The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli. RESULTS: No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli. CONCLUSION: These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.

Physical health, breastfeeding problems and maternal mood in the early postpartum: a prospective cohort study.

This study aimed to investigate prospectively the contribution of maternal physical health and/or breastfeeding problems to maternal mood (depression, anxiety, fatigue, irritability, confusion, vigor) at 8-weeks postpartum. A prospective study was conducted. Participants were recruited antenatally from a public and a private maternity hospital in Melbourne, Australia. Nulliparous pregnant women (N = 229), ≥ 18 years of age, ≥ 36-week gestation, singleton pregnancy and with sufficient English were eligible. Data were collected by self-report questionnaire (pregnancy, weeks 1-4 postpartum) and telephone interview (week 8 postpartum). A high burden of physical problems was classified as ≥ 3 problems (caesarean/perineal pain; back pain; constipation; haemorrhoids; urinary and bowel incontinence) for ≥ 2 time points. A high burden of breastfeeding problems was having ≥ 2 problems (mastitis; nipple pain; frequent expressing; over- or under-supply of milk) for ≥ 2 time points. Multivariate linear regression was used to investigate the relationship between maternal mood, assessed using Profile of Mood States (8-week postpartum), and a high burden of breastfeeding and/or physical health problems. Forty-six women (20.1%) had a high burden of physical symptoms, 44 (19.2%) a high burden of breastfeeding problems only and 25 women (11.0%) had both. A high burden of breastfeeding problems alone (ß = 10.6, p = 0.01) or with co-morbid physical problems (ß = 15.35, p = 0.002) was significantly associated with poorer maternal mood at 8 weeks. Early, effective postnatal treatment of maternal health and breastfeeding problems could reduce women's risk for poor mental health.

The effect of skin-to-skin care on cerebral oxygenation during nasogastric feeding of preterm infants.

AIM: To describe cerebral oxygenation during gavage feeding of preterm infants during incubator and skin-to-skin care. METHODS: Further analysis of data from two crossover studies comparing cerebral oxygenation, heart rate and oxygen saturation during skin-to-skin care with incubator care. Data were analysed in three epochs; 10 minutes prefeed, during-feed and 10 minutes postfeed. Measurements from infants fed during incubator care were compared with those obtained during skin-to-skin care. RESULTS: In 39 infants [median (IQR) 27.8 (26.1-30.0) weeks' gestation], there was no difference in cerebral oxygenation between pre-, during- and postfeed. Heart rate increased by three beats per minute postfeed compared with during-feed. Twenty infants received two gavage feeds, one feed in the incubator and another during skin-to-skin care. There was no difference in cerebral oxygenation and heart rate; peripheral oxygen saturation decreased by 3% during feeding whilst skin-to-skin care compared with feeding in the incubator. CONCLUSION: Cerebral oxygenation remained stable before, during and after gavage feeding in an incubator and during skin-to-skin care. The small decrease in oxygen saturation whilst receiving gavage feeding during skin-to-skin care is unlikely to be clinically important, providing reassurance that preterm infants maintain physiological stability during skin-to-skin care.

Determining Effects of Superfine Sheep wool in INfantile Eczema (DESSINE): a randomized paediatric crossover study.

BACKGROUND: Despite limited evidence, woollen clothing has traditionally been considered to be an irritant that should be avoided by individuals with atopic dermatitis (AD). Wool fibres come in a range of diameters, and have beneficial thermodynamic and moisture transport properties. OBJECTIVES: This study examines the effects of superfine merino wool on symptoms in participants with mild-to-moderate AD. METHODS: The trial was a 12-week, randomized, assessor-blinded, crossover, prospective, cohort study of 39 patients with mild-to-moderate AD, aged between 4 weeks and 3 years, comparing superfine merino wool ensembles with standard cotton clothing chosen by parents. Participants were assigned to wool or cotton clothing and assessed every 3 weeks for 6 weeks, before crossing over to wear the other clothing material for a further 6-week period, with similar 3-weekly reviews. The primary end point was the SCORing Atopic Dermatitis (SCORAD) index after each 6-week period, with Atopic Dermatitis Severity Index (ADSI), Infants' Dermatitis Quality Of Life Index (IDQOL) and topical steroid use as secondary end points to measure AD severity and quality of life. RESULTS: Overall, compared with baseline, superfine wool ensembles were associated with a reduction in mean SCORAD of 2·5 [95% confidence interval (CI) -4·7 to -0·4] at 3 weeks and 7·6 (95% CI -10·4 to -4·8) at 6 weeks when compared with the cotton ensembles. A similar change was observed in ADSI and IDQOL scores for the same period. Body steroid use was also reduced. Conversely, changing ensembles from wool to cotton resulted in an increase in scores. CONCLUSIONS: Superfine merino wool may assist in the management of childhood AD.

