Daily Duration of Eating for Children and Adolescents: A Systematic Review and Meta-Analysis.

Time-limited eating is a dietary intervention whereby eating is limited to a specific window of time during the day. The usual eating windows of adults, and how these can be manipulated for dietary interventions, is well documented. However, there is a paucity of data on eating windows of young people, the manipulation of which may be a useful intervention for reducing obesity. This paper reviewed the existing literature on the eating windows of children and adolescents, aged 5-18 years, plus clock times of first and last intakes and variations by subgroup. Two databases (Medline and Embase) were searched for eligible papers published between February 2013 and February 2023, with forward searching of the citation network of included studies on Web of Science. Articles were screened, and data extracted, in duplicate by two independent reviewers. Ten studies were included, with both observational and experimental designs. Narrative synthesis showed large variations in eating windows with average values ranging from 9.7 h to 16.4 h. Meta-analysis, of five studies, showed a pooled mean daily eating window of 11.3 h (95% CI 11.0, 11.7). Large variations in eating windows exist across different study populations; however, the pooled data suggest that it may be possible to design time-limited eating interventions in paediatric populations aimed at reducing eating windows. Further high-quality research, investigating eating windows and subsequent associations with health outcomes, is needed.

Development of Momentary Appetite Capture (MAC): A versatile tool for monitoring appetite over long periods.

Understanding how an intervention impacts appetite in real-life settings and over several days remains a challenging and under-explored research question. To this end, we developed Momentary Appetite Capture (MAC), a form of ecological momentary assessment that combines automated text messaging with an online platform. Participants report their appetite using visual analogue scales (hunger, desire to eat, and fullness) and a virtual portion-size selection task. In two separate studies, we assessed the feasibility and test-retest reliability of MAC. Participants were prompted every 2 hours over a 14-hour window, and they repeated this assessment over two consecutive weekdays. For each participant, we calculated a daily time-averaged area under the curve (AUC) for each appetite measure. In Study One (N = 25) time-averaged AUC was significantly positively correlated across test days for hunger (r = 0.563, p = .003), desire to eat (r = 0.515, p = .008) and prospective portion size (r = 0.914, p < .001), but not for fullness (r = 0.342, p = .094). Participants completed 95% of MACs (380 of 400), and we used participant feedback to improve the MAC tool and study protocol for Study Two. In Study Two (N = 31), 94% of MACs were completed (468 of 496). Across days, time-averaged AUC was significantly positively correlated for hunger (r = 0.595, p = < .001), fullness (r = 0.501, p = .004), desire to eat (r = 0.585, p < .001), and prospective portion size (r = 0.757, p < .001). Together, these studies suggest that MAC could be an acceptable and reliable tool to track appetite throughout the day. In the future, MAC could be used to explore the impact of weight-loss interventions on natural fluctuations in appetite.

Evaluating Eating Behaviour, Energy Homeostasis, and Obesity in Childhood-Onset Craniopharyngioma: A Feasibility Study.

INTRODUCTION: Craniopharyngiomas are rare brain tumours (incidence 1.1-1.7 cases/million/year). Although non-malignant, craniopharyngioma causes major endocrine and visual morbidities including hypothalamic obesity, yet mechanisms leading to obesity are poorly understood. This study investigated the feasibility and acceptability of eating behaviour measures in patients with craniopharyngioma to inform the design of future trials. METHODS: Patients with childhood-onset craniopharyngioma and controls matched for sex, pubertal stage, and age were recruited. After an overnight fast, participants received the following measures: body composition, resting metabolic rate, oral glucose tolerance test including magnetic resonance imaging (patients only), appetite ratings, eating behaviour, and quality of life questionnaires, ad libitum lunch, and an acceptability questionnaire. Data are reported as median ± IQR, with effect size measure (Cliff's delta) and Kendall's tau for correlations, due to the small sample size. RESULTS: Eleven patients (median age = 14 years; 5 F/6 M) and matched controls (median age = 12 years; 5 F/6 M) were recruited. All patients had received surgery, and 9/11 also received radiotherapy. Hypothalamic damage post-surgery was graded (Paris grading): grade 2 n = 6; grade 1 n = 1; grade 0 n = 2. The included measures were deemed highly tolerable by participants and their parent/carers. Preliminary data suggest a difference in hyperphagia between patients and controls (d = 0.5), and a relationship between hyperphagia with body mass index standard deviation score (BMISDS) in patients (τ = 0.46). DISCUSSION: These findings demonstrate that eating behaviour research is feasible and acceptable to craniopharyngioma patients and there is an association between BMISDS and hyperphagia in patients. Thus, food approach and avoidance behaviours may be useful targets for interventions to manage obesity in this patient group.

