The Effectiveness of Strategies to Improve User Engagement With Digital Health Interventions Targeting Nutrition, Physical Activity, and Overweight and Obesity: Systematic Review and Meta-Analysis.

BACKGROUND: Digital health interventions (DHIs) are effective in improving poor nutrition, physical inactivity, overweight and obesity. There is evidence suggesting that the impact of DHIs may be enhanced by improving user engagement. However, little is known about the overall effectiveness of strategies on engagement with DHIs. OBJECTIVE: This study aims to assess the overall effectiveness of strategies to improve engagement with DHIs targeting nutrition, physical activity, and overweight or obesity and explore associations between strategies and engagement outcomes. The secondary aim was to explore the impact of these strategies on health risk outcomes. METHODS: The MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, Scopus, and Academic Source Complete databases were searched up to July 24, 2023. Eligible studies were randomized controlled trials that evaluated strategies to improve engagement with DHIs and reported on outcomes related to DHI engagement (use or user experience). Strategies were classified according to behavior change techniques (BCTs) and design features (eg, supplementary emails). Multiple-variable meta-analyses of the primary outcomes (usage and user experience) were undertaken to assess the overall effectiveness of strategies. Meta-regressions were conducted to assess associations between strategies and use and user experience outcomes. Synthesis of secondary outcomes followed the "Synthesis Without Meta-Analysis" guidelines. The methodological quality and evidence was assessed using the Cochrane risk-of-bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation tool respectively. RESULTS: Overall, 54 studies (across 62 publications) were included. Pooled analysis found very low-certainty evidence of a small-to-moderate positive effect of the use of strategies to improve DHI use (standardized mean difference=0.33, 95% CI 0.20-0.46; P<.001) and very low-certainty evidence of a small-to-moderate positive effect on user experience (standardized mean difference=0.29, 95% CI 0.07-0.52; P=.01). A significant positive association was found between the BCTs social support (effect size [ES]=0.40, 95% CI 0.14-0.66; P<.001) and shaping knowledge (ES=0.39, 95% CI 0.03-0.74; P=.03) and DHI use. A significant positive association was found among the BCTs social support (ES=0.70, 95% CI 0.18-1.22; P=.01), repetition and substitution (ES=0.29, 95% CI 0.05-0.53; P=.03), and natural consequences (ES=0.29, 95% CI 0.05-0.53; P=.02); the design features email (ES=0.29, 95% CI 0.05-0.53; P=.02) and SMS text messages (ES=0.34, 95% CI 0.11-0.57; P=.01); and DHI user experience. For secondary outcomes, 47% (7/15) of nutrition-related, 73% (24/33) of physical activity-related, and 41% (14/34) of overweight- and obesity-related outcomes reported an improvement in health outcomes. CONCLUSIONS: Although findings suggest that the use of strategies may improve engagement with DHIs targeting such health outcomes, the true effect is unknown because of the low quality of evidence. Future research exploring whether specific forms of social support, repetition and substitution, natural consequences, emails, and SMS text messages have a greater impact on DHI engagement is warranted. TRIAL REGISTRATION: PROSPERO CRD42018077333; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=77333.

Healthy eating interventions delivered in early childhood education and care settings for improving the diet of children aged six months to six years.