Assessing the tongue colour of newly born infants may help to predict the need for supplemental oxygen in the delivery room.

AIM: It takes several minutes for infants to become pink after birth. Preductal oxygen saturation (SpO2) measurements are used to guide the delivery of supplemental oxygen to newly born infants, but pulse oximetry is not available in many parts of the world. We explored whether the pinkness of an infant's tongue provided a useful indication that supplemental oxygen was required. METHODS: This was a prospective observational study of infants delivered by Caesarean section. Simultaneous recording of SpO2 and visual assessment of whether the tongue was pink or not was made at 1-7 and 10 min after birth. RESULTS: The 38 midwives and seven paediatric trainees carried out 271 paired assessments on 68 infants with a mean (SD) birthweight of 3214 (545) grams and gestational age of 38 (2) weeks. When the infant did not have a pink tongue, this predicted SpO2 of <70% with a sensitivity of 26% and a specificity of 96%. CONCLUSION: Tongue colour was a specific but insensitive sign that indicated when SpO2 was <70%. When the tongue is pink, it is likely that an infant has an SpO2 of more than 70% and does not require supplemental oxygen.

The onset, recurrence and associated obstetric risk factors for urinary incontinence in the first 18 months after a first birth: an Australian nulliparous cohort study.

OBJECTIVE: To investigate the contribution of obstetric risk factors to persistent urinary incontinence (UI) between 4 and 18 months postpartum. DESIGN: Prospective pregnancy cohort. SETTING: Six metropolitan public hospitals in Victoria, Australia. SAMPLE: A total of 1507 nulliparous women recruited to the Maternal Health Study in early pregnancy (≤24 weeks of gestation). METHODS: Data from hospital records and self-administered questionnaires/telephone interviews at ≤24 and 30-32 weeks of gestation and at 3, 6, 9, 12 and 18 months postpartum analysed using logistic regression. MAIN OUTCOME MEASURES: Persistent UI 4-18 months postpartum in women continent before pregnancy. RESULTS: Of the women who were continent before pregnancy, 44% reported UI 4-18 months postpartum, and 25% reported persistent UI (symptoms at multiple follow ups). Compared with spontaneous vaginal birth, women who had a caesarean before labour (adjusted odds ratio [aOR] 0.4, 95% confidence interval [95% CI] 0.2-0.9), in first-stage labour (aOR 0.4, 95% CI 0.2-0.6) or in second-stage labour (aOR 0.4, 95% CI 0.2-1.0) were less likely to report persistent UI 4-18 months postpartum. Prolonged second-stage labour in women who had an operative vaginal birth was associated with increased likelihood of UI (aOR 2.5, 95% CI 1.3-4.6). Compared with women who were continent in pregnancy, women reporting UI in pregnancy had a seven-fold increase in odds of persistent UI (aOR 7.4, 95% CI 5.1-10.7). CONCLUSIONS: Persistent UI is common after childbirth and is more likely following prolonged labour in combination with operative vaginal birth. The majority of women reporting persistent UI at 4-18 months postpartum also experienced symptoms in pregnancy.

Depressive symptoms and intimate partner violence in the 12 months after childbirth: a prospective pregnancy cohort study.

OBJECTIVE: To examine maternal depressive symptoms during and after pregnancy and explore their relationship with intimate partner violence in the 12 months after birth. DESIGN: Prospective pregnancy cohort study of nulliparous women. SETTING: Melbourne, Australia. POPULATION: In all, 1507 eligible women completed baseline data (mean gestation 15 weeks). Analyses are presented for 1305 women who completed all follow-up questionnaires. METHODS: Women were recruited from six public hospitals at between 6 and 24 weeks of gestation. Written questionnaires were completed at recruitment and at 3, 6 and 12 months postpartum. MAIN OUTCOME MEASURES: Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Intimate partner violence was assessed using the short version of the Composite Abuse Scale. RESULTS: Sixteen per cent of women reported depressive symptoms (EPDS ≥ 13) in the 12 months postpartum, with most women first reporting depressive symptoms in the second 6 months after birth. Around 40% of women reporting depressive symptoms at each follow up also reported intimate partner violence. Factors associated with postpartum depressive symptoms in multivariable models were: emotional abuse alone (adjusted odds ratio [OR] 2.72, 95% CI 1.72-4.13), physical abuse (adjusted OR 3.94, 95% CI 2.44-6.36), depression in pregnancy (adjusted OR 2.89, 95% CI 1.75-4.77) and unemployment in early pregnancy (adjusted OR 1.60, 95% CI 1.03-2.48). CONCLUSIONS: Screening for maternal depression at 3 months postpartum or earlier may miss over half the women with depression in the first 12 months after birth. Intimate partner violence is common among women reporting postnatal depressive symptoms and may be an important factor for health professionals to consider in their management.