Integrating COM-B and the person-based approach to develop an ACT based therapy programme to raise self-determination in adolescents with obesity.

BACKGROUND: This paper details the development of the Adolescent Intrinsic Motivation 'AIM2Change' intervention to support weight-management in young people previously unable to make changes whilst attending a tier 3 weight management service for children and young people. AIM2Change is an acceptance and commitment therapy based intervention that will be delivered one-to-one online over a seven-week period. METHODS: To develop this intervention, we have triangulated results from a qualitative research study, patient and public involvement groups (PPI) and a COM-B (capability, opportunity, motivation, behaviour) analysis, in a method informed by the person-based approach. RESULTS: The integrated development approach yielded a broad range of perspectives and facilitated the creation of a tailored intervention to meet the needs of the patient group whist remaining pragmatic and deliverable. CONCLUSIONS: The next steps for this intervention will be in-depth co-development of the therapy sessions with service users, before implementing a proof of concept trial.

Current evidence for designing self-management support for underserved populations: an integrative review using the example of diabetes.

AIMS: With numerous and continuing attempts at adapting diabetes self-management support programmes to better account for underserved populations, its important that the lessons being learned are understood and shared. The work we present here reviews the latest evidence and best practice in designing and embedding culturally and socially sensitive, self-management support programmes. METHODS: We explored the literature with regard to four key design considerations of diabetes self-management support programmes: Composition - the design and content of written materials and digital tools and interfaces; Structure - the combination of individual and group sessions, their frequency, and the overall duration of programmes; Facilitators - the combination of individuals used to deliver the programme; and Context - the influence and mitigation of a range of individual, socio-cultural, and environmental factors. RESULTS: We found useful and recent examples of design innovation within a variety of countries and models of health care delivery including Brazil, Mexico, Netherlands, Spain, United Kingdom, and United States of America. Within Composition we confirmed the importance of retaining best practice in creating readily understood written information and intuitive digital interfaces; Structure the need to offer group, individual, and remote learning options in programmes of flexible duration and frequency; Facilitators where the benefits of using culturally concordant peers and community-based providers were described; and finally in Context the need to integrate self-management support programmes within existing health systems, and tailor their various constituent elements according to the language, resources, and beliefs of individuals and their communities. CONCLUSIONS: A number of design principles across the four design considerations were identified that together offer a promising means of creating the next generation of self-management support programme more readily accessible for underserved communities. Ultimately, we recommend that the precise configuration should be co-produced by all relevant service and patient stakeholders and its delivery embedded in local health systems.

Views of children with diabetes from underserved communities, and their families on diabetes, glycaemic control and healthcare provision: A qualitative evidence synthesis.

AIMS: Children and young people with diabetes (CYPD) from socio-economically deprived and/or ethnic minority groups tend to have poorer glucose control and greater risk of diabetes-related complications. In this systematic review of qualitative evidence (qualitative evidence synthesis, QES), we aimed to explore the experiences and views of clinical encounters in diabetes care from the perspectives of CYPD and their family/carers from underserved communities and healthcare professionals in diabetes care. METHODS: We searched 6 databases to March 2022 with extensive search terms, and used a thematic synthesis following methods of Thomas and Harden. RESULTS: We identified 7 studies and described 11 descriptive themes based on primary and secondary constructs. From these, three "analytical themes" were developed. (1) "Alienation of CYPD" relates to their social identity and interaction with peers, family and health service practitioners in the context of diabetes self- and family/carer management and is impacted by communication in the clinical encounter. (2) "Empowerment of CYPD and family/carers" explores families' understanding of risks and consequences of diabetes and taking responsibility for self- and family/carer management in the context of their socio-cultural background. (3) "Integration of diabetes (into self and family)" focuses on the ability to integrate diabetes self-management into the daily lives of CYPD and family/carers beyond the clinical consultation. CONCLUSIONS: The analytical themes are interdependent and provide a conceptual framework from which to explore and strengthen the therapeutic alliance in clinical encounters and to foster greater concordance with treatment plans. Communicating the biomedical aspects of managing diabetes in the clinical encounter is important, but should be balanced with addressing socio-emotional factors important to CYPD and family/carers.