BACKGROUND: Dietary intake during early childhood can have implications on child health and developmental trajectories. Early childhood education and care (ECEC) services are recommended settings to deliver healthy eating interventions as they provide access to many children during this important period. Healthy eating interventions delivered in ECEC settings can include strategies targeting the curriculum (e.g. nutrition education), ethos and environment (e.g. menu modification) and partnerships (e.g. workshops for families). Despite guidelines supporting the delivery of healthy eating interventions in this setting, little is known about their impact on child health. OBJECTIVES: To assess the effectiveness of healthy eating interventions delivered in ECEC settings for improving dietary intake in children aged six months to six years, relative to usual care, no intervention or an alternative, non-dietary intervention. Secondary objectives were to assess the impact of ECEC-based healthy eating interventions on physical outcomes (e.g. child body mass index (BMI), weight, waist circumference), language and cognitive outcomes, social/emotional and quality-of-life outcomes. We also report on cost and adverse consequences of ECEC-based healthy eating interventions. SEARCH METHODS: We searched eight electronic databases including CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, ERIC, Scopus and SportDiscus on 24 February 2022. We searched reference lists of included studies, reference lists of relevant systematic reviews, the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov and Google Scholar, and contacted authors of relevant papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster-RCTs, stepped-wedge RCTs, factorial RCTs, multiple baseline RCTs and randomised cross-over trials, of healthy eating interventions targeting children aged six months to six years that were conducted within the ECEC setting. ECEC settings included preschools, nurseries, kindergartens, long day care and family day care. To be included, studies had to include at least one intervention component targeting child diet within the ECEC setting and measure child dietary or physical outcomes, or both. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently screened titles and abstracts and extracted study data. We assessed risk of bias for all studies against 12 criteria within RoB 1, which allows for consideration of how selection, performance, attrition, publication and reporting biases impact outcomes. We resolved discrepancies via consensus or by consulting a third review author. Where we identified studies with suitable data and homogeneity, we performed meta-analyses using a random-effects model; otherwise, we described findings using vote-counting approaches and via harvest plots. For measures with similar metrics, we calculated mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. We calculated standardised mean differences (SMDs) for primary and secondary outcomes where studies used different measures. We applied GRADE to assess certainty of evidence for dietary, cost and adverse outcomes. MAIN RESULTS: We included 52 studies that investigated 58 interventions (described across 96 articles). All studies were cluster-RCTs. Twenty-nine studies were large (≥ 400 participants) and 23 were small (< 400 participants). Of the 58 interventions, 43 targeted curriculum, 56 targeted ethos and environment, and 50 targeted partnerships. Thirty-eight interventions incorporated all three components. For the primary outcomes (dietary outcomes), we assessed 19 studies as overall high risk of bias, with performance and detection bias being most commonly judged as high risk of bias. ECEC-based healthy eating interventions versus usual practice or no intervention may have a positive effect on child diet quality (SMD 0.34, 95% confidence interval (CI) 0.04 to 0.65; P = 0.03, I2 = 91%; 6 studies, 1973 children) but the evidence is very uncertain. There is moderate-certainty evidence that ECEC-based healthy eating interventions likely increase children's consumption of fruit (SMD 0.11, 95% CI 0.04 to 0.18; P < 0.01, I2 = 0%; 11 studies, 2901 children). The evidence is very uncertain about the effect of ECEC-based healthy eating interventions on children's consumption of vegetables (SMD 0.12, 95% CI -0.01 to 0.25; P =0.08, I2 = 70%; 13 studies, 3335 children). There is moderate-certainty evidence that ECEC-based healthy eating interventions likely result in little to no difference in children's consumption of non-core (i.e. less healthy/discretionary) foods (SMD -0.05, 95% CI -0.17 to 0.08; P = 0.48, I2 = 16%; 7 studies, 1369 children) or consumption of sugar-sweetened beverages (SMD -0.10, 95% CI -0.34 to 0.14; P = 0.41, I2 = 45%; 3 studies, 522 children). Thirty-six studies measured BMI, BMI z-score, weight, overweight and obesity, or waist circumference, or a combination of some or all of these. ECEC-based healthy eating interventions may result in little to no difference in child BMI (MD -0.08, 95% CI -0.23 to 0.07; P = 0.30, I2 = 65%; 15 studies, 3932 children) or in child BMI z-score (MD -0.03, 95% CI -0.09 to 0.03; P = 0.36, I2 = 0%; 17 studies; 4766 children). ECEC-based healthy eating interventions may decrease child weight (MD -0.23, 95% CI -0.49 to 0.03; P = 0.09, I2 = 0%; 9 studies, 2071 children) and risk of overweight and obesity (RR 0.81, 95% CI 0.65 to 1.01; P = 0.07, I2 = 0%; 5 studies, 1070 children). ECEC-based healthy eating interventions may be cost-effective but the evidence is very uncertain (6 studies). ECEC-based healthy eating interventions may have little to no effect on adverse consequences but the evidence is very uncertain (3 studies). Few studies measured language and cognitive skills (n = 2), social/emotional outcomes (n = 2) and quality of life (n = 3). AUTHORS' CONCLUSIONS: ECEC-based healthy eating interventions may improve child diet quality slightly, but the evidence is very uncertain, and likely increase child fruit consumption slightly. There is uncertainty about the effect of ECEC-based healthy eating interventions on vegetable consumption. ECEC-based healthy eating interventions may result in little to no difference in child consumption of non-core foods and sugar-sweetened beverages. Healthy eating interventions could have favourable effects on child weight and risk of overweight and obesity, although there was little to no difference in BMI and BMI z-scores. Future studies exploring the impact of specific intervention components, and describing cost-effectiveness and adverse outcomes are needed to better understand how to maximise the impact of ECEC-based healthy eating interventions.

The impact of an e-newsletter or animated video to disseminate outdoor free-play information in relation to COVID-19 guidelines in New South Wales early childhood education and care services: a randomised controlled trial.

