Heuchan A.M.,Royal Hospital for Sick Children |
Clyman R.I.,University of California at San Francisco
Archives of Disease in Childhood: Fetal and Neonatal Edition | Year: 2014
Optimal management of the patent ductus arteriosus (PDA) in the premature infant remains controversial. Despite considerable historical and physiological data indicating that a persistent PDA may be harmful, robust evidence of long-term benefits or harms from treatment is lacking. This has been equated to a lack of benefit but is also a reflection of the fact that most clinical trials were designed to assess the effects of short-term (2-8 days) rather than prolonged exposure to a PDA. No clinical trials have been designed to assess the effects of prolonged exposure of persistent PDA on morbidity and mortality of very premature infants in the era of antenatal corticosteroids, surfactant and non-invasive respiratory support. Further research is required, but new insights and novel therapies are evolving, which will allow greater individual patient assessment, understanding of risk and optimisation of treatment. In this paper, we review the current literature, evidence for treatment options, including a non-interventional approach, and research directions for infants <28 weeks' gestational age.
Wallace W.H.B.,Royal Hospital for Sick Children |
Wallace W.H.B.,University of Edinburgh |
Smith A.G.,University of Edinburgh |
Kelsey T.W.,University of St. Andrews |
And 2 more authors.
The Lancet Oncology | Year: 2014
Background: Ovarian tissue cryopreservation with later reimplantation has been shown to preserve fertility in adult women, but this approach remains unproven and experimental in children and adolescents. We aimed to assess the use of the Edinburgh selection criteria for ovarian tissue cryopreservation in girls and young women with cancer to determine whether we are offering this invasive procedure to the patients who are most at risk of premature ovarian insufficiency. Methods: Cryopreservation of ovarian tissue has been selectively offered to girls and young women with cancer who met the Edinburgh selection criteria since 1996. Between Jan 1, 1996, and June 30, 2012, 410 female patients younger than 18 years at diagnosis were treated for cancer (including leukaemia and brain tumours) at the Edinburgh Children's Cancer Centre, which serves the whole South East of Scotland region. We determined the ovarian status of these patients from review of clinical records and classified them as having premature ovarian insufficiency or not, or as unable to be determined. Patients younger than 12 years at time of data cutoff (Jan 31, 2013) were excluded from the analysis. Findings: 34 (8%) of the 410 patients met the Edinburgh selection criteria and were offered ovarian tissue cryopreservation before starting cancer treatment. 13 patients declined the procedure and 21 consented, and the procedure was completed successfully in 20 patients. Of the 20 patients who had ovarian tissue successfully cryopreserved, 14 were available for assessment of ovarian function. Of the 13 patients who had declined the procedure, six were available for assessment of ovarian function. Median age at the time of follow-up for the 20 assessable patients was 16·9 years (IQR 15·5-21·8). Of the 14 assessable patients who had successfully undergone ovarian cryopreservation, six had developed premature ovarian insufficiency at a median age of 13·4 years (IQR 12·5-14·6), one of whom also had a natural pregnancy. Of the six assessable patients who had declined the procedure, one had developed premature ovarian insufficiency. Assessment of ovarian function was possible for 141 of the 376 patients who were not offered cryopreservation; one of these patients had developed premature ovarian insufficiency. The cumulative probability of developing premature ovarian insufficiency after treatment was completed was significantly higher for patients who met the criteria for ovarian tissue cryopreservation than for those who did not (15-year probability 35% [95% CI 10-53] vs 1% [0-2]; p<0·0001; hazard ratio 56·8 [95% CI 6·2-521·6] at 10 years). Interpretation: The results of this analysis show that the Edinburgh selection criteria accurately identify the few girls and young women who will develop premature ovarian insufficiency, and validate their use for selection of patients for ovarian tissue cryopreservation. Further follow-up of this cohort of patients is likely to allow refinement of the criteria for this experimental procedure in girls and young women with cancer. Funding: UK Medical Research Council. © 2014 Wallace et al. Open Access article distributed under the terms of CC BY-NC-ND.
