ORCID Profile
0000-0002-8193-8994
Current Organisations
Eastern Health
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Monash University
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Publisher: Public Library of Science (PLoS)
Date: 13-10-2016
Publisher: Elsevier BV
Date: 11-2021
Publisher: JMIR Publications Inc.
Date: 10-05-2022
DOI: 10.2196/31736
Abstract: Type 2 diabetes (T2D) is increasingly prevalent in society, in part because of behavioral issues, with sedentary behavior, reduced exercise, and the consumption of foods with a high glycemic index being major contributors. There is evidence for the efficacy of mobile apps in promoting behavior change and lifestyle improvements in people with T2D. Many mobile phone apps help to monitor the condition of people with T2D and inform them about their health. Some of these digital interventions involve patients using apps on their own or in conjunction with health care professionals. This study aimed to test the acceptability of receiving app-based, daily physician feedback for patients with T2D that is informed by the continuous monitoring of their activity, food choices, and glucose profiles, with the aim of encouraging healthier behavior. The GLOOK! app was designed and developed by an academic research team and pilot-tested at an Australian public hospital. A total of 15 patients diagnosed with T2D wore a glucose monitor and an Apple Watch for 12 days. The uploaded data were integrated into the GLOOK! app on the patients’ smartphones, which also enabled the recording of activity and consumed food. A physician provided daily feedback to each in idual through the app based on their data from each of the 12 days. At the beginning and end of the study, data were collected on vital signs, anthropometry, hemoglobin A1c level, fructosamine level, and fasting lipids level. Participants were also interviewed at the beginning and end of the study to assess the acceptability of the intervention and its potential impact on promoting positive behavior change. Over the 12 days of the study, there was a significant reduction of 0.22% (P=.004) in hemoglobin A1c level. There were favorable changes in fructosamine and lipid fractions however, none reached significance. There was also a fall of 0.65 kg in body weight and falls in blood pressure and pulse rate that did not reach significance. Patient feedback on the GLOOK! system was positive. Of the 15 participants, 13 (87%) were enthusiastic about continuing to use the app system if some usability and reliability aspects were improved. All participants regarded the personalized physician feedback as supportive and helpful in understanding their own health behavior. Of the 15 participants, 4 (27%) felt that using the system encouraged long-term behavior changes. A mobile app system that provides people with T2D daily, physician-generated, personalized feedback can produce favorable changes in glycemic and cardiovascular risk parameters—even in the short term—and encourage better self-management of their condition. Study participants found the experience of using the mobile app system acceptable and were motivated to establish longer-term lifestyle improvements through behavior changes.
Publisher: Wiley
Date: 08-2014
DOI: 10.1111/IMJ.12476
Abstract: The majority of differentiated thyroid cancers are characterised by one of several point mutations or gene rearrangements. Limited data are available on the prevalence and clinical correlations of these mutations in the Australian population. The aim of the present study was to characterise the mutation profile of differentiated thyroid tumours in the local population. The study involved 148 patients with differentiated thyroid cancer. The following tumours were examined: 109 papillary carcinomas (PTC), 27 follicular carcinomas (FC) and 12 Hurthle cell carcinomas (HCC). Polymerase chain reaction (PCR) was performed for BRAF and RAS mutations (RNA and DNA) as well as for RET/PTC rearrangements and PAX8-PPARγ translocations (RNA). Clinicopathological parameters and outcome data were analysed according to BRAFV600E status in PTC and RAS mutation status in FC. BRAFV600E was identified in 74/109 (68%) PTC. BRAFV600E was not significantly correlated with clinicopathological features of aggressive disease. At a median follow up of 48 months, there was no significant difference between BRAFV600E and wild-type BRAF PTC with respect to the rates of nodal recurrence, distant metastases or disease-specific death. In FC, RAS mutations (five NRAS and three HRAS) were present in 8/27 (30%) tumours. RAS mutation was significantly associated with widely invasive histology (P = 0.01) and distant metastases (P = 0.01) on follow up. In the present study, BRAF mutation was not associated with negative prognostic indicators or adverse outcomes in PTC. RAS mutation was positively correlated with aggressive features in FC suggesting potential prognostic utility, although confirmation is required from larger studies.
Publisher: Wiley
Date: 02-2016
DOI: 10.1111/IMJ.12731
Abstract: Androgen deprivation therapy (ADT) is a standard systemic treatment for men with prostate cancer. Men on ADT may be elderly and have comorbidities that are exacerbated by ADT, such as cardiovascular disease, diabetes, obesity, sedentary lifestyle and osteoporosis. Studies on managing the impacts of ADT have focused on men with non-metastatic disease, where ADT is given for a limited duration. However, some men with advanced or metastatic prostate cancer will achieve long-term survival with palliative ADT and therefore also risk morbidity from prolonged ADT. Furthermore, ADT is continued during the use of other survival-prolonging therapies for men with advanced disease, and there is a general trend to use ADT earlier in the disease course. As survival improves, management of the metabolic effects of ADT becomes important for maintaining both quality and quantity of life. This review will outline the current data, offer perspectives for management of ADT complications in men with advanced prostate cancer and discuss avenues for further research.
