ORCID Profile
0000-0003-1131-020X
Current Organisations
QIMR Berghofer Medical Research Institute
,
Royal Brisbane and Women's Hospital
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Publications
Public perceptions of changing the terminology for low-risk thyroid cancer: A qualitative focus group study
Publisher: BMJ
Date: 02-2019
DOI: 10.1136/BMJOPEN-2018-025820
Abstract: To investigate public perceptions of overdiagnosis and overtreatment in low-risk thyroid cancer and explore opinions regarding the proposed strategy to change the terminology of low-risk cancers. Qualitative study using focus groups that included a guided group discussion and presentation explaining thyroid cancer, overdiagnosis and overtreatment, and proposed communication strategies. Transcripts were analysed thematically. Sydney, Australia. Forty-seven men and women of various ages from a range of socioeconomic backgrounds with no personal history of thyroid cancer. Participants had low pre-existing general awareness of concepts of overdiagnosis and overtreatment and expressed concern regarding this new information in relation to thyroid cancer. Overall, participants understood why the strategy to change the terminology was being proposed and could see potential benefits including reducing the negative psychological impact and stigma associated with the term ‘cancer’ however, many still had reservations about the strategy. The majority of the concerns were around their worry about the risk of further disease progression and that changing the terminology may create confusion and cause patients not to take the diagnosis and its associated managements seriously. Despite varied views towards the proposed strategy, there was a strong overarching desire for greater patient and public education around overdiagnosis and overtreatment in both thyroid cancer and cancer generally in order to complement any revised terminology and/or other mitigation strategies. We found a strong and apparently widely held desire for more information surrounding the topic of overdiagnosis and overtreatment. Careful consideration of how to inform both the public and current patients about the implications of a change in terminology, including changes to patients’ follow-up or treatments, would be needed if such a change were to go ahead.
Variation in Rates of Autoimmune Thyroid Disease by Race/Ethnicity in US Military Personnel
Publisher: American Medical Association (AMA)
Date: 16-04-2014
Controversies in primary treatment of low-risk papillary thyroid cancer
Publisher: Elsevier BV
Date: 03-2013
Understanding Pathways to the Diagnosis of Thyroid Cancer: Are There Ways We Can Reduce Over-Diagnosis?
Publisher: Mary Ann Liebert Inc
Date: 15-03-2019
Race/ethnicity and the prevalence of thyrotoxicosis in young Americans
Publisher: Mary Ann Liebert Inc
Date: 06-2015
Abstract: Race/ethnicity may be a newly recognized risk factor for Graves' disease. The aim of this study was to examine the prevalence of thyrotoxicosis by race/ethnicity in Americans aged 12-49 years using three National Health and Nutritional Examination Surveys (NHANES). Data were analyzed from 17,939 participants in NHANES III (1988-1994), NHANES 1999-2002, and NHANES 2007-2010 with available thyroid function test results. Thyrotoxicosis was defined as a serum thyrotropin (TSH) of ≤0.1 mIU/L or subjects taking methimazole or propylthiouracil, and overt thyrotoxicosis was defined as high serum thyroxine and a serum TSH of ≤0.1 mIU/L. Logistic regression was performed accounting for the complex s ling design of NHANES, and the results from all three NHANES surveys were combined using a random-effects model. There were 75 study participants with point prevalent thyrotoxicosis, representing a pooled prevalence of 0.4% for Americans aged 12-49 years. Prevalent thyrotoxicosis was nearly three times more likely in non-Hispanic black subjects compared with non-Hispanic whites (OR=2.9 [CI 1.5-5.7]), while there was no difference between the prevalence of thyrotoxicosis in Mexican Americans compared to non-Hispanic whites (OR=1.2 [CI 0.6-2.4] I2 for heterogeneity=0% for both). Among 27 patients with overt thyrotoxicosis, the odds ratio was 8.7 [CI 0.7-112.6] for non-Hispanic blacks and 4.6 [CI 0.4-59.3] for Mexican Americans compared with non-Hispanic whites. The results suggest there are race/ethnicity differences in the prevalence of thyrotoxicosis. Future studies should address whether these differences are due to heritable factors, environmental exposures, or a combination of both.
The effect of vitamin D supplementation on acute respiratory tract infection in older Australian adults: an analysis of data from the D-Health Trial
Publisher: Elsevier BV
Date: 02-2021
The incidence and prevalence of thyroid autoimmunity
Publisher: Springer Science and Business Media LLC
Date: 29-05-2012
DOI: 10.1007/S12020-012-9703-2
Abstract: The thyroid gland is the most common organ affected by autoimmune disease. Other autoimmune diseases, most notably type 1 diabetes mellitus, are increasing in incidence. It is unknown whether autoimmune thyroid diseases are following the same pattern. This review summarizes studies of autoimmune thyroid disease incidence and prevalence since 1950, not only for these measures of occurrences, but also for commenting on identified risk factors for thyroid autoimmunity. We find that incidence of autoimmune thyroid disease is currently higher than in historic series although the studies are so variable in design, patient population, disease definition, and laboratory methods that it is impossible to tell whether this difference is real. Further research is required to assess the possibility of changing disease patterns of autoimmune thyroid disease as opposed to simple changes in diagnostic thresholds.
Thyrotropin and Thyroid Cancer Diagnosis: A Systematic Review and Dose-Response Meta-Analysis
Publisher: The Endocrine Society
Date: 08-2012
DOI: 10.1210/JC.2012-1083
Abstract: TSH is the major growth factor for thyrocytes and may have a causative role in thyroid cancer. The objective of the study was to systematically assess the association between serum TSH and thyroid cancer. The MEDLINE and EMBASE databases were searched using synonyms for TSH and thyroid cancer, supplemented with reference list searches and author contact. Prospective cohort, case-control, and cross-sectional studies were identified with TSH the exposure and thyroid cancer the outcome. Three reviewers independently extracted data. Studies reporting odds ratio (OR) for TSH levels and thyroid cancer were analyzed via meta-analysis and generalized least-squares trend estimation for dose-response relationships. Data extracted from 28 studies included a total of 42,032 subjects and 5,786 thyroid cancer cases. Dose-response spline analysis revealed a nonlinear relationship (P < 0.001). For TSH levels less than 1 mU/liter, the OR for thyroid cancer was 1.72 (1.42, 2.07) per milliunits per liter. However, the relationship changed for TSH levels 1 mU/liter and greater, with the OR thereafter being 1.16 (1.12, 1.21) per milliunits per liter. Studies controlling for autoimmunity reported the lowest OR [TSH below 2.5 mU/liter, OR 1.23 (1.02-1.47) per milliunits per liter TSH 2.5 mU/liter or greater, OR 0.98 (0.89-1.09) per milliunits per liter]. Six groups assessed serum TSH in relation to markers of poor thyroid cancer prognosis, with three showing significant positive relationships. Higher serum TSH concentration is associated with an increased risk of thyroid cancer. Thyroid autoimmunity may partially explain the association, but further epidemiological assessment is required. Future clinical research should investigate the validity of including serum TSH in diagnostic nomograms, its prognostic importance, and the potential for therapeutic TSH suppression in thyroid cancer prevention.
