ORCID Profile
0000-0002-8476-220X
Current Organisations
University of Sydney
,
Children's Hospital at Westmead
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Publisher: Wiley
Date: 05-03-2021
DOI: 10.1111/JPC.15407
Abstract: Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder characterised by adrenocorticotropic hormone (ACTH) deficiency, red hair and hyperphagic obesity. Two unrelated cases presented with hypoglycaemia due to isolated ACTH deficiency in the neonatal period. POMC deficiency was suspected at age 2 years (c.133‐2A C) and at age 9 months (c.64del) due to infantile hyperphagic obesity. Neither patient had a convincing red hair phenotype at the time of diagnostic suspicion, illustrating the importance of suspecting POMC deficiency in isolated ACTH deficiency. Both patients have normal psychomotor development, whereas the only other reported case of c.64del had significant delay. This suggests, if ACTH deficiency is treated early in the neonatal period, that psychomotor retardation is not a part of the phenotype. We review 24 reported cases of POMC deficiency published to date. Although there is no current specific treatment for obesity in POMC deficiency, we anticipate that setmelanotide may be a useful future treatment option.
Publisher: S. Karger AG
Date: 2020
DOI: 10.1159/000510463
Abstract: Osteogenesis imperfecta (OI) is a heterogenous group of heritable bone dysplasias characterized by bone fragility, typically low bone mass, joint laxity, easy bruising, and variable short stature. Classical OI is caused by autosomal dominant pathogenic variants in i COL1A1 /i or i COL1A2 /i that result in either reduced production of normal type 1 collagen or structurally abnormal collagen molecules. Pathogenic variants in these genes generally result in low bone mass. Here, we report a family that had 2 affected in iduals who presented with minimal trauma fractures and were found to have elevated bone mineral density (BMD) and a previously unreported variant in i COL1A2 /i c.3356C& #x3e T p.(Ala1119Val). We report the change in BMD using dual-energy X-ray and peripheral quantitative computed tomography over a 2.3-year period in the proband. This case report highlights the importance of BMD studies and genetic testing in the diagnostic process for brittle bone disorders.
Publisher: SAGE Publications
Date: 2019
Abstract: Type 1 and type 2 diabetes are increasing in prevalence and diabetes complications are common. Diabetes complications are rarely studied in youth, despite the potential onset in childhood. Microvascular complications of diabetes include retinopathy, diabetic kidney disease or nephropathy, and neuropathy that may be somatic or autonomic. Macrovascular disease is the leading cause of death in patients with type 1 diabetes. Strict glycaemic control will reduce microvascular and macrovascular complications however, they may still manifest in youth. This article discusses the diagnosis and treatment of complications that arise from type 1 and type 2 diabetes mellitus in youth. Screening for complications is paramount as early intervention improves outcome. Screening should commence from 11 years of age depending on the duration of type 1 diabetes or at diagnosis for patients with type 2 diabetes. Diabetic retinopathy may require invasive treatment such as laser therapy or intravitreal antivascular endothelial growth factor therapy to prevent future blindness. Hypertension and albuminuria may herald diabetic nephropathy and require management with angiotensin converting enzyme (ACE) inhibition. In addition to hypertension, dyslipidaemia must be treated to reduce macrovascular complications. Interventional trials aimed at examining the treatment of diabetes complications in youth are few. Statins, ACE inhibitors and metformin have been successfully trialled in adolescents with type 1 diabetes with positive effects on lipid profile, microalbuminuria and measures of vascular health. Although relatively rare, complications do occur in youth and further research into effective treatment for diabetes complications, particularly therapeutics in children in addition to prevention strategies is required.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Wiley
Date: 26-05-2009
DOI: 10.1111/J.1751-0813.2009.00434.X
Abstract: To assess the incidence of lymphoma and wasting-related deaths in the National Baboon Colony of Australia and relate it to the presence of simian T-cell lymphotrophic virus 1 (STLV-1) infection. The records of all animals that had died since establishment of the National Baboon Colony in Australia were reviewed retrospectively. The clinical signs and histopathological findings were recorded and assessed to determine the involvement of lymphoma in the deaths. The presence of STLV-1 was recorded if known and correlated with the STLV-1 status of the colony. Of the deaths from disease or illness, 53% were diagnosed as or suspected to be lymphoma, occurring in mature animals with no sex predisposition. The most common presentation was rapidly occurring generalised lymphadenomegaly. This study has described a relatively high prevalence of lymphoma in a colony of captive-bred baboons, and it is evident that STLV-1 may play a role in the disease. Management practices in baboon colonies need to take into account the possible presence of STLV-1 and aim to reduce the transmission of the virus by preventing sexual contact between positive and negative animals. Lymphoma needs to be considered as one of the more common causes of wasting and death.
