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ItemNo Preview AvailableAntiepileptic Medications Increase Osteoporosis Risk in Male Fabry Patients: Bone Mineral Density in an Australian Cohort(SPRINGER-VERLAG BERLIN, 2014)BACKGROUND: Fabry disease (FD) is an inherited X-linked lysosomal storage disease with widespread clinical manifestations. Small prospective studies have shown increased osteopenia and osteoporosis in male FD patients. Limited information however exists about bone metabolism and osteoporosis risk factors within this group. We reviewed osteoporosis risk factors within our cohort. METHODS: A retrospective analysis of bone mineral density (BMD) results and fracture incidence in 44 patients (22 males and 22 females) was undertaken. Dual X-ray absorptiometry scans were performed at the lumbar spine, hip and femoral neck. The impact of risk factors including renal function, antiepileptic drug (AED), analgesia and vitamin D levels were assessed. RESULTS: Male FD patients had low T scores at all sites (spine -1.2 ± 1.06, hip -1.6 ± 0.9, femoral neck -2.23 ± 1.01). Female T scores showed more typical distribution (spine -0.07 ± 1.47, hip 0.02 ± 1.14, femoral neck -0.49 ± 1.31). A higher incidence of osteopenia and/or osteoporosis occurred in males versus females (spine 46.9% versus 31.8%, hip 75.5% versus 18.2% and femoral neck 86.4% versus 45.5%). Multiple regression analysis showed a 50.8% (p < 0.001) reduction in femoral neck BMD with AED usage, after adjustment for age, gender and renal function. Non-traumatic fractures occurred in 27.3% males over 205 patient-years versus 4.6% in females over 149 patient-years, p = 0.095. CONCLUSIONS: Low bone density was highly prevalent in male patients with increased incidence of non-traumatic fractures. AED usage significantly reduces BMD. Treatment to prevent BMD deterioration will depend on determining the bone turnover status.
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ItemNo Preview AvailableEffect of Reduced Agalsidase Beta Dosage in Fabry Patients: The Australian Experience(SPRINGER-VERLAG BERLIN, 2012)BACKGROUND: In Australia, enzyme replacement therapy (ERT) for Fabry Disease (FD), both Agalsidase alfa (Replagal, Shire HGT) and beta (Fabrazyme, Genzyme), is funded and monitored through a specific government program. Agalsidase beta supply has been rationed by Genzyme since 2009 due to manufacturing issues. Consequently, the Australian Fabry Disease Advisory Committee has treated patients on Agalsidase beta at 50% of their usual dose from mid-2009, with a further reduction to 30% for some patients from late 2009. AIM: To determine the clinical effect of Agalsidase beta dose reduction in the Australian FD patient cohort. METHODS: A questionnaire assessing FD symptoms was administered to 40 patients on long-term ERT. Clinical data from The Fabry Registry for patients receiving Agalsidase alfa or beta, for at least 2 years prior to the time of enforced Agalsidase beta dose reduction, were reviewed. Disease burden and quality of life (QOL) were graded using the Disease Severity Scoring System, Mainz Severity Score Index, Brief Pain Inventory and Short Form 36 Health Survey at 2 years before dose reduction, at the time of dose reduction and at the most recent clinical review following dose reduction. RESULTS: Disease severity and QOL scores did not change between the ERT groups. Males on Agalsidase beta reported lower energy levels after dose reduction, while no change was reported by females on either product or by males on a stable dose of Agalsidase alfa. CONCLUSION: This study suggests that energy levels in male patients worsen after dose reduction of Agalsidase beta.
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ItemNo Preview AvailableSevere Infusion Reactions to Fabry Enzyme Replacement Therapy: Rechallenge After Tracheostomy(SPRINGER-VERLAG BERLIN, 2012)A 34-year-old male patient with Fabry disease (OMIM 301500) commenced enzyme replacement therapy (ERT) with Agalsidase alfa, with positive clinical response. Infusion reactions, initially mild and easily managed, commenced during his 13th infusion, and continued over the next 3 years. Severity of reactions subsequently increased despite very slow infusion, extended prophylactic medication and attempted desensitisation, requiring regular intensive care unit (ICU) admissions. Facial oedema and flushing, throat tightness, headache and joint pain typically occurred 4-36 h after completion of most infusions, responding rapidly to subcutaneous adrenaline. Low titre specific IgG seroconversion was noted at 12 months, with subsequent reversion to negative after 5 years, despite persistence of infusion reactions. Specific IgE and skin testing was negative. Trial of ERT product switch to Agalsidase-beta resulted in no improvement in reactions. At 5 years, ERT was ceased in the face of recurrent ICU readmissions. In the face of progressive clinical deterioration, he underwent tracheostomy to allow recommencement of ERT. Two years later, he has clinically improved on regular attenuated dose Agalsidase-beta, administered by slow infusion in a local hospital setting.
