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Hawkes C.P.,The National Childrens Research Center | Hawkes C.P.,Childrens Hospital of Philadelphia | O'Connell S.M.,Cork University Hospital
Irish Medical Journal | Year: 2016

Many countries have established regulations regarding growth hormone (GH) treatment in children, to standardise care and control cost. In this study, we describe current practice in Ireland surrounding child measurement and the approach to diagnosis of GH deficiency. A questionnaire was sent to 139 paediatricians in Ireland and 35 (9 paediatric endocrinologists) responded. Only 13 (37.1%) use the recommended 2-person technique for measuring children under 2. Amongst GH prescribers, there were a variety of GH Stimulation Tests used, sex steroid priming was used by 8 (80%) and the general cut-off for a passed test was consistent (7 ng/ml). Brand rotation (n=5, 50%) and cost (n=3, 30%) were the most common criteria for deciding the formulation of GH prescribed. We recommend that departments review their child measurement technique and equipment. We also advise the establishment of national guidelines for the use of GH, and a prospective registry for GH treated children. © 2016, Irish Medical Association. All rights reserved. Source

Tarrant R.C.,Our Ladys Childrens Hospital | Tarrant R.C.,The National Childrens Research Center | Nugent M.,Our Ladys Childrens Hospital | Nugent A.P.,University College Dublin | And 5 more authors.
European Spine Journal | Year: 2014

Methods: Seventy-seven consecutive and eligible patients with AIS who underwent PSF were prospectively followed up from hospital admission (January 2010–April 2012). Pre- and postoperative anthropometric measurements were collected (weight, height, BMI), and clinically severe unintentional weight loss computed, defined as loss of >10 % body weight from admission to hospital discharge. The effect of weight loss >10 % was analysed in relation to radiographic, nutritional and perioperative complication data, and length of hospitalisation. A case–controlled study was then performed to establish potential differences in weight, height and BMI of this AIS cohort with healthy age- and gender-matched controls derived from the National Teens’ Food Survey (2005–2006). Anthropometric values were standardised by conversion to age- and gender-specific Z-scores; ‘undernutrition’ was defined as BMI Z-scores <−2.Purpose: Abnormal anthropometry including comparably lower weight and body mass index (BMI) in the adolescent idiopathic scoliosis (AIS) population is increasingly recognised, however, no study has examined postoperative weight loss or its clinical relevance in these relatively thin patients. This study aimed to assess perioperative nutritional status as well as clinically severe involuntary weight loss and its impact on outcomes in patients with AIS undergoing posterior spinal fusion (PSF). A further objective was to compare preoperative anthropometric measurements of the current AIS cohort with healthy controls.Results: Mean age of the cohort was 15 years (SD 1.89); 93.5 % of subjects were female. Clinically severe postoperative weight loss >10 %, identified in 22 patients (30.6 %), was associated with a significantly increased superficial wound infection incidence (13.6 vs. 2 %, P = 0.047), as well as lower serum albumin at hospital discharge (25 vs. 28 g/L, P < 0.05). A high prevalence of postoperative undernutrition was observed—over one quarter of patients had a BMI Z-score <−2 at hospital discharge (26.4 %); serum albumin, total protein and haemoglobin levels were below normal limits in 98, 66 and 91 % of patients, respectively. Significantly lower weight (52 vs. 59.8 kg, P < 0.0001), corrected height (162 vs. 166.3 cm, P < 0.0001) and BMI (19.72 vs. 21.6 kg/m2, P < 0.0001) measurements were identified in this AIS cohort, in comparison with those recorded in The National Teens’ Survey.Conclusions: This study demonstrated that clinically severe postoperative weight loss >10 %, identified in almost one-third of this AIS cohort, was associated with significantly increased wound infection incidence. Early detection and prevention of severe postoperative weight loss in patients with AIS who undergo spinal fusion may be beneficial in reducing wound infection risk. This study confirms a body of literature indicating the significantly lower weight and BMI in patients with AIS compared with healthy controls. © 2014, Springer-Verlag Berlin Heidelberg. Source

Nugent M.,Our Ladys Childrens Hospital | Tarrant R.C.,Our Ladys Childrens Hospital | Tarrant R.C.,The National Childrens Research Center | Queally J.M.,SpR in Trauma and Orthopaedic Surgery | And 6 more authors.
Irish Journal of Medical Science | Year: 2016