Publisher: Wiley
Date: 11-01-2021
DOI: 10.1111/JPC.15349
Abstract: Paediatric hypoglycaemia often requires specific investigations to determine aetiology. S les from the time of hypoglycaemia may not be available and a diagnostic fasting test may be required. Additionally, fasting studies can determine safe fasting intervals and prolonged oral glucose challenges can assess hypoglycaemia due to abnormal post‐prandial glucose handling. This audit reviewed the current utility and yield of fasting studies, prolonged oral glucose challenges and starch loads. Retrospective audit of clinical record to determine purpose and outcome of tests performed at a Tertiary Paediatric Endocrine/Metabolic Testing Unit in Sydney, Australia, from 2013 to 2018 inclusive. One hundred and thirty‐eight children (aged 3 weeks–17 years) underwent 170 tests: 122 fasting studies, 20 five‐hour OGTTs, 22 uncooked corn starch loads and six modified waxy maize starch (Glycosade) loads. The majority were for diagnostic purposes ( n = 113, 66%), with 57 (34%) to guide management in patients with known diagnoses. Following diagnostic studies, 35 (31%) patients received a pathological diagnosis, the most common of which ( n = 19, 17%) was accelerated starvation. Hypoglycaemia developed in n = 15/113 (13%) during the diagnostic studies. Management studies helped determine length of safe fast, adjustment of medication or diet and document resolution of pathology. Fasting studies remain a safe and effective method to assist with diagnoses, confirm or exclude pathological causes of childhood hypoglycaemia and to guide management of known diagnoses in the paediatric population.
Publisher: Wiley
Date: 25-07-2014
Publisher: The Endocrine Society
Date: 06-01-2023
Abstract: Primary adrenal insufficiency (PAI) occurs in 1 in 5 to 7000 adults. Leading etiologies are autoimmune adrenalitis in adults and congenital adrenal hyperplasia (CAH) in children. Oral replacement of cortisol is lifesaving, but poor quality of life, repeated adrenal crises, and dosing uncertainty related to lack of a validated biomarker for glucocorticoid sufficiency persists. Adrenocortical cell therapy and gene therapy may obviate many of the shortcomings of adrenal hormone replacement. Physiological cortisol secretion regulated by pituitary adrenocorticotropin could be achieved through allogeneic adrenocortical cell transplantation, production of adrenal-like steroidogenic cells from either stem cells or lineage conversion of differentiated cells, or for CAH, gene therapy to replace or repair a defective gene. The adrenal cortex is a high-turnover organ and thus failure to incorporate progenitor cells within a transplant will ultimately result in graft exhaustion. Identification of adrenocortical progenitor cells is equally important in gene therapy, for which new genetic material must be specifically integrated into the genome of progenitors to ensure a durable effect. Delivery of gene-editing machinery and a donor template, allowing targeted correction of the 21-hydroxylase gene, has the potential to achieve this. This review describes advances in adrenal cell transplants and gene therapy that may allow physiological cortisol production for children and adults with PAI.