Shah P.J.,University of Edinburgh |
Morton M.J.S.,Royal Hospital for Sick Children
British Journal of Psychiatry | Year: 2013
Attention-deficit hyperactivity disorder in adults evokes extreme responses within British psychiatrists, because its diagnostic validity and pharmacological treatments are heavily contested. We propose a model that accommodates apparently divergent evidence, and provides a clinical framework for clinicians and patients, allowing safe, responsible and ethically balanced clinical practice.
Tsirikos A.I.,Royal Hospital for Sick Children |
Jain A.K.,Royal Hospital for Sick Children
Journal of Bone and Joint Surgery - Series B | Year: 2011
This review of the literature presents the current understanding of Scheuermann's kyphosis and investigates the controversies concerning conservative and surgical treatment. There is considerable debate regarding the pathogenesis, natural history and treatment of this condition. A benign prognosis with settling of symptoms and stabilisation of the deformity at skeletal maturity is expected in most patients. Observation and programmes of exercise are appropriate for mild, flexible, non-progressive deformities. Bracing is indicated for a moderate deformity which spans several levels and retains flexibility in motivated patients who have significant remaining spinal growth. The loss of some correction after the completion of bracing with recurrent anterior vertebral wedging has been reported in approximately one-third of patients. Surgical correction with instrumented spinal fusion is indicated for a severe kyphosis which carries a risk of progression beyond the end of growth causing cosmetic deformity, back pain and neurological complications. There is no consensus on the effectiveness of different techniques and types of instrumentation. Techniques include posterior-only and combined anteroposterior spinal fusion with or without posterior osteotomies across the apex of the deformity. Current instrumented techniques include hybrid and all-pedicle screw constructs. ©2011 British Editorial Society of Bone and Joint Surgery.
Wallace W.H.B.,Royal Hospital for Sick Children
Cancer | Year: 2011
With increasing numbers of survivors from cancer at a young age, the issue of fertility preservation has assumed greater importance. This review describes normal ovarian and testicular function and summarizes what is known about the effect of chemotherapy and radiotherapy on the gonads and uterus. All young patients with cancer or leukemia should have their fertility prognosis discussed before the initiation of treatment. Sperm and embryo cryopreservation should be considered standard practice and be widely available for those at significant risk of infertility. For prepubertal girls, ovarian tissue cryopreservation should be considered if the risk of premature menopause is high, but for the prepubertal boy there are no established techniques in current practice. Copyright © 2011 American Cancer Society.
Morton N.S.,Royal Hospital for Sick Children
Paediatric Anaesthesia | Year: 2012
Over the last 25 years, pediatric care has changed dramatically with increased survival after premature birth, more complex care, better outcomes, and reduced mortality. There is a better understanding of how pain pathways and receptor systems develop and also how to assess pain at different stages of development. The myth that children do not feel pain has been comprehensively dispelled. Safe analgesic dose regimens for neonates, infants, and children have been developed based upon a better understanding of developmental pharmacokinetics and pharmacodynamics. It is a myth that pain in children cannot be prevented or treated safely and effectively because of the risks of adverse effects and addiction. Large-scale prospective audits have clarified the safety profile and risk-benefit balance for different techniques. There is now a substantial evidence base supporting many techniques of postoperative and procedural pain management for all age-groups of children. Guidelines based upon systematic review of this evidence have been published and updated, but the real challenge is in implementation of accurate pain assessment and safe, effective pain management comprehensively to all children whatever the procedure, clinical setting, developmental stage of the child, or comorbidities. In developed countries, these are core topics in the education of all doctors and nurses who care for children, and they are integrated into clinical practice by acute pediatric pain teams for most hospitals. However, it is disappointing that many country's healthcare systems do not give pediatric pain management a priority and in many parts of the world there are no analgesics available. So pain-free healthcare is sadly lacking in many hospitals. My hope is that the current knowledge can be used more effectively to relieve the unnecessary suffering of children in the 21st century. © 2012 Blackwell Publishing Ltd.