Subclinical hypothyroidism and related biochemical entities in pregnancy: implications and management.
Publisher: SAGE Publications
Date: 12-2010
Abstract: Subclinical hypothyroidism (SCH), thyroid autoimmunity and isolated maternal hypothyroxinaemia are diagnoses made on laboratory findings. The two former conditions are commonly identified in the general population, while the term isolated maternal hypothyroxinaemia was developed to highlight potential neurodevelopmental risks in progeny. Each entity has been associated with either obstetric, perinatal and/or child developmental harm in observational studies, although few interventional trials have been performed to guide diagnostic and therapeutic approaches. Once diagnosed, treatment of SCH is recommended by endocrine groups to limit potential risk, given that harm from appropriate therapy is unlikely. Screening for thyroid disorders in pregnancy has traditionally been controversial. Definitive trials are expected to report over coming years and updated consensus guidelines will hopefully resolve this issue.
Autoimmune thyroid disease: A novel risk factor for atherosclerosis?
Publisher: Springer Science and Business Media LLC
Date: 12-04-2013
Off-label use of recombinant factor VIIa in two tertiary hospitals in Queensland
Publisher: Wiley
Date: 09-11-2012
DOI: 10.1111/ANS.12005
Abstract: Recombinant factor VIIa (rFVIIa) is used for many off-label indications without high quality evidence to support its efficacy. The aim of this study was to determine indications for use of off-label rFVIIa, efficacy and safety, and adherence to institutional guidelines. We performed a retrospective review of off-label rFVIIa at two tertiary hospitals from 2007 to 2010. One hundred forty-five administrations were identified and analysed. Haemorrhage associated with cardiac surgery made up one-third of all rFVIIa usage, with trauma (20%) and other surgery (11%) the next most frequent indications. Compared with all others, cardiac surgery patients were older (60.0 years versus 47.4 years, P < 0.001) and had lower pre-rFVIIa transfusion requirements, a higher subjective response rate (88% versus 46%, P < 0.001) and lower mortality rates (6.1% versus 33%, P < 0.001), but higher rates of arterial thrombormbolic events (16.7% versus 2.1%, P = 0.002). Most patients received only one or two doses (n = 137 95%), with no subject receiving a third or subsequent dose having an appreciable reduction in bleeding. Only a small number of patients (n = 15 10.3%) had rFVIIa administered in accordance with our institutions' guidelines. Patients administered rFVIIa for haemorrhage not associated with cardiac surgery were severely unwell. Despite lack of evidence, administration of rFVIIa may be justified by the high mortality rate, but more than two doses are unlikely to provide further benefit. The high rate of arterial thromboembolism in cardiac surgical patients raises risk-benefit considerations. Adherence to our institutions' guidelines was poor.
Vitamin D and Sun Exposure: A Community Survey in Australia
Publisher: MDPI AG
Date: 18-02-2023
DOI: 10.3390/CURRONCOL30020188
Abstract: Sun exposure carries both harms and benefits. Exposing the skin to the sun is the main modifiable cause of skin cancers, which exert a considerable health and economic burden in Australia. The most well-established benefit of exposure to ultraviolet (UV) radiation is vitamin D production. Australia has the highest incidence of skin cancer in the world but, despite the high ambient UV radiation, approximately one quarter of the population is estimated to be vitamin D deficient. Balancing the risks and benefits is challenging and requires effective communication. We sought to provide a snapshot of public knowledge and attitudes regarding sun exposure and vitamin D and to examine the associations between these factors and sun protective behaviors. In 2020 we administered an online survey 4824 participants with self-reported fair or medium skin color were included in this analysis. Only 25% and 34% of participants were able to identify the amount of time outdoors needed to maintain adequate vitamin D status in summer and winter, respectively and 25% were concerned that sunscreen use inhibits vitamin D synthesis. This lack of knowledge was associated with suboptimal sun protection practices. Public education is warranted to prevent over-exposure, while supporting natural vitamin D production.
PTHrP-Mediated Hypercalcemia: Causes and Survival in 138 Patients
Publisher: The Endocrine Society
Date: 05-2015
DOI: 10.1210/JC.2014-4250
Abstract: Hypercalcemia is a common complication of cancer with PTHrP an important mediator. Literature on the underlying causes of PTHrP-mediated hypercalcemia, in both malignant and benign conditions, is limited to small case series and case reports. The purpose of this study was to systematically identify a large series of cases of PTHrP-mediated hypercalcemia and to document differences in demographics and the clinical course between malignant and benign etiologies. This was a hospital-based, retrospective case series that identified subjects from 1999 to 2010 from the public hospital system in Queensland, Australia. Included subjects were 18 years and older and had persistent hypercalcemia with simultaneously elevated PTHrP. A total of 138 cases were identified. Solid organ malignancies made up 82.6% (n = 114) of cases, with squamous cell carcinoma (28.2% of total) and adenocarcinomas (27.5%) almost equally as common. Hematological malignancy and benign conditions made up 8.7% (n = 12) each. Squamous cell carcinoma of the lung was the single most commonly identified etiology (10.9%). Causes not previously identified included myxoid sarcoma, plasma cell leukemia, duodenal adenocarcinoma, metastatic Merkel cell carcinoma, and epithelioid hemangioendothelioma. Median survival was different among the groups (52 days [interquartile range, 21-132 days] for solid organ malignancy, 362 days [18-652 days] for hematological malignancy, and 906 days [16 days to undefined] for the apparently benign group P < .0001). There were no differences in PTHrP among the groups. Although the mean corrected calcium level was lower in the benign group (3.03 mmol/L [2.80-3.29 mmol/L]) compared with that in the solid organ (3.11 mmol/L [2.89-3.46 mmol/L]) and hematological malignancy groups (3.60 mmol/L [3.01-3.79 mmol/L]) groups (P = .046), it was not a useful discriminator of etiology. PTHrP-mediated hypercalcemia is most frequently caused by solid organ malignancy, and it portends a poor prognosis. Although the solid organ malignancy group had the shortest survival, the hematological malignancy and apparently benign causes groups still had relatively short overall survival.
