Cortical tau is associated with microstructural imaging biomarkers of neurite density and dendritic complexity in Alzheimer's disease.

INTRODUCTION: In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. METHODS: We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals with young onset AD. Diffusion tensor imaging measured mean diffusivity (MD). Amyloid beta and tau positron emission tomography were acquired and associations with microstructural measures were assessed. RESULTS: When regional volume was adjusted for, in the medial temporal lobe there was a significant negative association between neurite density and tau (partial R2  = 0.56, p = 0.008) and between orientation dispersion and tau (partial R2  = 0.66, p = 0.002), but not between MD and tau. In a wider cortical composite, there was an association between orientation dispersion and tau (partial R2  = 0.43, p = 0.030), but not between other measures and tau. DISCUSSION: Our findings are consistent with tau causing first dendritic pruning (reducing dispersion/complexity) followed by neuronal loss. Advanced magnetic resonance imaging (MRI) microstructural measures have the potential to provide information relating to underlying tau deposition.

Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study.

Blood biomarkers have great potential to advance clinical care and accelerate trials in Alzheimer's disease (AD). Plasma phospho-tau181 (p-tau181) is a promising blood biomarker however, it is unknown if levels increase in presymptomatic AD. Therefore, we investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD). Plasma p-tau181 was measured, using an in-house single molecule array assay. We compared p-tau181 between symptomatic carriers, presymptomatic carriers, and non-carriers, adjusting for age and sex. We examined the relationship between p-tau181 and neurofilament light and estimated years to/from symptom onset (EYO), as well as years to/from actual onset in a symptomatic subgroup. In addition, we studied associations between p-tau181 and clinical severity, as well testing for differences between genetic subgroups. Twenty-four were presymptomatic carriers (mean baseline EYO -9.6 years) while 27 were non-carriers. Compared with non-carriers, plasma p-tau181 concentration was higher in both symptomatic (p < 0.001) and presymptomatic mutation carriers (p < 0.001). Plasma p-tau181 showed considerable intra-individual variability but individual values discriminated symptomatic (AUC 0.93 [95% CI 0.85-0.98]) and presymptomatic (EYO ≥ -7 years) (AUC 0.86 [95% CI 0.72-0.94]) carriers from non-carriers of the same age and sex. From a fitted model there was evidence (p = 0.050) that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Our finding that plasma p-tau181 concentration is increased in symptomatic and presymptomatic FAD suggests potential utility as an easily accessible biomarker of AD pathology.

Plasma amyloid-ß ratios in autosomal dominant Alzheimer's disease: the influence of genotype.

In vitro studies of autosomal dominant Alzheimer's disease implicate longer amyloid-ß peptides in disease pathogenesis; however, less is known about the behaviour of these mutations in vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from individuals who were at risk of inheriting a mutation or were symptomatic. We tested for differences in amyloid-ß (Aß)42:38, Aß42:40 and Aß38:40 ratios between presenilin 1 (PSEN1) and amyloid precursor protein (APP) carriers. We examined the relationship between plasma and in vitro models of amyloid-ß processing and tested for associations with parental age at onset. Thirty-nine participants were mutation carriers (28 PSEN1 and 11 APP). Age- and sex-adjusted models showed marked differences in plasma amyloid-ß between genotypes: higher Aß42:38 in PSEN1 versus APP (P < 0.001) and non-carriers (P < 0.001); higher Aß38:40 in APP versus PSEN1 (P < 0.001) and non-carriers (P < 0.001); while Aß42:40 was higher in both mutation groups compared to non-carriers (both P < 0.001). Amyloid-ß profiles were reasonably consistent in plasma and cell lines. Within the PSEN1 group, models demonstrated associations between Aß42:38, Aß42:40 and Aß38:40 ratios and parental age at onset. In vivo differences in amyloid-ß processing between PSEN1 and APP carriers provide insights into disease pathophysiology, which can inform therapy development.

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants.