BACKGROUND: State-based Guidelines were issued for Early Childhood Education and Care (ECEC) services (caring for children 0-6 years) recommending greater time outdoors and inclusion of indoor-outdoor programs to facilitate social distancing to reduce spread of COVID-19. The aim of this 3-arm randomised controlled trial (RCT) was to examine the impact of different dissemination strategies on increasing ECEC service intentions to adopt recommendations from the Guidelines. METHODS: This was a post-intervention only RCT. A sample of eligible ECEC services in New South Wales (n = 1026) were randomly allocated to one of three groups; (i) e-newsletter resource; (ii) animated video resource; or (iii) control (standard email). The intervention was designed to address key determinants of guideline adoption including awareness and knowledge. Following delivery of the intervention in September 2021, services were invited to participate in an online or telephone survey from October-December 2021. The primary trial outcome was the proportion of services intending to adopt the Guidelines, defined as intention to; (i) offer an indoor-outdoor program for the full day; or (ii) offer more outdoor play time. Secondary outcomes included awareness, reach, knowledge and implementation of the Guidelines. Barriers to Guideline implementation, cost of the dissemination strategies and analytic data to measure fidelity of intervention delivery were also captured. RESULTS: Of the 154 services that provided post-intervention data, 58 received the e-newsletter (37.7%), 50 received the animated video (32.5%), and 46 received the control (29.9%). Services who received the animated video had nearly five times the odds (OR: 4.91 [1.03, 23.34] p = 0.046) than those in the control group, to report having intentions to adopt the Guidelines. There were no statistically significant differences in awareness or knowledge of the Guidelines between either intervention or control services. Development costs were greatest for the animated video. The extent to which the dissemination strategy was viewed in full, were similar for both the e-newsletter and animated video. CONCLUSION: This study found potential for the inclusion of interactive strategies to disseminate policy and guideline information within the ECEC setting, in the context of the need for rapid communication. Further research should explore the added benefits of embedding such strategies within a multi-strategy intervention. TRIAL REGISTRATION: Retrospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) on the 23/02/2023 (ACTRN 12,623,000,198,628).

Healthy eating interventions delivered in early childhood education and care settings for improving the diet of children aged six months to six years.

BACKGROUND: Dietary intake during early childhood can have implications on child health and developmental trajectories. Early childhood education and care (ECEC) services are recommended settings to deliver healthy eating interventions as they provide access to many children during this important period. Healthy eating interventions delivered in ECEC settings can include strategies targeting the curriculum (e.g. nutrition education), ethos and environment (e.g. menu modification) and partnerships (e.g. workshops for families). Despite guidelines supporting the delivery of healthy eating interventions in this setting, little is known about their impact on child health. OBJECTIVES: To assess the effectiveness of healthy eating interventions delivered in ECEC settings for improving dietary intake in children aged six months to six years, relative to usual care, no intervention or an alternative, non-dietary intervention. Secondary objectives were to assess the impact of ECEC-based healthy eating interventions on physical outcomes (e.g. child body mass index (BMI), weight, waist circumference), language and cognitive outcomes, social/emotional and quality-of-life outcomes. We also report on cost and adverse consequences of ECEC-based healthy eating interventions. SEARCH METHODS: We searched eight electronic databases including CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, ERIC, Scopus and SportDiscus on 24 February 2022. We searched reference lists of included studies, reference lists of relevant systematic reviews, the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov and Google Scholar, and contacted authors of relevant papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster-RCTs, stepped-wedge RCTs, factorial RCTs, multiple baseline RCTs and randomised cross-over trials, of healthy eating interventions targeting children aged six months to six years that were conducted within the ECEC setting. ECEC settings included preschools, nurseries, kindergartens, long day care and family day care. To be included, studies had to include at least one intervention component targeting child diet within the ECEC setting and measure child dietary or physical outcomes, or both. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently screened titles and abstracts and extracted study data. We assessed risk of bias for all studies against 12 criteria within RoB 1, which allows for consideration of how selection, performance, attrition, publication and reporting biases impact outcomes. We resolved discrepancies via consensus or by consulting a third review author. Where we identified studies with suitable data and homogeneity, we performed meta-analyses using a random-effects model; otherwise, we described findings using vote-counting approaches and via harvest plots. For measures with similar metrics, we calculated mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. We calculated standardised mean differences (SMDs) for primary and secondary outcomes where studies used different measures. We applied GRADE to assess certainty of evidence for dietary, cost and adverse outcomes.  MAIN RESULTS: We included 52 studies that investigated 58 interventions (described across 96 articles). All studies were cluster-RCTs. Twenty-nine studies were large (≥ 400 participants) and 23 were small (< 400 participants). Of the 58 interventions, 43 targeted curriculum, 56 targeted ethos and environment, and 50 targeted partnerships. Thirty-eight interventions incorporated all three components. For the primary outcomes (dietary outcomes), we assessed 19 studies as overall high risk of bias, with performance and detection bias being most commonly judged as high risk of bias. ECEC-based healthy eating interventions versus usual practice or no intervention may have a positive effect on child diet quality (SMD 0.34, 95% confidence interval (CI) 0.04 to 0.65; P = 0.03, I2 = 91%; 6 studies, 1973 children) but the evidence is very uncertain. There is moderate-certainty evidence that ECEC-based healthy eating interventions likely increase children's consumption of fruit (SMD 0.11, 95% CI 0.04 to 0.18; P < 0.01, I2 = 0%; 11 studies, 2901 children). The evidence is very uncertain about the effect of ECEC-based healthy eating interventions on children's consumption of vegetables (SMD 0.12, 95% CI -0.01 to 0.25; P =0.08, I2 = 70%; 13 studies, 3335 children). There is moderate-certainty evidence that ECEC-based healthy eating interventions likely result in little to no difference in children's consumption of non-core (i.e. less healthy/discretionary) foods (SMD -0.05, 95% CI -0.17 to 0.08; P = 0.48, I2 = 16%; 7 studies, 1369 children) or consumption of sugar-sweetened beverages (SMD -0.10, 95% CI -0.34 to 0.14; P = 0.41, I2 = 45%; 3 studies, 522 children). Thirty-six studies measured BMI, BMI z-score, weight, overweight and obesity, or waist circumference, or a combination of some or all of these. ECEC-based healthy eating interventions may result in little to no difference in child BMI (MD -0.08, 95% CI -0.23 to 0.07; P = 0.30, I2 = 65%; 15 studies, 3932 children) or in child BMI z-score (MD -0.03, 95% CI -0.09 to 0.03; P = 0.36, I2 = 0%; 17 studies; 4766 children). ECEC-based healthy eating interventions may decrease child weight (MD -0.23, 95% CI -0.49 to 0.03; P = 0.09, I2 = 0%; 9 studies, 2071 children) and risk of overweight and obesity (RR 0.81, 95% CI 0.65 to 1.01; P = 0.07, I2 = 0%; 5 studies, 1070 children). ECEC-based healthy eating interventions may be cost-effective but the evidence is very uncertain (6 studies). ECEC-based healthy eating interventions may have little to no effect on adverse consequences but the evidence is very uncertain (3 studies). Few studies measured language and cognitive skills (n = 2), social/emotional outcomes (n = 2) and quality of life (n = 3). AUTHORS' CONCLUSIONS: ECEC-based healthy eating interventions may improve child diet quality slightly, but the evidence is very uncertain, and likely increase child fruit consumption slightly. There is uncertainty about the effect of ECEC-based healthy eating interventions on vegetable consumption. ECEC-based healthy eating interventions may result in little to no difference in child consumption of non-core foods and sugar-sweetened beverages. Healthy eating interventions could have favourable effects on child weight and risk of overweight and obesity, although there was little to no difference in BMI and BMI z-scores. Future studies exploring the impact of specific intervention components, and describing cost-effectiveness and adverse outcomes are needed to better understand how to maximise the impact of ECEC-based healthy eating interventions.