Obesity Is Associated with BRAFV600E-Mutated Thyroid Cancer
Publisher: Mary Ann Liebert Inc
Date: 10-2020
The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality
Publisher: Elsevier BV
Date: 02-2022
State-of-the-art review on the time-dependent behaviour of composite steel-concrete beams
Publisher: International Association for Bridge and Structural Engineering (IABSE)
Date: 2021
DOI: 10.2749/SED018.CH4
Abstract: This chapter provides an overview of the work carried out to date on the long-term behaviour of composite steel-concrete beams. In the first part of the chapter, a description of the components forming a composite member is presented. This is followed by an outline of the main kinematic concepts, such as full and partial shear interaction, that influence the structural response of this form of construction due to the flexibility of the shear connection provided between the concrete and steel components. The review of the work performed on the time-dependent behaviour of concrete and its influence on the long-term structural response of composite beams for building and bridge applications is then presented. The modelling and experimental work considered in the review highlights the importance of considering concrete time effects, when predicting the in-service response of composite beams.
Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis
Publisher: Mary Ann Liebert Inc
Date: 10-2015
Predicting deseasonalised serum 25 hydroxy vitamin D concentrations in the D-Health Trial: an analysis using boosted regression trees
Publisher: Cold Spring Harbor Laboratory
Date: 25-08-2020
DOI: 10.1101/2020.08.23.20180422
Abstract: The D-Health Trial aims to determine whether monthly high-dose vitamin D supplementation can reduce the mortality rate and prevent cancer. We did not have adequate statistical power for subgroup analyses, so could not justify the high cost of collecting blood s les at baseline. To enable future exploratory analyses stratified by baseline vitamin D status, we developed a model to predict baseline serum 25 hydroxy vitamin D [25(OH)D] concentration. We used data and serum 25(OH)D concentrations from participants who gave a blood s le during the trial for compliance monitoring and were randomised to placebo. Data were partitioned into training (80%) and validation (20%) datasets. Deseasonalised serum 25(OH)D concentrations were dichotomised using cut-points of 50 nmol/L, 60 nmol/L and 75 nmol/L. We fitted boosted regression tree models, based on 13 predictors, and evaluated model performance using the validation data. The training and validation datasets had 1788 (10.5% nmol/L, 23.1% nmol, 48.8 nmol/L) and 447 (11.9% nmol/L, 25.7% nmol/L, and 49.2% nmol/L) s les, respectively. Ambient UV radiation and total intake of vitamin D were the strongest predictors of ‘low’ serum 25(OH)D concentration. The area under the receiver operating characteristic curves were 0.71, 0.70, and 0.66 for cut-points of nmol/L, nmol/L and nmol/L respectively. We exploited compliance monitoring data to develop models to predict serum 25(OH)D concentration for D-Health participants at baseline. This approach may prove useful in other trial settings where there is an obstacle to exhaustive data collection.
Progress towards improving initial risk stratification for patients with papillary thyroid cancer
Publisher: Wiley
Date: 03-02-2020
DOI: 10.1111/CEN.14163
Vitamin D Supplementation and Antibiotic Use in Older Australian Adults: An Analysis of Data From the D-Health Trial
Publisher: Oxford University Press (OUP)
Date: 03-07-2022
Abstract: Vitamin D supplementation may reduce the risk or severity of infection, but this has been investigated in few large population-based trials. We analyzed data from the D-Health Trial, using prescription of antibiotics as a surrogate for infection. The D-Health Trial is a randomized, double-blind, placebo-controlled trial in which 21 315 Australians aged 60–84 years were randomized to 60 000 IU of supplementary vitamin D3 or placebo monthly for 5 years. For this analysis, the primary outcome was the number of antibiotic prescription episodes secondary outcomes were total number of prescriptions, repeat prescription episodes, and antibiotics for urinary tract infection. We estimated incidence rate ratios (IRRs) using negative binomial regression, and odds ratios using logistic regression. Vitamin D supplementation slightly reduced the number of prescription episodes (IRR, 0.98 95% confidence interval [CI], .95–1.01), total prescriptions (IRR, 0.97 95% CI, .93–1.00), and repeat prescription episodes (IRR, 0.96 95% CI, .93–1.00). There was stronger evidence of benefit in people predicted to have insufficient vitamin D at baseline (prescription episodes IRR, 0.93 95% CI, .87–.99). Vitamin D may reduce the number of antibiotic prescriptions, particularly in people with low vitamin D status. This supports the hypothesis that vitamin D has a clinically relevant effect on the immune system. Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. www.anzctr.org.au/.
The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.CCT.2016.04.005
Abstract: Vitamin D, specifically serum 25(OH)D has been associated with mortality, cancer and multiple other health endpoints in observational studies, but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population-wide supplementation. We have therefore launched the D-Health Trial, a randomized trial of vitamin D supplementation for prevention of mortality and cancer. Here we report the methods and describe the trial cohort. The D-Health Trial is a randomized placebo-controlled trial, with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers. Participants aged 65-84years were recruited from the general population of Australia. The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo. The primary outcome is all-cause mortality. Secondary outcomes are total cancer incidence and colorectal cancer incidence. We recruited 21,315 participants to the trial between February 2014 and May 2015. The participants in the two arms of the trial were well-balanced at baseline. Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health, to be current smokers or to have diabetes than the Australian population. However, the proportion overweight or with health conditions such as arthritis and angina was similar. Observational data cannot be considered sufficient to support interventions delivered at a population level. Large-scale randomized trials such as the D-Health Trial are needed to inform public health policy and practice.
Pre-existing Thyroid Autoimmunity and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study of US Active-Duty Personnel
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-08-2022
DOI: 10.1200/JCO.21.02618
Abstract: Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies. We conducted a case-control study nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date. We also assessed whether diagnosis of thyroid autoimmunity mediated any associations identified and if thyroid cancer features differed by autoimmunity status. Among 451 incident cases of papillary thyroid cancer and matched controls (median age 36 years, 61.4% men), TPO antibody positivity ( v negative) 7-10 years prediagnosis was associated with thyroid cancer (odds ratio [OR] 1.90 [95% CI, 1.33 to 2.70]). Exploratory analyses suggested an increasing risk of thyroid cancer with higher TPO antibody titer (TPO antibody 550-1,399 IU/mL: OR 2.95 [95% CI, 1.37 to 6.36] and ≥ 1,400 IU/mL: OR 3.91 [95% CI, 1.66 to 9.24]). Positive TPO antibody status remained associated with thyroid cancer after those with diagnosed autoimmunity were excluded, and the association was not mediated by diagnosis of thyroid autoimmunity. Among the cases with diagnosed autoimmunity, 58% thyroid cancers were ≤ 10 mm diameter. Longstanding prior thyroid autoimmunity up to 10 years before thyroid cancer diagnosis was associated with papillary thyroid cancer risk. The results could not be fully explained by diagnosis of thyroid autoimmunity although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage.
