The Eat Smart Study: A randomised controlled trial of a reduced carbohydrate versus a low fat diet for weight loss in obese adolescents

Background Despite the recognition of obesity in young people as a key health issue, there is limited evidence to inform health professionals regarding the most appropriate treatment options. The Eat Smart study aims to contribute to the knowledge base of effective dietary strategies for the clinical management of the obese adolescent and examine the cardiometablic effects of a reduced carbohydrate diet versus a low fat diet. Methods and design Eat Smart is a randomised controlled trial and aims to recruit 100 adolescents over a 2½ year period. Families will be invited to participate following referral by their health professional who has recommended weight management. Participants will be overweight as defined by a body mass index (BMI) greater than the 90th percentile, using CDC 2000 growth charts. An accredited 6-week psychological life skills program ‘FRIENDS for Life’, which is designed to provide behaviour change and coping skills will be undertaken prior to volunteers being randomised to group. The intervention arms include a structured reduced carbohydrate or a structured low fat dietary program based on an individualised energy prescription. The intervention will involve a series of dietetic appointments over 24 weeks. The control group will commence the dietary program of their choice after a 12 week period. Outcome measures will be assessed at baseline, week 12 and week 24. The primary outcome measure will be change in BMI z-score. A range of secondary outcome measures including body composition, lipid fractions, inflammatory markers, social and psychological measures will be measured. Discussion The chronic and difficult nature of treating the obese adolescent is increasingly recognised by clinicians and has highlighted the need for research aimed at providing effective intervention strategies, particularly for use in the tertiary setting. A structured reduced carbohydrate approach may provide a dietary pattern that some families will find more sustainable and effective than the conventional low fat dietary approach currently advocated. This study aims to investigate the acceptability and effectiveness of a structured reduced dietary carbohydrate intervention and will compare the outcomes of this approach with a structured low fat eating plan. Trial Registration: The protocol for this study is registered with the International Clinical Trials Registry (ISRCTN49438757)

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Accuracy of self-reported physical activity levels in obese adolescents

Introduction. Self-reported measures of habitual physical activity rely completely on the respondent's ability to provide accurate information on their own physical activity behaviours. Our aim was to investigate if obese adolescents could accurately report their physical activity levels (PAL) using self-reported diaries. Methods. Total energy expenditure (TEE) was measured using doubly labelled water (DLW) and resting energy expenditure (REE) was measured via indirect calorimetry. Activity energy expenditure (AEE) and PAL values were derived from measured TEE and REE. Self-reported, four-day activity diaries were used to calculate daily MET values and averaged to give an estimated PAL value (ePAL). Results. Twenty-two obese adolescents, mean age 13.2 ± 1.8 years, mean BMI 31.3 ± 4.6 kg/m2, completed the study. No significant differences between mean measured and estimated PAL values were observed (1.37 ± 0.13 versus 1.40 ± 0.34, P = 0.74). Bland Altman analysis illustrated a significant relationship (r = - 0. 76, P < 0.05) between the two methods; thus the bias was not consistent across a range of physical activity levels, with the more inactive overreporting their physical activity. Conclusion. At an individual level, obese adolescents are unlikely to be able to provide an accurate estimation of their own activity

Educators and child health nurses: Working together to support responsive infant and young child feeding practices in early childhood education and care

The NOURISH:ECE project explored the role of maternal and child health nurses (MCHNs) in early childhood education and care (ECEC) through the design and pilot of professional learning (PL) regarding responsive feeding practices. Eight focus groups were conducted in Queensland (MCHNs, n = 20; educators, n = 29) to explore attitudes regarding partnerships, PL, and feeding practices. Subsequently, a PL module was developed - incorporating videos, group discussion and reflection - and delivered to 64 educators by a MCHN. Educator practices were compared pre- and post-PL. The proportion of meals at which an educator was observed to use responsive feeding practices increased (praise for eating healthy foods, 11.3%–29.2%), but educators were observedpressuring children to eat more often (19.9%–40.1%). NOURISH:ECE provided promising preliminary results regarding PL. However, adequate resourcing and workforce issues in both sectors are barriers to developing effective partnerships across education and health