BACKGROUND: Neonatal hypoglycaemia, a common condition, can be associated with brain injury. It is frequently managed by providing infants with an alternative source of glucose, often given enterally with milk-feeding or intravenously with dextrose solution, which may decrease breastfeeding success. Intravenous dextrose also often requires that mother and baby are cared for in separate environments. Oral dextrose gel is simple and inexpensive, and can be administered directly to the buccal mucosa for rapid correction of hypoglycaemia, in association with continued breastfeeding and maternal care. This is an update of a previous review published in 2016. OBJECTIVES: To assess the effectiveness of oral dextrose gel in correcting hypoglycaemia in newborn infants from birth to discharge home and reducing long-term neurodevelopmental impairment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase from database inception to October 2021.  We also searched international clinical trials networks, the reference lists of included trials, and relevant systematic reviews identified in the search.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing oral dextrose gel versus placebo, no treatment, or other therapies for the treatment of neonatal hypoglycaemia in newborn infants from birth to discharge home. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted data; they did not assess publications for which they were study authors. We contacted investigators to obtain additional information. We used fixed-effect models and the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included two studies conducted in high-income countries, involving 312 late preterm and at-risk term infants and comparing oral dextrose gel (40% concentration) to placebo gel. One study was at low risk of bias, and the other (an abstract) was at unclear to high risk of bias. Oral dextrose gel compared with placebo gel probably increases correction of hypoglycaemic events (rate ratio 1.08, 95% confidence interval (CI) 0.98 to 1.20; rate difference 66 more per 1000, 95% CI 17 fewer to 166 more; 1 study; 237 infants; moderate-certainty evidence), and may result in a slight reduction in the risk of major neurological disability at age two years or older, but the evidence is uncertain (risk ratio (RR) 0.46, 95% CI 0.09 to 2.47; risk difference (RD) 24 fewer per 1000, 95% CI 41 fewer to 66 more; 1 study, 185 children; low-certainty evidence). The evidence is very uncertain about the effect of oral dextrose gel compared with placebo gel or no gel on the need for intravenous treatment for hypoglycaemia (RR 0.78, 95% CI 0.46 to 1.32; RD 37 fewer per 1000, 95% CI 91 fewer to 54 more; 2 studies, 312 infants; very low-certainty evidence). Investigators in one study of 237 infants reported no adverse events (e.g. choking or vomiting at the time of administration) in the oral dextrose gel or placebo gel group (low-certainty evidence).  Oral dextrose gel compared with placebo gel probably reduces the incidence of separation from the mother for treatment of hypoglycaemia (RR 0.54, 95% CI 0.31 to 0.93; RD 116 fewer per 1000, 95% CI 174 fewer to 18 fewer; 1 study, 237 infants; moderate-certainty evidence), and increases the likelihood of exclusive breastfeeding after discharge (RR 1.10, 95% CI 1.01 to 1.18; RD 87 more per 1000, 95% CI 9 more to 157 more; 1 study, 237 infants; moderate-certainty evidence).   AUTHORS' CONCLUSIONS: Oral dextrose gel (specifically 40% dextrose concentration) used to treat hypoglycaemia in newborn infants (specifically at-risk late preterm and term infants) probably increases correction of hypoglycaemic events, and may result in a slight reduction in the risk of major neurological disability at age two years or older. Oral dextrose gel treatment probably reduces the incidence of separation from the mother for treatment and increases the likelihood of exclusive breastfeeding after discharge. No adverse events have been reported. Oral dextrose gel is probably an effective and safe first-line treatment for infants with neonatal hypoglycaemia in high-income settings.  More evidence is needed about the effects of oral dextrose gel treatment on later neurological disability and the need for other treatments for hypoglycaemia. Future studies should be conducted in low-and middle-income settings, in extremely and moderately preterm infants, and compare oral dextrose gel with other therapies such as intravenous dextrose. There are two ongoing studies that may alter the conclusions of this review when published.

Alternative Cerebral Fuels in the First Five Days in Healthy Term Infants: The Glucose in Well Babies (GLOW) Study.