Routine screening for vitamin D deficiency in early pregnancy
Publisher: AMPCo
Date: 10-2011
DOI: 10.5694/MJA11.10469
Withholding Radioactive Iodine for Lower-Risk Papillary Thyroid Cancers Is Safe, but Delays the Certainty of Treatment Response
Publisher: Mary Ann Liebert Inc
Date: 03-2021
Nicotine binds to the transthyretin-thyroxine complex and reduces its uptake by placental trophoblasts
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.MCE.2022.111642
Abstract: A supply of maternal thyroid hormone (thyroxine, T4) is essential for normal human fetal development. Human placental trophoblasts synthesize, secrete and take up the T4 binding protein transthyretin, providing a route for maternal T4 to enter the placenta. Transthyretin is also involved in T4 transport in other tissues such as the brain choroid plexus. Nicotine alters transthyretin synthesis and function in rat choroid plexus. If nicotine influences trophoblast turnover of transthyretin, then it may directly affect placental transfer of T4 to the developing fetus and contribute to the negative impacts of smoking on fetal growth, development and placental function. The effect of nicotine on trophoblast uptake of Alexa-labelled transthyretin was measured using live cell imaging. The effect of nicotine on protein expression was measured by western blotting. Interactions between transthyretin, T4 and nicotine were investigated using chemical cross-linking techniques and molecular dynamic simulations. Nicotine blocks uptake of transthyretin-T4 by human placental trophoblast cells. Nicotine reduces the expression of the trophoblast scavenger receptor class B type 1 (SR-B1) that plays a role in transthyretin-T4 uptake. Molecular dynamic modelling suggests that when T4 is bound to transthyretin, nicotine binding increases tetramer stability, reducing the ability of the transthyretin-T4 complex to enter trophoblast cells. Our data suggest that nicotine exposure during pregnancy reduces transplacental transport of transthyretin and T4 to the placenta and developing fetus. This may contribute to the negative effects of smoking on fetal growth, development and pregnancy viability.
Health-Related Quality of Life after Diagnosis and Treatment of Differentiated Thyroid Cancer and Association with Type of Surgical Treatment
Publisher: American Medical Association (AMA)
Date: 03-2019
Cancer Risk and Its Dose-Response Association with Radioactive Iodine Treatment for Hyperthyroidism
Publisher: Mary Ann Liebert Inc
Date: 04-01-2022
Immune reconstitution inflammatory syndrome manifesting as development of multiple autoimmune disorders and skin cancer progression
Publisher: Wiley
Date: 09-2011
DOI: 10.1111/J.1445-5994.2011.02546.X
Abstract: We report the case of a 56-year-old man with the rare autoimmune pathologies of alternating hypothyroidism and hyperthyroidism due to thyroid-stimulating hormone receptor antibodies, and rheumatoid arthritis as manifestations of a human immunodeficiency virus-related immune reconstitution inflammatory syndrome. The patient also developed overt progression of a pre-existing skin malignancy that may also be related. This case highlights immune reconstitution syndrome as an important differential diagnosis following antiretroviral therapy commencement, and that a high index of suspicion should be maintained for this rare but important cluster of conditions. Furthermore, the patient's genetic predisposition to autoimmunity provides helpful insights into the pathogenesis of these disorders.
Cigarette smoking and estrogen-related cancer—letter
Publisher: American Association for Cancer Research (AACR)
Date: 10-2021
Calcitriol-Mediated Hypercalcemia: Causes and Course in 101 Patients
Publisher: The Endocrine Society
Date: 10-2013
DOI: 10.1210/JC.2013-2016
Abstract: Hypercalcemia mediated by 1,25-dihydroxy vitamin D (calcitriol) is uncommon, with evidence on etiology limited to small case series or case reports. The objective of the study was to systematically identify a large series of cases of calcitriol-mediated hypercalcemia and document the presentation, demographics, and clinical course across etiologies. The study was a hospital-based, retrospective case series, identifying subjects from 1999 through 2009 across the public hospital system in Queensland, Australia. All patients aged over 18 years were identified that had persistent hypercalcemia associated with elevated or inappropriately normal calcitriol concentration or elevated serum angiotensin-converting enzyme. A total of 101 cases were identified. Sarcoidosis was the most common etiology (49%), followed by hematological malignancy (17%) and infections (8%). Etiologies not previously described include squamous cell carcinoma of the tongue, ovarian cystadenocarcinoma, and chronic lymphocytic leukemia. Median serum angiotensin-converting enzyme was higher in sarcoid patients compared with all other causes [218 U/L (176–277) vs 155 U/L (110–208), P & .001], but a level above the normal range did not discriminate well between cases of sarcoidosis and other causes (specificity at cutoff of 130 U/L was only 31%). However, a value greater than 250 U/L was highly specific (89%) for sarcoidosis but lacked sensitivity (31%). A calcitriol level greater than 300 pmol/L was not seen in sarcoidosis but was seen with other etiologies. Cases with neoplastic etiologies were older (61.4 ± 11.4 y) than all other subjects (51.7 ± 15.0 y, P = .006). Hypercalcemia mediated by calcitriol remains a rare presentation. In almost half the cases, sarcoidosis was the underlying cause, whereas a third of patients had cancer or systemic infections.
Predicting deseasonalised serum 25 hydroxy vitamin D concentrations in the D-Health Trial: An analysis using boosted regression trees
Publisher: Elsevier BV
Date: 05-2021
Development of a fasting blood glucose-based strategy to diagnose women with gestational diabetes mellitus at increased risk of adverse outcomes in a COVID-19 environment
Publisher: Public Library of Science (PLoS)
Date: 03-12-2020
DOI: 10.1371/JOURNAL.PONE.0243192
Abstract: To evaluate the role of fasting blood glucose (FBG) to minimise the use of the oral glucose tolerance test in pregnancy (POGTT) for the diagnosis of gestational diabetes mellitus (GDM). We analysed the POGTTs of 26,242 pregnant women in Queensland, Australia, performed between 1 January 2015 and 30 June 2015. A receiver operator characteristics (ROC) assessment was undertaken to indicate the FBG level that most effectively identified women at low risk of an abnormal result. There were 3,946 (15.0%) patients having GDM with 2,262 (8.6%) having FBG ≥ 5.1mmol/l. The ROC identified FBG levels .6mmol/l having the best specificity (77%) and sensitivity (54%) for elevated 1 and/or 2hr BGLs. There were 19,321 (73.7%) women having FBG 4.7mmol/l with a prevalence of GDM of 4.0%, less than 1/3 rd the overall rate. Only 4,638 (17.7%) women having FBGs from 4.7–5.0mmol/l would require further evaluation to confirm or exclude the diagnosis. This contemporary study of women across the state of Queensland, Australia suggests the FBG can be used effectively to define glucose tolerance in pregnancy, minimising their contact with pathology laboratories and potential exposure to the corona virus. This analysis, used in conjunction with outcome data from the HAPO study, provides reassurance to women and their health professionals that FBG 4.7mmol/l has both a low rate of abnormal glucose tolerance and minimal adverse pregnancy-associated complications.
