Growth of HIV-exposed uninfected, compared with HIV-unexposed, Zambian children: a longitudinal analysis from infancy to school age

BACKGROUND: Early growth of HIV-exposed, uninfected (HEU) children is poorer than that of their HIV-unexposed, uninfected (HUU) counterparts but there is little longitudinal or longer term information about the growth effects of early HIV exposure. METHODS: We performed a longitudinal analysis to compare growth of HEU and HUU infants and children using data from two cohort studies in Lusaka, Zambia. Initially 207 HUU and 200 HEU infants from the Breastfeeding and Postpartum Health (BFPH) study and 580 HUU and 165 HEU from the Chilenje Infant Growth, Nutrition and Infection Study (CIGNIS) had anthropometric measurements taken during infancy and again when school-aged, at which time 66 BFPH children and 326 CIGNIS children were available. We analysed the data from the two cohorts separately using linear mixed models. Linear regression models were used as a secondary analysis at the later time points, adjusting for breastfeeding duration. We explored when the main group differences in growth emerged in order to estimate the largest 'effect periods'. RESULTS: After adjusting for socioeconomic status and maternal education, HEU children had lower weight-for-age, length-for-age and BMI-for-age Z-scores during early growth and these differences still existed when children were school-aged. Exposure group differences changed most between 1 and 6 weeks and between 18 months and ~7.5 years. CONCLUSIONS: HEU children have poorer early growth than HUU children which persists into later growth. Interventions to improve growth of HEU children need to target pregnant women and infants

Allowance for learning and clustering effects in the design and analysis of multicentre randomised trials: current practice and experiences

Meeting abstract from the 5th International Clinical Trials Methodology Conference (ICTMC 2019

National survey of feasibility of NIV trials for management of children with bronchiolitis.

Background: Bronchiolitis is a major cause of admission to hospital in children. Non-invasive ventilation (NIV) support with continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) oxygen is routinely used for infants in the UK with bronchiolitis. Objective: To establish UK paediatric practice regarding management of bronchiolitis, and to explore issues pertinent to the design of a potential future randomised controlled trial of NIV. Design: Screening logs were completed in hospitals in England capturing information on paediatric bronchiolitis admissions. An online national survey of clinical practice was disseminated to healthcare professionals (HCPs) across the UK to ascertain current management strategies. Results: Screening logs captured data on 393 infants from 8 hospitals. Reasons for admission were most commonly respiratory distress and/or poor fluid intake. Oxygen was administered for 54% of admissions. Respiratory (CPAP and HFNC) and non-respiratory support administered varied considerably. The national survey was completed by 111 HCPs from 76 hospitals. Data were obtained on criteria used to commence and wean NIV, responsibilities for altering NIV settings, minimum training requirements for staff managing a child on NIV, and numbers of trained staff. Most centres were interested in and capable of running a trial of NIV, even out of normal office hours. Conclusions: Respiratory and non-respiratory management of bronchiolitis in UK centres varies widely. A trial of HFNC oxygen therapy in this group of patients is feasible and HCPs would be willing to randomise patients into such a trial. Future work should focus on defining trial eligibility criteria

Methodological challenges in online trials: an update and insights from the REACT trial

There has been a growth in the number of web-based trials of web-based interventions, adding to an increasing evidence base for their feasibility and effectiveness. However, there are challenges associated with such trials, which researchers must address. This discussion paper follows the structure of the Down Your Drink trial methodology paper, providing an update from the literature for each key trial parameter (recruitment, registration eligibility checks, consent and participant withdrawal, randomization, engagement with a web-based intervention, retention, data quality and analysis, spamming, cybersquatting, patient and public involvement, and risk management and adverse events), along with our own recommendations based on designing the Relatives Education and Coping Toolkit randomized controlled trial for relatives of people with psychosis or bipolar disorder. The key recommendations outlined here are relevant for future web-based and hybrid trials and studies using iterative development and test models such as the Accelerated Creation-to-Sustainment model, both within general health research and specifically within mental health research for relatives. Researchers should continue to share lessons learned from conducting web-based trials of web-based interventions to benefit future studies

Predictors of myocardial fibrosis and response to anti-fibrotic therapy in heart failure with preserved ejection fraction

AbstractMyocardial fibrosis, measured using magnetic resonance extracellular volume (ECV), associates with adverse outcome in heart failure with preserved ejection fraction (HFpEF). In the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial, the novel anti-fibrotic agent pirfenidone reduced myocardial fibrosis. We sought to identify baseline characteristics that associate with myocardial fibrotic burden, the change in myocardial fibrosis over a year, and predict response to pirfenidone in patients with HFpEF. Amongst patients enrolled in the PIROUETTE trial (n = 107), linear regression models were used to assess the relationship between baseline variables and baseline myocardial ECV, with change in myocardial ECV adjusting for treatment allocation, and to identify variables that modified the pirfenidone treatment effect. Body mass index, left atrial reservoir strain, haemoglobin and aortic distensibility were associated with baseline ECV in stepwise modelling, and systolic blood pressure, and log N-terminal pro B-type natriuretic peptide were associated with baseline ECV in clinically-guided modelling. QRS duration, left ventricular mass and presence of an infarct at baseline were associated with an increase in ECV from baseline to week 52. Whilst QRS duration, presence of an infarct, global longitudinal strain and left atrial strain modified the treatment effect of pirfenidone when considered individually, no variable modified treatment effect on multivariable modelling. Baseline characteristics were identified that associate with myocardial fibrosis and predict change in myocardial fibrosis. No variables that independently modify the treatment effect of pirfenidone were identified (PIROUETTE, NCT02932566).</jats:p