OBJECTIVES: To determine plasma lactate and beta-hydroxybutyrate (BHB) concentrations of healthy infants in the first 5 days and their relationships with glucose concentrations. STUDY DESIGN: Prospective masked observational study in Hamilton, New Zealand. Term, appropriately grown singletons had heel-prick blood samples, 4 in the first 24 hours then twice daily. RESULTS: In 67 infants, plasma lactate concentrations were higher in the first 12 hours (median, 20; range, 10-55 mg/dL [median, 2.2 mmol/L; range, 1.1-6.2 mmol/L]), decreasing to 12 mg/dL (range, 7-29 mg/dL [median, 1.4 mmol/L; range, 0.8-3.3 mmol/L]) after 48 hours. Plasma BHB concentrations were low in the first 12 hours (median, 0.9 mg/dL; range, 0.5-5.2 mg/dL [median, 0.1 mmol/L; range, 0.05-0.5 mmol/L]), peaked at 48-72 hours (median, 7.3 mg/dL; range, 1.0-25.0 mg/dL [median, 0.7 mmol/L; range, 0.05-2.4 mmol/L]), and decreased by 96 hours (median, 0.9 mg/dL; range, 0.5-16.7 mg/dL [median, 0.1 mmol/L; range, 0.05-1.6 mmol/L]). Compared with infants with plasma glucose concentrations above the median (median, 67 mg/dL [median, 3.7 mmol/L]), those with lower glucose had lower lactate concentrations in the first 12 hours and higher BHB concentrations between 24 and 96 hours. Lower interstitial glucose concentrations were also associated with higher plasma BHB concentrations, but only if the lower glucose lasted greater than 12 hours. Glucose contributed 72%-84% of the estimated potential adenosine triphosphate throughout the 5 days, with lactate contributing 25% on day 1 and BHB 7% on days 2-3. CONCLUSIONS: Lactate on day 1 and BHB on days 2-4 may contribute to cerebral fuels in healthy infants, but are unlikely to provide neuroprotection during early or acute hypoglycemia. TRIAL REGISTRATION: The Australian and New Zealand Clinical Trials Registry: ACTRN12615000986572.

Delayed versus Immediate Cord Clamping in Preterm Infants.

BACKGROUND: The preferred timing of umbilical-cord clamping in preterm infants is unclear. METHODS: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births. RESULTS: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. CONCLUSIONS: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).

Glucose Profiles in Healthy Term Infants in the First 5 Days: The Glucose in Well Babies (GLOW) Study.

OBJECTIVES: To determine postnatal changes in plasma and interstitial glucose concentrations of healthy infants receiving current recommended care and to compare the incidence of low concentrations with recommended thresholds for treatment of at-risk infants. STUDY DESIGN: A prospective masked observational study in Hamilton, New Zealand. Healthy, term, appropriately grown singletons had continuous glucose monitoring and repeated heel-prick plasma glucose measurements (4 in the first 24 hours then twice daily using the glucose oxidase method) from birth to 120 hours. RESULTS: The 67 infants had a mean birth weight of 3584 ± 349 g, and gestational age of 40.1 ± 1.2 weeks. The mean glucose concentrations increased over the first 18 hours, remained stable to 48 hours (59 ± 11 mg/dL; 3.3 ± 0.6 mmol/L)] before increasing to a new plateau by the fourth day (89 ± 13 mg/dL; 4.6 ± 0.7 mmol/L). Plasma glucose concentrations of 47 mg/dL (2.6 mmol/L) approximated the 10th percentile in the first 48 hours, and 39% of infants had ≥1 episode below this threshold. Early term infants had lower mean glucose concentrations than those born at later gestational ages and were more likely to have episodes <47 mg/dL (<2.6 mmol/L) (19/32 [59%] vs 7/35 [20%]; relative risk, 3.0; 95% CI, 1.4-6.1; P = .001). CONCLUSIONS: Healthy infants seem to complete their metabolic transition by day 4. Many have glucose concentrations below the accepted thresholds for treatment of hypoglycemia. TRIAL REGISTRATION: ACTRN: 12615000986572.

Glycolysis and oxidative phosphorylation are essential for purinergic receptor-mediated angiogenic responses in vasa vasorum endothelial cells.