A rapid review of the scalability of interventions targeting obesity prevention in infants.

ISSUE ADDRESSED: Obesity in children is one of the most significant public health issues globally. Given the high prevalence of overweight and obesity in children, there is a need to identify effective obesity prevention efforts that can be delivered at scale to improve child health. We aimed to (i) identify obesity prevention interventions targeted at children aged 0-2 that have been scaled-up, and their relative efficacy compared to their pre-scale trial, (ii) describe adaptations made, and the extent to which factors related to scalability have been reported. METHODS: We conducted a rapid review of pre-scale randomised controlled trials targeting nutrition, physical activity and obesity prevention in infants, and calculated the relative effect size for relevant outcomes in the corresponding scaled up trial. We documented adaptations made to the pre-scale trial for scale up, and explored how different components of scalability had been reported according to the Intervention Scalability Assessment Tool. RESULTS: Of the 14 identified pre-scale trials, only one formal evaluation of the scale-up trial was identified. For body mass index, <10% of the effect was retained, however for nutrition and behavioural outcomes, the proportion of effect retained varied from -11.1% to 144%. Significant adaptations to modality were made in the scaled up trial primarily to reduce cost and increase reach of the intervention. Reporting of scalability components varied across the 14 trials, with only one trial reporting information for all assessed components. CONCLUSIONS: The majority of effective interventions targeting obesity prevention in infants have not been evaluated in a scaled up form. The magnitude of effect retained for the single trial that was scaled up was variable. In general, reporting of components of scalability was sub-optimal. SO WHAT?: The findings suggest that there is substantial need for the development and rigorous evaluation of obesity prevention interventions in children aged 0-2 which are amenable for scale.

A Pilot Randomised Controlled Trial to Increase the Sustainment of an Indoor-Outdoor-Free-Play Program in Early Childhood Education and Care Services: A Study Protocol for the Sustaining Play, Sustaining Health (SPSH) Trial.

Early Childhood Education and Care (ECEC) settings are important environments to support children's physical activity (PA). In 2021, COVID-19 regulations recommended the provision of indoor-outdoor free-play programs in ECEC settings to reduce the transmission of COVID-19, resulting in an increased uptake of this practice. As the context has since changed, research suggests that ECEC services could cease the implementation of these practices. Therefore, this pilot randomised controlled trial (RCT) aims to examine the feasibility, acceptability, and impact of a sustainment strategy to ensure the ongoing implementation (sustainment) of ECEC-delivered indoor-outdoor free-play programs. Twenty ECEC services located in New South Wales, Australia that have implemented indoor-outdoor free-play programs since the release of COVID-19 guidelines will be recruited. The services will be randomly allocated either the sustainment strategy or usual care. The "Sustaining Play, Sustaining Health" program consists of eight strategies, developed to address key barriers against and facilitators of sustainment informed by the Integrated Sustainability Framework. The outcomes will be assessed via internal project records, staff surveys, and a self-reported measure of free play. This study will provide important data to support the performance of a fully powered trial within Australian ECEC settings and to inform the development of future sustainment strategies.