Prevalence and factors associated with persistent transmission of Schistosoma haematobium among primary school children after five rounds of mass drug administration using praziquantel: A cross sectional study in Mkuranga district, Tanzania.

Despite a human schistosomiasis control programme through praziquantel mass drug administration (MDA) between 2011 and 2015,there was still persistent transmission among primary schoolchildren (PSC) in Mkuranga district, Tanzania. Our cross-sectional study was conducted among 396 PSC who provided urine for diagnosis of Schistosoma haematobium infection. Observations were conducted to determine PSC water contact activities. Logistic regression was used to test association between dependent and independent variables. We found MDA uptake among PSC as 72.5%, and the prevalence of Schistosoma haematobium infection 5.8%. The risk of infection increased among PSC engaged in fetching water and adjusted odds ratio (AOR) for swimming, bathing, fishing, crossing ponds and paddy fields were 0.123, 0.166, 0.232, 0.202 and 0.093 respectively. Thus we conclude that multiple water contact activities and low participation in MDA is responsible for persistent Schistosoma transmission.

Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial.

BACKGROUND: Probiotic supplementation in early life may be effective for preventing eczema. Previous studies have suggested that prenatal administration may be particularly important for beneficial effects. OBJECTIVE: We examined whether prenatal treatment with the probiotic Lactobacillus rhamnosus GG (LGG) can influence the risk of eczema during infancy. METHODS: We recruited 250 pregnant women carrying infants at high risk of allergic disease to a randomized controlled trial of probiotic supplementation (LGG 1.8 × 10(10) cfu/day) from 36 weeks gestation until delivery. Infants were assessed during their first year for eczema or allergic sensitization. Immunological investigations were performed in a subgroup. Umbilical cord blood was examined for dendritic cell and regulatory T cell numbers and production of TGFß, IL-10, IL-12, IL-13, IFN-γ and TNFα. Maternal breast milk was examined for total IgA, soluble CD14 and TGFß. RESULTS: Prenatal probiotic treatment was not associated with reduced risk of eczema (34% probiotic, 39% placebo; RR 0.88; 95% CI 0.63, 1.22) or IgE-associated eczema (18% probiotic, 19% placebo; RR 0.94; 95% CI 0.53, 1.68). Prenatal probiotic treatment was not associated with any change in cord blood immune markers, but was associated with decreased breast milk soluble CD14 and IgA levels. CONCLUSIONS: Prenatal treatment with Lactobacillus rhamnosus GG was not sufficient for preventing eczema. If probiotics are effective for preventing eczema, then a postnatal component to treatment or possibly an alternative probiotic strain is necessary.

Poor adherence to integral daily tasks limits the efficacy of CSII in youth.

INTRODUCTION/AIMS: Many young people experience improved glycemia with continuous subcutaneous insulin infusion (CSII) regimens; however, sustained glycemic benefit eludes a significant proportion. Our aims were to assess adherence to recommended CSII-related behaviors in a representative pediatric cohort and to identify potentially modifiable behaviors that impact on HbA1c in youth. RESEARCH DESIGN AND METHODS: Data uploaded from insulin pump devices of 100 youth with type 1 diabetes were analyzed. RESULTS: Ability to translate recommended behaviors into daily self-management varied widely in youth. Mean bolus frequency was 6.1/d; however, 69/100 entered <4 blood glucose levels (BGL)/d. HbA1c decreased by 0.2% for each additional BGL (p=0.001) and bolus event (p<0.001) per day. Prandial insulin omission was common and associated with significantly increased HbA1c. On average, if breakfast insulin was missed ≥4 times per fortnight, HbA1c increased 1.0% (p<0.001). If one or more days per fortnight with ≤2 food boluses/d were recorded, then HbA1c increased 0.8% (p=0.001). Increasing age and duration of CSII correlated with poorer adherence to recommended behaviors. CONCLUSIONS: Glycemic advantage obtained with CSII regimens is closely related to the manner in which CSII is employed. Poor adherence to integral CSII-related tasks is frequently encountered in adolescents and limits the efficacy of CSII in these youth.

