = 0.03); for BMI z-score (-0.07 unit; -0.12 to -0.02; p = 0.006). Short sleep duration is a risk factor or marker of the development of obesity in preschool children. Intervention studies suggest that improved sleep may be beneficially associated with a reduced weight gain in these children.

Viability and thresholds for treatment of extremely preterm infants: survey of UK neonatal professionals.

BACKGROUND: Decisions about treatments for extremely preterm infants (EPIs) born in the 'grey zone' of viability can be ethically complex. This 2020 survey aimed to determine views of UK neonatal staff about thresholds for treatment of EPIs given a recently revised national Framework for Practice from the British Association of Perinatal Medicine. METHODS: The online survey requested participants indicate the lowest gestation at which they would be willing to offer active treatment and the highest gestation at which they would withhold active treatment of an EPI at parental request (their lower and upper thresholds). Relative risks were used to compare respondents' views based on profession and neonatal unit designation. Further questions explored respondents' conceptual understanding of viability. RESULTS: 336 respondents included 167 consultants, 127 registrars/fellows and 42 advanced neonatal nurse practitioners (ANNPs). Respondents reported a median grey zone for neonatal resuscitation between 22+1 and 24+0 weeks' gestation. Registrars/fellows were more likely to select a lower threshold at 22+0 weeks compared with consultants (Relative Risk (RR)=1.37 (95% CI 1.07 to 1.74)) and ANNPs (RR=2.68 (95% CI 1.42 to 5.06)). Those working in neonatal intensive care units compared with other units were also more likely to offer active treatment at 22+0 weeks (RR=1.86 (95% CI 1.18 to 2.94)). Most participants understood a fetus/newborn to be 'viable' if it was possible to survive, regardless of disability, with medical interventions accessible to the treating team. CONCLUSION: Compared with previous studies, we found a shift in the reported lower threshold for resuscitation in the UK, with greater acceptance of active treatment for infants <23 weeks' gestation.