Implementation of flash glucose monitoring in four pediatric diabetes clinics: controlled before and after study to produce real-world evidence of patient benefit.

AIMS: To assess the real-world evidence for flash glucose monitoring (Abbott FreeStyle Libre) for children with type 1 diabetes in terms of glucose control, secondary healthcare resources and costs. RESEARCH DESIGN AND METHODS: We conducted a controlled before and after study (approximately 12 months before and after) using routinely collected health record data on children who start using flash monitors and a control population of children with self-monitoring of blood glucose (SMBG). Our population-based sample of eligible individuals using flash monitoring (n=114) and controls (n=80) aged between 4 and 18 years was drawn from four paediatric diabetes clinics (secondary care) in the South West England. Outcome measures included: glycated hemoglobin (HbA1c), frequency of BG tests; frequency of sensor scans; time in recommended glucose range; short-term complications (hypoglycemia, diabetic ketoacidosis and related illness resulting in investigation) and secondary care costs. RESULTS: After adjustment for age, time since diagnosis, deprivation and the test modality (point of care or laboratory), the mean HbA1c reading for controls was 61.2 (mmol/mol) for the period before and 63.9 after. For individuals using flash monitoring, the adjusted mean HbA1c reading was 64.6 for the period before implementation and 63.8 after. Rates of short-term complications were low across all groups in the study. Whereas the 'after' flash monitoring group had substantially higher incremental costs (+£703 vs the flash monitoring 'before' comparison and +£841 vs contemporaneous SMBG controls), these cost differences were driven by primary care prescribing (sensor costs). CONCLUSIONS: There was some indication that flash monitoring might help young people improve the control of their diabetes but for our sample, the difference between finger-prick testing and flash monitoring was not clinically significant (HbA1c improvement <5 mmol/mol). Given the pace of technological change within diabetes, research efforts should now facilitate the real-time analysis of long-term routine data on flash and continuous glucose monitors.

Case report: Molecular characterisation of adipose-tissue derived cells from a patient with ROHHAD syndrome.

There have been over 100 cases of Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome reported, but there is currently no curative treatment for children with this condition. We aimed to better characterise adipose cells from a child with ROHHAD syndrome. We isolated pre-adipocytes from a 4 year-old female patient with ROHHAD syndrome and assessed proliferation rate of these cells. We evaluated levels of DLP-Pref-1(pre-adipocyte marker) using western blotting, and concentrations of interleukin-6(IL-6) using ELISA. We performed next-generation sequencing (NGS) and bioinformatic analyses on these cells compared to tissue from an age/sex-matched control. The two most up-/down-regulated genes were validated using QPCR. We successfully isolated pre-adipocytes from a fat biopsy, by confirming the presence of Pref-1 and differentiated them to mature adipocytes. Interleukin 6, (Il-6) levels were 5.6-fold higher in ROHHAD cells compared to a control age/sex-matched biopsy. NGS revealed 25,703 differentially expressed genes (DEGs) from ROHHAD cells vs. control of which 2,237 genes were significantly altered. The 20 most significantly up/down-regulated genes were selected for discussion. This paper describes the first transcriptomic analysis of adipose cells from a child with ROHHAD vs. normal control adipose tissue as a first step in identifying targetable pathways/mechanisms underlying this condition with novel therapeutic interventions.

The Effect of Intermittent Fasting on Appetite: A Systematic Review and Meta-Analysis.

