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Elizabeth Vale, Australia

Morris J.M.,University of Sydney | Roberts C.L.,University of Sydney | Bowen J.R.,University of Sydney | Patterson J.A.,University of Sydney | And 5 more authors.
The Lancet | Year: 2016

Background Preterm pre-labour ruptured membranes close to term is associated with increased risk of neonatal infection, but immediate delivery is associated with risks of prematurity. The balance of risks is unclear. We aimed to establish whether immediate birth in singleton pregnancies with ruptured membranes close to term reduces neonatal infection without increasing other morbidity. Methods The PPROMT trial was a multicentre randomised controlled trial done at 65 centres across 11 countries. Women aged over 16 years with singleton pregnancies and ruptured membranes before the onset of labour between 34 weeks and 36 weeks and 6 days weeks who had no signs of infection were included. Women were randomly assigned (1:1) by a computer-generated randomisation schedule with variable block sizes, stratified by centre, to immediate delivery or expectant management. The primary outcome was the incidence of neonatal sepsis. Secondary infant outcomes included a composite neonatal morbidity and mortality indicator (ie, sepsis, mechanical ventilation ≥24 h, stillbirth, or neonatal death); respiratory distress syndrome; any mechanical ventilation; and duration of stay in a neonatal intensive or special care unit. Secondary maternal outcomes included antepartum or intrapartum haemorrhage, intrapartum fever, postpartum treatment with antibiotics, and mode of delivery. Women and caregivers could not be masked, but those adjudicating on the primary outcome were masked to group allocation. Analyses were by intention to treat. This trial is registered with the International Clinical Trials Registry, number ISRCTN44485060. Findings Between May 28, 2004, and June 30, 2013, 1839 women were recruited and randomly assigned: 924 to the immediate birth group and 915 to the expectant management group. One woman in the immediate birth group and three in the expectant group were excluded from the primary analyses. Neonatal sepsis occurred in 23 (2%) of 923 neonates whose mothers were assigned to immediate birth and 29 (3%) of 912 neonates of mothers assigned to expectant management (relative risk [RR] 0·8, 95% CI 0·5-1·3; p=0·37). The composite secondary outcome of neonatal morbidity and mortality occurred in 73 (8%) of 923 neonates of mothers assigned to immediate delivery and 61 (7%) of 911 neonates of mothers assigned to expectant management (RR 1·2, 95% CI 0·9-1·6; p=0·32). However, neonates born to mothers in the immediate delivery group had increased rates of respiratory distress (76 [8%] of 919 vs 47 [5%] of 910, RR 1·6, 95% CI 1·1-2·30; p=0·008) and any mechanical ventilation (114 [12%] of 923 vs 83 [9%] of 912, RR 1·4, 95% CI 1·0-1·8; p=0·02) and spent more time in intensive care (median 4·0 days [IQR 0·0-10·0] vs 2·0 days [0·0-7·0]; p<0·0001) compared with neonates born to mothers in the expectant management group. Compared with women assigned to the immediate delivery group, those assigned to the expectant management group had higher risks of antepartum or intrapartum haemorrhage (RR 0·6, 95% CI 0·4-0·9), intrapartum fever (0·4, 0·2-0·9), and use of postpartum antibiotics (0·8, 0·7-1·0), and longer hospital stay (p<0·0001), but a lower risk of caesarean delivery (RR 1·4, 95% CI 1·2-1·7). Interpretation In the absence of overt signs of infection or fetal compromise, a policy of expectant management with appropriate surveillance of maternal and fetal wellbeing should be followed in pregnant women who present with ruptured membranes close to term. Funding Australian National Health and Medical Research Council, the Women's and Children's Hospital Foundation, and The University of Sydney. © 2016 Elsevier Ltd.

Rasi Ghaemi S.,University of South Australia | Harding F.J.,University of South Australia | Delalat B.,University of South Australia | Gronthos S.,University of Adelaide | And 2 more authors.
Biomaterials | Year: 2013

In the field of stem cell technology, future advancements rely on the effective isolation, scale-up and maintenance of specific stem cell populations and robust procedures for their directed differentiation. The stem cell microenvironment - or niche - encompasses signal inputs from stem cells, supporting cells and from the extracellular matrix. In this context, the contribution of physicochemical surface variables is being increasingly recognised. This paradigm can be exploited to exert control over cellular behaviour. However, the number of parameters at play, and their complex interactions, presents a formidable challenge in delineating how the decisions of cell fate are orchestrated within the niche. Additionally, in the case of mesenchymal stem cells (MSC), more than one type of stem cell niche has been identified. By employing high throughput screening (HTS) strategies, common and specific attributes of each MSC niche can be probed. Here, we explore biological, chemical and physical parameters that are known to influence MSC self-renewal and differentiation. We then review techniques and strategies that allow the HTS of surface properties for conditions that direct stem cell fate, using MSC as a case study. Finally, challenges in recapturing the niche, particularly its three dimensional nature, in surface-based HTS formats are discussed. © 2013 Elsevier Ltd.