Contemporary Debates in Adult Papillary Thyroid Cancer Management
Publisher: The Endocrine Society
Date: 19-07-2019
Abstract: An ever-increasing population of patients with papillary thyroid cancer is engaging with health care systems around the world. Numerous questions about optimal management have arisen that challenge conventional paradigms. This is particularly the case for patients with low-risk disease, who comprise most new patients. At the same time, new therapies for patients with advanced disease are also being introduced, which may have the potential to prolong life. This review discusses selected controversial issues in adult papillary thyroid cancer management at both ends of the disease spectrum. These topics include: (i) the role of active surveillance for small papillary cancers (ii) the extent of surgery in low-risk disease (lobectomy vs total thyroidectomy) (iii) the role of postoperative remnant ablation with radioiodine (iv) optimal follow-up strategies in patients, especially those who have only undergone lobectomy and (v) new therapies for advanced disease. Although our current management is h ered by the lack of large randomized controlled trials, we are fortunate that data from ongoing trials will be available within the next few years. This information should provide additional evidence that will decrease morbidity in low-risk patients and improve outcomes in those with distant metastatic disease.
Optimal Differentiated Thyroid Cancer Management in the Elderly
Publisher: Springer Science and Business Media LLC
Date: 04-2015
DOI: 10.1007/S40266-015-0256-Y
Abstract: The incidence of differentiated thyroid cancer is increasing worldwide across all age groups. While most patients with differentiated thyroid cancer have a good prognosis, aggressive disease is more common in the elderly and disease-specific mortality is higher. Treatment options for differentiated thyroid cancer include surgery, levothyroxine, radioactive iodine, external beam radiotherapy and kinase inhibitors. Rational and evidence-based management is particularly important in older in iduals because they may experience greater toxicities from the therapeutic options. We advocate an explicit risk-benefit analytic approach to thyroid cancer care that emphasises in idual patient factors, likely disease biology and progression, and age-dependent treatment characteristics to ensure optimal treatment. In particular, this risk-benefit approach should seek to identify patients with aggressive disease, and, within a multidisciplinary setting, balance the likelihood of treatment success with the probability of treatment-related adverse effects.
A randomized placebo-controlled trial of vitamin D supplementation for reduction of mortality and cancer: Statistical analysis plan for the D-Health Trial
Publisher: Elsevier BV
Date: 06-2019
The effect of monthly vitamin D supplementation on fractures: a tertiary outcome from the population-based, double-blind, randomised, placebo-controlled D-Health trial
Publisher: Elsevier BV
Date: 05-2023
Transthyretin binds soluble endoglin and increases its uptake by hepatocytes: A possible role for transthyretin in preeclampsia?
Publisher: Elsevier BV
Date: 02-2023
Can one point-of-care glucose meter be used for all pediatric and adult hospital patients? Evaluation of three meters, including recently modified test strips
Publisher: Mary Ann Liebert Inc
Date: 2011
Abstract: within hospitals, bedside blood glucose measurements are widely used for investigating suspected hyper- or hypoglycemia, monitoring diabetes, and adjusting glucose-lowering medication. Numerous point-of-care glucose meters are available, but for large hospitals using the same meter in all settings has practical and economic advantages. This investigation sought to identify a meter that was accurate, precise, and free from interferences, making it suitable for use across all ages and diseases. lithium-heparinized whole blood was analyzed, under various conditions, on the HemoCue Glucose 201 (Hemocue AB, Ängelhom, Sweden), Accu-Chek Performa (Roche Diagnostics, Basel Switzerland) (using the newly reformulated maltose-insensitive strips), and Optium (Abbott Diabetes, Alameda, CA, USA) glucose meters and compared with plasma glucose measurements on the Vitros 5,1 FS analyzer (Ortho Clinical Diagnostics, Neckargemund, Germany). biases of 3.2%, -5.8%, and -8% were found with Accu-Chek, Optium, and HemoCue, respectively. Within-run imprecision was 2.5-5.8%. Between-run imprecision was 3.1-6.8%, with the Accu-Chek performing best. All meters measured to 1.3 mmol/L with acceptable precision (coefficient of variation, <14%). Varying hematocrits between 0.2 and 0.7 L/L affected results of all meters. Interference at clinically relevant concentrations of galactose and possibly maltose was demonstrated with the Accu-Chek. all three meters are sufficiently accurate and precise for in-hospital use. Because of possible interference by galactosemia or high hematocrit, the Accu-Chek is not the safest option for neonatal use. Patients receiving high doses of maltose in therapeutic infusions may still be at risk of being falsely classified as euglycemic or hyperglycemic with the reformulated Accu-Chek strips, and clinical evaluation of these strips in patients receiving maltose-containing infusions is urgently needed.
Teprotumumab Improves the Clinical Course of Thyroid Eye Disease Across Multiple Subgroups of Patients with Durable Responses
Publisher: Mary Ann Liebert Inc
Date: 07-2021
Papillary thyroid cancer with microscopic extra-thyroidal extension
Publisher: Springer International Publishing
Date: 16-12-2020
Competing Risks of Death in Aging Individuals with Thyroid Cancer
Publisher: Mary Ann Liebert Inc
Date: 06-2021
The effect of vitamin D supplementation on risk of keratinocyte cancer: an exploratory analysis of the D-Health randomized controlled trial
Publisher: Oxford University Press (OUP)
Date: 11-2022
DOI: 10.1111/BJD.21742
Abstract: Vitamin D may play a role in prevention of keratinocyte cancer (KC), but observational studies examining the association between serum 25-hydroxy vitamin D concentration and KC are largely uninformative because sun exposure causes both KC and vitamin D production. There is scant evidence from clinical trials of supplementary vitamin D. To examine the effect of vitamin D supplementation on the risk of developing KC. We used data from the D-Health Trial, a randomized placebo-controlled trial of vitamin D supplementation (60 000 international units monthly for 5 years) among Australians aged ≥60 years. KC outcomes were captured through linkage to a national administrative dataset for those who consented (N = 20 334 95%). We used negative binomial regression to analyse the incidence of KC excisions and the incidence of actinic lesions treated using cryotherapy or serial curettage, and flexible parametric survival models for analysis of time to first KC excision. Randomization to vitamin D supplementation did not reduce the incidence of KC lesions treated by excision [incidence rate ratio (IRR) 1·04 95% confidence interval (CI) 0·98–1·11], the incidence of actinic lesions treated using other methods (IRR 1·01 95% CI 0·95–1·08) or time to first histologically confirmed KC excision (hazard ratio 1·02 95% CI 0·97–1·08). However, in subgroup analysis vitamin D increased the incidence of KC excisions in adults aged ≥ 70 years (IRR 1·13, 95% CI 1·04–1·23 P-value for interaction = 0·01). Vitamin D supplementation did not reduce the incidence of KC or other actinic lesions. What is already known about this topic? Laboratory studies have suggested possible protective effects of vitamin D on skin cancer.Observational studies investigating the association between vitamin D and risk of keratinocyte cancer are largely uninformative as ultraviolet radiation both causes skin cancer and is the primary source of vitamin D.The evidence from randomized controlled trials of vitamin D is limited and inconclusive. What does this study add? This population-based, randomized controlled trial suggests that supplementing older adults with a high monthly dose of vitamin D for 5 years does not affect the incidence of keratinocyte cancer.