Previously, narrative reviews have considered the effects of intermittent fasting on appetite. One suggestion is that intermittent fasting attenuates an increase in appetite that typically accompanies weight loss. Here, we conducted the first systematic review and meta-analysis to quantify the effects of intermittent fasting on appetite, when compared to a continuous energy restriction intervention. Five electronic databases and trial registers were searched in February 2021 and February 2022. Abstracts (N = 2800) were screened and 17 randomized controlled trials (RCTs), consisting of a variety of intermittent fasting regimes, met our inclusion criteria. The total number of participants allocated to interventions was 1111 and all RCTs were judged as having either some concerns or a high risk of bias (Cochrane RoB 2.0 tool). Random effects meta-analyses were conducted on change-from-baseline appetite ratings. There was no clear evidence that intermittent fasting affected hunger (WMD = -3.03; 95% CI [-8.13, 2.08]; p = 0.25; N = 13), fullness (WMD = 3.11; 95% CI [-1.46, 7.69]; p = 0.18; N = 10), desire to eat (WMD = -3.89; 95% CI [-12.62, 4.83]; p = 0.38; N = 6), or prospective food consumption (WMD = -2.82; 95% CI [-3.87, 9.03]; p = 0.43; N = 5), differently to continuous energy restriction interventions. Our results suggest that intermittent fasting does not mitigate an increase in our drive to eat that is often associated with continuous energy restriction.

Exploring the acute effects of running on cerebral blood flow and food cue reactivity in healthy young men using functional magnetic resonance imaging.

Acute exercise suppresses appetite and alters food-cue reactivity, but the extent exercise-induced changes in cerebral blood flow (CBF) influences the blood-oxygen-level-dependent (BOLD) signal during appetite-related paradigms is not known. This study examined the impact of acute running on visual food-cue reactivity and explored whether such responses are influenced by CBF variability. In a randomised crossover design, 23 men (mean ± SD: 24 ± 4 years, 22.9 ± 2.1 kg/m2 ) completed fMRI scans before and after 60 min of running (68% ± 3% peak oxygen uptake) or rest (control). Five-minute pseudo-continuous arterial spin labelling fMRI scans were conducted for CBF assessment before and at four consecutive repeat acquisitions after exercise/rest. BOLD-fMRI was acquired during a food-cue reactivity task before and 28 min after exercise/rest. Food-cue reactivity analysis was performed with and without CBF adjustment. Subjective appetite ratings were assessed before, during and after exercise/rest. Exercise CBF was higher in grey matter, the posterior insula and in the region of the amygdala/hippocampus, and lower in the medial orbitofrontal cortex and dorsal striatum than control (main effect trial p ≤ .018). No time-by-trial interactions for CBF were identified (p ≥ .087). Exercise induced moderate-to-large reductions in subjective appetite ratings (Cohen's d = 0.53-0.84; p ≤ .024) and increased food-cue reactivity in the paracingulate gyrus, hippocampus, precuneous cortex, frontal pole and posterior cingulate gyrus. Accounting for CBF variability did not markedly alter detection of exercise-induced BOLD signal changes. Acute running evoked overall changes in CBF that were not time dependent and increased food-cue reactivity in regions implicated in attention, anticipation of reward, and episodic memory independent of CBF.

An App-Based Intervention for Pediatric Weight Management: Pre-Post Acceptability and Feasibility Trial.

BACKGROUND: A multidisciplinary approach to weight management is offered at tier 3 pediatric weight management services in the United Kingdom. Encouraging dietary change is a major aim, with patients meeting with dieticians, endocrinologists, psychologists, nurse specialists, and social workers on average every other month. OBJECTIVE: This research sought to trial an inhibitory control training smartphone app-FoodT-with the clinic population of a pediatric weight management service. FoodT has shown positive impacts on food choice in adult users, with resulting weight loss. It was hoped that when delivered as an adjunctive treatment alongside the extensive social, medical, psychological, and dietetic interventions already offered at the clinic, the introduction of inhibitory control training may offer patients another tool that supports eating choice. In this feasibility trial, recruitment, retention, and app use were the primary outcomes. An extensive battery of measures was included to test the feasibility and acceptability of these measures for future powered trials. METHODS: FoodT was offered to pediatric patients and their parents during a routine clinic appointment, and patients were asked to use the app at home every day for the first week and once per week for the rest of the month. Feasibility and acceptability were measured in terms of recruitment, engagement with the app, and retention to the trial. A battery of psychometric tests was given before and after app use to assess the acceptability of collecting data on changes to food choices and experiences that would inform future trial work. RESULTS: A total of 12 children and 10 parents consented (22/62, 35% of those approached). Further, 1 child and no parents achieved the recommended training schedule. No participants completed the posttrial measures. The reasons for not wanting to be recruited to the trial included participants not considering their weight to be connected to eating choices and not feeling that the app suited their needs. No reasons are known for noncompletion. CONCLUSIONS: It is unclear whether the intervention itself or the research processes, including the battery of measures, prevented completion. It is therefore difficult to make any decisions as to the value that the app has within this setting. Important lessons have been learned from this research that have potential broad relevance, including the importance of co-designing interventions with service users and avoiding deterring people from early-stage participation in extensive data collection.

Evaluating the benefit of early patient and public involvement for product development and testing with small companies.

INTRODUCTION: There is a growing understanding of the benefits of patient and public involvement (PPI), and its evaluation, in research. An online version of the CUBE PPI evaluation framework has been developed. We sought to use the CUBE to evaluate the value of early PPI with two small healthcare companies during product development. METHODS: Contributors were recruited online and had lived experience of either type 1 diabetes or obesity. Two 1-h sessions were run with a company developing a smartphone application to manage diabetes (DEE-EM): one with young people (YP; n = 5) and one with parents (n = 7). Two 1-h sessions were run with a company developing a weight-loss product, both with adults (n = 7 in each session). Sessions were facilitated by an independent University researcher and attended by company representatives, who presented their product. One facilitator led the evaluation of the session by giving a demonstration of the CUBE and asking simple questions in the YP session. RESULTS: A high proportion of contributors completed the CUBE (80.5% DEE-EM; 93% Oxford Medical Products). Responses were positive to all four CUBE dimensions (in italics). Contributors felt there were diverse ways to contribute to the sessions, and that they had a strong voice to add to the discussion. Balance was achieved regarding whose concerns (public or company) led the agenda, and contributors felt that both companies would make changes based on the discussion. The supportive attitude of both companies resulted in most contributors feeling comfortable participating in PPI sessions with the industry, while recognising the profit-making aspect of their work. CONCLUSIONS: PPI with small healthcare companies is both feasible and worthwhile. The CUBE framework facilitated the evaluation of the interaction between experts in different knowledge spaces. We provide recommendations for future projects, including considerations of who should participate and the level of implicit endorsement of the product that participation implies. PATIENT OR PUBLIC CONTRIBUTION: People with lived experience of type 1 diabetes or obesity were invited to contribute to one of four PPI sessions, which they then evaluated. One contributor agreed to contribute to the analysis of the evaluation data and interpretation and preparation of the manuscript.

Rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome - neuro-endocrine tumours (ROHHAD-NET): case series and learning points.

OBJECTIVES: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation (ROHHAD) is a rare syndrome associated with high morbidity and mortality. Diagnosis is often challenging. We describe three cases of ROHHAD with heterogeneous presentations but some consistent clinical features, including hyperprolactinaemia at diagnosis. We highlight when the diagnosis of ROHHAD should be considered at an early stage. CASE PRESENTATION: All three patients presented between 4 and 6 years old with rapid-onset obesity. They all have central hypoventilation requiring nocturnal BiPAP, varying degrees of hypothalamic dysfunction with hyperprolactinaemia being a consistent feature, and autonomic dysfunction. One patient has a neuro-endocrine tumour (NET) and two have glucose dysregulation. CONCLUSIONS: High prolactin was a consistent early feature. Central hypoventilation and NET may present later and therefore regular sleep studies and screening for NETs are required. A high suspicion of ROHHAD is warranted in patients with rapid, early-onset obesity and hyperprolactinaemia without structural pituitary abnormality.

