Abman S.H.,Aurora University |
Kinsella J.P.,Aurora University |
Rosenzweig E.B.,Columbia University |
Krishnan U.,Columbia University |
And 10 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2013
Pulmonary arterial hypertension (PAH) contributes to disability and death in children with diverse cardiac, pulmonary, or systemic diseases, and therapeutic options are currently limited. Data from adult studies provide the basis for most PAH-specific therapies; however, many of these medications are commonly used in children on an off-label basis due to the life-threatening nature of PAH. Although currently approved for use in adult PAH, sildenafil is used extensively off-label for the treatment of neonates, infants, and children with PAH. Past studies have generally suggested favorable effects and outcomes in infants and young children with PAH, but these reports are generally uncontrolled observations, except for one single-center trial for persistent pulmonary hypertension of the newborn. Despite extensive clinical experience with sildenafil therapy in children and approval by the European Medicines Agency for its pediatric use in Europe, the U.S. Food and Drug Administration recently issued a warning against the use of sildenafil for pediatric PAH between 1 and 17 years of age due to an apparent increase in mortality during long-term therapy. Although these data are extremely limited, this U.S. Food and Drug Administration review challenges the pediatric PAH community to further assess the efficacy and safety of sildenafil, especially with chronic treatment. Although low doses of sildenafil are likely safe in pediatric PAH, further studies should carefully examine its role in the long-term therapy of children, especially with diverse causes of PAH. Pediatric patients with PAH require close surveillance and frequent monitoring, and persistent sildenafil monotherapy is likely insufficient with disease progression. Copyright © 2013 by the American Thoracic Society.
Richmond E.,National Childrens Hospital |
Rogol A.D.,Indiana University |
Rogol A.D.,University of Virginia
Endocrine Development | Year: 2010
Growth hormone (GH) therapy has been appropriate for severely GH-deficient children and adolescents since the 1960s. Use for other conditions for which short stature was a component could not be seriously considered because of the small supply of human pituitary-derived hormone. That state changed remarkably in the mid-1980s because of Creutzfeldt-Jakob disease associated with human pituitary tissue-derived hGH and the development of a (nearly) unlimited supply of recombinant, 22 kDa (r)hGH. The latter permitted all GH-deficient children to have access to treatment and one could design trials using rhGH to increase adult height in infants, children and adolescents with causes of short stature other than GH deficiency, as well as trials in adult GH-deficient men and women. Approved indications (US Food and Drug Administration) include: GH deficiency, chronic kidney disease, Turner syndrome, small-for-gestational age with failure to catch up to the normal height percentiles, Prader-Willi syndrome, idiopathic short stature, SHOX gene haploinsufficiency and Noonan syndrome (current to October 2008). The most common efficacy outcome in children is an increase in height velocity, although rhGH may prevent hypoglycemia in some infants with congenital hypopituitarism and increase the lean/fat ratio in most children - especially those with severe GH deficiency or Prader-Willi syndrome. Doses for adults, which affect body composition and health-related quality of life, are much lower than those for children, per kilogram of lean body mass. The safety profile is quite favorable with a small, but significant, incidence of raised intracranial pressure, scoliosis, muscle and joint discomfort, including slipped capital femoral epiphysis. The approval of rhGH therapy for short, non-GH-deficient children has validated the notion of GH sensitivity, which gives the opportunity to some children with significant short stature, but with normal stimulated GH test results, to benefit from rhGH therapy and perhaps attain an adult height within the normal range and appropriate for their mid-parental target height (genetic potential). Copyright © 2010 S. Karger AG, Basel.
Richmond E.,National Childrens Hospital |
Rogol A.D.,University of Virginia
Endocrine | Year: 2014
Traumatic brain injury (TBI) is a common cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioral, psychological and social defects. Recent data suggest that pituitary hormone deficiency is not infrequent among TBI survivors; the prevalence of reported hypopituitarism following TBI varies widely among published studies. The most common cause of TBI is motor vehicle accidents, including pedestrian-car and bicycle car encounters, falls, child abuse, violence and sports injuries. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90 %. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Endocrine dysfunction after TBI in children and adolescents is common. Adolescence is a time of growth, freedom and adjustment, consequently TBI is also common in this group. Sports-related TBI is an important public health concern, but many cases are unrecognized and unreported. Sports that are associated with an increased risk of TBI include those involving contact and/or collisions such as boxing, football, soccer, ice hockey, rugby, and the martial arts, as well as high velocity sports such as cycling, motor racing, equestrian sports, skiing and roller skating. The aim of this paper is to summarize the best evidence of TBI as a cause of pituitary deficiency in children and adults. © 2013 Springer Science+Business Media New York.