Effects of prolonged second stage, method of birth, timing of caesarean section and other obstetric risk factors on postnatal urinary incontinence: an Australian nulliparous cohort study.

OBJECTIVE: To investigate the contribution of prolonged labour, method of birth, timing of caesarean section and other obstetric risk factors to postpartum urinary incontinence. DESIGN: Prospective pregnancy cohort. SETTING: Six metropolitan public hospitals in Victoria, Australia. SAMPLE: A total of 1507 nulliparous women recruited to the maternal health study in early pregnancy (≤24 weeks). METHOD: Data from hospital medical records and self-administered questionnaires/telephone interviews at ≤24 and 30-32 weeks of gestation and 3 months postpartum analysed using univariable and multivariable logistic regression. MAIN OUTCOME MEASURE: Urinary incontinence 3 months postpartum in women continent before the index pregnancy. RESULTS: Of the women continent before pregnancy, 26% reported new incontinence at 3 months postpartum. Compared with women who had a spontaneous vaginal birth, women who had a caesarean section before labour (adjusted odds ratio [OR] 0.2, 95% CI 0.1-0.5) or in the first stage of labour (adjusted OR 0.2, 95% CI 0.1-0.4) were less likely to be incontinent 3 months postpartum. Adjusted OR for incontinence after caesarean section in the second stage of labour compared with spontaneous vaginal birth was 0.5 (95% CI 0.2-1.0). Prolonged second stage labour was associated with increased likelihood of postpartum incontinence in women who had a spontaneous vaginal birth (adjusted OR 1.9, 95% CI 1.1-3.4) or operative vaginal birth (adjusted OR 1.7, 95% CI 1.0-2.8). CONCLUSIONS: In addition to pregnancy itself, physiological changes associated with the second stage of labour appear to play a role in postpartum urinary incontinence.

Is bedtime supper necessary for older children with diabetes using glargine insulin in multiple daily injection regimens?

AIMS: Current guidelines for dietary management of Type 1 diabetes in children recommend a carbohydrate supper before bed. However, with the introduction of insulin analogues such as glargine (with a basal insulin profile), supper may be unnecessary. The purpose of this study was to investigate whether supper is required to prevent nocturnal hypoglycaemia when using multiple daily injections, with glargine as the basal insulin and rapid-acting insulin pre-meals, in older children with Type 1 diabetes. METHODS: Thirty-five children aged 10-18 years with Type 1 diabetes were recruited to a randomized cross-over trial (supper vs. no supper). Each phase consisted of three consecutive days of wearing a continuous glucose-monitoring system (CGMS) to record nocturnal blood glucose levels in the home setting. The supper phase included one 15-g carbohydrate dairy snack consumed before bed. The evening meals were standardized. Activity was restricted. RESULTS: Valid CGMS data were obtained for 163 nights (85 supper, 78 no supper). Nocturnal hypoglycaemia rates were similar in the supper and no-supper groups (32.9% vs. 33.3% of nights; P = 0.96). CONCLUSIONS: This study suggests that supper is not necessary for all children to prevent nocturnal hypoglycaemia when using glargine insulin. The recommendation for inclusion of supper should be individually tailored and not mandatory.

Improvements in cognition, mood and behaviour following commencement of continuous subcutaneous insulin infusion therapy in children with type 1 diabetes mellitus: a pilot study.

AIMS/HYPOTHESIS: Anecdotally, parents and teachers of children with type 1 diabetes mellitus report improvements in behaviour and learning following the commencement of continuous subcutaneous insulin infusion (CSII). This study aimed to investigate changes in cognition, mood and behaviour following commencement of CSII in children with type 1 diabetes. METHODS: Children (n = 32) with type 1 diabetes aged 6-16 years and starting CSII at two Australian centres underwent behavioural, cognitive and glycaemic assessments prior to the commencement of CSII and 6-8 weeks after its start. A comprehensive cognitive test battery was administered, comprising measures of intelligence, attention, processing speed and executive skills. Behaviour and mood were assessed using the Behaviour Assessment System for Children--Second Edition. Continuous glucose monitoring was performed over a 72 h period and HbA(1c) was measured at both time-points. RESULTS: After commencement of CSII, there were significant improvements in HbA(1c), a reduction in hyperglycaemia and blood glucose variation and an increase in normoglycaemia. Significant improvements were observed in perceptual reasoning, selective attention, divided attention, cognitive flexibility and working memory. Fewer mood-related symptoms were reported (parent, teacher and self-report) and fewer behavioural problems (parent reports) CONCLUSIONS/INTERPRETATION: In this uncontrolled pilot study, children with type 1 diabetes demonstrated significant improvements in measures of metabolic control, mood and behaviour and in some complex cognitive skills after commencing CSII therapy.

Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy. METHODS: An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management; no instructive guidelines in interpreting real-time data were provided ('patient-led' use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA(1c) level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4-10 mmol/l). Secondary outcomes were difference in HbA(1c), time in hypoglycaemic (< or =3.9 mmol/l) and hyperglycaemic (> or =10.1 mmol/l) ranges and glycaemic variability. RESULTS: Sixty-two participants were recruited and randomised; 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA(1c) was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75%; p = 0.009). No difference was observed in CGM-derived time in target (measured difference 1.72; 95% CI -5.37 to 8.81), hypoglycaemic (0.54; 95% CI -3.48 to 4.55) or hyperglycaemic (-2.18; 95% CI -10.0 to 5.69) range or in glycaemic variability (-0.29; 95% CI -0.34 to 0.28). Within the intervention group, HbA(1c) was 0.51% lower in participants with sensor use > or =70% compared with participants with sensor use <70% (95% CI -0.98 to -0.04, p = 0.04). Five episodes of device malfunction occurred. CONCLUSIONS/INTERPRETATION: Individuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control. An apparent dose-dependent effect of sensor usage was noted; however, frequent use of this technology (> or =70%) was not universally acceptable. TRIAL REGISTRATION: ACTRN12606000049572

GAPDH, 18S rRNA and YWHAZ are suitable endogenous reference genes for relative gene expression studies in placental tissues from human idiopathic fetal growth restriction.

Comparative gene expression studies in the placenta may provide insights into molecular mechanisms of important genomic alterations in pregnancy disorders. Endogenous reference genes often referred to as housekeeping genes, are routinely used to normalise gene expression levels. For this reason, it is important that these genes be empirically evaluated for stability between placental samples including samples from complicated pregnancies. To address this issue, six candidate housekeeping genes including several commonly used ones (ACTB, GAPDH, 18S rRNA, TBP, SDHA and YWHAZ) were investigated for their expression stability in placentae obtained from pregnancies complicated by idiopathic FGR (n=25) and gestation-matched control pregnancies (n=25). Real-time PCR was performed using pre-validated gene expression assay kits. The geNorm program was used for gene stability measure (M) for the entire housekeeping genes in all control and FGR-affected placental samples. Results showed that GAPDH and 18S rRNA were most stable, with an average expression stability of M=0.441 and 0.443, respectively, followed by YWHAZ (M=0.472). SDHA, ACTB and TBP were the least stable housekeeping genes (M=0.495, 0.548 and 1.737, respectively). We recommend geometric averaging of two or more housekeeping genes to determine relative gene expression levels between FGR-affected and control placentae.

Twice-daily variable insulin regimens: proportions of insulin types have little impact on glycaemic control in primary school-aged children.

AIM: To ascertain the relationship between glycaemic outcome and proportions and timing of insulin admixture in a cohort of primary school-aged children who were receiving insulin in a twice-daily regimen. METHODS: Children aged 4-10 years with Type 1 diabetes of > 2 years duration and on twice-daily variable insulin regimens were eligible for inclusion in this study, which took place over a 12-month period. Characteristics of insulin regimen [total daily dose (TDD), proportion of total daily dose given in the morning and proportion of the TDD given as intermediate-acting insulin] were compared with parameters of glycaemia including glycated haemoglobin (HbA(1c)) and continuous glucose monitoring measures (mean glucose, per cent time in various glycaemic ranges, and intra- and inter-day glycaemic variation). RESULTS: Forty-nine children completed the study. Participants were all prepubertal at the start of the study and representative of the local diabetes population aged 4-10 years (mean age 8.2 years, mean duration of diabetes 3.5 years, mean HbA(1c) 8.1%). The mean TDD was 0.9 units/kg/day (range 0.6-1.3). The TDD, percentage of TDD given as intermediate-acting insulin and the percentage of TDD given as the morning dose were not associated with HbA(1c), mean continuous glucose monitoring system glucose, per cent time in various glycaemic ranges or intra- and inter-day glycaemic variation. CONCLUSIONS: Insulin proportions in twice-daily, variable insulin regimens are not associated with any short- or medium-term glycaemic outcomes.

