Princess Margaret Hospital for Children

About: Princess Margaret Hospital for Children is a healthcare organization based out in Perth, Western Australia, Australia. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 1501 authors who have published 2068 publications receiving 75773 citations. The organization is also known as: Perth Children's Hospital & PMH.

Irreversible growth plate fusions in children with medulloblastoma treated with a targeted hedgehog pathway inhibitor.

Abstract: The permanent defects in bone growth observed in preclinical studies of hedgehog (Hh) pathway inhibitors were not substantiated in early phase clinical studies of vismodegib in children. Consequently, vismodegib advanced into pediatric trials for malignancies suspected of being driven by aberrant activation of the Hh pathway. In one multicenter phase II trial, vismodegib was added to the therapy regimen for newly diagnosed Hh pathway activated medulloblastoma. Herein, we report on 3 children (2 on trial and one off trial) treated with vismodegib who developed widespread growth plate fusions that persist long after cessation of therapy. Currently, all 3 patients exhibit profound short stature and disproportionate growth, and 2 subsequently developed precocious puberty. Notably, the growth plate fusions only developed after a prolonged exposure to the drug (> 140 days). These findings resulted in a major trial amendment to restrict the agent to skeletally mature patients as well as a product label warning and update. Moreover, these findings alter the risk-benefit ratio of Hh inhibitors and underscore the importance of careful study of targeted agents in children.

The Changing Epidemiology of Invasive Pneumococcal Disease in Aboriginal and Non-Aboriginal Western Australians from 1997 through 2007 and Emergence of Nonvaccine Serotypes

Abstract: BACKGROUND. In 2001, Australia introduced a unique 7-valent pneumococcal conjugate vaccine (7vPCV) 2-, 4-, and 6-month schedule with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster for Aboriginal children, and in 2005, 7vPCV alone in a 2-, 4-, and 6-month schedule for non-Aboriginal children. Aboriginal adults are offered 23vPPV but coverage is poor. We investigated trends in invasive pneumococcal disease (IPD) in Western Australia (WA). METHODS. Enhanced IPD surveillance has been ongoing since 1996. We calculated IPD incidence rates for Aboriginal and non-Aboriginal Australians before and after introduction of 7vPCV. RESULTS. A total of 1792 cases occurred during the period 1997-2007; the IPD incidence rate was 47 cases per 100,000 population per year among Aboriginal people and 7 cases per 100,000 population per year in non-Aboriginal people. After introduction of 7vPCV, IPD rates among Aboriginal children decreased by 46% for those 30% in non-Aboriginal people 50 years of age but increased among Aboriginal adults (eg, from 59.1 to 109.6 cases per 100,000 population per year among those 30-49 years of age). Although IPD due to 7vPCV serotypes decreased in all age groups, IPD incidence due to non-7vPCV serotypes increased, and it almost doubled among Aboriginal adults 30-49 years of age (from 48.3 to 97.0 cases per 100,000 population per year). Among non-Aboriginal children, 37% of IPD is now due to serotype 19A. CONCLUSIONS. IPD incidence rates have decreased markedly among children and non-Aboriginal adults with a 3-dose infant 7vPCV schedule. However, IPD due to non-7vPCV serotypes has increased and is of particular concern among young Aboriginal adults, for whom an intensive 23vPPV campaign is needed. An immunization register covering all age groups should be established.

Reducing Rates of Severe Hypoglycemia in a Population-Based Cohort of Children and Adolescents With Type 1 Diabetes Over the Decade 2000–2009

Abstract: OBJECTIVE To examine rates of severe hypoglycemia (SH) in a large population-based cohort of children with type 1 diabetes and relationships to HbA 1c . RESEARCH DESIGN AND METHODS Data from 1,683 children (mean [SD] age at diagnosis 10.5 [4.2]; range 1–18 years) from 2000 to 2009 were analyzed from the Western Australian Children9s Diabetes Database. Rates of SH were related to HbA 1c using negative binomial regression. RESULTS A total of 7,378 patient-years of data and 780 SH events were recorded. The rate of SH per 100 patient-years peaked at 17.3 in 2001 and then declined from 2004 to a nadir of 5.8 in 2006. HbA 1c P = 0.29) compared with HbA 1c of 8–9%. CONCLUSIONS In a sample of youth with type 1 diabetes, there has been a decrease in rates of SH and a weaker relationship with glycemic control than previously observed.

Early Loss of the Glucagon Response to Hypoglycemia in Adolescents With Type 1 Diabetes

Abstract: OBJECTIVE To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects. RESEARCH DESIGN AND METHODS Hyperinsulinemic hypoglycemic clamp studies were performed in all participants. The glucagon response to both hypoglycemia and arginine was measured, as well as epinephrine, cortisol, and growth hormone responses to hypoglycemia. Residual β-cell function was assessed using fasting and stimulated C-peptide. RESULTS Twenty-eight nonobese adolescents with type 1 diabetes (14 female, mean age 14.9 years [range 11.2–19.8]) and 12 healthy control subjects (6 female, 15.3 years [12.8–18.7]) participated in the study. Median duration of type 1 diabetes was 0.66 years (range 0.01–9.9). The glucagon peak to arginine stimulation was similar between groups ( P = 0.27). In contrast, the glucagon peak to hypoglycemia was reduced in the group with diabetes (95% CI): 68 (62–74) vs. 96 (87–115) pg/mL ( P R = −0.41, P 1c . Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups. CONCLUSIONS The glucagon response to hypoglycemia in adolescents with type 1 diabetes is influenced by the duration of diabetes and can be lost early in the course of the disease.

Altered lung structure and function in mid-childhood survivors of very preterm birth

Abstract: Rationale Survivors of preterm birth are at risk of chronic and lifelong pulmonary disease. Follow-up data describing lung structure and function are scarce in children born preterm during the surfactant era. Objectives To obtain comprehensive data on lung structure and function in mid-childhood from survivors of preterm birth. We aimed to explore relationships between lung structure, lung function and respiratory morbidity as well as early life contributors to poorer childhood respiratory outcomes. Methods Lung function was tested at 9–11 years in children born at term (controls) and at ≤32 weeks gestation. Tests included spirometry, oscillatory mechanics, multiple breath nitrogen washout and diffusing capacity of the lung for carbon monoxide. Preterm children had CT of the chest and completed a respiratory symptoms questionnaire. Main results 58 controls and 163 preterm children (99 with bronchopulmonary dysplasia) participated. Preterm children exhibited pulmonary obstruction and hyperinflation as well as abnormal peripheral lung mechanics compared with term controls. FEV 1 was improved by 0.10 z-scores for every additional week of gestation (95% CI 0.028 to 0.182; p=0.008) and by 0.34 z-scores per z-score increase in birth weight (0.124 to 0.548; p=0.002). Structural lung changes were present in 92% of preterm children, with total CT score decreased by 0.64 (−0.99 to −0.29; p Conclusions Abnormal lung structure in mid-childhood resulting from preterm birth in the contemporary era has important functional consequences.