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D'Souza R.,Mt. Sinai Hospital | Arulkumaran S.,St Georges, University of London
Journal of Perinatal Medicine | Year: 2013

The last few decades have seen an unrelenting rise in caesarean section (CS) rates. In addition to an increase in numbers of CS performed worldwide, there has also been a change in the indications for CS, a refl ection of changing times. A new dilemma facing obstetricians is the increasing demand for CS in the absence of any medical indication (caesarean delivery on maternal request - CDMR). The paucity of evidence either in favour or against, the poor understanding of long-term health and financial implications and the complex ethical issues surrounding CDMR make counselling extremely challenging. Needless to say, CDMR has generated enormous interest both in the media and among health-care providers, and many national and international bodies have now issued guidelines on the topic. In this editorial, we have aimed to explore the factors responsible for the increase in CDMR rates, assess the safety and cost implications of CS and review the recent guidelines and recommendations on CDMR. Copyright © by Walter de Gruyter. Source

Al-Wassia H.,King Abdulaziz University | Shah P.S.,Mt. Sinai Hospital | Shah P.S.,University of Toronto
JAMA Pediatrics | Year: 2015

IMPORTANCE: Umbilical cord milking (UCM) is suggested to improve neonatal outcomes. OBJECTIVES: To perform a systematic review and meta-analysis of the efficacy and safety of UCM in full-term and preterm neonates. DATA SOURCES: A systematic search of MEDLINE, EMBASE, CINAHL, the Cochrane Database of Clinical Trials, the clinicaltrails.gov database, and the reference list of retrieved articles from 1940 to 2014. STUDY SELECTION: Randomized clinical trials comparing UCM with other strategies of handling the umbilical cord at birth in full-term and preterm infants. Seven of the 18 initially identified studies were selected. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed the risk for bias in included trials using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN OUTCOMES AND MEASURES: Neonatal mortality before discharge from the hospital. RESULTS: We included 7 randomized clinical trials involving 501 infants. Infants with a gestational age of less than 33 weeks allocated to UCM compared with control conditions showed no difference in the risk for mortality (risk ratio [RR], 0.75 [95%CI, 0.35 to 1.64]; risk difference [RD], -0.02 [95%CI, -0.09 to 0.04]), hypotension requiring volume expanders (RR, 0.71 [95%CI, 0.41 to 1.25]; RD, -0.09 [95%CI, -0.22 to 0.05]), or inotrope support (RR, 0.77 [95%CI, 0.51 to 1.17]; RD, -0.10 [95%CI, -0.25 to 0.05]). Higher initial levels of hemoglobin (mean difference, 2.0 [95%CI, 1.3-2.7] g/dL) and hematocrit (mean difference, 4.5%[95%CI, 1.5%-7.4%]) were identified in the UCM groups. We found a reduced risk for oxygen requirement at 36 weeks (RR, 0.42 [95%CI, 0.21 to 0.83]; RD, -0.14 [95%CI, -0.25 to -0.04]) and for intraventricular hemorrhage of all grades (RR, 0.62 [95%CI, 0.41 to 0.93]; RD, -0.12 [95%CI, -0.22 to -0.02]) in infants assigned to UCM. Among infants with a gestational age of at least 33 weeks, UCM was associated with higher hemoglobin levels in the first 48 hours in 224 infants (mean difference, 1.2 [95%CI, 0.8-1.5] g/dL) and at 6 weeks of life in 170 infants (mean difference, 1.1 [95%CI, 0.7-1.5] g/dL). CONCLUSIONS AND RELEVANCE: Umbilical cord milking was associated with some benefits and no adverse effects in the immediate postnatal period in preterm infants (gestational age, <33 weeks); however, further studies are warranted to assess the effect of UCM on neonatal and long-term outcomes. Copyright 2015 American Medical Association. All rights reserved. Source

Shahinas D.,University of Toronto | MacMullin G.,Mt. Sinai Hospital | Benedict C.,University of Toronto | Crandall I.,University of Toronto | Pillaid D.R.,University of Calgary
Antimicrobial Agents and Chemotherapy | Year: 2012

Previous studies have shown an antimalarial effect of total alkaloids extracted from leaves of Guiera senegalensis from Mali in West Africa. We independently observed that the beta-carboline alkaloid harmine obtained from a natural product library screen inhibited Plasmodium falciparum heat shock protein 90 (PfHsp90) ATP-binding domain. In this study, we confirmed harmine-PfHsp90-specific affinity using surface plasmon resonance analysis (dissociation constant [Kd] of 40 7mu;M). In contrast, the related compound harmalol bound human Hsp90 (HsHsp90) (Kd of 224 μM) more tightly than PfHsp90 (Kd of 7,010 μM). Site-directed mutagenesis revealed that Arg98 in PfHsp90 is essential for harmine selectivity. In keeping with our model indicating that Hsp90 inhibition affords synergistic combinations with existing antimalarials, we demonstrated that harmine potentiates the effect of chloroquine and artemisinin in vitro and in the Plasmodium berghei mouse model. These findings have implications for the development of novel therapeutic combinations that are synergistic with existing antimalarials. Copyright © 2012, American Society for Microbiology. All Rights Reserved. Source