Angiogenesis is an energy-demanding process; however, the role of cellular energy pathways and their regulation by extracellular stimuli, especially extracellular nucleotides, remain largely unexplored. Using metabolic inhibitors of glycolysis (2-deoxyglucose) and oxidative phosphorylation (OXPHOS) (oligomycin, rotenone, and FCCP), we demonstrate that glycolysis and OXPHOS are both essential for angiogenic responses of vasa vasorum endothelial cell (VVEC). Treatment with P2R agonists, ATP, and 2-methylthioadenosine diphosphate trisodium salt (MeSADP), but not P1 receptor agonist, adenosine, increased glycolytic activity in VVEC (measured by extracellular acidification rate and lactate production). Stimulation of glycolysis was accompanied by increased levels of phospho-phosphofructokinase B3, hexokinase (HK), and GLUT-1, but not lactate dehydrogenase. Moreover, extracellular ATP and MeSADP, and to a lesser extent adenosine, increased basal and maximal oxygen consumption rates in VVEC. These effects were potentiated when the cells were cultured in 20 mM galactose and 5 mM glucose compared with 25 mM glucose. Treatment with P2R agonists decreased phosphorylation of pyruvate dehydrogenase (PDH)-E1α and increased succinate dehydrogenase (SDH), cytochrome oxidase IV, and ß-subunit of F1F0 ATP synthase expression. In addition, P2R stimulation transiently elevated mitochondrial Ca2+ concentration, implying involvement of mitochondria in VVEC angiogenic activation. We also demonstrated a critical role of phosphatidylinositol 3-kinase and Akt pathways in lactate production, PDH-E1α phosphorylation, and the expression of HK, SDH, and GLUT-1 in ATP-stimulated VVEC. Together, our findings suggest that purinergic and metabolic regulation of VVEC energy pathways is essential for VV angiogenesis and may contribute to pathologic vascular remodeling in pulmonary hypertension.

What Happens to Blood Glucose Concentrations After Oral Treatment for Neonatal Hypoglycemia?

OBJECTIVE: To determine the change in blood glucose concentration after oral treatment of infants with hypoglycemia in the first 48 hours after birth. STUDY DESIGN: We analyzed data from 227 infants with hypoglycemia (blood glucose <46.8 mg/dL, 2.6 mmol/L) born at a tertiary hospital who experienced 295 episodes of hypoglycemia. Blood glucose concentrations were measured (glucose oxidase) within 90 minutes after randomization to dextrose or placebo gel plus feeding with formula, expressed breast milk, or breast feeding. RESULTS: The overall mean increase in blood glucose concentration was 11.7 mg/dL (95% CI 10.4-12.8). The increase was greater after buccal dextrose gel than after placebo gel (+3.0 mg/dL; 95% CI 0.7-5.3; P = .01) and greater after infant formula than after other feedings (+3.8 mg/dL; 95% CI 0.8-6.7; P = .01). The increase in blood glucose concentration was not affected by breast feeding (+2.0 mg/dL; 95% CI -0.3 to 44.2; P = .09) or expressed breast milk (-1.4 mg/dL; 95% CI -3.7 to 0.9; P = .25). However, breast feeding was associated with reduced requirement for repeat gel treatment (OR = 0.52; 95% CI 0.28-0.94; P = .03). CONCLUSIONS: Treatment of infants with hypoglycemia with dextrose gel or formula is associated with increased blood glucose concentration and breast feeding with reduced need for further treatment. Dextrose gel and breast feeding should be considered for first-line oral treatment of infants with hypoglycemia.

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants.

BACKGROUND: Neonatal hypoglycaemia, a common condition, can be associated with brain injury. It is frequently managed by providing infants with an alternative source of glucose, given enterally with formula or intravenously with dextrose solution. This often requires that mother and baby are cared for in separate environments and may inhibit breast feeding. Dextrose gel is simple and inexpensive and can be administered directly to the buccal mucosa for rapid correction of hypoglycaemia, in association with continued breast feeding and maternal care. OBJECTIVES: To assess the effectiveness of dextrose gel in correcting hypoglycaemia and in reducing long-term neurodevelopmental impairment. SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science from inception of the database to February 2016. We also searched international clinical trials networks and handsearched proceedings of specific scientific meetings. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing dextrose gel versus placebo, no treatment or other therapies for treatment of neonatal hypoglycaemia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data and did not assess publications for which they themselves were study authors. MAIN RESULTS: We included two trials involving 312 infants. No data were available for correction of hypoglycaemia for each hypoglycaemic event. We found no evidence of a difference between dextrose gel and placebo gel for major neurosensory disability at two-year follow-up (risk ratio (RR) 6.27, 95% confidence interval (CI) 0.77 to 51.03; one trial, n = 184; quality of evidence very low). Dextrose gel compared with placebo gel or no gel did not alter the need for intravenous treatment for hypoglycaemia (typical RR 0.78, 95% CI 0.46 to 1.32; two trials, 312 infants; quality of evidence very low). Infants treated with dextrose gel were less likely to be separated from their mothers for treatment of hypoglycaemia (RR 0.54, 95% CI 0.31 to 0.93; one trial, 237 infants; quality of evidence moderate) and were more likely to be exclusively breast fed after discharge (RR 1.10, 95% CI 1.01 to 1.18; one trial, 237 infants; quality of evidence moderate). Estimated rise in blood glucose concentration following dextrose gel was 0.4 mmol/L (95% CI -0.14 to 0.94; one trial, 75 infants). Investigators in one trial reported no adverse outcomes (n = 237 infants). AUTHORS' CONCLUSIONS: Treatment of infants with neonatal hypoglycaemia with 40% dextrose gel reduces the incidence of mother-infant separation for treatment and increases the likelihood of full breast feeding after discharge compared with placebo gel. No evidence suggests occurrence of adverse effects during the neonatal period or at two years' corrected age. Oral dextrose gel should be considered first-line treatment for infants with neonatal hypoglycaemia.

Discrimination of voice gender in the human auditory cortex.

Discerning a speaker's gender from their voice is a basic and crucial aspect of human communication. Voice pitch height, the perceptual correlate of fundamental frequency, is higher in females and provides a cue for gender discrimination. However, male and female voices are also differentiated by multiple other spectral and temporal characteristics, including mean formant frequency and spectral flux. The robust perceptual segregation of male and female voices is thought to result from processing the combination of discriminating features, which in neural terms may correspond to early sound object analysis occurring in non-primary auditory cortex. However, the specific mechanism for gender perception has been unclear. Here, using functional magnetic resonance imaging, we show that discrete sites in non-primary auditory cortex are differentially activated by male and female voices, with female voices consistently evoking greater activation in the upper bank of the superior temporal sulcus and posterior superior temporal plane. This finding was observed at the individual subject-level in all 24 subjects. The neural response was highly specific: no auditory regions were more activated by male than female voices. Further, the activation associated with female voices was 1) larger than can be accounted for by a sole effect of fundamental frequency, 2) not due to psychological attribution of female gender and 3) unaffected by listener gender. These results demonstrate that male and female voices are represented as distinct auditory objects in the human brain, with the mechanism for gender discrimination being a gender-dependent activation-level cue in non-primary auditory cortex.

Metabolic acidosis in the first 14 days of life in infants of gestation less than 26 weeks.

UNLABELLED: Extremely immature newborns develop a self-limiting normal anion gap metabolic acidosis in early life. This study examined the natural history of this acidosis in a population of infants of gestation less than 26 weeks in the first 14 days of life. The acidosis was maximal on day 4 with a mean base deficit of 10.6 mmol/l and had resolved in 90 % of infants by day 11. Dopamine usage was the only independent predictor of the acidosis. Its use was associated with a greater degree of acidosis. CONCLUSION: Extremely preterm infants experience a self-limiting normal anion gap metabolic acidosis in the first 2 weeks of life which is consistent with renal tubular immaturity.

Isolation, propagation, genome analysis and epidemiology of HKU1 betacoronaviruses.

From 1 January 2009 to 31 May 2013, 15 287 respiratory specimens submitted to the Clinical Virology Laboratory at the Children's Hospital Colorado were tested for human coronavirus RNA by reverse transcription-PCR. Human coronaviruses HKU1, OC43, 229E and NL63 co-circulated during each of the respiratory seasons but with significant year-to-year variability, and cumulatively accounted for 7.4-15.6 % of all samples tested during the months of peak activity. A total of 79 (0.5 % prevalence) specimens were positive for human betacoronavirus HKU1 RNA. Genotypes HKU1 A and B were both isolated from clinical specimens and propagated on primary human tracheal-bronchial epithelial cells cultured at the air-liquid interface and were neutralized in vitro by human intravenous immunoglobulin and by polyclonal rabbit antibodies to the spike glycoprotein of HKU1. Phylogenetic analysis of the deduced amino acid sequences of seven full-length genomes of Colorado HKU1 viruses and the spike glycoproteins from four additional HKU1 viruses from Colorado and three from Brazil demonstrated remarkable conservation of these sequences with genotypes circulating in Hong Kong and France. Within genotype A, all but one of the Colorado HKU1 sequences formed a unique subclade defined by three amino acid substitutions (W197F, F613Y and S752F) in the spike glycoprotein and exhibited a unique signature in the acidic tandem repeat in the N-terminal region of the nsp3 subdomain. Elucidating the function of and mechanisms responsible for the formation of these varying tandem repeats will increase our understanding of the replication process and pathogenicity of HKU1 and potentially of other coronaviruses.

Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Neonatal hypoglycaemia is common, and a preventable cause of brain damage. Dextrose gel is used to reverse hypoglycaemia in individuals with diabetes; however, little evidence exists for its use in babies. We aimed to assess whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. METHODS: We undertook a randomised, double-blind, placebo-controlled trial at a tertiary centre in New Zealand between Dec 1, 2008, and Nov 31, 2010. Babies aged 35-42 weeks' gestation, younger than 48-h-old, and at risk of hypoglycaemia were randomly assigned (1:1), via computer-generated blocked randomisation, to 40% dextrose gel 200 mg/kg or placebo gel. Randomisation was stratified by maternal diabetes and birthweight. Group allocation was concealed from clinicians, families, and all study investigators. The primary outcome was treatment failure, defined as a blood glucose concentration of less than 2·6 mmol/L after two treatment attempts. Analysis was by intention to treat. The trial is registered with Australian New Zealand Clinical Trials Registry, number ACTRN12608000623392. FINDINGS: Of 514 enrolled babies, 242 (47%) became hypoglycaemic and were randomised. Five babies were randomised in error, leaving 237 for analysis: 118 (50%) in the dextrose group and 119 (50%) in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (16 [14%] vs 29 [24%]; relative risk 0·57, 95% CI 0·33-0·98; p=0·04). We noted no serious adverse events. Three (3%) babies in the placebo group each had one blood glucose concentration of 0·9 mmol/L. No other adverse events took place. INTERPRETATION: Treatment with dextrose gel is inexpensive and simple to administer. Dextrose gel should be considered for first-line treatment to manage hypoglycaemia in late preterm and term babies in the first 48 h after birth. FUNDING: Waikato Medical Research Foundation, the Auckland Medical Research Foundation, the Maurice and Phyllis Paykel Trust, the Health Research Council of New Zealand, and the Rebecca Roberts Scholarship.

A survey of the management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network.

BACKGROUND: Neonatal hypoglycaemia is a common problem linked to both brain damage and death. There is controversy regarding both the definition of and best treatment for neonatal hypoglycaemia. AIM: To determine current management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network (ANZNN). METHODS: Four questionnaires were sent to the Director of each of the 45 nurseries within the ANZNN. The Director was asked to complete one questionnaire and give the remaining three to other doctors involved with the management of babies with hypoglycaemia in the nursery. RESULTS: One hundred and eighty surveys were sent and 127 were returned (71%), including at least one from each nursery. Almost all respondents (120, 94%) reported using a protocol to treat hypoglycaemia. Only 2 (2%) reported screening all babies for neonatal hypoglycaemia, with the remainder screening babies at risk. Only 67, (53%) reported that blood glucose levels were tested on an analyser generally considered to be reliable at low levels. Most respondents (99, 78%) reported the clinical threshold for treatment was <2.6 mmol/L. However, when provided with clinical scenarios, respondents reported a variety of interventions, including no treatment. CONCLUSION: Doctors within the ANZNN are consistent about definition and screening for neonatal hypoglycaemia. However, frequently, the diagnosis is made using unreliable analysers. There is also wide variation in treatment, suggesting a lack of reliable evidence on which to base practice.

The use of mini-CEX in UK foundation training six years following its introduction: lessons still to be learned and the benefit of formal teaching regarding its utility.

BACKGROUND: The mini-clinical evaluation exercise (mini-CEX) is a widely used tool with a strong theoretical basis. It was introduced to UK foundation training in 2005. AIMS: To assess current experiences, opinions and attitudes towards mini-CEX amongst foundation doctors, and explore what factors underpin these. METHODS: Data were collected from foundation trainees via an on-line questionnaire. RESULTS: Ninety-eight per cent of respondents had used mini-CEX during FY1, however, only 32% had ever received formal teaching regarding its use. In terms of understanding of the purpose of mini-CEX, only 30% of trainees commented on there being a formative aspect or requirement for feedback. The majority of trainees did not feel that mini-CEX was a useful part of their training. The main themes were the poor attitude and understanding of assessors and difficulties finding sufficient time. However, those who had received formal teaching as students regarding the use of mini-CEX were significantly more likely as postgraduates to find it beneficial (p = 0.031). CONCLUSIONS: A more concerted effort to educate trainees and assessors regarding the correct use of mini-CEX will enhance its educational value. Increased education during undergraduate training regarding use of formative assessment may lead to more effective utilisation in the postgraduate setting.