Publisher: Frontiers Media SA
Date: 09-06-2020
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.RESUSCITATION.2013.11.024
Abstract: During paediatric resuscitation it is essential to be able to estimate the child's weight as it determines drug doses and equipment sizes. Age and length-based estimations exist, with age-based estimations being especially useful in the preparation phase and the length-based Broselow tape having weight-based drug doses and equipment already assigned via a colour code system. The aim of this study was to compare the actual recorded weights of Australian children to the predicted weights using the original and updated APLS, Luscombe and Owens and Best Guess formulae and the Broselow tape. A retrospective observational study of children attending an Australian tertiary children's hospital. From 49,565 patients extracted from the database, 37,114 children with age and weight and 37,091 children with age and height recorded were included in the analysis. Best Guess was the most accurate, with the smallest overall mean difference 0.86 kg. For <1 year old, Broselow tape was the most accurate (mean difference -0.43 kg), Best Guess was the most accurate for ages 1-5 years and 11-14 years (mean difference 0.27 and 0.20 kg respectively), and the updated APLS formula was the most accurate for 6-10 year-old (mean difference 0.42 kg). The Broselow tape was able to only classify 48.9% of children into the correct weight colour band. For an age-based weight estimation, in infants less than one year the new APLS formula is the most accurate and over one year the Best Guess formulae should be used.
Publisher: Wiley
Date: 07-10-2023
DOI: 10.1111/JPC.16242
Abstract: To determine if the timing of manuscript submissions to The Journal of Paediatrics and Child Health (JPCH) changed following the onset of the COVID‐19 pandemic and to determine if the timing of manuscript submissions influenced editorial decisions. A retrospective observational study of submissions to JPCH from 1 January 2015 to 1 August 2022 was performed. Regression models were used to explore the change over time. Editorial decisions were examined using a multinomial regression model with the three‐category ordinal outcome of reject, revise and accept. All statistical models were fitted using a Bayesian approach and show 95% credible intervals (CI). The analyses included 11 499 manuscript submissions between 2015 and 2022. The mean number of manuscript submissions increased by 17 papers per month (CI 15–19), with a larger 4‐month long increase after the COVID‐19 pandemic was declared of 86 submissions per month (CI 67–103). There was no clear effect of the pandemic on weekend submissions, mean difference in probability 0.003 (CI –0.021 to 0.026). Throughout the study period, the peak submission time was later in the day and was shifted +37 min later post‐March 2020 (CI +22 to +52 min). Throughout the study period, submissions out‐of‐hours and on weekends were less likely to get an editorial decision of ‘accept’ or ‘revise’: odds ratio weekend versus weekday 0.87 (CI 0.78–0.97). The COVID‐19 pandemic had a limited effect on the timing of manuscript submissions to JPCH. However, the timing of manuscript submission impacted the likelihood of a more positive editorial decision. While the time of manuscript submission is only one part of the research process, it is postulated that it may be associated with research quality.
Publisher: Hindawi Limited
Date: 23-09-2021
DOI: 10.1111/PEDI.13265
Abstract: In adults, there has been a decline in the incidence of diabetic retinopathy (DR) associated with improvements in diabetes management. Data on incident severe DR in adolescents are sparse. In our established diabetes complications assessment service, we recorded nine cases of sight-threatening retinopathy in youth aged 15-17.9 years from 2017 to 2021. Proliferative retinopathy and clinically significant macular oedema were identified. The subjects were diagnosed with type 1 diabetes before the age of 10 years and had a history of poor glycaemic control (HbA1c 86-130 mmol/mol, 10%-15%). Five cases of retinopathy developed rapidly within 2.5 years of a previously normal retinal examination on seven-field stereoscopic retinal photography. Three adolescents required laser photocoagulation therapy. Two adolescents were diagnosed with retinopathy following improvement in diabetes control after being lost to medical follow-up and their retinopathy improved with improved glycaemic control. Thus, we support repeated retinal screening in adolescents with diabetes duration >10 years with suboptimal glycaemic control, even when initial retinal examination is normal, as retinopathy can progress rapidly during adolescence.
No related grants have been discovered for Lara Graves.