Weisz D.E.,Sunnybrook Health science Center | More K.,Hospital for Sick Children | McNamara P.J.,Hospital for Sick Children | McNamara P.J.,Hospital for Sick Children Research Institute | And 2 more authors.
Pediatrics | Year: 2014

BACKGROUND AND OBJECTIVE: Patent ductus arteriosus (PDA) liǵation has been variably associated with neonatal morbidities and neurodevelopmental impairment (NDI). The objective was to systematically review and meta-analyze the impact of PDA liǵation in preterm infants at ,< 32 weeks' ǵestation on the risk of mortality, severe neonatal morbidities, and NDI in early childhood. METHODS: Medline, Embase, Cochrane Central Reǵister of Controlled Trials, Education Resources Information Centre (ERIC), Cumulative Index to Nursinǵ and Allied Health (CINAHL), PsycINFO, and the Dissertation database were searched (1947 through Auǵust 2013). Risk of bias was assessed by usinǵ the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. Meta-analyses were performed by using a randomeffects model. Unadjusted and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were pooled when appropriate. RESULTS: Thirty-nine cohort studies and 1 randomized controlled trial were included. Nearly all cohort studies had at least moderate risk of bias mainly due to failure to adjust for survival bias and important postnatal preliǵation confounders such as ventilator dependence, intraventricular hemorrhage, and sepsis. Compared with medical treatment, surǵical liǵation was associated with increases in NDI (aOR: 1.54; 95% CI: 1.01-2.33), chronic lunǵ disease (aOR: 2.51; 95% CI: 1.98-3.18), and severe retinopathy of prematurity (aOR: 2.23; 95% CI: 1.62-3.08) but with a reduction in mortality (aOR: 0.54; 95% CI: 0.38-0.77). There was no difference in the composite outcome of death or NDI in early childhood (aOR: 0.95; 95% CI: 0.58-1.57). CONCLUSIONS: Surǵical liǵation of PDA is associated with reduced mortality, but survivinǵ infants are at increased risk of NDI. However, there is a lack of studies addressing survival bias and confoundinǵ by indication. © 2014 by the American Academy of Pediatrics. Source

O'Donnell E.,University of Toronto | Goodman J.M.,University of Toronto | Mak S.,Mt. Sinai Hospital | Harvey P.J.,University of Toronto
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Introduction: Exercise-trained hypoestrogenic premenopausal women with functional hypothalamic amenorrhea (ExFHA) exhibit impaired endothelial function. The vascular effects of an acute bout of exercise, a potent nitric oxide stimulus, in these women are unknown. Methods: Three groups were studied: recreationally active ExFHA women (n=12; 24.2±1.2 years of age;mean±SEM), and recreationally active (ExOv; n=14; 23.5±1.2 years of age) and sedentary (SedOv; n=15; 23.1±0.5 years of age) ovulatory eumenorrheic women. Calf blood flow (CBF) and brachial artery flow-mediated dilation (FMD) were evaluated using plethysmographic and ultrasound techniques, respectively, both before and 1 hour after 45 minutes of moderate-intensity exercise. Endothelium-independent dilation was assessed at baseline using glyceryl trinitrate. Calf vascular resistance (CVR) and brachial peak shear rate, as determined by the area under the curve (SRAUCpk), were also calculated. Results: FMD and glyceryl trinitrate responses were lower (P < .05) in ExFHA (2.8% ± 0.4% and 11.6%±0.7%, respectively) than ExOv (8.8%±0.7% and 16.7%±1.3%) and SedOv (8.0%±0.5% and 17.1% ± 1.8%). SRAUCpk was also lower (P < .05) in ExFHA. Normalization of FMD for SRAUCpk (FMD/SRAUCpk) did not alter (P .05) the findings. CBF was lower (P < .05) and CVR higher (P < .05) in ExFHA. After exercise, FMD and SRAUCpk were augmented (P < .05), but remained lower (P < .05), in ExFHA. FMD/SRAUCpk no longer differed (P .05) between the groups. CBF in ExFHA was increased (P < .05) and CVR decreased (P < .05) to levels observed in ovulatory women. Conclusions: Acute dynamic exercise improves vascular function in ExFHA women. Although the role of estrogen deficiency per se is unclear, our findings suggest that low shear rate and increased vasoconstrictor tone may play a role in impaired basal vascular function in these women. © 2014 by the Endocrine Society. Source

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