National Childrens Hospital and Ohio State Innovation Foundation | Date: 2013-07-31
The present invention relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as SMA and ALS as well as Pompe disease and lysosomal storage disorders. It is disclosed that administration of a non-ionic, low-osmolar contrast agent, together with a rAA9 vector for the expression of Survival Motor Neuron protein, improves the survival of SMN mutant mice as compared to the administration of the expression vector alone.
Greally P.,National Childrens Hospital |
Whitaker P.,University of Leeds |
Peckham D.,University of Leeds
Current Medical Research and Opinion | Year: 2012
Background: Pseudomonas aeruginosa (Pa) is the predominant pathogen infecting the airways of patients with cystic fibrosis (CF). Initial colonization is usually transient and associated with non-mucoid strains, which can be eradicated if identified early. This strategy can prevent, or at least delay, chronic Pa infection, which eventually develops in the majority of patients by their late teens or early adulthood. This article discusses the management and latest treatment developments of Pa lung infection in patients with CF, with a focus on nebulized antibiotic therapy. Methods: PubMed was searched to identify English language articles published up until August 2011 using combinations of the following key words: 'antibiotics', 'chronic', 'cystic fibrosis', 'eradication', 'exacerbations', 'guidelines', 'inhaled', 'intravenous', 'lung infection', 'burden', 'adherence', 'patient segregation', 'pseudomonas aeruginosa' and 'resistance'. Findings: Antibiotics form a central part of the treatment regimens for chronic Pa lung infection. Current treatment guidelines recommend that patients with chronic pulmonary infection with Pa should receive long-term inhaled anti-pseudomonal therapy to preserve lung function, and to reduce the frequency of pulmonary exacerbations and hospital admissions. While antibiotic resistance seems to increase with frequent antibiotic use, this does not appear to impact on clinical outcome. Negative aspects of therapy include the time needed for drug administration and subsequent cleaning of the equipment. These factors cause a significant treatment burden and impact on adherence. The availability of more convenient formulations and delivery vehicles for anti-pseudomonal antibiotics may help overcome some of these challenges. Conclusions: Current challenges in the management of CF patients with chronic Pa lung infection are numerous. The availability of novel anti-pseudomonal antibiotic formulations/devices is anticipated to improve treatment adherence in patients with CF, and could improve clinical outcomes. Thus, there is hope for improved survival in individuals with CF suffering from chronic pulmonary infection with Pa. © 2012 Informa UK Ltd. All rights reserved.
O'Malley G.,Temple University |
Hussey J.,Trinity College Dublin |
Roche E.,National Childrens Hospital
Pediatric Physical Therapy | Year: 2012
PURPOSE: Evidence suggests a negative effect of obesity on musculoskeletal health in children. A pilot study was undertaken to investigate the presence of musculoskeletal impairments in children with obesity and to explore the relationships among body mass index, physical activity, and musculoskeletal measures. METHODS: Lower limb musculoskeletal health (pain, power, balance, flexibility, and range of motion), physical activity, and screen time were assessed using standardized methods. RESULTS: Seventeen children (mean age = 12.21 years) participated. Mean values for lower limb musculoskeletal measures are presented. Moderate negative correlations were found between body composition and range of motion, flexibility, and strength. Genu valgum deformity was moderately positively correlated to body mass index. CONCLUSIONS: The results of this pilot study suggest that children who are obese may present with musculoskeletal impairments of the lower limb. Clinicians working with children who are obese should conduct a thorough musculoskeletal assessment and consider the presence of impairments when promoting physical activity. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins and Section on Pediatrics of the American Physical Therapy Association.