An mHealth Intervention to Reduce the Packing of Discretionary Foods in Children's Lunch Boxes in Early Childhood Education and Care Services: Cluster Randomized Controlled Trial.

BACKGROUND: Interventions in early childhood education and care (ECEC) services have the potential to improve children's diet at the population level. OBJECTIVE: This study aims to test the efficacy of a mobile health intervention in ECEC services to reduce parent packing of foods high in saturated fat, sugar, and sodium (discretionary foods) in children's (aged 3-6 years) lunch boxes. METHODS: A cluster randomized controlled trial was undertaken with 355 parent and child dyads recruited by phone and in person from 17 ECEC services (8 [47%] intervention and 9 [53%] control services). Parents in the intervention group received a 10-week fully automated program targeting barriers to packing healthy lunch boxes delivered via an existing service communication app. The program included weekly push notifications, within-app messages, and links to further resources, including websites and videos. The control group did not receive any intervention. The primary outcomes were kilojoules from discretionary foods and associated nutrients (saturated fat, free sugars, and sodium) packed in children's lunch boxes. Secondary outcomes included consumption of kilojoules from discretionary foods and related nutrients and the packing and consumption of serves of discretionary foods and core food groups. Photography and weights of foods in children's lunch boxes were recorded by trained researchers before and after the trial to assess primary and secondary outcomes. Outcome assessors were blinded to service allocation. Feasibility, appropriateness, and acceptability were assessed via an ECEC service manager survey and a parent web-based survey. Use of the app was assessed via app analytics. RESULTS: Data on packed lunch box contents were collected for 88.8% (355/400) of consenting children at baseline and 84.3% (337/400) of children after the intervention. There was no significant difference between groups in kilojoule from discretionary foods packed (77.84 kJ, 95% CI -163.49 to 319.18; P=.53) or the other primary or secondary outcomes. The per-protocol analysis, including only data from children of parents who downloaded the app, also did not find any statistically significant change in primary (-1.98 kJ, 95% CI -343.87 to 339.90; P=.86) or secondary outcomes. Approximately 61.8% (102/165) of parents in the intervention group downloaded the app, and the mean service viewing rate of weekly within-app messages was 26% (SD 14.9). Parents who responded to the survey and participating services agreed that it was appropriate to receive lunch box information via the app (40/50, 80% and 6/8, 75%, respectively). CONCLUSIONS: The intervention was unable to demonstrate an impact on kilojoules or associated nutrients from discretionary foods packed in children's lunch boxes. Low app downloads and program message views indicate a need to explore how to improve factors related to implementation before further testing similar mobile health interventions in this setting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000133235; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374379.

A randomised controlled trial of an implementation strategy delivered at scale to increase outdoor free play opportunities in early childhood education and care (ECEC) services: a study protocol for the get outside get active (GOGA) trial.

BACKGROUND: Increased outdoor play time in young children is associated with many health and developmental benefits. This study aims to evaluate the impact of a multi-strategy implementation strategy delivered at scale, to increase opportunities for outdoor free play in Early Childhood Education and Care (ECEC) services. METHODS: The study will employ a parallel-group randomised controlled trial design. One hundred ECEC services in the Hunter New England region of New South Wales, Australia, will be recruited and randomised to receive either a 6-month implementation strategy or usual care. The trial will seek to increase the implementation of an indoor-outdoor routine (whereby children are allowed to move freely between indoor and outdoor spaces during periods of free play), to increase their opportunity to engage in outdoor free play. Development of the strategy was informed by the Behaviour Change Wheel to address determinants identified in the Theoretical Domains Framework. ECEC services allocated to the control group will receive 'usual' implementation support delivered as part of state-wide obesity prevention programs. The primary trial outcome is the mean minutes/day (calculated across 5 consecutive days) of outdoor free play opportunities provided in ECEC services measured at baseline, 6-months (primary end point) and 18-months post baseline. Analyses will be performed using an intention-to-treat approach with ECEC services as the unit of analysis, using a linear mixed effects regression model to assess between-group differences. A sensitivity analysis will be undertaken, adjusting for service characteristics that appear imbalanced between groups at baseline, and a subgroup analysis examining potential intervention effect among services with the lowest baseline outdoor free play opportunities. DISCUSSION: Identifying effective strategies to support the implementation of indoor-outdoor routines in the ECEC setting at scale is essential to improve child population health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12621000987864 ). Prospectively registered 27th July 2021, ANZCTR - Registration.

Quantitative Tyrosine Phosphoproteome Profiling of AXL Receptor Tyrosine Kinase Signaling Network.