Developments in the design and delivery of self-management support for children and young people with diabetes: A narrative synthesis of systematic reviews.

AIMS: Facilitated self-management support programmes have become central to the treatment of chronic diseases including diabetes. For many children and young people with diabetes (CYPD), the impact on glycated haemoglobin (HbA1c ) and a range of self-management behaviours promised by these programmes remain unrealised. This warrants an appraisal of current thinking and the existing evidence to guide the development of programmes better targeted at this age group. METHODS: Create a narrative review of systematic reviews produced in the last 3 years that have explored the impact on CYPD of the four key elements of self-management support programmes: education, instruction and advice including peer support; psychological counselling via a range of therapies; self-monitoring, including diaries and telemetric devices; and telecare, the technology-enabled follow-up and support by healthcare providers. RESULTS: Games and gamification appear to offer a promising means of engaging and educating CYPD. Psychological interventions when delivered by trained practitioners, appear to improve HbA1c and quality of life although effect sizes were small. Technology-enabled interactive diaries can increase the frequency of self-monitoring and reduce levels of HbA1c . Telecare provided synchronously via telephone produced significant improvements in HbA1c . CONCLUSIONS: The cost-effective flexibility of increasing the reliance on technology is an attractive proposition; however, there are resource implications for digital connectivity in underserved populations. The need remains to improve the understanding of which elements of each component are most effective in a particular context, and how to optimise the influence and input of families, caregivers and peers.

Preference for high-carbohydrate foods does not change for children and adolescents in insulin-induced hypoglycemia.

INTRODUCTION: Hypoglycemia elicits coordinated counter-regulatory neuroendocrine responses. The extent to which this process involves an increased drive to eat, together with greater preference for foods high in carbohydrate content, is unclear. Our objective was to examine this effect in children and adolescents (age 5-19 years) without diabetes and no prior known experience of hypoglycemic episodes. RESEARCH DESIGN AND METHODS: We administered a computerised task designed to examine preference for high-carbohydrate foods (sweet and savory) to pediatric patients (n=26) undergoing an insulin tolerance test as part of the routine clinical assessment of pituitary hormone secretory capacity. The task was completed at baseline and three time points after intravenous infusion of insulin (approximately 7, 20 and 90 min). RESULTS: Although all patients reached insulin-induced hypoglycemia (mean venous glucose at nadir=1.9 mmol/L), there was moderate evidence of no effect on preference for high-carbohydrate foods (moderate evidence for the null hypothesis) compared with euglycemia. Patients also did not display an increase in selection of foods of high compared with low energy density. Sensitivity of the task was demonstrated by decreased preference for sweet, high-carbohydrate foods after consumption of sweet food and drink. CONCLUSIONS: Results support the view that acute hypoglycemia does not automatically prompt the choice of high-carbohydrate foods for rapid glucose restoration, and further stresses the importance that people and families with children vulnerable to hypoglycemic episodes ensure that 'rapidly absorbed glucose rescue therapy' is always available.