Keijzer R.,Erasmusmc Sophia |
Puri P.,National Childrens Hospital
Seminars in Pediatric Surgery | Year: 2010
Congenital diaphragmatic hernia (CDH) is a congenital anomaly consisting of a posterolateral defect in the diaphragm also known as a Bochdalek hernia. It occurs in 1 in 2000 to 3000 newborns and is associated with a variable degree of pulmonary hypoplasia (PH) and persistent pulmonary hypertension (PPH). Despite remarkable advances in neonatal resuscitation and intensive care and the new postnatal treatment strategies, many newborns with CDH continue to have high rates of mortality and morbidity as the result of severe respiratory failure secondary to PH and PPH. The pathogenesis of CDH and associated PH and PPH is poorly understood. Herein, we aim to review diaphragm and pulmonary development and correlate this to the abnormalities found in CDH. © 2010 Elsevier Inc.
McNally P.,National Childrens Hospital
Pediatric pulmonology | Year: 2010
We present the case of a child with asthma who continued to have marked exercise induced dyspnea despite appropriate treatment, and in the face of adequate control of all other asthma symptoms. Spirometry showed a marked truncation of inspiratory flow, and laryngoscopy performed immediately after exercise showed laryngomalacia with dynamic, partial inspiratory obstruction. Exercise induced laryngomalacia (EIL) is a rare cause of exercise induced dyspnea which is diagnosed by post exercise flexible laryngoscopy and may require supraglottoplasty. © 2010 Wiley-Liss, Inc.
Kutasy B.,National Childrens Hospital |
Hunziker M.,National Childrens Hospital |
Laxamanadass G.,National Childrens Hospital |
Puri P.,National Childrens Hospital
Pediatric Surgery International | Year: 2011
Purpose: In recent years there has been worldwide increase in childhood obesity. However, in the beginning laparoscopic appendectomy in obese children was contraindicated, now it is commonly used for the treatment of appendicitis. The purpose of this study was to compare open versus laparoscopic appendectomy in extremely obese children. Methods: The hospital records of 1,383 consecutive patients, who underwent appendectomy for acute appendicitis between 2000 and 2009 were analyzed. 238 children (17.2%) were extremely obese. Extremely obese was defined, as greater than 2 standard deviations above the standardized mean weight for age. 61 of 238 (25.6%) patients had open appendectomy and 177 (74.3%) underwent laparoscopic appendectomy. The length of hospital stay, operation time, complication rate and frequency of taking postoperative pain relief were compared between open and laparoscopic appendectomy in extremely obese children. Results: The incidence of complicated and non-complicated appendicitis was similar both in open and laparoscopic appendectomy group. Laparoscopic appendectomy for acute appendicitis in extremely obese children is associated with significantly shorter operating time (46.8 vs. 59.87 min, P < 0.05), lower overall complication rate (5 vs. 8.2%, P < 0.05) and lesser postoperative analgesia requirement (6.97× vs. 4.73×, P < 0.05). Conclusion: Laparoscopic appendectomy should be the procedure of choice for the treatment of acute appendicitis in extremely obese children. © 2011 Springer-Verlag.
Conroy P.H.,National Childrens Hospital |
O'Rourke J.,National Childrens Hospital
Surgeon | Year: 2013
Tumescent anaesthesia describes the practice of injecting a very dilute solution of local anaesthetic combined with epinephrine and sodium bicarbonate into tissue until it becomes firm and tense (tumescent). It was initially described in the field of liposuction but now surgical applications for the technique are widely varied ranging across vascular surgery, breast surgery, plastic surgery and ENT procedures. It is widely used in both hospital- and office-based environments and may form the sole method of anaesthesia for surgery. Advantages include a reduction in blood loss through both epinephrine-induced vasoconstriction as well as hydrostatic compression from the tumescent effect. Sodium bicarbonate reduces pain associated with the injection of an acidic local anaesthetic solution. Due to the unique pharmacokinetic profile of this technique lidocaine doses of 35mg/kg bodyweight have been shown to be safe for liposuction procedures. Tumescent lidocaine is absorbed very slowly from subcutaneous tissues producing lower, and more delayed, peak blood levels compared to other routes, as well as extended postoperative analgesia. Slow systemic absorption allows the rapid hepatic plasma clearance of lidocaine to maintain safe local anaesthetic blood levels. This slow absorption from subcutaneous tissue has been likened to a depot injection. Careful attention must be given to appropriate local anaesthetic dosage alterations in cases of co-administration with agents affecting hepatic drug clearance or conditions reducing liver blood supply. Adherence to these pharmacological principles has produced an exemplary safety record for this technique to date. © 2013 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland.