ORCID Profile
0000-0002-3246-6281
Current Organisations
University of New South Wales
,
University of Technology Sydney
,
King's College London
,
UNSW Sydney
,
Tâm Anh Research Institute
,
University of Westminster
,
University of Notre Dame Australia
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Publications
Discordance between quantitative ultrasound and dual-energy X-ray absorptiometry in bone mineral density: The Vietnam Osteoporosis Study
Publisher: Elsevier BV
Date: 03-2021
A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer
Publisher: The Endocrine Society
Date: 19-06-2021
Abstract: Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT. A 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL. 42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs −0.7 (−1.5 to 0.2) nmol/L P & 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ −0.4 (−0.9 to −0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (−0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g P & 0.02] and lean mass [∆ 0.8 (−0.1 to 1.7) kg P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels. LTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women.
Hip Fracture and Mortality: A Loss of Life Expectancy Interpretation
Publisher: Wiley
Date: 27-06-2021
DOI: 10.1002/JBMR.4385
Teaching open and reproducible scholarship: a critical review of the evidence base for current pedagogical methods and their outcomes
Publisher: The Royal Society
Date: 05-2023
DOI: 10.1098/RSOS.221255
Abstract: In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (i) students' scientific literacies (i.e. students’ understanding of open research, consumption of science and the development of transferable skills) (ii) student engagement (i.e. motivation and engagement with learning, collaboration and engagement in open research) and (iii) students' attitudes towards science (i.e. trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship.
A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly
Publisher: Wiley
Date: 30-07-2020
DOI: 10.1002/JBMR.4100
Toward the era of precision fracture risk assessment
Publisher: The Endocrine Society
Date: 21-04-2020
BONEcheck: A digital tool for personalized bone health assessment
Publisher: Elsevier BV
Date: 09-2023
‘Skeletal Age’ for mapping the impact of fracture on mortality
Publisher: eLife Sciences Publications, Ltd
Date: 16-05-2023
DOI: 10.7554/ELIFE.83888
Abstract: Fragility fracture is associated with an increased risk of mortality, but mortality is not part of doctor-patient communication. Here, we introduce a new concept called ‘Skeletal Age’ as the age of an in idual’s skeleton resulting from a fragility fracture to convey the combined risk of fracture and fracture-associated mortality for an in idual. We used the Danish National Hospital Discharge Register which includes the whole-country data of 1,667,339 adults in Denmark born on or before January 1, 1950, who were followed up to December 31, 2016 for incident low-trauma fracture and mortality. Skeletal age is defined as the sum of chronological age and the number of years of life lost (YLL) associated with a fracture. Cox’s proportional hazards model was employed to determine the hazard of mortality associated with a specific fracture for a given risk profile, and the hazard was then transformed into YLL using the Gompertz law of mortality. During the median follow-up period of 16 years, there had been 307,870 fractures and 122,744 post-fracture deaths. A fracture was associated with between 1 and 7 years of life lost, with the loss being greater in men than women. Hip fractures incurred the greatest loss of life years. For instance, a 60-year-old in idual with a hip fracture is estimated to have a skeletal age of 66 for men and 65 for women. Skeletal Age was estimated for each age and fracture site stratified by gender. We propose ‘Skeletal Age’ as a new metric to assess the impact of a fragility fracture on an in idual’s life expectancy. This approach will enhance doctor-patient risk communication about the risks associated with osteoporosis. National Health and Medical Research Council in Australia and Amgen Competitive Grant Program 2019.
Systematic Review and Meta-analysis: Screening Tools for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.JAAC.2021.11.031
Abstract: This systematic review and meta-analysis aimed to determine the accuracies of a broad range of screening tools for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, and to compare the diagnostic accuracy of tools between population-based and clinical/high-risk s les, and across reporters. MEDLINE, PsycINFO, EMBASE, and PubMed were searched up until February 20, 2020, with no language restrictions. Studies reporting diagnostic accuracy of a screening tool against a diagnosis of ADHD in children and adolescents <18 years of age were eligible for inclusion. Meta-analyses were undertaken to provide pooled estimates of the area under the curve (AUC), and sensitivity and specificity of groups of measures. A total of 75 studies published between 1985 and 2021 reporting on 41 screening tools that were grouped into 4 categories (Achenbach System of Empirically Based Assessment [ASEBA], DSM-IV symptom scales, SDQ, and Other Scales) were retained. The pooled AUC for studies using a combined ADHD symptoms score was 0.82 (95% CI = 0.78-0.86), although this varied considerably across reporters (0.67-0.92) and populations (CI = 0.60-0.95). None of the measures met minimal standards for acceptable sensitivity (0.8) and specificity (0.8). Most tools have excellent overall diagnostic accuracy as indicated by the AUC. However, a single measure completed by a single reporter is unlikely to have sufficient sensitivity and specificity for clinical use or population screening.
Genetic Prediction of Lifetime Risk of Fracture
Publisher: The Endocrine Society
Date: 11-05-2023
Abstract: Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth. To examine the association between a polygenic risk score (PRS) and lifetime fracture risk. This population-based prospective study involved 3515 community-dwelling in iduals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis. The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. In iduals with PRS & 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively. A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment.
Low-trauma rib fracture in the elderly: Risk factors and mortality consequence
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.BONE.2018.08.016
Abstract: Low trauma rib fracture (hereinafter, rib fracture) is common in the elderly, but its risk factors and mortality consequence are rarely studied. We sought to define the epidemiology of rib fracture and the association between rib fracture and postfracture mortality. The study was part of the Dubbo Osteoporosis Epidemiology Study, which was designed as a population-based prospective study, and consisted of 2041 women and men (aged ≥ 60). The incidence of rib fracture was ascertained from X-ray reports. Bone mineral density (BMD) was measured by DXA (GE-Lunar). The time-dependent Cox model was used to access the relationship between rib fracture and mortality. During the median follow-up of 13 years, 59 men and 78 women had sustained a rib fracture, making the annual incidence of 4.8/1000 person-years. Each SD (0.15 g/cm A rib fracture signifies an increased risk of subsequent fractures and mortality. The increased risk of mortality during the first 2.5 years postfracture suggests a window of opportunity for treatment.
Post‐GWAS Polygenic Risk Score: Utility and Challenges
Publisher: Wiley
Date: 19-09-2020
DOI: 10.1002/JBM4.10411
New Guidelines for Data Reporting and Statistical Analysis: Helping Authors With Transparency and Rigor in Research
Publisher: Wiley
Date: 24-10-2019
DOI: 10.1002/JBMR.3885
Effect of Steroids on Coronavirus Disease 2019 (COVID-19) Mortality Risk: A Bayesian Interpretation
Publisher: Oxford University Press (OUP)
Date: 29-11-2021
DOI: 10.1093/CID/CIAA1783
BONEcheck: a digital tool for personalized bone health assessment
Publisher: Cold Spring Harbor Laboratory
Date: 11-05-2023
DOI: 10.1101/2023.05.10.23289825
Abstract: Osteoporotic fracture is a significant public health burden associated with increased mortality risk and substantial healthcare costs. Accurate and early identification of high-risk in iduals and mitigation of their risks is a core part of the treatment and prevention of fractures. We aimed to introduce a digital tool called ’BONEcheck’ for personalized bone health assessment. The development of BONEcheck primarily utilized data from the prospective population-based Dubbo Osteoporosis Epidemiology Study and the Danish Nationwide Registry. BONEcheck has 3 modules: input data, risk estimates, and risk context. Input variables include age, gender, prior fracture, fall incidence, bone mineral density (BMD), comorbidities, and genetic variants associated with BMD. By utilizing published methodologies, BONEcheck generates output related to the likelihood of fracture and its associated outcomes. The vocabulary utilized to convey risk estimation and management is tailored to in iduals with a reading proficiency at level 8 or above. The tool is designed for men and women aged 50 years and older who either have or have not sustained a fracture. Based on the input variables, BONEcheck estimates the probability of any fragility and hip fracture within 5 years, skeletal age, subsequent fracture, genetic risk score, and recommended interval for repeating BMD. The probability of fracture is shown in both numeric and human icon array formats. The risk is also presented in the context of treatment and management options based on Australian guidelines. Skeletal age was estimated as the sum of chronological age and years of life lost due to a fracture or exposure to risk factors that elevate mortality risk. In its entirety, BONEcheck is a system of algorithms translated into a single platform for personalized osteoporosis and fracture risk assessment. BONEcheck is a new system of algorithms that aims to offer not only fracture risk probability but also contextualize the efficacy of anti-fracture measures concerning the survival benefits. The tool can enable doctors and patients to engage in well-informed discussions and make decisions based on the patient’s risk profile. Public access to BONEcheck is available via bonecheck.org and in Apple Store (iOS) and Google Play (Android).
Prevention of Hip Fractures: Trade‐off between Minor Benefits to Individuals and Large Benefits to the Community
Publisher: Wiley
Date: 26-09-2023
DOI: 10.1002/JBMR.4907
Abstract: Goeffrey Rose postulated that a population‐based measure bringing a small benefit to each in idual can yield large benefits to the community. We aimed to test this axiom by quantifying the relationship between change in bone mineral density (BMD) and hip fracture incidence between two prospective cohorts separated by ~10 years. In this prospective population‐based Dubbo Osteoporosis Epidemiology Study (DOES), the participants aged 60+ were recruited in two waves: the initial cohort (1311 women, 842 men) in 1989‐1992, and the second cohort (974 women, 544 men) in 1999‐2001. The incident hip fracture was radiologically ascertained. Femoral neck BMD was measured biannually. Multivariable‐adjusted Cox's proportional hazards models were adjusted for the predefined covariates such as age, BMI, lifestyle factors, falls, and prior fracture. Compared with the initial cohort, the second cohort had a higher femoral neck BMD by ~ 0.04 g/cm 2 in women and 0.03 g/cm 2 in men. However, the prevalence of osteoporosis in the second cohort was halved (prevalence ratio 0.51, 95% CI 0.36‐0.73 in women 0.45, 0.24‐0.84 in men), and its hip fracture incidence was significantly reduced (hazard ratio 0.54, 95% CI, 0.38‐0.78 in women 0.39, 0.19‐0.80 in men). Sensitivity analyses indicated that the “effect” was unlikely due to unmeasured confounders. These findings suggest that a population‐wide strategy aiming at enhancing BMD across the entire population could lead to a substantial decrease in the incidence of hip fractures. This article is protected by copyright. All rights reserved.
An epidemiologic profile of COVID-19 patients in Vietnam
Publisher: Cold Spring Harbor Laboratory
Date: 15-04-2020
DOI: 10.1101/2020.04.10.20061226
Abstract: There is a paucity of data on the COVID-19 pandemic in Vietnam. In this paper, we sought to provide an epidemiologic description of patients who were infected with SARS-Cov-2 in Vietnam. Data were abstracted from the wikipedia’s COVID-19 information resource and Johns Hopkins University Dashboard. Demographic data and treatment status were obtained for each patient in each day. The coverage period was from 23/1/2020 to 10/4/2020. Descriptive analyses of incident cases were stratified by gender and age group. The estimation of the reproduction ratio was done with a bootstrap method using the R statistical environment. During the coverage period, Vietnam has recorded 257 cases of COVID-19. Approximately 54% of the cases were women. The median age of patients was 30 years (range: 3 months to 88 years), with 78% of patients aged 49 or younger. About 66% (n = 171) of patients were overseas tourists (20%) and Vietnamese students or workers returning from overseas (46%). Approximately 57% (n = 144) of patients have been recovered and discharged from hospitals. There have been no mortality. The reproduction ratio was estimated to range between 0.95 and 1.24. These data indicate that a majority of COVID-19 patients in Vietnam was imported cases in overseas tourists and young students and workers who had returned from overseas.
Reply to: The Association Between Cognitive Decline and Bone Loss and Fracture Risk Is Not Affected by Medication With Anticholinergic Effect
Publisher: Wiley
Date: 14-03-2022
DOI: 10.1002/JBMR.4530
Common methodological issues and suggested solutions in bone research
Publisher: Elsevier BV
Date: 12-2020
Harmonization of Osteoporosis Guidelines: Paving the Way for Disrupting the Status Quo in Osteoporosis Management in the Asia Pacific
Publisher: Wiley
Date: 04-2022
DOI: 10.1002/JBMR.4544
Abstract: In the Asia Pacific (AP) region, osteoporosis and its consequence of fragility fractures are not widely recognized as a major public health problem. Several challenges including underdiagnosis and undertreatment exist. The Asia Pacific Consortium on Osteoporosis (APCO) is a nonpartisan and apolitical organization comprising musculoskeletal experts and stakeholders from both private and public sectors who have united to develop tangible solutions for these substantive challenges. APCO's vision is to reduce the burden of osteoporosis and fragility fractures in the AP region. Heterogeneity in both scope and recommendations among the available clinical practice guidelines (CPGs) contribute to the large osteoporosis treatment gap in the Asia Pacific. APCO has therefore developed a pan Asia‐Oceania harmonized set of standards of care (The Framework), for the screening, diagnosis, and management of osteoporosis. First, a structured analysis of the 18 extant AP CPGs was completed. Subsequently, a prioritization of themes and agreement on fundamental principles in osteoporosis management were made through a Delphi process of consensus building. This approach, ensuring the opinions of all participating members were equally considered, was especially useful for a geographically erse group such as APCO. It is hoped that the Framework will serve as a platform upon which new AP national CPGs can be developed and existing ones be revised. APCO is currently embarking on country‐specific engagement plans to embed the Framework in clinical practice in the AP region. This is through partnering with regulatory bodies and national guidelines development authorities, through peer‐to‐peer health care professional education and by conducting path finder audits to benchmark current osteoporosis services against the Framework standards. The principles underpinning the harmonization of guidelines in the AP region can also be utilized in other parts of the world that have similar socioeconomic ersity and heterogeneity of healthcare resources. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Cognitive decline is associated with an accelerated rate of bone loss and increased fracture risk in women: a prospective study from the Canadian Multicentre Osteoporosis Study