Evaluating future risk of NAFLD in adolescents: a prediction and decision curve analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex. METHODS: Aged 24 years, 4018 ALSPAC participants had transient elastography (TE) and controlled attenuation parameter (CAP) measurement using Echosens 502 Touch. 513 participants with harmful alcohol consumption were excluded. Logistic regression models examined which variables measured at 17 years were predictive of NAFL and NAFLD fibrosis in young adults. Predictors included sex, BMI, central adiposity, lipid profile, blood pressure, liver function tests, homeostatic model assessment for insulin resistance (HOMA-IR), and ultrasound defined NAFL at 17 years (when examining fibrosis outcomes). A model including all these variables was termed "routine clinical measures". Models were compared using area under the receiver operator curve (AUROC) and Bayesian Information Criterion (BIC), analysis, which penalises model complexity. Models were tested in all participants and those with overweight or obese standardised BMIs (BMI SDS) centiles at the 17-year time point. A decision curve analysis (DCA) was performed to evaluate the clinical utility of models in overweight and obese adolescents predicting NAFLD fibrosis at a threshold probability of 0.1. RESULTS: The "routine clinical measures" model had the highest AUROC for predicting NAFL in all adolescent participants (AUROC 0.79 [SD 0.00]) and those with an overweight/obese BMI SDS centile (AUROC 0.77 [SD 0.01]). According to BIC analysis, insulin resistance was the best predictor of NAFL in all adolescents, whilst central adiposity was the best predictor in those with an overweight/obese BMI SDS centile. The "routine clinical measures" model also had the highest AUROC for predicting NAFLD fibrosis in all adolescent participants (AUROC 0.78 [SD 0.02]) and participants with an overweight/obese BMI SDS centile (AUROC 0.84 [SD 0.03]). However, following BIC analysis, BMI was the best predictor of NAFLD fibrosis in all adolescents including those with an overweight/obese BMI SDS centile. A decision curve analysis examining overweight/obese adolescent participants showed the model that had the greatest net benefit for increased NAFLD fibrosis detection, above a treat all overweight and obese adolescents' assumption, was the "routine clinical measures" model. However, the net benefit was marginal (0.0054 [0.0034-0.0075]). CONCLUSION: In adolescents, routine clinical measures were not superior to central adiposity and BMI at predicting NAFL and NAFLD fibrosis respectively in young adulthood. Additional routine clinical measurements do provide incremental benefit in detecting true positive fibrosis cases, but the benefit is small. Thus, to reduce morbidity and mortality associated with NASH cirrhosis in adults, the ultimate end point of NAFLD, the focus must be on obesity management at a population level.

Rituximab therapy in ROHHAD(NET) syndrome.

OBJECTIVES: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation, and neural-crest tumour (ROHHAD(NET)) is a rare syndrome presenting in early childhood associated with high morbidity and mortality. There is no specific diagnostic biomarker and diagnosis is based on clinical features. An autoimmune origin has been postulated. CASE PRESENTATION: Management is largely supportive. We report a case of a five-year old female who presented in respiratory arrest after 6-months of rapid weight gain. She had central hypoventilation, central diabetes insipidus, growth hormone deficiency and hyperprolactinaemia. She displayed elevated interleukin-6 levels on cytokine serology which normalised after rituximab treatment. After rituximab treatment, her weight reduced significantly from greatly above the 99.6th to the 50th centile in 12 months. CONCLUSIONS: This response possibly reflects an underlying, immune-inflammatory pathology driving excess adiposity in this condition. Potentially, other aspects of ROHHAD(NET) may be mediated through autoimmune dysregulation in which case rituximab may provide benefits for prognosis and survival.

The feasibility, acceptability, and benefit of interventions that target eating speed in the clinical treatment of children and adolescents with overweight or obesity: A systematic review and meta-analysis.

Eating at a faster speed is positively correlated with having a higher BMI. Modifying eating speed may offer a treatment opportunity for those with overweight and obesity. This review sought to understand the feasibility, acceptability, and benefit to using eating speed interventions in paediatric clinical weight-management settings. The PICO Framework was used. Clinical studies of eating speed interventions as a treatment for paediatric patients with overweight or obesity were included. No limits to search date were implemented. A systematic search of MEDLINE, PsychINFO and EMBASE via OVID, Web of Science and JBI, Database of systematic reviews and Implementation reports, along with trial registers NICE, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials was conducted. Two authors were responsible for screening, extraction, and evaluation of the risk of bias. Fifteen papers reporting twelve interventions addressing eating-speed were identified, involving a total of 486 active participants (range 7-297). Study design was weak with only one full RCT and there were some concerns over quality and risk of bias (Cochrane RoB 2.0). Limited sample sizes and different measured outcomes did not allow powered evaluations of effect for all outcomes. There is some indication, overall, that addressing eating speed has the potential to be a beneficial adjunct to clinical obesity treatment, although the pooled effect estimate did not demonstrate a difference in BMISDS status following eating speed interventions compared to control [pooled mean difference (0.04, 95% CI -0.39 to 0.46, N = 3)]. Developments to improve the engagement to, and acceptability of, interventions are required, alongside rigorous high-quality trials to evaluate effectiveness.