Gatford K.L.,Robinson Institute | Simmons R.A.,University of Pennsylvania | De Blasio M.J.,Robinson Institute | Robinson J.S.,Robinson Institute | Owens J.A.,Robinson Institute
Placenta | Year: 2010

Being born small due to poor growth before birth increases the risk of developing metabolic disease, including type 2 diabetes, in later life. Inadequate insulin secretion and decreasing insulin sensitivity contribute to this increased diabetes risk. Impaired placental growth, development and function are major causes of impaired fetal growth and development and therefore of IUGR. Restricted placental growth (PR) and function in non-human animals induces similar changes in insulin secretion and sensitivity as in human IUGR, making these valuable tools to investigate the underlying mechanisms and to test interventions to prevent or ameliorate the risk of disease after IUGR. Epigenetic changes induced by an adverse fetal environment are strongly implicated as causes of later impaired insulin action. These have been well-characterised in the PR rat, where impaired insulin secretion is linked to epigenetic changes at the Pdx-1 promotor and reduced expression of this transcription factor. Present research is particularly focussed on developing intervention strategies to prevent or reverse epigenetic changes, and normalise gene expression and insulin action after PR, in order to translate this to treatments to improve outcomes in human IUGR. © 2010 Elsevier Ltd. All rights reserved.

Wilkinson D.,Hyperbaric Unit | Chapman I.M.,University of Adelaide | Heilbronn L.K.,University of Adelaide | Heilbronn L.K.,Robinson Institute
Diabetic Medicine | Year: 2012

Aim Hyperbaric oxygen therapy is known to reduce fasting blood glucose in individuals with Type2 diabetes. However, the mechanisms of this effect are not clear. The aim of this study was to determine whether peripheral insulin sensitivity by hyperinsulinaemic euglycaemic clamp is increased in patients presenting for hyperbaric oxygen therapy. Methods Participants were non-obese individuals without Type2 diabetes (n=5) or obese patients with Type2 diabetes (n=5). Patients were given 100% oxygen at 2.0 absolute atmospheres for 2h, six sessions per week for 5weeks. Results Peripheral insulin sensitivity was increased in the whole cohort (P=0.04). Subsequent analysis revealed that this was significant at both treatment3 (+37.3±12.7%, P=0.02) and treatment30 (+40.6±12.6%, P=0.009). HbA 1c was significantly reduced in subjects without diabetes only (P<0.05). Conclusion Insulin sensitivity increased within 3days of hyperbaric oxygen treatment and this was maintained for 30 sessions. This increase in insulin sensitivity is equivalent to that observed following moderate weight loss. The mechanisms underlying the insulin-sensitizing effect of hyperbaric oxygen require further elucidation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Froessler B.,Lyell McEwin Hospital | Froessler B.,University of Adelaide | Collingwood J.,Ballarat Base Hospital | Hodyl N.A.,University of Adelaide | And 2 more authors.
BMC Pregnancy and Childbirth | Year: 2014

Background: Iron deficiency is a common nutritional deficiency amongst women of childbearing age. Peri-partum iron deficiency anaemia (IDA) is associated with significant maternal, fetal and infant morbidity. Current options for treatment are limited: these include oral iron supplementation, which can be ineffective and poorly tolerated, and red blood cell transfusions, which carry an inherent risk and should be avoided. Ferric carboxymaltose is a new treatment option that may be better tolerated.The study was designed to assess the safety and efficacy of iron deficiency anaemia (IDA) correction with intravenous ferric carboxymaltose in pregnant women with mild, moderate and severe anaemia in the second and third trimester.Methods: Prospective observational study; 65 anaemic pregnant women received ferric carboxymaltose up to 15 mg/kg between 24 and 40 weeks of pregnancy (median 35 weeks gestational age, SD 3.6). Treatment effectiveness was assessed by repeat haemoglobin (Hb) measurements and patient report of well-being in the postpartum period. Safety was assessed by analysis of adverse drug reactions and fetal heart rate monitoring during the infusion.Results: Intravenous ferric carboxymaltose infusion significantly increased Hb values (p < 0.01) above baseline levels in all women. Increased Hb values were observed at 3 and 6 weeks post infusion and up to 8 weeks post-infusion. Ferritin values increased significantly after the infusion. Only 4 women had repeat ferritin values post-partum which remained above baseline levels. Fetal heart rate monitoring did not indicate a drug related negative impact on the fetus. Of the 29 (44.6%) women interviewed, 19 (65.5%) women reported an improvement in their well-being and 9 (31%) felt no different after the infusion. None of the women felt worse. No serious adverse effects were found and minor side effects occurred in 13 (20%) patients.Conclusions: Our prospective data is consistent with existing observational reports of the safe and effective use of ferric carboxymaltose in the treatment of iron deficiency anaemia in pregnancy. © 2014 Froessler et al.; licensee BioMed Central Ltd.

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