Overexpression and amplification of AXL receptor tyrosine kinase (RTK) has been found in several hematologic and solid malignancies. Activation of AXL can enhance tumor-promoting processes such as cancer cell proliferation, migration, invasion and survival. Despite the important role of AXL in cancer development, a deep and quantitative mapping of its temporal dynamic signaling transduction has not yet been reported. Here, we used a TMT labeling-based quantitative proteomics approach to characterize the temporal dynamics of the phosphotyrosine proteome induced by AXL activation. We identified >1100 phosphotyrosine sites and observed a widespread upregulation of tyrosine phosphorylation induced by GAS6 stimulation. We also detected several tyrosine sites whose phosphorylation levels were reduced upon AXL activation. Gene set enrichment-based pathway analysis indicated the activation of several cancer-promoting and cell migration/invasion-related signaling pathways, including RAS, EGFR, focal adhesion, VEGFR and cytoskeletal rearrangement pathways. We also observed a rapid induction of phosphorylation of protein tyrosine phosphatases, including PTPN11 and PTPRA, upon GAS6 stimulation. The novel molecules downstream of AXL identified in this study along with the detailed global quantitative map elucidating the temporal dynamics of AXL activation should not only help understand the oncogenic role of AXL, but also aid in developing therapeutic options to effectively target AXL.

Proximity-Dependent Biotinylation to Elucidate the Interactome of TNK2 Nonreceptor Tyrosine Kinase.

Nonreceptor tyrosine kinases (NRTKs) represent an important class of signaling molecules driving diverse cellular pathways. Aberrant expression and hyperphosphorylation of TNK2, an NRTK, have been implicated in multiple cancers. However, the exact proteins and cellular events that mediate phenotypic changes downstream of TNK2 are unclear. Biological systems that employ proximity-dependent biotinylation methods, such as BioID, are being increasingly used to map protein-protein interactions, as they provide increased sensitivity in discovering interaction partners. In this study, we employed stable isotope labeling with amino acids in cell culture and BioID coupled to the biotinylation site identification technology (BioSITe) method that we recently developed to quantitatively explore the interactome of TNK2. By performing a controlled comparative analysis between full-length TNK2 and its truncated counterpart, we were able to not only identify site-level biotinylation of previously well-established TNK2 binders and substrates including NCK1, NCK2, CTTN, and STAT3, but also discover several novel TNK2 interacting partners. We also performed co-immunoprecipitation and immunofluorescence analysis to validate the interaction between TNK2 and CLINT1, a novel TNK2 interacting protein. Overall, this work reveals the power of the BioSITe method coupled to BioID and highlights several molecules that warrant further exploration to assess their functional significance in TNK2-mediated signaling.

eHealth interventions targeting nutrition, physical activity, sedentary behavior, or obesity in adults: A scoping review of systematic reviews.

A vast body of evidence regarding eHealth interventions for nutrition, physical activity, sedentary behavior, and obesity exists. This scoping review of systematic reviews aimed to evaluate the current level of evidence in this growing field. Seven electronic databases were searched for systematic reviews published until October 27, 2019. The systematic reviews must have included adult participants only and have evaluated eHealth behavioral interventions with the primary aim of changing nutrition, physical activity, and sedentary behavior or treating or preventing overweight and obesity. One hundred and six systematic reviews, published from 2006 to 2019, were included. Almost all (n = 98) reviews evaluated the efficacy of interventions. Over half (n = 61) included interventions focused on physical activity, followed by treatment of obesity (n = 28), nutrition (n = 22), prevention of obesity (n = 18), and sedentary behavior (n = 6). Many reviews (n = 46) evaluated one type of eHealth intervention only, while 60 included two or more types. Most reviews (n = 67) were rated as being of critically low methodological quality. This scoping review identified an increasing volume of systematic reviews evaluating eHealth interventions. It highlights several evidence gaps (e.g., evaluation of other outcomes, such as reach, engagement, or cost effectiveness), guiding future research efforts in this area.

Gut Microbiota Represent a Major Thermogenic Biomass.

Evidence supports various roles for microbial metabolites in the control of multiple aspects of host energy flux including feeding behaviors, digestive efficiency, and energy expenditure, but few studies have quantified the energy utilization of the biomass of the gut microbiota itself. Because gut microbiota exist in an anoxic environment, energy flux is expected to be anaerobic; unfortunately, commonly utilized O2/CO2 respirometry-based approaches are unable to detect anaerobic energy flux. To quantify the contribution of the gut microbial biomass to whole-animal energy flux, we examined the effect of surgical reduction of gut biomass in C57BL/6J mice via cecectomy and assessed energy expenditure using methods sensitive to anaerobic flux, including bomb and direct calorimetry. First, we determined that cecectomy caused an acceleration of weight gain over several months due to a reduction in combined total host plus microbial energy expenditure, as reflected by an increase in energy efficiency (ie, weight gained per calorie absorbed). Second, we determined that under general anesthesia, cecectomy caused immediate changes in heat dissipation that were significantly modified by short-term pretreatment with dietary or pharmaceutical interventions known to modify the microbiome, and confirmed that these effects were undetectable by respirometry. We conclude that while the cecum only contributes approximately 1% of body mass in the mouse, this organ contributes roughly 8% of total resting energy expenditure, that this contribution is predominantly anaerobic, and that the composition and abundance of the cecal microbial contents can significantly alter its contribution to energy flux.