Background: Posterior spinal instrumentation and fusion for correction of adolescent idiopathic scoliosis (AIS) typically requires lengthy operating time and may be associated with significant blood loss and subsequent transfusion. This study aimed to identify factors predictive of duration of surgery, intraoperative blood loss and transfusion requirements in an Irish AIS cohort. Methods: A retrospective review of 77 consecutive patients with AIS who underwent single-stage posterior spinal instrumentation and fusion over a two-year period at two Dublin tertiary hospitals was performed. Data were collected prospectively and parameters under analysis included pre- and postoperative radiographic measurements, intraoperative blood loss, surgical duration, blood products required, laboratory blood values and perioperative complications. Results: Mean preoperative primary curve Cobb angle was 62.3°; mean surgical duration was 5.6 h. The perioperative allogeneic red blood cell transfusion rate was 42.8 % with a median requirement of 1 unit. Larger curve magnitudes were positively correlated with longer fusion segments, increased operative time and greater estimated intraoperative blood loss. Preoperative Cobb angles greater than 70° [Relative Risk (RR) 4.42, p = 0.003] and estimated intraoperative blood loss greater than 1400 ml (RR 3.01, p = 0.037) were independent predictors of red blood cell transfusion risk. Conclusion: Larger preoperative curve magnitudes in AIS increase operative time and intraoperative blood loss; preoperative Cobb angles greater than 70o and intraoperative blood loss greater than 1400 ml are predictive of red blood cell transfusion requirement in this patient group. © 2015, Royal Academy of Medicine in Ireland. Source

Tarrant R.C.,Our Ladys Childrens Hospital | Tarrant R.C.,The National Childrens Research Center | Queally J.M.,Our Ladys Childrens Hospital | O'Loughlin P.F.,Our Ladys Childrens Hospital | And 6 more authors.
Irish Journal of Medical Science | Year: 2016

Background: Surgical procedures to correct larger curve magnitudes >70° in patients with adolescent idiopathic scoliosis (AIS) are still common; despite their increased complexity, limited research has assessed the effect of preoperative curve severity on outcomes. Aim: This study aimed to examine the impact of preoperative curves >70° vs. those ≤70° on perioperative, functional and financial outcomes in patients with AIS undergoing posterior spinal fusion (PSF). Methods: Seventy seven eligible AIS patients who underwent PSF were prospectively followed-up, until return to preoperative function was reported. Preoperative curves >70° vs. ≤70° were analysed in relation to surgical duration, estimated blood loss, perioperative complications, length of hospitalisation, return to function and cost of surgical treatment per patient. Results: Severe preoperative curves >70°, identified in 21 patients (27.3 %), were associated with significantly longer surgical duration (median 6.5 vs. 5 h, p = 0.001) and increased blood loss (median 1250 vs. 1000 ml, p = 0.005)—these patients were 2.1 times more likely to receive a perioperative blood product transfusion (Relative Risk 2.1, CI 1.4–2.7, p = 0.004). Curves >70° were also associated with a significantly delayed return to school/college, and an increased cost of surgical treatment (€33,730 vs. €28,620, p < 0.0001). Conclusion: Surgeons can expect a longer surgical duration, greater intraoperative blood loss and double the blood product transfusion risk when performing PSF procedures on AIS patients with curves greater than 70° vs. those ≤70°. Surgical correction for curves >70°, often as a result of lengthy surgical waiting lists, also incurs added expense and results in a partial delay in early functional recovery. © 2016, Royal Academy of Medicine in Ireland. Source

Lennon J.C.,Trinity College Dublin | Lennon J.C.,The National Childrens Research Center | Butini S.,University of Siena | Campiani G.,University of Siena | And 3 more authors.
Investigational New Drugs | Year: 2016

Summary: Neuroblastoma, a paediatric malignancy of the sympathetic nervous system, accounts for 15 % of childhood cancer deaths. Despite advances in understanding the biology, it remains one of the most difficult paediatric cancers to treat partly due to the development of multidrug resistance. There is thus a compelling demand for new treatment strategies that can bypass resistance mechanisms. The pyrrolo-1,5-benzoxazepine (PBOX) compounds are a series of novel microtubule-targeting agents that potently induce apoptosis in various tumour models. We have previously reported that PBOX compounds induce apoptosis in drug sensitive and multidrug resistant neuroblastoma cells and synergistically enhance apoptosis induced by chemotherapeutics such as carboplatin. In this study we present further data concerning the molecular basis of PBOX-induced apoptosis in neuroblastoma. We demonstrate that PBOX-6 induced AMP-activated protein kinase (AMPK) activation and downstream acetyl-CoA carboxylase phosphorylation. Increased reactive oxygen species (ROS) appeared to serve as the upstream signal for AMPK activation as pretreatment of cells with the antioxidant N-acetylcysteine inhibited both AMPK activation and PBOX-induced apoptosis. Furthermore, activation of AMPK by PBOX-6 was found to inhibit mTOR complex 1 (mTORC1) signalling. Finally, we demonstrate the efficacy of PBOX-6 in an in vivo xenograft model of neuroblastoma. This study provides new insights into understanding the molecular and cellular mechanisms involved in PBOX-induced cell death in neuroblastoma and further supports their future use as novel anti-cancer agents for the treatment of neuroblastoma. © 2016 Springer Science+Business Media New York Source

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