Shetty J.,Royal Hospital for Sick Children
Developmental Medicine and Child Neurology | Year: 2015
The risk of seizures is at its highest during the neonatal period, and the most common cause of neonatal seizures is hypoxic-ischaemic encephalopathy (HIE). This enhanced vulnerability is caused by an imbalance in the expression of receptors for excitatory and inhibitory neurotransmission, which is age dependent. There has been progress in detecting the electrophysiological abnormalities associated with seizures using amplitude-integrated electroencephalography (aEEG). Data from animal studies indicate a variety of risk factors for seizures, but there are limited clinical data looking at the long-term neurodevelopmental consequences of seizures alone. Neonatal seizures are also associated with increased risk of further epileptic seizures; however, it is less clear whether or not this results from an underlying pathology, and whether or not seizures confer additional risk. Phenobarbital and phenytoin are still the first-line antiepileptic drugs (AEDs) used to treat neonatal seizures, although they are effective in only one-third of affected infants. Furthermore, based on findings from animal studies, there are concerns regarding the risks associated with using these AEDs. Clinicians face a difficult challenge because, although seizures can be easily identified using aEEG, treatment options are limited, and there are uncertainties regarding treatment outcomes. There is a need to obtain long-term follow-up data, comparing groups of infants treated with or without current therapies. If these analyses indicate a definite benefit of treating neonatal seizures, then novel therapeutic approaches should be developed. © The Authors.
Anderson R.A.,Queens Medical Research Institute |
Wallace W.H.B.,Royal Hospital for Sick Children
Fertility and Sterility | Year: 2013
The accurate assessment of the ovarian reserve has long been a key goal in reproductive medicine. The recognition that serum antimüllerian hormone provides an indirect measure of the ovarian reserve has led to its rapid adoption in assisted conception, and wide exploration of its potential across the reproductive lifespan from the neonate to the menopause. In this short review we discuss its relationship with the ovarian reserve in its varied meanings, and in various contexts. These include in childhood and adolescence, and in the assessment of the impact of cancer therapy on the female reproductive tract. These therapies can adversely impact all aspects of female reproduction, including hypothalamic, pituitary, and ovarian hormonal activity, and the ability of the uterus to support a successful pregnancy. © 2013 by American Society for Reproductive Medicine.
Eunson P.,Royal Hospital for Sick Children
Developmental Medicine and Child Neurology | Year: 2015
Infants who suffer hypoxic-ischaemic encephalopathy (HIE) at term are at risk of dying or developing severe cerebral palsy (CP). Children with severe CP often have other neurodevelopmental disabilities, which may affect their quality of life as much as the CP itself. New treatments for HIE, such as cooling, may improve motor outcomes, but affected infants may still have significant cognitive or communication problems. Infants who have experienced HIE and develop CP will require significant medical input throughout childhood and adult life. The costs of this medical input are high, but the indirect costs to the child, his or her family, and the relevant social services and education systems are many times greater. When demonstrating the cost-effectiveness of interventions aimed at preventing or treating HIE, these additional costs should be taken into account. © The Authors.
McMaster M.E.,Royal Hospital for Sick Children
Environmental Health: A Global Access Science Source | Year: 2011
Background: In a case-control study a statistically significant association was recorded between the introduction of infants to heated indoor swimming pools and the development of adolescent idiopathic scoliosis (AIS). In this paper, a neurogenic hypothesis is formulated to explain how toxins produced by chlorine in such pools may act deleteriously on the infant's immature central nervous system, comprising brain and spinal cord, to produce the deformity of AIS. Presentation of the hypothesis. Through vulnerability of the developing central nervous system to circulating toxins, and because of delayed epigenetic effects, the trunk deformity of AIS does not become evident until adolescence. In mature healthy swimmers using such pools, the circulating neurotoxins detected are chloroform, bromodichloromethane, dibromochloromethane, and bromoform. Cyanogen chloride and dichloroacetonitrile have also been detected. Testing the hypothesis. In infants, the putative portals of entry to the blood could be dermal, oral, or respiratory; and entry of such circulating small molecules to the brain are via the blood-brain barrier, blood-cerebrospinal fluid barrier, and circumventricular organs. Barrier mechanisms of the developing brain differ from those of adult brain and have been linked to brain development. During the first 6 months of life cerebrospinal fluid contains higher concentrations of specific proteins relative to plasma, attributed to mechanisms continued from fetal brain development rather than immaturity. Implications of the hypothesis. The hypothesis can be tested. If confirmed, there is potential to prevent some children from developing AIS. © 2011McMaster; licensee BioMed Central Ltd.