Increasing thyroid cancer incidence in Queensland, Australia 1982-2008 - True increase or overdiagnosis
Publisher: Wiley
Date: 17-02-2016
DOI: 10.1111/CEN.12724
Abstract: Thyroid cancer incidence has been increasing worldwide. Some suggest greater ascertainment of indolent tumours is the only driver, but others suggest there has been a true increase. Increases in Australia appear to have been among the largest in the world, so we investigated incidence trends in the Australian state of Queensland to help understand reasons for the rise. Thyroid cancers diagnoses in Queensland 1982-2008 were ascertained from the Queensland Cancer Registry. We calculated age-standardized incidence rates (ASR) and used Poisson regression to estimate annual percentage change (APC) in thyroid cancer incidence by socio-demographic and tumour-related factors. Thyroid cancer ASR in Queensland increased from 2·2 to 10·6/100 000 between 1982 and 2008 equating to an APC of 5·5% [95% confidence interval (CI) 4·7-6·4] in men and 6·1% (95% CI 5·5-6·6) in women. The rise was evident, and did not significantly differ, across socio-economic and remoteness-of-residence categories. The largest increase seen was in the papillary subtype in women (APC 7·9%, 95% CI 7·3-8·5). Incidence of localized and more advanced-stage cancers rose over time although the increase was greater for early-stage cancers. There has been a marked increase in thyroid cancer incidence in Queensland. The increase is evident in men and women across all adult age groups, socio-economic strata and remoteness-of-residence categories as well as in localized and more advanced-stage cancers. Our results suggest 'overdiagnosis' may not entirely explain rising incidence. Contemporary aetiological data and in idual-level information about diagnostic circumstances are required to further understand reasons for rising thyroid cancer incidence.
Thyroid Dysfunction from Treatments for Solid Organ Cancers
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.ECL.2021.12.006
Abstract: In recent years, cancer care has been transformed by immune-based and targeted treatments. Although these treatments are effective against various solid organ malignancies, multiple adverse effects can occur, including thyroid dysfunction. In this review, the authors consider treatments for solid organ cancers that affect the thyroid, focusing on immune checkpoint inhibitors, kinase inhibitors, and radioactive iodine-conjugated treatments (I-131-metaiodobenzylguanidine). They discuss the mechanisms causing thyroid dysfunction, provide a framework for their diagnosis and management, and explore the association of thyroid dysfunction from these agents with patient survival.
Methodological considerations in D-health cancer mortality results – Authors' reply
Publisher: Elsevier BV
Date: 05-2022
Tobacco smoking and risk of thyroid cancer according to BRAF
Publisher: Wiley
Date: 04-07-2021
DOI: 10.1111/CEN.14545
Abstract: Smoking has been associated with a reduced risk of thyroid cancer, but whether the association varies between higher- and lower-risk cancers remains unclear. We aimed to assess the association between smoking and risk of thyroid cancer overall as well as by tumour BRAF mutational status as a marker of potentially higher-risk cancer. We recruited 1013 people diagnosed with thyroid cancer and 1057 population controls frequency-matched on age and sex. Multivariable logistic regression was used to assess the association overall and in analyses stratified by tumour characteristics. We used sensitivity analysis to assess the potential for selection bias. We found little evidence of an association with current smoking (odds ratio [OR] = 0.93 95% confidence interval [CI]: 0.69-1.26 current vs. never smoking), but a higher number of pack-years of smoking was associated with a lower risk of thyroid cancer (OR = 0.75 95% CI: 0.57-0.99 ≥20 pack-years vs. never). However, after correcting for potential selection bias, we observed a statistically significant inverse association between current smoking and risk of thyroid cancer (bias-corrected OR = 0.65 95% CI: 0.51-0.83). Those with BRAF-positive cancers were less likely to be current smokers than those with BRAF-negative cancers (prevalence ratio: 0.79 95% CI: 0.62-0.99). We found smoking was inversely related to thyroid cancer risk and, in particular, current smoking was associated with a reduced risk of potentially more aggressive BRAF-positive than the likely more indolent BRAF-negative papillary thyroid cancers.
Risk of thyroid cancer following hysterectomy
Publisher: Elsevier BV
Date: 06-2021
Vitamin D supplementation and cognition—Results from analyses of the D-Health trial
Publisher: Wiley
Date: 30-01-2023
DOI: 10.1111/JGS.18247
Abstract: Observational studies have consistently found a link between low serum 25‐hydroxyvitamin D concentration and higher risk of cognitive impairment. Results from randomized controlled trials have been mixed, and few have been conducted in the general population. We recruited 21,315 community‐dwelling Australians aged between 60 and 84 years to participate in the D‐Health Trial, a randomized, double‐blind, placebo‐controlled trial. The intervention was monthly oral doses of 60,000 international units of vitamin D or placebo for 5 years. We assessed cognitive function in a randomly s led group of participants aged ≥70 years using the Telephone Interview for Cognitive Status (TICS) at 2 and 5 years after randomization. The primary outcome for this analysis was TICS score the secondary outcome was the proportion of people who had cognitive impairment (defined as TICS score ≤25). We analyzed data using mixed models (linear and logistic). We interviewed 3887 participants at year 2 and 3614 participants at year 5. The mean TICS score at these time points was 32.3 and 32.2, respectively. Vitamin D supplementation did not affect cognitive function as measured by TICS score (mean difference between vitamin D and placebo groups 0.04 95% CI −0.14 to 0.23), or alter risk of cognitive impairment (odds ratio 1.00 95% CI 0.75 to 1.33). Monthly bolus doses of vitamin D supplementation neither enhanced nor hindered cognitive function among older adults. Population‐wide vitamin D supplementation of older adults that are largely vitamin D replete is unlikely to substantially benefit cognition.
Role of Serum Thyroid Antibody Status in Predicting Checkpoint Inhibitor–Associated Thyroid Immune-Related Adverse Events
Publisher: Mary Ann Liebert Inc
Date: 07-2022
Adoptive Cell Therapy Using Genetically Engineered T Cells to Target CEA, Calcitonin, and RET M918T in Medullary Thyroid Cancer Cells
Publisher: Mary Ann Liebert Inc
Date: 09-2022
Histoplasmosis in Australia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2011
The epidemiology of amyloidosis in Australia.
Publisher: Informa UK Limited
Date: 29-03-2019
The effect of vitamin D supplementation on pain: An analysis of data from the D-Health randomised controlled trial
Publisher: Cambridge University Press (CUP)
Date: 25-11-2023
DOI: 10.1017/S0007114522003567
Abstract: Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial). 21 315 participants (aged 60–84 years) were randomly assigned to a monthly dose of 60 000 IU vitamin D 3 or matching placebo. Pain was measured using the six-item Pain Impact Questionnaire (PIQ-6), administered 1, 2 and 5 years after enrolment. We used regression models (linear for continuous PIQ-6 score and log-binomial for binary categorisations of the score, namely ‘some or more pain impact’ and ‘presence of any bodily pain’) to estimate the effect of vitamin D on pain. We included 20 423 participants who completed ≥1 PIQ-6. In blood s les collected from 3943 randomly selected participants (∼800 per year), the mean ( sd ) 25(OH)D concentrations were 77 ( sd 25) and 115 ( sd 30) nmol/l in the placebo and vitamin D groups, respectively. Most (76 %) participants were predicted to have 25(OH)D concentration nmol/l at baseline. The mean PIQ-6 was similar in all surveys (∼50·4). The adjusted mean difference in PIQ-6 score (vitamin D cf placebo) was 0·02 (95 % CI (−0·20, 0·25)). The proportion of participants with some or more pain impact and with the presence of bodily pain was also similar between groups (both prevalence ratios 1·01, 95 % CI (0·99, 1·03)). In conclusion, supplementation with 60 000 IU of vitamin D 3 /month had negligible effect on bodily pain.
Associations of serum vitamin D concentrations with obstetric glucose metabolism in a subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study cohort
Publisher: Wiley
Date: 15-07-2012
DOI: 10.1111/J.1464-5491.2011.03551.X
Abstract: To assess associations between maternal serum vitamin D concentration and glucose metabolism in a cohort of pregnant women living in an Australian subtropical environment. Cross-sectional assessment of 25-hydroxy vitamin D concentrations in 399 Hyperglycemia and Adverse Pregnancy Outcome ancillary study participants, treated at an obstetric teaching hospital in Brisbane, Australia. All patients underwent a blinded 75-g oral glucose tolerance test at 24-32 (target 28) weeks' gestation. The mean (± standard deviation) fasting plasma glucose was 4.5 ± 0.4 mmol/l. Mean (± standard deviation) serum 25-hydroxy vitamin D was 132.5 ± 44.0 nmol/l. A difference of one standard deviation in maternal 25-hydroxy vitamin D was inversely related to fasting glucose (fasting glucose lower by 0.047 mmol/l, P=0.012) when assessed with multiple linear regression after adjusting for confounders. Maternal 25-hydroxy vitamin D correlated with β-cell function as estimated by the log-transformed homeostasis model assessment-β-cell function equation (r=0.131, P=0.009), but not with the homeostasis model assessment of insulin resistance. An association between mid-gestational 25-hydroxy vitamin D and fasting glucose was confirmed in a largely normoglycaemic and vitamin D-replete pregnant population. The correlation between 25-hydroxy vitamin D and β-cell function suggests that vitamin D may influence glucose metabolism through this mechanism. Intervention studies are required to determine causality and the role of vitamin D replacement in deficient in iduals.
Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo-controlled D-Health Trial
Publisher: Wiley
Date: 08-2021
DOI: 10.1002/JCSM.12759
Abstract: Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high‐dose vitamin D supplementation reduces risk and incidence of falls. We used data from the randomized, double‐blind, placebo‐controlled D‐Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60–84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking IU/day supplementary vitamin D were ineligible. Each year, we collected blood s les from ~450 randomly s led participants from each trial arm and measured 25‐hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3‐month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random s les of participants (surveys, n = 16 000 diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention‐to‐treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763) registered 4 July 2013. Mean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively approximately half were randomized to vitamin D (surveys: 50.1% diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95–1.10). There was an interaction with body mass index (BMI) ( P ‐interaction = 0.001) vitamin D increased risk in participants with BMI 25 kg/m 2 (OR 1.25, 95% CI 1.09–1.43), but there was no effect in those with BMI ≥ 25 kg/m 2 (OR 0.95, 95% CI 0.87–1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups. Monthly high‐dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.
Vitamin D Supplementation and the Incidence of Cataract Surgery in Older Australian Adults
Publisher: Elsevier BV
Date: 03-2023
DOI: 10.1016/J.OPHTHA.2022.09.015
Abstract: Observational studies suggest that higher serum 25-hydroxyvitamin D concentration may be associated with lower risk of cataract. However, no randomized controlled trials (RCTs) have assessed the effect of vitamin D supplementation on the incidence of cataract. We aimed to assess whether vitamin D supplementation reduces the incidence of cataract surgery. We conducted an ancillary study of D-Health Trial, a randomized, double-masked, placebo-controlled trial of monthly vitamin D for the prevention of all-cause mortality conducted from 2014 to 2020 within the Australian general population. We invited 421,207 men and women aged 60-84 years to participate including an additional 1,896 volunteers, 40,824 expressed interest. Those with hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia or sarcoidosis, or who were taking >500 international units (IU) supplemental vitamin D per day were excluded. 21,315 people were randomized. 1,390 participants did not fulfil the eligibility criteria for this analysis (linked data available, no cataract within first 6 months) leaving 19,925 included. The median follow-up was 5 years. . 60,000 IU of vitamin D The primary outcome for this analysis was the first surgical treatment for cataract, ascertained through linkage to universal health insurance records and hospital data. Among 19,925 participants eligible for the analysis of incident cataract (mean age 69.3 years, 46% women) 3,668 (18.4%) underwent cataract surgery during follow-up (n=1,841 (18.5%) of the vitamin D group and n=1,827 (18.3%) of the placebo group). The incidence of cataract surgery was similar between the two groups (incidence rate 41.6 and 41.1 per 1,000 person-years in the vitamin D and placebo groups, respectively hazard ratio 1.02 95% CI 0.95 to 1.09). In pre-specified subgroup analyses, the effect of vitamin D supplementation on the incidence of cataract surgery was not modified by age, sex, body mass index, predicted serum 25-hydroxyvitamin D concentration, or ambient ultraviolet radiation. Routinely supplementing older adults who live in an area with a low prevalence of vitamin D deficiency with high-dose vitamin D is unlikely to reduce the need for cataract surgery.