An Overview of Research Opportunities to Increase the Impact of Nutrition Intervention Research in Early Childhood and Education Care Settings According to the RE-AIM Framework.

Objective: To highlight opportunities for future nutrition intervention research within early childhood and education care (ECEC) settings, with a focus on generating evidence that has applicability to real-world policy and practice. Methods: An overview of opportunities to progress the field was developed by the authors using a collaborative writing approach and informed by recent research in the field. The group developed a list of recommendations aligned with the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework. Pairs of authors drafted individual sections of the manuscript, which were then reviewed by a separate pair. The first and senior author consolidated all sections of the manuscript and sought critical input on the draft iterations of the manuscript. Results: Interventions that employ digital platforms (reach) in ECEC settings, as well as research in the family day care setting (effectiveness) were identified as areas of opportunities. Research understanding the determinants of and effective strategies for dissemination (adoption), the implementation of nutrition programs, in addition to de-implementation (implementation) of inappropriate nutrition practices, is warranted. For maintenance, there is a need to better understand sustainability and the sustainment of interventions, in addition to undertaking policy-relevant research. Conclusions: The ECEC setting is prime for innovative and practical nutrition intervention research.

Absence of Nonlinear Coupling Between Electric Vestibular Stimulation and Evoked Forces During Standing Balance.

The vestibular system encodes motion and orientation of the head in space and is essential for negotiating in and interacting with the world. Recently, random waveform electric vestibular stimulation has become an increasingly common means of probing the vestibular system. However, many of the methods used to analyze the behavioral response to this type of stimulation assume a linear relationship between frequencies in the stimulus and its associated response. Here we examine this stimulus-response frequency linearity to determine the validity of this assumption. Forty-five university-aged subjects stood on a force-plate for 4 min while receiving vestibular stimulation. To determine the linearity of the stimulus-response relationship we calculated the cross-frequency power coupling between a 0 and 25 Hz bandwidth limited white noise stimulus and induced postural responses, as measured using the horizontal forces acting at the feet. Ultimately, we found that, on average, the postural response to a random stimulus is linear across stimulation frequencies. This result supports the use of analysis methods that depend on the assumption of stimulus-response frequency linearity, such as coherence and gain, which are commonly used to analyze the body's response to random waveform electric stimuli.

Vestibular attenuation to random-waveform galvanic vestibular stimulation during standing and treadmill walking.

The ability to move and maintain posture is critically dependent on motion and orientation information provided by the vestibular system. When this system delivers noisy or erred information it can, in some cases, be attenuated through habituation. Here we investigate whether multiple mechanisms of attenuation act to decrease vestibular gain due to noise added using supra-threshold random-waveform galvanic vestibular stimulation (GVS). Forty-five participants completed one of three conditions. Each condition consisted of two 4-min standing periods with stimulation surrounding a 1-h period of either walking with stimulation, walking without stimulation, or sitting quietly. An instrumented treadmill recorded horizontal forces at the feet during standing and walking. We quantified response attenuation to GVS by comparing vestibular stimulus-horizontal force gain between conditions. First stimulus exposure caused an 18% decrease in gain during the first 40 s of standing. Attenuation recommenced only when subjects walked with stimulation, resulting in a 38% decrease in gain over 60 min that did not transfer to standing following walking. The disparity in attenuation dynamics and absent carry over between standing and walking suggests that two mechanisms of attenuation, one associated with first exposure to the stimulus and another that is task specific, may act to decrease vestibulomotor gain.

The Association between Australian Childcare Centre Healthy Eating Practices and Children's Healthy Eating Behaviours: A Cross-Sectional Study within Lunchbox Centres.

The association between healthy eating practices and child dietary intake in childcare centres where parents pack foods from home has received little attention. This study aimed to: (1) Describe the nutritional content of foods and beverages consumed by children in care; and (2) Assess the association between centre healthy eating practices and child intake of fruit and vegetable servings, added sugar(grams), saturated fat(grams) and sodium(milligrams) in care. A cross-sectional study amongst 448 children attending 22 childcare centres in New South Wales, Australia, was conducted. Child dietary intake was measured via weighed lunchbox measurements, photographs and researcher observation, and centre healthy eating practices were assessed via researcher observation of centre nutrition environments. Children attending lunchbox centres consumed, on average 0.80 servings (standard deviation 0.69) of fruit and 0.27 servings (standard deviation 0.51) of vegetables in care. The availability of foods within children's lunchboxes was associated with intake of such foods (p < 0.01). Centre provision of intentional healthy eating learning experiences (estimate -0.56; p = 0.01) and the use of feeding practices that support children's healthy eating (estimate -2.02; p = 0.04) were significantly associated with reduced child intake of saturated fat. Interventions to improve child nutrition in centres should focus on a range of healthy eating practices, including the availability of foods packed within lunchboxes.

Changing landscape of nutrition and dietetics research? A bibliographic analysis of top-tier published research in 1998 and 2018.