Treatment of Barth Syndrome by Cardiolipin Manipulation (CARDIOMAN) With Bezafibrate: Protocol for a Randomized Placebo-Controlled Pilot Trial Conducted in the Nationally Commissioned Barth Syndrome Service.

BACKGROUND: Barth syndrome is a rare, life-threatening, X-linked recessive genetic disease that predominantly affects young males and is caused by abnormal mitochondrial lipid metabolism. Currently, there is no definitive treatment for Barth syndrome other than interventions to ameliorate acute symptoms, such as heart failure, cardiac arrhythmias, neutropenia, and severe muscle fatigue. Previous mechanistic studies have identified the lipid-lowering drug bezafibrate as a promising potential treatment; however, to date, no human trials have been performed in this population. OBJECTIVE: The aim of this study is to determine whether bezafibrate (and resveratrol in vitro) will increase mitochondrial biogenesis and potentially modify the cellular ratio of monolysocardiolipin (MLCL) to tetralinoleoyl-cardiolipin (L4-CL), ameliorating the disease phenotype in those living with the disease. METHODS: The CARDIOMAN (Cardiolipin Manipulation) study is a UK single-center, double-blinded, randomized, placebo-controlled crossover study investigating the efficacy of bezafibrate in participants with Barth syndrome. Treatment was administered in two 15-week phases with a minimum washout period of 1 month between the phases where no treatment was administered. The primary outcome is peak oxygen consumption (VO2 peak). Secondary outcomes include MLCL/L4-CL ratio and CL profile in blood cells, amino acid expression, phosphocreatine to adenosine triphosphate ratio in cardiac muscle and skeletal muscle oxidative function on phosphorus-31 magnetic resonance spectroscopy, quality of life using the Pediatric Quality of Life Inventory questionnaire, absolute neutrophil count, cardiac function and rhythm profiles at rest and during exercise, and mitochondrial organization and function assessments. Outcomes were assessed at baseline and during the final week of each treatment phase. RESULTS: A total of 12 patients were scheduled to participate across three consecutive research clinics between March and April 2019. In total, 11 participants were recruited, and the follow-up was completed in January 2020. Data analysis is ongoing, with publication expected in 2021. CONCLUSIONS: This trial was approved by the United Kingdom National Research Ethics Service Committee and the Medicines and Healthcare products Regulatory Agency. The feasibility of the CARDIOMAN study will help to inform the future conduct of randomized controlled trials in rare disease populations as well as testing the efficacy of bezafibrate as a potential treatment for the disease and advancing the mechanistic understanding of Barth syndrome. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 58006579; https://www.isrctn.com/ISRCTN58006579. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/22533.

When do children learn how to select a portion size?

The reduction of portion sizes supports weight-loss. This study looks at whether children have a conceptual understanding of portion size, by studying their ability to manually serve a portion size that corresponds to what they eat. In a clinical setting, discussion around portion size is subjective thus a computerised portion size tool is also trialled, with the portion sizes chosen on the screen being compared to amounts served manually. Children (n = 76) age 5-6, 7-8 and 10-11 were asked to rate their hunger (VAS scale), liking (VAS scale) and 'ideal portion size for lunch' of eight interactive meal images using a computerised portion size tool. Children then manually self-served and consumed a portion of pasta. Plates were weighed to allow for the calculation of calories served and eaten. A positive correlation was found between manually served food portions and the amount eaten (r = 0.53, 95%CI [0.34, 0.82, P < .001), indicating that many children were able to anticipate their likely food intake prior to meal onset. A regression model demonstrates that age contributes to 9.4% of the variance in portion size accuracy (t(68) = -2.3, p = .02). There was no relationship between portion size and either hunger or liking. The portion sizes chosen on the computer at lunchtime correlated to the amount manually served overall (r = .34, 95%CI [0.07, 0.55], p < .01), but not in 5-6-year-old children. Manual portion-size selection can be observed in five-year olds and from age seven, children's 'virtual' responses correlate with their manual portion selections. The application of the computerised portion-size tool requires further development but offers considerable potential.