Parental Feeding Practices in Families Experiencing Food Insecurity: A Scoping Review

Parental feeding practices and styles influence child diet quality and growth. The extent to which these factors have been assessed in the context of disadvantage, particularly household food insecurity (HFI), is unknown. This is important, as interventions designed to increase responsive practices and styles may not consider the unique needs of families with HFI. To address this gap, a scoping review of studies published from 1990 to July 2021 in three electronic databases was conducted. A priori inclusion criteria were, population: families with children aged 0–5 years experiencing food insecurity and/or disadvantage; concept: parental feeding practices/behaviours/style; and context: high income countries. The search identified 12,950 unique papers, 504 full-text articles were screened and 131 met the inclusion criteria. Almost all the studies (91%) were conducted in the United States with recruitment via existing programs for families on low incomes. Only 27 papers assessed feeding practices or styles in the context of HFI. Of the eleven interventions identified, two assessed the proportion of participants who were food insecure. More research is required in families outside of the United States, with an emphasis on comprehensive and valid measures of HFI and feeding practices. Intervention design should be sensitive to factors associated with poverty, including food insecurity

Feeding Practices in Australian Early Childhood Education and Care Settings

Objective: Feeding practices used by educators in Early Childhood Education and Care (ECEC) settings can influence the diet quality of young children. However Australian data is scarce and limited to describing barriers to responsive feeding. This study describes the use of feeding practices amongst a group of Australian educators.Design: Direct observation of feeding practices and assessment of centre policy were conducted using the ‘Environment and Policy Assessment and Observation’ tool. Self-reported feeding practices and demographic data were collected via online survey using the Childcare Food and Activity Practices Questionnaire.Setting: Ten centre-based ECEC services in South East Queensland, Australia.Participants: Educators working in ECEC.Results: A total of 120 meals were observed and 88 educators provided self-report data (n=84 female). Centre policy supported the use of responsive feeding practices, and this was reflected in the high frequency with which children could decide what and how much to eat, across both observed and self-report data as well as low levels of pressure to eat and use of food as a reward (observed at 19.9% and 0% of meals). The only apparent discrepancy was regarding modelling. Median score for self-reported role-modelling was 5.0 (4.3-5.0) and educators were observed to sit with children at 75% of meals, however observed occasions of enthusiastic role modelling was only 22% (0-33.3) of meals.Conclusions: Research addressing how educators conceptualise feeding practices, as well under what circumstances they are used, particularly in centres with different models of food provision, may shed light on why modelling is rarely implemented in practice

A new model of integrated primary-secondary care for complex diabetes in the community: Study protocol for a randomised controlled trial

Background: A new model of complex diabetes care is provided by a multidisciplinary team which incorporates general practitioner (GP) Clinical Fellows supported by an Endocrinologist and diabetes educator within a community-based general practice setting. This study evaluates the health and clinical benefits of the new model of care, assesses the acceptability of the model to patients, GPs and other health professionals, and examines the cost-effectiveness of the model.Methods/Design: The study is an open, non-inferiority randomised controlled trial with data collected at baseline, 6 and 12 months. Participants are identified from new patients on hospital-based diabetes outpatient clinic waiting lists and new GP referrals. Eligible consenting patients are randomised to either a community practice site (intervention) or a hospital site (usual care). In the intervention model, medical care is led by a GP Clinical Fellow in partnership with an Endocrinologist. Quantitative measures include clinical indicators with HbA1c as the primary outcome; patient-reported outcomes include health-related quality of life, mental health and satisfaction with care. Qualitative methods will be used to explore the perspectives and experiences of patients and providers regarding the new model of care. An economic evaluation will also be undertaken.Discussion: This model of care seeks to improve the quality and safety of healthcare at the interface between the hospital and primary care sectors for patients with complex diabetes. The study will provide empirical evidence about the impact of the model of care on health outcomes, patient and clinician satisfaction, as well as any economic impacts. Trial registration: Clinical Trials Registry Number: ACTRN12612000380897.</p