OBJECTIVE: The current study sought to describe and compare study type, research design and translation phase of published research in nutrition and dietetic journals in 1998 and 2018. DESIGN: This was a repeat cross-sectional bibliographic analysis of Nutrition and Dietetics research. All eligible studies in the top eight Nutrition and Dietetics indexed journals in 1998 and 2018 were included. Two independent reviewers coded each study for research design (study type and study design) and translation phase (T0-T4) of the research using seminal texts in the field. SETTING: Not relevant. PARTICIPANTS: Not relevant. RESULTS: The number of publications (1998, n 1030; 2018, n 1016) has not changed over time, but the research type, design and translation phases have. The proportion of intervention studies in 1998 (43·8 %) was significantly higher than 2018 (19·4 %). In 2018, more reviews (46·9 % v. 15·6 % in 1998) and less randomised trials (14·3 % v. 37·8 % in 1998) were published. In regard to translation phase, there was a higher proportion of T2-T4 research in 2018 (18·3 % v. 3·8 % in 1998); however, the proportion of T3/T4 (dissemination, implementation and population-level research) research was still low (<3 %). Our sensitivity analysis with the four journals that remained in the top eight journal across the two time periods found no differences in the research type, design and translation phases across time. CONCLUSIONS: There was a reduction in intervention and T0 publications, alongside higher publication of clinical study designs over time; however, published T3/T4 research in Nutrition and Dietetics is low. A greater focus on publishing interventions and dissemination and implementation may be needed.

Hearing care and management priority among parents of children with Down syndrome: a grounded theory.

OBJECTIVE: This study qualitatively explored the factors that influence how parents of children who are Deaf or hard-of-hearing with Down syndrome prioritise hearing care and management and developed an associated theory to explain that priority. DESIGN: Grounded theory was used for the purposes of this qualitative study. Data were collected using in-depth interviews which were analysed using a three-tiered qualitative coding process. STUDY SAMPLE: Eighteen mothers of children who are Deaf or hard-of-hearing with Down syndrome participated in this study. RESULTS: The higher the extent of engaged professional support, perception of benefit for child, parent activation, and family engagement, the higher the priority for hearing care and management will likely be among parents of children who are Deaf or hard-of-hearing with Down syndrome. CONCLUSIONS: Understanding how parents of children who are Deaf or hard-of-hearing with Down syndrome decide to prioritise hearing care and management has implications for how hearing health providers and others provide care to parents to enhance priority for hearing-related needs.

A cross-sectional study of packed lunchbox foods and their consumption by children in early childhood education and care services.

AIM: To (a) describe lunchbox foods packed and consumed by children attending early childhood education and care services; (b) compare the serves of foods packed and consumed with nutrition guideline recommendations; and (c) explore associations between parent characteristics and serves of food groups packed in lunchboxes. METHODS: A cross sectional study was conducted on a sample of early childhood education and care services where parents provide food in the Hunter New England region of NSW, Australia. Lunchbox contents were assessed using photography and pre- and post-meal weights. Descriptive statistics were used to describe packing and consumption of core food groups and discretionary foods. RESULTS: Data on food packed and consumed were collected for 355 children's lunchboxes from 17 services (preschools n = 14, long day care services n = 3). Less than half (44%) of lunchboxes contained vegetables, and 54% contained at least one serve of discretionary foods. Less than 1% of lunchboxes met all setting-specific nutrition guidelines. On average, children consumed 68% of lunchbox contents, with the lowest consumption rate being for vegetables. An association was found between parent education level and packing of discretionary foods (-0.36, P = <.01) but not for packing of fruit or vegetables. CONCLUSIONS: Lunchboxes contained an over-representation of discretionary foods and under-representation of vegetables, and children had a low preference for consuming vegetables compared with other food groups. Interventions to support parent packing of lunchboxes in line with nutrition guidelines and strategies to expand child preference for foods such as vegetables are warranted.

Guidance for conducting feasibility and pilot studies for implementation trials.

BACKGROUND: Implementation trials aim to test the effects of implementation strategies on the adoption, integration or uptake of an evidence-based intervention within organisations or settings. Feasibility and pilot studies can assist with building and testing effective implementation strategies by helping to address uncertainties around design and methods, assessing potential implementation strategy effects and identifying potential causal mechanisms. This paper aims to provide broad guidance for the conduct of feasibility and pilot studies for implementation trials. METHODS: We convened a group with a mutual interest in the use of feasibility and pilot trials in implementation science including implementation and behavioural science experts and public health researchers. We conducted a literature review to identify existing recommendations for feasibility and pilot studies, as well as publications describing formative processes for implementation trials. In the absence of previous explicit guidance for the conduct of feasibility or pilot implementation trials specifically, we used the effectiveness-implementation hybrid trial design typology proposed by Curran and colleagues as a framework for conceptualising the application of feasibility and pilot testing of implementation interventions. We discuss and offer guidance regarding the aims, methods, design, measures, progression criteria and reporting for implementation feasibility and pilot studies. CONCLUSIONS: This paper provides a resource for those undertaking preliminary work to enrich and inform larger scale implementation trials.