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Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose-response association with body mass index (BMI) has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects. The Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity. In observational analysis, a 3.3 kg/m² (one standard deviation) higher BMI was associated with 22.3 (95% CI, 17.0, 27.6) movement counts/min less total physical activity (p = 1.6×10⁻¹⁶), 2.6 (2.1, 3.1) min/d less moderate-to-vigorous-intensity activity (p = 3.7×10⁻²⁹), and 3.5 (1.5, 5.5) min/d more sedentary time (p = 5.0×10⁻⁴). In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9) movement counts/min less total physical activity (p = 0.04) (∼5.3% of the mean counts/minute), 2.8 (0.1, 5.5) min/d less moderate-to-vigorous-intensity activity (p = 0.04), and 13.2 (1.3, 25.2) min/d more sedentary time (p = 0.03). There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI. Our results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to increase childhood activity levels. Importantly, this does not exclude lower physical activity also leading to increased adiposity, i.e., bidirectional causation.

Epigenetic markings acquired in early life may have phenotypic consequences later in development through their role in transcriptional regulation with relevance to the developmental origins of diseases including obesity. The goal of this study was to investigate whether DNA methylation levels at birth are associated with body size later in childhood. A study design involving two birth cohorts was used to conduct transcription profiling followed by DNA methylation analysis in peripheral blood. Gene expression analysis was undertaken in 24 individuals whose biological samples and clinical data were collected at a mean ± standard deviation (SD) age of 12.35 (0.95) years, the upper and lower tertiles of body mass index (BMI) were compared with a mean (SD) BMI difference of 9.86 (2.37) kg/m(2). This generated a panel of differentially expressed genes for DNA methylation analysis which was then undertaken in cord blood DNA in 178 individuals with body composition data prospectively collected at a mean (SD) age of 9.83 (0.23) years. Twenty-nine differentially expressed genes (>1.2-fold and p<10(-4)) were analysed to determine DNA methylation levels at 1-3 sites per gene. Five genes were unmethylated and DNA methylation in the remaining 24 genes was analysed using linear regression with bootstrapping. Methylation in 9 of the 24 (37.5%) genes studied was associated with at least one index of body composition (BMI, fat mass, lean mass, height) at age 9 years, although only one of these associations remained after correction for multiple testing (ALPL with height, p(Corrected) = 0.017). DNA methylation patterns in cord blood show some association with altered gene expression, body size and composition in childhood. The observed relationship is correlative and despite suggestion of a mechanistic epigenetic link between in utero life and later phenotype, further investigation is required to establish causality.

Previous studies have been unable to characterise the association between physical activity and obesity, possibly because most relied on inaccurate measures of physical activity and obesity. We carried out a cross sectional analysis on 5,500 12-year-old children enrolled in the Avon Longitudinal Study of Parents and Children. Total physical activity and minutes of moderate and vigorous physical activity (MVPA) were measured using the Actigraph accelerometer. Fat mass and obesity (defined as the top decile of fat mass) were measured using the Lunar Prodigy dual x-ray emission absorptiometry scanner. We found strong negative associations between MVPA and fat mass that were unaltered after adjustment for total physical activity. We found a strong negative dose-response association between MVPA and obesity. The odds ratio for obesity in adjusted models between top and the bottom quintiles of minutes of MVPA was 0.03 (95% confidence interval [CI] 0.01-0.13, p-value for trend <0.0001) in boys and 0.36 (95% CI 0.17-0.74, p-value for trend = 0.006) in girls. We demonstrated a strong graded inverse association between physical activity and obesity that was stronger in boys. Our data suggest that higher intensity physical activity may be more important than total activity.

In the last two decades, India has witnessed a substantial decrease in infant mortality attributed to infectious disease and malnutrition. However, the mortality attributed to birth defects remains constant. Studies on the prevalence of birth defects such as neural tube defects and orofacial clefts in India have reported inconsistent results. Therefore, we conducted a systematic review of observational studies to document the birth prevalence of neural tube defects and orofacial clefts. A comprehensive literature search for observational studies was conducted in MEDLINE and EMBASE databases using key MeSH terms (neural tube defects OR cleft lip OR cleft palate AND Prevalence AND India). Two reviewers independently reviewed the retrieved studies, and studies satisfying the eligibility were included. The quality of included studies was assessed using selected criteria from STROBE statement. The overall pooled birth prevalence (random effect) of neural tube defects in India is 4.5 per 1000 total births (95% CI 4.2 to 4.9). The overall pooled birth prevalence (random effect) of orofacial clefts is 1.3 per 1000 total births (95% CI 1.1 to 1.5). Subgroup analyses were performed by region, time period, consanguinity, and gender of newborn. The overall prevalence of neural tube defects from India is high compared to other regions of the world, while that of orofacial clefts is similar to other countries. The majority of studies included in the review were hospital based. The quality of these studies ranged from low to moderate. Further well-designed, high quality community-based observational studies are needed to accurately estimate the burden of neural tube defects and orofacial clefts in India.