Clival prolactinoma masquerading as a chordoma: a case report
Publisher: Elsevier BV
Date: 06-2021
Cost-utility analysis comparing radioactive iodine, anti-Thyroid drugs and total thyroidectomy for primary treatment of Graves' disease
Publisher: Oxford University Press (OUP)
Date: 12-2016
DOI: 10.1530/EJE-16-0527
Abstract: Little data is in existence about the most cost-effective primary treatment for Graves’ disease. We performed a cost–utility analysis comparing radioactive iodine (RAI), anti-thyroid drugs (ATD) and total thyroidectomy (TT) as first-line therapy for Graves’ disease in England and Australia. We used a Markov model to compare lifetime costs and benefits (quality-adjusted life-years (QALYs)). The model included efficacy, rates of relapse and major complications associated with each treatment, and alternative second-line therapies. Model parameters were obtained from published literature. One-way sensitivity analyses were conducted. Costs were presented in 2015£ or Australian Dollars (AUD). RAI was the least expensive therapy in both England (£5425 QALYs 34.73) and Australia (AUD5601 30.97 QALYs). In base case results, in both countries, ATD was a cost-effective alternative to RAI (£16 866 35.17 QALYs incremental cost-effectiveness ratio (ICER) £26 279 per QALY gained England AUD8924 31.37 QALYs ICER AUD9687 per QALY gained Australia), while RAI dominated TT (£7115 QALYs 33.93 England AUD15 668 30.25 QALYs Australia). In sensitivity analysis, base case results were stable to changes in most cost, transition probabilities and health-relative quality-of-life (HRQoL) weights however, in England, the results were sensitive to changes in the HRQoL weights of hypothyroidism and euthyroidism on ATD. In this analysis, RAI is the least expensive choice for first-line treatment strategy for Graves’ disease. In England and Australia, ATD is likely to be a cost-effective alternative, while TT is unlikely to be cost-effective. Further research into HRQoL in Graves’ disease could improve the quality of future studies.
Clinical guidance for radioiodine refractory differentiated thyroid cancer
Publisher: Wiley
Date: 24-11-2017
DOI: 10.1111/CEN.13508
Abstract: Prognosis from differentiated thyroid cancer is worse when the disease becomes refractory to radioiodine. Until recently, treatment options have been limited to local therapies such as surgery and radiotherapy, but the recent availability of systemic therapies now provides some potential for disease control. Multitargeted kinase inhibitors (TKIs) including lenvatinib and sorafenib have been shown to improve progression-free survival in phase III clinical trials, but are also associated with a spectrum of adverse effects. Other TKIs have been utilized as "redifferentiation" agents, increasing sodium iodide symporter expression in metastases and thus restoring radioiodine avidity. Some patients whose disease progresses on initial TKI therapy will still respond to a different TKI and clinical trials currently in progress will clarify the best options for such patients. As these drugs are not inexpensive, care needs to be taken to minimize not only biological but also financial toxicity. In this review, we examine the basic biology of radioiodine refractory disease and discuss optimal treatment approaches, with specific focus on choice and timing of TKI treatment. This clinical field remains fluid, and directions for future research include exploring biomarkers and considering adjuvant TKI use in certain patient groups.
Erratum: The incidence and prevalence of thyroid autoimmunity (Endocrine DOI: 10.1007/s12020-012-9703-2)
Publisher: Springer Science and Business Media LLC
Date: 28-08-2013
Effect of vitamin D supplementation on depression in older Australian adults
Publisher: Wiley
Date: 03-12-2023
DOI: 10.1002/GPS.5847
Abstract: To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use. We used data from the D‐Health Trial ( N = 21,315), a randomized double‐blind placebo‐controlled trial of monthly vitamin D 3 for the prevention of all‐cause mortality. Participants were Australians aged 60–84 years. Participants completed the Patient Health Questionnaire (PHQ–9) at 1, 2 and 5 years after randomization to measure depressive symptoms national prescribing records were used to capture antidepressant use. We used mixed models and survival models. Analyses of PHQ‐9 scores included 20,487 participants (mean age 69·3 years, 46% women) the mean difference (MD) in PHQ‐9 score (vitamin D vs. placebo) was 0·02 (95% CI −0·06, 0·11). There was negligible difference in the prevalence of clinically relevant depression (PHQ‐9 score ≥10) (odds ratio 0·99 95% CI 0·90, 1·08). We included 16,670 participants in the analyses of incident antidepressant use (mean age 69·4 years, 43% women). Incidence of antidepressant use was similar between the groups (hazard ratio [HR] 1·04 95% CI 0·96, 1·12). In subgroup analyses, vitamin D improved PHQ‐9 scores in those taking antidepressants at baseline (MD −0·25 95% CI −0·49, −0·01 p‐interaction = 0·02). It decreased risk of antidepressant use in participants with predicted 25(OH)D concentration nmol/L (HR 0·88 95% CI 0·75, 1·02 p‐interaction = 0·01) and increased risk in those with predicted 25(OH) D ≥ 50 nmol/L (HR 1·10 95% CI 1·01, 1·20). Monthly supplementation with high‐dose vitamin D 3 was not of benefit for measures of depression overall, but there was some evidence of benefit in subgroup analyses. The trial is registered on the Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. www.anzctr.org.au/ .
A papillary thyroid cancer with minimal extra-thyroidal extension
Publisher: Springer International Publishing
Date: 2016
Thyrotropin in the development and management of differentiated thyroid cancer
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.ECL.2014.02.012
Abstract: Thyrotropin (TSH) is the major regulator and growth factor of the thyroid. TSH may be important in the development of human thyroid cancer, with both suggestive animal models and clinical evidence, although definitive proof is still required. Applications for TSH in thyroid cancer management include TSH stimulation of radioiodine uptake, enhancement of biochemical monitoring through thyroglobulin measurement, and long-term suppression of TSH with supraphysiologic levothyroxine. This review synthesizes current knowledge of TSH in both the development and management of differentiated thyroid cancer.
Prognosis of Differentiated Thyroid Cancer in Relation to Serum Thyrotropin and Thyroglobulin Antibody Status at Time of Diagnosis
Publisher: Mary Ann Liebert Inc
Date: 2014
Terminology Change for Small Low-Risk Papillary Thyroid Cancer As a Response to Overtreatment: Results from Three Australian Community Juries
Publisher: Mary Ann Liebert Inc
Date: 07-2021
Vitamin D supplementation and hospitalization for infection in older adults: A post-hoc analysis of data from the Australian D-Health Trial
Publisher: Elsevier BV
Date: 02-2023
K1-70 — A Thyrotropin Receptor Antagonist with Therapeutic Potential in Graves' Disease, Thyroid Eye Disease, and Differentiated Thyroid Cancer
Publisher: Mary Ann Liebert Inc
Date: 10-2021
Prevalence of “Higher-Risk” Adverse Histological Features Found at Autopsy in Patients with Occult Differentiated Thyroid Cancer
Publisher: Mary Ann Liebert Inc
Date: 03-2022
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