Publisher: Wiley
Date: 11-2019
DOI: 10.1111/IMJ.14636
Publisher: Wiley
Date: 15-09-2008
DOI: 10.1111/J.1463-1326.2007.00839.X
Abstract: To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [haemoglobin A(1c) (HbA(1c)) 7-11%] on metformin monotherapy. Patients (n = 273) on metformin (>/=1500 mg/day) were randomized to receive the addition of once-daily placebo, sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks. The efficacy analysis was based on the all-patients-treated population using an analysis of co-variance with change in HbA(1c) from baseline as the primary endpoint. The mean baseline HbA(1c) was 7.7% for the entire cohort. After 18 weeks, both active add-on therapies led to greater improvements in HbA(1c) from baseline: -0.73% for sitagliptin (p < 0.001 vs. placebo) and -0.79% for rosiglitazone compared with -0.22% for placebo. No difference was observed between the sitagliptin and rosiglitazone treatments (0.06% [95% confidence interval (CI): -0.14 to 0.25]). The proportion of patients achieving an HbA(1c) < 7% was greater with sitagliptin (55%) and rosiglitazone (63%) compared with placebo (38%). Body weight increased from baseline with rosiglitazone (1.5 kg) compared with body weight reduction with sitagliptin (-0.4 kg) and placebo (-0.8 kg). The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg (95% CI: 1.3-2.5). In a prespecified analysis, the proportion of patients experiencing a greater than 3-kg increase in body weight was 21% in the rosiglitazone group compared with 2% in both the sitagliptin and placebo groups. Both active treatments were generally well tolerated, with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo. In this 18-week study, the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Treatment with sitagliptin produced similar reductions in HbA(1c) compared with the addition of rosiglitazone.
Publisher: Informa UK Limited
Date: 27-04-2022
DOI: 10.1080/09638288.2022.2065540
Abstract: To determine the prevalence of metabolic syndrome in patients attending outpatient community rehabilitation in Melbourne, Australia and to compare health literacy, physical activity, and dietary intake of people with and without metabolic syndrome. A cross-sectional, multi-centre, observational study of adults ( One hundred and twenty three participants (64%) had metabolic syndrome. Of these, only three (2%) knew they had it. People with metabolic syndrome scored lower on health literacy (S-TOFHLA MD -2.10, 95% confidence interval (CI) -3.98 to -0.22) and took 1311 (95%CI 375 to 2246) fewer daily steps than those without metabolic syndrome. There were no differences in dietary intake. Metabolic syndrome is a prevalent and under-recognised condition in community rehabilitation. Community healthcare professionals and health services may need to consider a broader approach to management including lifestyle assessment and intervention of patients with various conditions. Implications for rehabilitationAlmost two-thirds of adults in community rehabilitation had underlying, undetected metabolic syndrome.Adults with metabolic syndrome completed less objectively measured physical activity and had lower health literacy levels than those without metabolic syndrome.A broader approach to management may need to be considered in community rehabilitation where patients presenting for rehabilitation of various conditions would likely benefit from lifestyle assessment and intervention.
Publisher: Oxford University Press (OUP)
Date: 02-2022
Abstract: Sarcopenia is assessed by several methods, including dual energy X-ray absorptiometry (DEXA), which provide a height-adjusted skeletal muscle index (H-SMI). A SMI 2 standard deviation below the young adult reference [1] combined with low muscle strength or performance is used to identify sarcopenia. As height declines with age, H-SMI may underestimate low skeletal muscle mass in the older population. Our study aims to evaluate an alternative SMI and to examine its relationship to grip strength in a group of Australian women. Women from two cohorts were analysed. 2041 women had body composition data (112 had calf circumference, 137 had leg length measurements) without grip strength, and 49 women had grip strength measured (40 had body composition data).The relationship between leg length-adjusted SMI (LL-SMI) to grip strength and anthropometric variables to skeletal muscle mass by DEXA were examined by linear regression analysis. Cohort 1: Older women were compared to younger women. Older women were shorter but leg length did not differ between different age groups. H-SMI was not different between groups (P = 0.528). LL-SMI was lower in older women (P = 0.002). Cohort 2: LL-SMI was significantly associated with grip strength (P = 0.048) after adjustment for age. Older women were shorter, while leg length did not differ from the younger group. H-SMI may obscure and may underestimate low muscle mass in older in iduals. LL-SMI may be a better measure of skeletal muscle mass in older in iduals. These alternate SMI would benefit from further exploration in older in iduals.
Publisher: Wiley
Date: 08-2019
DOI: 10.1111/IMJ.14210
Abstract: Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid-stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice. To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals. Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement. Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay-specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut-off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto-antibody status. The recommended starting dose of levothyroxine is 50 μg daily, with a therapeutic TSH target of 0.1-2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman's general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow-up. Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.
Publisher: Bentham Science Publishers Ltd.
Date: 29-05-2019
DOI: 10.2174/1573402114666180607090205
Abstract: Ambulatory blood pressure (ABP) monitoring in type 2 diabetes (T2DM) is not yet routine in clinical practice. To quantify abnormal ABP patterns and their associations with diabetic complications, and to assess the reliability of office blood pressure (OBP) for assessing BP in T2DM. In a cross-sectional study, eligible patients with T2DM underwent OBP and 24- hour ABP measurements under standardized conditions and screening for diabetic complications. 56 patients (mean age 67 ± 10 years, males 50%) completed assessment. 43(73%) had a known history of hypertension. Non-dipping and nocturnal systolic hypertension (SHT) were prevalent in 31(55%) and 32(57%) patients, respectively. 16(29%) demonstrated masked phenomenon, but only three (7%) demonstrated white coat effect. Nocturnal SHT had a significant association with composite microvascular complications independent of daytime systolic BP control (adjusted odds ratio (OR) 1.72(CI 1.41-4.25). There was no association between other abnormal ABP patterns and diabetic complications. The sensitivity and specificity of OBP for diagnosing HT or assessing BP control was 59% and 68% respectively. The positive and negative predictive values were 74% and 52% respectively. Non-dipping, reverse dipping, nocturnal SHT and masked phenomenon are highly prevalent in patients with T2DM with or without a known history of hypertension. Compared with non-dipping, nocturnal SHT may be a stronger predictor of end organ damage. The reliability of OBP for assessing BP in T2DM is only modest. Patients with T2DM are likely to benefit from routine ABP monitoring.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.JDIACOMP.2022.108188
Abstract: Liraglutide is an effective treatment for the management of type 2 diabetes mellitus (T2DM). In addition to glycemic control and potential cardioprotective effects, recent studies suggest a possible role for liraglutide in the inhibition of platelet reactivity, further attenuating atherothrombotic risk in patients with T2DM. We evaluated the in-vivo antiplatelet effect of liraglutide in T2DM patients without macrovascular disease or concurrent anti-platelet therapy. A double-blind, placebo-controlled pilot study of 16 T2DM patients, 51-69 y/o, (mean age 60.4 y/o, 63.0% male) randomised to receive liraglutide (1.8 mg/day) or placebo (saline) for 6 months was conducted. Platelet aggregation studies at baseline and after initiation of the study intervention: days 1, 7, and 14 and months 1, 3 and 6 were performed. Liraglutide (n = 7) and placebo (n = 9) treated patients demonstrated normal platelet aggregation responses although transient and significant attenuation in maximum slope of platelet aggregation in response to collagen (p ≤ 0.05), arachidonic acid (p ≤ 0.05) and ADP (p ≤ 0.02) was observed in liraglutide compared to placebo treated patients in the first week. In this pilot study of patients with T2DM liraglutide treatment was associated with a significant, early and transient decrease in maximum slope of platelet aggregation. The clinical significance of this effect is currently unknown and may warrant further investigation. UTN 1111-1181-9567.
Publisher: Bioscientifica
Date: 24-09-2018
DOI: 10.1530/EDM-18-0091
Abstract: Mitochondrial diseases are rare, heterogeneous conditions affecting organs dependent on high aerobic metabolism. Presenting symptoms and signs vary depending on the mutation and mutant protein load. Diabetes mellitus is the most common endocrinopathy, and recognition of these patients is important due to its impact on management and screening of family members. In particular, glycemic management differs in these patients: the use of metformin is avoided because of the risk of lactic acidosis. We describe a patient who presented with gradual weight loss and an acute presentation of hyperglycemia complicated by the superior mesenteric artery syndrome. His maternal history of diabetes and deafness and a personal history of hearing impairment led to the diagnosis of a mitochondrial disorder. The constellation of diabetes, multi-organ involvement and maternal inheritance should prompt consideration of a mitochondrial disorder. Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) and maternally inherited diabetes and deafness (MIDD) are the most common mitochondrial diabetes disorders caused by a mutation in m.3243A G in 80% of cases. Metformin should be avoided due to the risk of lactic acidosis. There is more rapid progression to insulin therapy and higher prevalence of diabetic complications compared to type 2 diabetes. Diagnosis of a mitochondrial disorder leads to family screening, education and surveillance for future complications. Superior mesenteric artery syndrome, an uncommon but important cause of intestinal pseudo-obstruction in cases of significant weight loss, has been reported in MELAS patients.
Publisher: Wiley
Date: 2016
DOI: 10.1111/IMJ.12913
Abstract: Demand for inpatient beds is increasing whilst supply is diminishing. General medical services are feeling this demand as the ageing population presents more patients with undifferentiated illness traditionally cared for by this service. Redesign efforts need to focus on improving the quality and speed of decision-making to utilise resources efficiently. The aim of this study was to improve patient flow through general medical services by undertaking a comprehensive redesign process targeting each stage of the patient journey. We utilised a rapid improvement event to identify waste and design a new model of care (MOC) that eliminated as much waste as possible. The model had three main elements: (i) ward-based teams (ii) 7-day per week standard work and (iii) pull systems to operate for all transfers and referrals. Here, we analyse the first 12 months of the new MOC with regard to key outcomes: length of stay, occupancy, weekend discharges, clinical incidents and Medical Emergency Team (MET) calls, emergency department length of stay and National Emergency Access Target (NEAT) performance and elective surgical throughput. The new MOC resulted in a 0.88-day reduction in length of stay. This resulted in reduced general medical bed occupancy of 19 beds. Weekend discharges improved by 54.6%. There were no significant increases in serious clinical incidents or MET calls. Emergency department admitted NEAT performance improved also. Redesign of the general medicine model of care eliminating waste has resulted in a significant improvement in patient flow and reduced length of stay without compromising quality of care.
Publisher: Wiley
Date: 04-11-2001
Publisher: Wiley
Date: 10-1994
DOI: 10.1111/J.1365-2265.1994.TB02576.X
Abstract: Follistatin (FS/FSH-suppressing protein/activin-binding protein) is a single-chain glycoprotein, structurally distinct from inhibin, that has been shown to have inhibin-like activity in suppressing FSH secretion both in vivo and in vitro. The aim of these studies was to develop and validate a radioimmunoassay (RIA) for FS in human serum, and to describe the physiological variations of serum FS in humans. Serum was collected from normal men, and normal women in the follicular and luteal phases of the menstrual cycle. Clinical s les were also collected from male patients with hypogonadism, post-menopausal women and pregnant women in the first, second and third trimesters. A RIA for FS in human serum was developed using antisera raised against purified bovine FS and using bovine FS as tracer and standard. Serial dilutions of serum were non-parallel to purified bovine FS standard in the RIA. The addition of sodium dodecyl sulphate (SDS 0.05%) to the assay buffer resolved the non-parallelism suggesting that the interference of serum in the RIA was an assay matrix effect. To characterize the serum FS immunoactivity further, serum was fractionated by gel filtration on Sephadex G-100. At neutral pH, FS immunoactivity eluted as a major peak in the molecular weight range > 200 kDa. In 0.1 M HCl, a second peak of FS immunoactivity eluted in the molecular weight range 30-60 kDa consistent with the known sizes of FS. This suggested that FS was dissociating from a larger complex. Fractions taken from the low molecular weight region diluted in parallel with bovine FS in contrast with fractions from the high molecular weight region which were non-parallel. It is concluded that the non-parallelism of human serum in the FS RIA is due to the binding of serum FS to an unknown high molecular weight factor. This interference is eliminated by the inclusion of 0.05% SDS in the assay buffer. The RIA in 0.05% SDS has been applied to the description of the normal and pathophysiological variations of FS in human serum. There were no significant differences between FS levels in serum from hypogonadal men, normal women in the follicular phase of the menstrual cycle, post-menopausal women and pregnant women from the first, second and third trimesters. FS levels in serum of women in the luteal phase of the menstrual cycle were significantly lower than all other groups. FS levels in normal men were significantly higher than those in both luteal phase women and women in the first trimester of pregnancy (P < 0.05). These findings argue against a role for circulating follistatin in the control of gonadotrophin secretion and suggest that the gonads and/or conceptus are not the primary source of follistatin immunoactivity in serum. The lower follistatin levels in the luteal phase of the menstrual cycle remain unexplained.
Publisher: Wiley
Date: 04-2016
DOI: 10.1111/IMJ.13035
Publisher: Cambridge University Press (CUP)
Date: 02-2003
DOI: 10.1375/136905203762687870
Abstract: Dizygotic twinning in humans is influenced by genetic factors suggesting inherited variation affects follicle development and predisposes to double ovulations. In a previous study, we conducted a detailed examination of follicle development and variation in hormone concentrations during the menstrual cycle in mothers of DZ twins (MODZT) compared with an age-matched control group of mothers of singletons. We did not detect differences in FSH concentrations between mothers of twins and mothers of singletons. Serum inhibin concentrations were measured by a radioimmunoassay that did not distinguish between dimeric inhibin A and B forms and free inhibin alpha subunit. We therefore analyzed the s les from this study with specific assays to determine whether concentrations of inhibin A and B were different between MODZT and controls and therefore contribute to the twinning phenotype. There were no significant differences between MODZT with single ovulations and control women in inhibin A and B concentrations during the cycle, including the critical period for the selection of the dominant follicle. These data suggest that the genetic cause of twinning is not associated with changes in FSH concentrations or recognised feedback mechanisms regulating FSH release.
Publisher: Wiley
Date: 09-2014
DOI: 10.5694/MJA13.00104
Abstract: To determine the prevalence of diabetes in inpatients in Melbourne hospitals. Point prevalence survey of all inpatients in each hospital on a single day between 30 November 2010 and 22 November 2012. 11 hospitals in metropolitan Melbourne including community, secondary and tertiary hospitals and one aged care and rehabilitation centre. 2308 adult inpatients in all wards apart from intensive care, emergency, obstetrics and psychiatry. Point prevalence of self-reported diabetes, details of current medication, self-reported frequency of complications. Diabetes status was obtained in 2273 of 2308 inpatients (98.5%). Of these, 562 (24.7%) had diabetes (95% CI, 22.9%-26.5%). Diabetes prevalence ranged from 15.7% to 35.1% in different hospitals (P < 0.001). Patients with diabetes were older, heavier and more likely to be taking lipid-lowering, antihypertensive and blood-thinning medications. Of 388 patients with complete medication information, 270 (69.6%) were taking oral hypoglycaemic agents alone or in combination with insulin, 158 (40.7%) were treated with insulin (67 [17.3%] with insulin alone) and 51 (13.1%) were not taking medication for diabetes. The frequency of diabetes complications was very high: 207/290 (71.4%) for any microvascular complication, 275/527 (52.2%) for any macrovascular complication and 227/276 (82.2%) for any complication. The high burden of diabetes in Melbourne hospital inpatients has major implications for patient health and health care expenditure. Optimising care of these high-risk patients has the potential to decrease inpatient morbidity and length of stay as well as preventing or delaying future complications. A formal Australian national audit of inpatient diabetes would determine its true prevalence and consequences, allowing rational planning to deal with shortcomings in its management.
Publisher: Mary Ann Liebert Inc
Date: 06-2014
Abstract: Nuclear receptors (NRs) play a key role in endocrine signaling and metabolism and are important therapeutic targets in a number of hormone-dependent malignancies. Studies on the role of NRs in thyroid cancer are limited. The objective of the study was to examine systematically the expression of the 48 human NRs in a series of benign and malignant thyroid tissues. Within the papillary carcinoma cohort, we sought to determine if NR expression differed significantly by BRAF mutation status. RNA was isolated from multinodular goiter (MNG n=6), papillary carcinoma (PTC, n=14), follicular carcinoma (FC n=5), and Hürthle cell carcinoma (HCC n=7). The 48 human NRs were profiled in this panel by quantitative real time polymerase chain reaction. Protein expression for selected NRs (Rev-erbα and LXR-β) was examined by immunohistochemistry (IHC) on tissue microarrays comprising benign and malignant thyroid tissues. Across all groups of benign and malignant thyroid tissue, there was prominent expression of LXR-β and ROR-γ. Key findings in PTC were marked overexpression of RXR-γ and Rev-erbα compared to MNG. Within the PTC cohort, when BRAF(V600E) tumors were compared with wild type BRAF, there was relative upregulation of RXR-γ and Rev-erbα and downregulation of AR, ERR-γ, and ROR-γ. In FC, EAR-2 was overexpressed, while PPAR-α and PPAR-δ were underexpressed compared to MNG. The NR expression profile of HCC was distinct, characterized by significant downregulation of a wide range of NRs. IHC for Rev-erbα and LXR-β localized protein expression to the tumor cells. Moderate to strong Rev-erbα immunostaining was seen in 22 out of 23 PTC, and, overall, staining was stronger than in the benign group. These results represent the first systematic examination of NR expression in thyroid cancer. Our finding of tumor-specific patterns of NR expression, as well as significant differences in NR expression between BRAF(V600E) and wild type BRAF PTC, provides a basis for further mechanistic studies and highlights potential novel therapeutic targets for this malignancy.
Publisher: Wiley
Date: 12-03-2020
DOI: 10.1111/DOM.14010
Publisher: Wiley
Date: 24-09-2007
DOI: 10.1111/J.1445-5994.2007.01503.X
Abstract: The aim of this study was to examine current fracture prevention strategies through the recognition, investigation and treatment of osteoporosis in patients presenting to acute hospitals with minimal-trauma fracture. A retrospective audit using a standardized database was conducted in 16 Australian hospitals. This involved 1829 cases of minimal-trauma fracture initially presenting to hospital emergency departments during 2003-2005. Cases of minimal-trauma fracture were retrospectively identified using diagnosis-related group fracture codes and case record review at each site. Relevant data were entered into a standardized database and analysed centrally and independently. Risk factors for osteoporosis, investigations, interventions and discharge follow up were recorded. The percentage of minimal-trauma fracture patients who underwent investigation or initiated therapy designed to prevent subsequent minimal-trauma fracture was obtained. Less than 13% of patients presenting to hospital with minimal-trauma fractures had risk factors for fracture identified. Ten per cent were appropriately investigated, 12% were commenced on calcium and 12% on vitamin D. Eight per cent started bisphosphonates and 1% selective oestrogens receptor modulators in the acute setting. Most patients presenting to Australian hospitals with minimal-trauma fracture are neither investigated nor treated for osteoporosis. As this group is at high risk of subsequent fracture, this is a missed opportunity to reduce fracture burden.
Publisher: Wiley
Date: 2010
DOI: 10.1111/J.1445-2197.2009.05173.X
Abstract: Background: Thyroid nodules are common, but only a small proportion harbour malignancy. Despite this, the frequency of thyroid cancer is on the increase and thyroid malignancy is the most common endocrine malignancy. Preoperative diagnosis is based on ultrasound and radionucleotide imaging as well as the fine‐needle aspiration biopsy (FNAB). These biopsies yield a large proportion of indeterminate results due to inadequate material for cytological diagnosis, or due to the cytological similarity of FAs and follicular carcinomas. Recent advances in the understanding of the molecular pathogenesis of thyroid malignancy have led to the detection of characteristic genetic alterations in FNABs. This technology has the potential to increase the specificity of this test, combining cytological with genetic testing to reduce the number of indeterminate results, thereby reducing the number of thyroidectomies performed for benign disease. Methods: This review examines the evidence for the presence of the common genetic alterations in thyroid cancer and outlines the pathological and clinical correlations of these mutations. The practicality and utility of measuring these genetic alterations in FNAB specimens is also outlined as well as the potential for these tests to alter primary management and follow‐up of patients with nodular thyroid disease. Conclusion: It is likely that a combination of molecular testing and cytological examination of FNAB specimens will prove to be the most efficient and specific method of diagnosing thyroid cancer preoperatively.
Publisher: Springer Science and Business Media LLC
Date: 04-08-2021
DOI: 10.1038/S41598-021-94178-5
Abstract: This study investigated the diagnostic performance, feasibility, and end-user experiences of an artificial intelligence (AI)-assisted diabetic retinopathy (DR) screening model in real-world Australian healthcare settings. The study consisted of two components: (1) DR screening of patients using an AI-assisted system and (2) in-depth interviews with health professionals involved in implementing screening. Participants with type 1 or type 2 diabetes mellitus attending two endocrinology outpatient and three Aboriginal Medical Services clinics between March 2018 and May 2019 were invited to a prospective observational study. A single 45-degree (macula centred), non-stereoscopic, colour retinal image was taken of each eye from participants and were instantly screened for referable DR using a custom offline automated AI system. A total of 236 participants, including 174 from endocrinology and 62 from Aboriginal Medical Services clinics, provided informed consent and 203 (86.0%) were included in the analysis. A total of 33 consenting participants (14%) were excluded from the primary analysis due to ungradable or missing images from small pupils (n = 21, 63.6%), cataract (n = 7, 21.2%), poor fixation (n = 2, 6.1%), technical issues (n = 2, 6.1%), and corneal scarring (n = 1, 3%). The area under the curve, sensitivity, and specificity of the AI system for referable DR were 0.92, 96.9% and 87.7%, respectively. There were 51 disagreements between the reference standard and index test diagnoses, including 29 which were manually graded as ungradable, 21 false positives, and one false negative. A total of 28 participants (11.9%) were referred for follow-up based on new ocular findings, among whom, 15 (53.6%) were able to be contacted and 9 (60%) adhered to referral. Of 207 participants who completed a satisfaction questionnaire, 93.7% specified they were either satisfied or extremely satisfied, and 93.2% specified they would be likely or extremely likely to use this service again. Clinical staff involved in screening most frequently noted that the AI system was easy to use, and the real-time diagnostic report was useful. Our study indicates that AI-assisted DR screening model is accurate and well-accepted by patients and clinicians in endocrinology and indigenous healthcare settings. Future deployments of AI-assisted screening models would require consideration of downstream referral pathways.
Publisher: JMIR Publications Inc.
Date: 02-07-2021
Abstract: ype 2 diabetes (T2D) is increasingly prevalent in society, in part because of behavioral issues, with sedentary behavior, reduced exercise, and the consumption of foods with a high glycemic index being major contributors. There is evidence for the efficacy of mobile apps in promoting behavior change and lifestyle improvements in people with T2D. Many mobile phone apps help to monitor the condition of people with T2D and inform them about their health. Some of these digital interventions involve patients using apps on their own or in conjunction with health care professionals. his study aimed to test the acceptability of receiving app-based, daily physician feedback for patients with T2D that is informed by the continuous monitoring of their activity, food choices, and glucose profiles, with the aim of encouraging healthier behavior. The i GLOOK! /i app was designed and developed by an academic research team and pilot-tested at an Australian public hospital. total of 15 patients diagnosed with T2D wore a glucose monitor and an Apple Watch for 12 days. The uploaded data were integrated into the i GLOOK! /i app on the patients’ smartphones, which also enabled the recording of activity and consumed food. A physician provided daily feedback to each in idual through the app based on their data from each of the 12 days. At the beginning and end of the study, data were collected on vital signs, anthropometry, hemoglobin A sub c /sub level, fructosamine level, and fasting lipids level. Participants were also interviewed at the beginning and end of the study to assess the acceptability of the intervention and its potential impact on promoting positive behavior change. ver the 12 days of the study, there was a significant reduction of 0.22% ( i P /i =.004) in hemoglobin A sub c /sub level. There were favorable changes in fructosamine and lipid fractions however, none reached significance. There was also a fall of 0.65 kg in body weight and falls in blood pressure and pulse rate that did not reach significance. Patient feedback on the i GLOOK! /i system was positive. Of the 15 participants, 13 (87%) were enthusiastic about continuing to use the app system if some usability and reliability aspects were improved. All participants regarded the personalized physician feedback as supportive and helpful in understanding their own health behavior. Of the 15 participants, 4 (27%) felt that using the system encouraged long-term behavior changes. mobile app system that provides people with T2D daily, physician-generated, personalized feedback can produce favorable changes in glycemic and cardiovascular risk parameters—even in the short term—and encourage better self-management of their condition. Study participants found the experience of using the mobile app system acceptable and were motivated to establish longer-term lifestyle improvements through behavior changes. >
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 12-1994
DOI: 10.1016/0378-5122(94)90017-5
Abstract: In order to evaluate the role of single photon absorptiometry (SPA) in the prediction of osteoporotic fracture risk, 1935 women, referred for measurement of forearm mineral density (FMD) at the distal radial site, were studied by questionnaire in a cross-sectional design. There was no significant decline in FMD until the age of 47, after which there was a linear decline with age of about 1.2% per year. There was no relationship between age and FMD, or forearm mineral content (FMC), in premenopausal women. There was a fall in FMD with the number of years since menopause, after correcting for the effects of age, of approximately 0.5% per year. Body weight was positively correlated with FMC in postmenopausal women. The duration of exposure to hormone replacement therapy (HRT) was positively correlated with FMD, and the magnitude of this effect was reduced the longer the delay between the onset of the menopause and the commencement of HRT. There was no significant association of FMD with calcium intake, weight-bearing exercise, tobacco or alcohol consumption, or family history of osteoporosis. FMD was significantly lower in postmenopausal women who reported fractures after the age of 25, after correcting for age and years postmenopause. In conclusion, a low FMD is predictive of a past history of fractures and may therefore be capable of predicting future fracture risk.
Publisher: The Endocrine Society
Date: 04-1996
DOI: 10.1210/JCEM.81.4.8636367
Abstract: Dizygotic twinning is familial, suggesting that there may be an inherited abnormality of the control of ovulation that predisposes to double ovulation and, therefore, dizygotic twins. The present study examines 17 mothers of dizygotic twins (MODZT) and 8 control mothers of singletons by daily blood s ling throughout an entire menstrual cycle. Blood s les were assayed for LH, FSH, estradiol, progesterone, and inhibin. The process of follicular development was followed by transvaginal ultrasound. The pituitary LH response to iv GnRH was also assessed. Three of the 16 MODZT double ovulated during the study compared to none of the 8 control mothers (P < 0.05). The number of small follicles (<6 mm) declined significantly in control women at midcycle, but not in MODZT. There was no significant difference in serum FSH, LH, estradiol, or inhibin levels between the 2 groups at any stage of the menstrual cycle. During the follicular phase, serum progesterone levels were significantly higher in MODZT. The response to GnRH stimulation was not different between MODZT and controls. In conclusion, this study demonstrates an increased tendency to double ovulate in MODZT that may be due to a reduced rate of atresia in advanced follicles. Furthermore, the elevated progesterone levels in MODZT during the follicular phase suggest altered intrafollicular steroidogenesis that is independent of gonadotropins.
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Springer Science and Business Media LLC
Date: 09-2006
DOI: 10.1007/S00223-006-0314-X
Abstract: Beta-thalassaemia major is associated with low bone mass and fractures. We conducted a 2 year randomized controlled trial of zoledronic acid 4 mg administered intravenously every 3 months or placebo in the treatment of beta-thalassaemia-associated osteopenla. We recruited 23 subjects from 2 university hospitals with a T score of less than -1.0 at either the lumbar spine or hip, and 23 subjects completed the study (17 M, 6 F). Treatment groups did not differ significantly with respect to bone mineral density (BMD), age, height, weight and body mass index (BMI) at baseline. BMD was assessed at baseline, 12 months and 24 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral reek, total hip and total body. After two years average lumbar spine BMD was 8.9% greater (95%CI 2.3-15.5%, P = 0.011), average femoral neck BMD was 9.1% greater (95%CI 5.5-12.7%, P < 0.0001), average total hip BMD was 9.6% greater (95%CI 6.5-12.6%, P < 0.0001) and average total body BMD was 4.7% greater (95%CI 2.7-6.8%, P < 0.0001) in the treated group compared to placebo. The absolute change in BMD from baseline to 2 years and the annualized rate of change of BMD was significantly greater in treated patients at all four sites. Age, gender, height, weight and BMI did not interact with the effect of treatment and so unadjusted data was used. The serum total ALP decreased 45% by 12 months (P = 0.004) and urinary deoxypyridinoline/creatinine ratio decreased 47% by 3 months (NS). We conclude that zoledronic acid (4 mg i.v. 3 monthly) suppresses bone turnover and increases BMD in beta-thalassaemia-associated osteopenia.
Publisher: Mary Ann Liebert Inc
Date: 08-2015
Abstract: Population-based studies have demonstrated an association of single nucleotide polymorphisms close to the thyroid transcription factor forkhead box E1 (FOXE1) gene with thyroid cancer. The dysregulation of forkhead proteins is increasingly recognized to play a role in the development and progression of cancer. The objective of the study was to seek to identify novel mutations in FOXE1 in papillary thyroid cancer (PTC) and to assess the effect of these mutations on protein expression and transcriptional function on FOXE1 responsive promoters. The study was conducted at two tertiary referral hospitals. The coding region of FOXE1 was sequenced in tissue-derived DNA or RNA from 120 patients with PTC and 110 patients with multinodular goiter (MNG). In vitro studies were performed to examine the protein expression and transcriptional function of FOXE1 mutants. A molecular model of the forkhead domain (FHD) of FOXE1 was generated using the SWISS-MODEL online server with the three-dimensional structure of FOXD3 as a template. Three somatic missense mutations were detected in PTC resulting in the amino acid substitutions P54Q, K95Q, and L112F. One additional mutation was detected in a MNG (G140R). In vitro studies demonstrated marked impairment in transcriptional activation by all four FOXE1 mutants, which was not explained by differences in protein expression. Molecular modeling localized three of the mutations to highly conserved regions of the FHD. We have identified novel somatic mutations of FOXE1 in PTC. Mutational inactivation of FOXE1 is an uncommon event in thyroid tumors but may contribute to thyroid carcinogenesis and dedifferentiation in concert with other oncogenic drivers.
Publisher: Springer Science and Business Media LLC
Date: 11-07-2018
DOI: 10.1007/S00125-018-4677-0
Abstract: This multicentre randomised double-blind placebo-controlled clinical trial assessed the efficacy and safety of a methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib, in in iduals with obesity (BMI ≥30 kg/m Participants were randomised (via a centralised interactive web response system) to placebo, 1.2 or 1.8 mg beloranib s.c. twice weekly for 26 weeks. Participants, investigators and the sponsor were blinded to group assignment. The primary endpoint was the change in weight from baseline to week 26. The trial was terminated early when beloranib development was stopped because of an imbalance of venous thromboembolism events in beloranib-treated in iduals vs placebo that became evident during late-stage development of the drug. In total, 153 participants were randomised, 51 to placebo, 52 to 1.2 mg beloranib and 50 to 1.8 mg beloranib. In participants who completed week 26, the least squares mean ± SE weight change (baseline 111 kg) was -3.1 ± 1.2% with placebo (n = 22) vs -13.5 ± 1.1% and -12.7 ± 1.3% with 1.2 and 1.8 mg beloranib, respectively (n = 25 n = 19 p < 0.0001). The change in HbA MetAP2 inhibitors represent a novel mechanism for producing meaningful weight loss and improvement in HbA ClinicalTrials.gov NCT02324491 FUNDING: The study was funded by Zafgen, Inc.
Publisher: Massachusetts Medical Society
Date: 05-08-2021
No related grants have been discovered for Christopher Gilfillan.