ObjectiveTo determine the benefits and harms of pre-admission interventions (prehabilitation) on postoperative outcomes in patients undergoing major elective surgery.DesignSystematic review and meta-analysis of randomised controlled trials (RCTs) (published or unpublished). We searched Medline, Embase, CENTRAL, DARE, HTA and NHS EED, The Cochrane Library, CINAHL, PsychINFO and ISI Web of Science (June 2020).SettingSecondary care.ParticipantsPatients (≥18 years) undergoing major elective surgery (curative or palliative).InterventionsAny intervention administered in the preoperative period with the aim of improving postoperative outcomes.Outcomes and measuresPrimary outcomes were 30-day mortality, hospital length of stay (LoS) and postoperative complications. Secondary outcomes included LoS in intensive care unit or high dependency unit, perioperative morbidity, hospital readmission, postoperative pain, heath-related quality of life, outcomes specific to the intervention, intervention-specific adverse events and resource use.Review methodsTwo authors independently extracted data from eligible RCTs and assessed risk of bias and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation. Random-effects meta-analyses were used to pool data across trials.Results178 RCTs including eight types of intervention were included. Inspiratory muscle training (IMT), immunonutrition and multimodal interventions reduced hospital LoS (mean difference vs usual care: −1.81 days, 95% CI −2.31 to −1.31; −2.11 days, 95% CI −3.07 to −1.15; −1.67 days, 95% CI −2.31 to −1.03, respectively). Immunonutrition reduced infective complications (risk ratio (RR) 0.64 95% CI 0.40 to 1.01) and IMT, and exercise reduced postoperative pulmonary complications (RR 0.55, 95% CI 0.38 to 0.80, and RR 0.54, 95% CI 0.39 to 0.75, respectively). Smoking cessation interventions reduced wound infections (RR 0.28, 95% CI 0.12 to 0.64).ConclusionsSome prehabilitation interventions may reduce postoperative LoS and complications but the quality of the evidence was low.PROSPERO registration numberCRD42015019191.

The Enhanced Recovery After Surgery programme (ERAS) is an approach to the perioperative care of patients encompassing multiple interventions and involving a wide range of different actors. It can thus be defined as a complex intervention. Despite the strength of the evidence-base in its support, the implementation of ERAS has been slow. This paper specifically explores the utility of Normalization Process Theory (NPT) as a methodological framework to aid exploration of ERAS implementation, with a focus on the core NPT construct coherence. The study employed qualitative methods guided by NPT. Semi-structured interviews were conducted with twenty-six healthcare professionals working in three specialities (thoracic, colorectal, head and neck) in a UK hospital. Data were analysed using an adapted Framework Approach. Coherence, or sense-making work, was key to successful implementation and demonstrated in the importance of participants believing in ERAS both as an individual and as a team. In order to invest in ERAS individuals needed to be able to differentiate its practices favourably with those enacted pre-implementation (differentiation). Participants also needed to understand their specific tasks and responsibilities (individual specification) and build a shared understanding (communal specification), resolving differences in planning meetings. Belief in the worth of ERAS was often aligned to evidence for its effectiveness or benefit to patients (internalization), so implementing ERAS therefore 'made sense'. Sense-making work had strong links with aspects of implementation related to other NPT constructs including resource issues such as funding for data collection and feedback (reflexive monitoring: systemization) and failure to replace key staff members (collective action: skill set workability). NPT was found to be a valuable heuristic device to employ in the exploration of ERAS implementation processes. NPT was useful in facilitating recognition of the importance of coherence work to successful implementation. However despite participants' strong beliefs in the worth of ERAS, it was in translating these beliefs into action that barriers were encountered, highlighting the interconnectedness of NPT constructs and the complicated nature of implementing complex interventions.

Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL- and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight.

Background The Enhanced Recovery After Surgery (ERAS) programme is an approach to the perioperative care of patients which aims to improve outcomes and speed up recovery after surgery. Although the evidence base appears strong for this programme, the implementation of ERAS has been slow. This study aimed to gain an understanding of the facilitating factors and challenges of implementing the programme with a view to providing additional contextual information to aid implementation. The study had a particular focus on the nutritional elements as these have been highlighted as important. Methods The study employed qualitative research methods, guided by the Normalisation Process Theory (NPT) to explore the experiences and opinions of 26 healthcare professionals from a range of disciplines implementing the programme. Results This study identified facilitating factors to the implementation of ERAS: alignment with evidence based practice, standardising practice, drawing on the evidence base of other specialties, leadership, teamwork, ERAS meetings, patient involvement and education, a pre-operative assessment unit, staff education, resources attached to obtaining The Commissioning for Quality and Innovation (CQUIN) money, the ward layout, data collection and feedback, and adapting the care pathway. A number of implementation challenges were also identified: resistance to change, standardisation affecting personalised patient care, the buy-in of relevant stakeholders, keeping ERAS visible, information provision to patients, resources, palatability of nutritional drinks, aligning different ward cultures, patients going to non-ERAS departments, spreading the programme within the hospital, differences in health issue, and utilising a segmental approach.  Conclusions The findings presented here provide useful contextual information from diverse surgical specialties to inform healthcare providers when implementing ERAS in practice. Addressing the challenges and utilising the facilitating factors identified in this study, could speed up the rate at which ERAS is adopted, implemented and embedded.

Objective: To measure the levels and patterns of physical activity, using accelerometers, of 11-year-old children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Design: Cross-sectional analysis. Setting: ALSPAC is a birth cohort study located in the former county of Avon, in the southwest of England. This study used data collected when the children were 11 years old. Participants: 5595 children (2662 boys, 2933 girls). The children are the offspring of women recruited to a birth cohort study during 1991–2. The median age (95% CI) of the children is now 11.8 (11.6 to 11.9) years. Methods: Physical activity was measured over a maximum of 7 consecutive days using the MTI Actigraph accelerometer. Main outcome measures: Level and pattern of physical activity. Results: The median physical activity level was 580 counts/min. Boys were more active than girls (median (IQR) 644 (528–772) counts/min vs 529 (444–638) counts/min, respectively). Only 2.5% (95% CI 2.1% to 2.9%) of children (boys 5.1% (95% CI 4.3% to 6.0%), girls 0.4% (95% CI 0.2% to 0.7%) met current internationally recognised recommendations for physical activity. Children were most active in summer and least active in winter (difference = 108 counts/min). Both the mother and partner’s education level were inversely associated with activity level (p for trend <0.001 (both mother and partner)). The association was lost for mother’s education (p for trend = 0.07) and attenuated for partner’s education (p for trend = 0.02), after adjustment for age, sex, season, maternal age and social class. Conclusions: A large majority of children are insufficiently active, according to current recommended levels for health.

Background Walking is a simple activity that could help to reduce the prevalence of chronic diseases in all populations. Furthermore, an inverse dose–response relationship exists between steps taken and risk of premature death and cardiovascular events in middle-aged and older adults. There is a lack of information on how to effectively engage older adults around retirement age in walking. This qualitative study explored attitudes towards walking in older people with regard to habits, intensity, preferences and strategies for increasing walking behaviour. Methods In-depth qualitative interviews were conducted with 26 older adults who were either close to retirement or recently retired. An inductive thematic analysis was conducted. Results Three themes were identified from the data; 1) Engagement and perceived value of walking; was focused on the meaning of walking for the participant and the attributes they associate with their walking practice. 2) Integration and connectivity of walking; was focused on how participants integrate walking in their daily lives and whether walking can be practiced as a viable means of connectivity. 3) Strategies to increase walking; was focused on what factors motivate participants in their walking practice and what strategies they perceived to be beneficial to increase walking distance and intensity at an individual level. Discussion The views of walking in people of retirement age were represented within 3 key themes. The factors contained in these themes that may influence future walking practice are discussed with regard to future strategies to promote walking in the retirement life change. Conclusion It may be beneficial to promote qualitative aspects of walking practice and strive for regularity rather than intensity of walking to accrue the social, psychological and intellectual benefits reported by individuals in the retirement life change.