Thresholds for hypoglycaemic screening-a cause for concern?

The new Framework for Practice highlights the limited evidence for our current clinical practice (1). It is helpful in emphasising the importance of accurate measurement of glucose concentrations, listening to the concerns of parents and acknowledging that untreated hypoglycaemia can have devastating longterm consequences. However we have the following concerns: Screening thresholds The Framework recommends lowering a commonly accepted screening threshold in infants considered to be at risk of hypoglycaemia to a level that at any other time of life would be considered harmful. It fails to acknowledge the differences between screening and diagnostic thresholds; something neonatologists are very familiar with in the management of babies with jaundice. Phototherapy is provided to many babies with bilirubin levels well below a harmful level to prevent a harmful level being reached. Screening interventions are intended to prevent harmful events. Such thresholds will inevitably mean many individuals are treated ‘unnecessarily’ to avoid the risk of significant harm. In 2000 Cornblath et al published guidance on ‘operational thresholds’ in keeping with the current BAPM framework (2). However, and possibly reflecting concerns about the lack of evidence for the safety of this lower operational threshold, in 2017 in the UK, >80% of neonatal units still used <2.6mmol/ as their defined hypoglycaemic threshold (3). A threshold of <2.6mmol/l provides an opportunity for intervention before damaging neuroglycopaenia occurs

Antenatal Determinants of Childhood Obesity in High-Risk Offspring: Protocol for the DiGest Follow-Up Study.

Childhood obesity is an area of intense concern internationally and is influenced by events during antenatal and postnatal life. Although pregnancy complications, such as gestational diabetes and large-for-gestational-age birthweight have been associated with increased obesity risk in offspring, very few successful interventions in pregnancy have been identified. We describe a study protocol to identify if a reduced calorie diet in pregnancy can reduce adiposity in children to 3 years of age. The dietary intervention in gestational diabetes (DiGest) study is a randomised, controlled trial of a reduced calorie diet provided by a whole-diet replacement in pregnant women with gestational diabetes. Women receive a weekly dietbox intervention from enrolment until delivery and are blinded to calorie allocation. This follow-up study will assess associations between a reduced calorie diet in pregnancy with offspring adiposity and maternal weight and glycaemia. Anthropometry will be performed in infants and mothers at 3 months, 1, 2 and 3 years post-birth. Glycaemia will be assessed using bloodspot C-peptide in infants and continuous glucose monitoring with HbA1c in mothers. Data regarding maternal glycaemia in pregnancy, maternal nutrition, infant birthweight, offspring feeding behaviour and milk composition will also be collected. The DiGest follow-up study is expected to take 5 years, with recruitment finishing in 2026

Drug delivery from a solid formulation during breastfeeding-A feasibility study with mothers and infants.

Funder: University of Cambridge WD Armstrong TrustFunder: University of Cambridge Kurt Hahn TrustFunder: Studienstiftung des Deutschen Volkes; funder-id: http://dx.doi.org/10.13039/501100004350BACKGROUND: Breastfeeding is critical to health outcomes, particularly in low-resource settings where there is little access to clean water. For infants in their first twelve months of life, the delivery of medications is challenging, and use of oral syringes to deliver liquid formulations can pose both practical and emotional challenges. OBJECTIVE: To explore the potential to deliver medicine to infants via a solid formulation during breastfeeding. METHODS: Single center feasibility study within a tertiary level neonatal unit in the UK, involving twenty-six breastfeeding mother-infant dyads. A solid formulation of Vitamin B12 was delivered to infants during breastfeeding. Outcomes included the quantitative change in serum vitamin B12 and assessment of maternal expectations and experiences. RESULTS: Delivery of Vitamin B12 through a solid formulation that dissolved in human milk did not impair breastfeeding, and Vitamin B12 levels rose in all infants from a mean baseline (range) 533 pg/mL (236-925 pg/mL) to 1871 pg/mL (610-4981 pg/mL) at 6-8 hours post-delivery. Mothers described the surprising ease of 'drug' delivery, with 85% reporting a preference over the use of syringes. CONCLUSIONS: Solid drug formulations can be delivered during breastfeeding and were preferred by mothers over the delivery of liquid formulations via a syringe

Twin boundaries in d-wave superconductors

Twin boundaries in orthorhombic d-wave superconductors are investigated numerically using the Bogoliubov-deGennes formalism within the context of an extended Hubbard model. The twin boundaries are represented by tetragonal regions of variable width, with a reduced chemical potential. For sufficiently large twin boundary width and change in chemical potential, an induced s-wave component may break time-reversal symmetry at a low temperature. This temperature, and the magnitude of the complex component, are found to depend strongly on electron density. The results are compared with recent tunneling measurements.Comment: ReVTeX, 4 pages, 4 postscript figure

A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe).

BACKGROUND: Studies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and beta cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer beta cells are linked to risk of type 2 diabetes later in life. METHODS: A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4-8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth

Comparison between Spanish young and elderly people evaluated using Rivermead Behavioural Memory Test

The first objective of this work was to compare scores obtained in the daily memory function between young and elderly people, and to check whether there are differences between the groups for each of the profile scores obtained in the memory test. A second aim of this paper is to study the relationship between everyday memory and age, while controlling for gender and educational level. The total and profile scores obtained in the Rivermead Behavioural Memory Test were compared in a sample of 60 young and 120 elderly people from Valencia (Spain). Results showed significant differences between the two groups: those between 18 and 30 years obtained a higher average than those over 65. Once the group comparison was controlled for gender and educational level, the statistical effect of age group disappeared. The non-significant effect of group can not be explained by the introduction of gender, because both its main effect and the interaction were not statistically significant. However, educational level had a statistically significant effect which may explain the non-significant effect of group in this new analysis. The main conclusion is the need to carefully control for educational level in all studies related with everyday memory and ageing, as the differences found could be due to generational differences more than to biological deterioratio

The fitness for the Ageing Brain Study II (FABS II): protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

Background: Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II) study is a multicentre randomized controlled clinical trial (RCT) aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods

Effects of early feeding on growth velocity and overweight/obesity in a cohort of HIV unexposed South African infants and children

BACKGROUND: South Africa has the highest prevalence of overweight/obesity in Sub-Saharan Africa. Assessing the effect of modifiable factors such as early infant feeding on growth velocity and overweight/obesity is therefore important. This paper aimed to assess the effect of infant feeding in the transitional period (12 weeks) on 12–24 week growth velocity amongst HIV unexposed children using WHO growth velocity standards and on the age and sex adjusted body mass index (BMI) Z-score distribution at 2 years. METHODS: Data were from 3 sites in South Africa participating in the PROMISE-EBF trial. We calculated growth velocity Z-scores using the WHO growth standards and assessed feeding practices using 24-hour and 7-day recall data. We used quantile regression to study the associations between 12 week infant feeding and 12–24 week weight velocity (WVZ) with BMI-for-age Z-score at 2 years. We included the internal sample quantiles (70th and 90th centiles) that approximated the reference cut-offs of +2 (corresponding to overweight) and +3 (corresponding to obesity) of the 2 year BMI-for-age Z-scores. RESULTS: At the 2-year visit, 641 children were analysed (median age 22 months, IQR: 17–26 months). Thirty percent were overweight while 8.7% were obese. Children not breastfed at 12 weeks had higher 12–24 week mean WVZ and were more overweight and obese at 2 years. In the quantile regression, children not breastfed at 12 weeks had a 0.37 (95% CI 0.07, 0.66) increment in BMI-for-age Z-score at the 50th sample quantile compared to breast-fed children. This difference in BMI-for-age Z-score increased to 0.46 (95% CI 0.18, 0.74) at the 70th quantile and 0.68 (95% CI 0.41, 0.94) at the 90th quantile . The 12–24 week WVZ had a uniform independent effect across the same quantiles. CONCLUSIONS: This study demonstrates that the first 6 months of life is a critical period in the development of childhood overweight and obesity. Interventions targeted at modifiable factors such as early infant feeding practices may reduce the risks of rapid weight gain and subsequent childhood overweight/obesity.Scopu