Fasting ghrelin levels are not elevated in children with hypothalamic obesity.

Morbid obesity is a common problem after damage to the hypothalamus. Hypothalamic dysfunction is also thought to underlie the obesity that is typical of Prader-Willi syndrome. Elevated fasting levels of the appetite-stimulating hormone ghrelin have been reported in Prader-Willi syndrome. The aim of this study was to determine whether fasting ghrelin levels are increased in children with hypothalamic obesity. Fasting total ghrelin levels were compared in three groups: normal-weight controls (n = 16), obese controls (n = 16), and patients with hypothalamic obesity (n = 16). Obese children had lower fasting total ghrelin levels than normal controls, but there was no difference between the fasting total ghrelin level in obese controls and children with hypothalamic obesity (P = 0.88). These data suggest that it is unlikely that an elevation in fasting total ghrelin is responsible for the obesity that occurs after hypothalamic damage. Therapeutic interventions aimed at reducing fasting total ghrelin may prove ineffective in controlling weight gain in this group.

Androgen levels in adult females: changes with age, menopause, and oophorectomy.

CONTEXT: Changes in androgen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established. OBJECTIVE: The objective of this study was to document the effects of age on androgen levels in healthy women and to explore the effects of natural and surgical menopause. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted of 1423 non-healthcare-seeking women, aged 18-75 yr, randomly recruited from the community over 15 months. MAIN OUTCOME MEASURES: Serum levels by age of total testosterone (T), calculated free T, dehydroepiandrosterone sulfate, and androstenedione in a reference group of women free of confounding factors. Women in the reference group had no usage of exogenous steroid therapy; no history of tubal ligation, hysterectomy, or bilateral oophorectomy; and no hyperprolactinemia or polycystic ovarian syndrome. The effects of natural and surgical menopause on sex steroid levels were also examined. RESULTS: In the reference population (n = 595), total T, calculated free T, dehydroepiandrosterone sulfate, and androstenedione declined steeply with age (P < 0.001), with the decline of each being greater in the earlier than the later decades. Examination of serum androgen levels by year in women aged 45-54 yr showed no independent effect of menopausal status on androgen levels. In women aged 55 yr or older, those who reported bilateral oophorectomy and were not on exogenous steroids had significantly lower total T and free T levels than women 55 yr or older in the reference group. CONCLUSIONS: We report that serum androgen levels decline steeply in the early reproductive years and do not vary because a consequence of natural menopause and that the postmenopausal ovary appears to be an ongoing site of testosterone production. These significant variations in androgens with age must be taken into account when normal ranges are reported and in studies of the role of androgens in women.

A novel approach to continuous glucose analysis utilizing glycemic variation.

BACKGROUND: Various methodologies have been proposed for analysis of continuous glucose measurements. These methods have mainly focused on the proportion of low or high glucose readings and have not attempted to analyze other dimensions of the data obtained. This study proposes an algorithm for analysis of continuous glucose data including a novel method of assessing glycemic variability. METHODS: Mean blood glucose and mean of daily differences (MODD) assessed the degree that the Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Northridge, CA) trace was representative of the 3-month glycemic pattern. Percentages of times in low, normal, and high glucose ranges were used to assess marked glycemic excursion. Continuous overall net glycemic action (CONGA), a novel method developed by the authors, assessed intra-day glycemic variability. These methods were applied to 10 CGMS traces chosen randomly from those completed by children with type 1 diabetes from the Royal Children's Hospital, Melbourne, Victoria, Australia and 10 traces recorded by healthy volunteer controls. RESULTS: The healthy controls had lower values for mean blood glucose, MODD, and CONGA. Patients with diabetes had higher percentages of time spent in high and low glucose ranges. There was no overlap between the CONGA values for patients with diabetes and for controls, and the difference between controls and patients with diabetes increased markedly as the CONGA time period increased. CONCLUSIONS: We advocate an approach to the analysis of CGMS data based upon a hierarchy of relevant clinical questions alluding to the representative nature of the data, the amount of time spent in glycemic excursions, and the degree of glycemic variation. Integrated use of these algorithms distinguishes between various patterns of glycemic control in those with and without diabetes.