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ItemNo Preview AvailableCarpal Tunnel Syndrome in Fabry Disease(SPRINGER-VERLAG BERLIN, 2012)Carpal tunnel syndrome (CTS) is a common peripheral mononeuropathy affecting up to 4% of the general population, typically women in late middle age. The incidence in patients with Fabry disease (FD) is unclear, but may affect 25% of patients with this X-linked lysosomal storage disease. We report three cases of CTS in young Caucasian male patients with classical FD, who developed CTS symptoms with supportive nerve conduction study (NCS) findings. Two patients had bilateral CTS and two had evidence of concurrent ulnar nerve neuropathy on NCS, suggesting a systemic process contributed to nerve compression. All were receiving enzyme replacement therapy (ERT) and had a moderate burden of FD complications. It is possible that an increase in connective tissue in the intracarpal canal in FD patients may be incited by injury to fibroblasts, via either accumulation of globotriaosylceramide (GL3) or local ischaemia through endothelial injury. The former hypothesis may be a more plausible explanation for the development of CTS, as histology of the flexor retinaculae from our patients has demonstrated fibroblasts with characteristic vacuolation and excessive myxomatous stroma, despite endothelial clearance of GL3 in these patients receiving ERT. CTS should not be overlooked in FD patients and young patients presenting with CTS should be evaluated for an underlying systemic or genetic disorder. Surgical carpal tunnel decompression was effective in our patients, already troubled by long-standing acroparesthesia, in providing sustained relief of symptoms.
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ItemNo Preview AvailableAnthony George Klein 1935–2021(CSIRO Publishing, 2024)Professor Anthony (Tony) George Klein AM, FAA (1935–2021) was an outstanding physicist, university teacher, leader, mentor and science communicator. We recount Tony’s life from his childhood in wartime Romania, his early interest in mathematics, the family’s migration to Australia via Israel in 1953, high school and university education in Melbourne, appointment as a research scientist at the AAEC in Sydney, followed by a distinguished career as an academic, researcher and leader in the School of Physics at the University of Melbourne where he retired as Emeritus Professor. The memoir describes Tony Klein’s personal qualities, the influences and experiences shaping his career, his major research contributions and collaborations in the field of neutron optics and neutron interferometry, his service to scientific and medical organisations and recognition by the university, the Australian Academy of Science and the nation. We evaluate Tony Klein’s contribution to science, knowledge and higher education.
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ItemNo Preview AvailableResponse to Lombardi and Mesnard(ELSEVIER SCIENCE INC, 2024-01)
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ItemUncertainty-aware non-invasive patient–ventilator asynchrony detection using latent Gaussian mixture generative classifier with noisy label correction(Springer Science and Business Media LLC, 2024-01-01)Abstract Patient–ventilator asynchrony (PVA) refers to instances where a mechanical ventilator’s cycles are desynchronised from the patient’s breathing efforts, and may result in patient discomfort and potential ineffective ventilation. Typically, they are identified with constant monitoring by trained clinicians. Such expertise is often limited; therefore, it is desirable to automate PVA detection with machine learning methods. However, there are three major challenges to applying machine learning to the problem: data collected from non-invasive ventilation are often noisy, there exists high variability between patients or between setting changes, and manual annotations of PVA events are not always consistent. To produce meaningful inference from such noisy data, a model needs to not only provide a measure of uncertainty, but also take into account potential inconsistencies in the training signal it is based on. In this work, we propose a conditional latent Gaussian mixture generative classifier with noisy label correction, which is capable of capturing variations within and between classes, providing well-calibrated class probabilities, detecting unlikely input instances that deviates from training data, while also taking into account possible mislabelling of event classes. We show that our model is able to match the performance of a well-tuned gradient boosting classifier, but also produce better calibrated predictions and smaller performance variability between patients.
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ItemA festival in disarray: the 2002 Adelaide festival: A debacle or another model of arts organization and leadership?(HELDREF PUBLICATIONS, 2004-01-01)
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ItemPrivilege or problem: The distinct role of government in arts development in South Australia(ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2005-01-01)
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ItemNo Preview AvailableDoes it matter who is in charge? The influence of the business paradigm on arts leadership and management.(International Graduate School of Management, University of South Australia, 2005)