Publisher: Wiley
Date: 20-07-2021
DOI: 10.1002/JBMR.4402
Abstract: Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss and (ii) clinically significant cognitive decline (≥3 points) on Mini Mental State Examination (MMSE) over the first 5 years and subsequent fracture risk over the following 10 years. A total of 1741 women and 620 men aged ≥65 years from the population‐based Canadian Multicentre Osteoporosis Study were followed from 1997 to 2013. Association between cognitive decline and (i) bone loss was estimated using mixed‐effects models and (ii) fracture risk was estimated using adjusted Cox models. Over 95% of participants had normal cognition at baseline (MMSE ≥ 24). The annual % change in MMSE was similar for both genders (women −0.33, interquartile range [IQR] −0.70 to +0.00 and men −0.34, IQR: −0.99 to 0.01). After multivariable adjustment, cognitive decline was associated with bone loss in women (6.5% 95% confidence interval [CI], 3.2% to 9.9% for each percent decline in MMSE from baseline) but not men. Approximately 13% of participants experienced significant cognitive decline by year 5. In women, fracture risk was increased significantly (multivariable hazard ratio [HR], 1.61 95% CI, 1.11 to 2.34). There were too few men to analyze. There was a significant association between cognitive decline and both bone loss and fracture risk, independent of aging, in women. Further studies are needed to determine mechanisms that link these common conditions. © 2021 American Society for Bone and Mineral Research (ASBMR).
Uncertain effects of hydroxychloroquine and azithromycin on SARS-Cov-2 viral load
Publisher: Elsevier BV
Date: 2021
An integrative framework for planning and conducting Non-Intervention, Reproducible, and Open Systematic Reviews (NIRO-SR).
Publisher: Linnaeus University
Date: 10-07-2023
Abstract: Most of the commonly used and endorsed guidelines for systematic review protocols and reporting standards have been developed for intervention research. These excellent guidelines have been adopted as the gold-standard for systematic reviews as an evidence synthesis method. In the current paper, we highlight some issues that may arise from adopting these guidelines beyond intervention designs, including in basic behavioural, cognitive, experimental, and exploratory research. We have adapted and built upon the existing guidelines to establish a complementary, comprehensive, and accessible tool for designing, conducting, and reporting Non-Intervention, Reproducible, and Open Systematic Reviews (NIRO-SR). NIRO-SR is a checklist composed of two parts that provide itemised guidance on the preparation of a systematic review protocol for pre-registration (Part A) and reporting the review (Part B) in a reproducible and transparent manner. This paper, the tool, and an open repository (osf.io/f3brw) provide a comprehensive resource for those who aim to conduct a high quality, reproducible, and transparent systematic review of non-intervention studies.
A niche-dependent myeloid transcriptome signature defines dormant myeloma cells
Publisher: American Society of Hematology
Date: 04-07-2019
Abstract: The era of targeted therapies has seen significant improvements in depth of response, progression-free survival, and overall survival for patients with multiple myeloma. Despite these improvements in clinical outcome, patients inevitably relapse and require further treatment. Drug-resistant dormant myeloma cells that reside in specific niches within the skeleton are considered a basis of disease relapse but remain elusive and difficult to study. Here, we developed a method to sequence the transcriptome of in idual dormant myeloma cells from the bones of tumor-bearing mice. Our analyses show that dormant myeloma cells express a distinct transcriptome signature enriched for immune genes and, unexpectedly, genes associated with myeloid cell differentiation. These genes were switched on by coculture with osteoblastic cells. Targeting AXL, a gene highly expressed by dormant cells, using small-molecule inhibitors released cells from dormancy and promoted their proliferation. Analysis of the expression of AXL and coregulated genes in human cohorts showed that healthy human controls and patients with monoclonal gammopathy of uncertain significance expressed higher levels of the dormancy signature genes than patients with multiple myeloma. Furthermore, in patients with multiple myeloma, the expression of this myeloid transcriptome signature translated into a twofold increase in overall survival, indicating that this dormancy signature may be a marker of disease progression. Thus, engagement of myeloma cells with the osteoblastic niche induces expression of a suite of myeloid genes that predicts disease progression and that comprises potential drug targets to eradicate dormant myeloma cells.
Related Organisations
King's College London
Location: United Kingdom of Great Britain and Northern Ireland
University Of Westminster
Location: United Kingdom of Great Britain and Northern Ireland
University Of Wolverhampton
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
Prediction Of Fracture By Clinico-genetic Profiling
Start Date: Start date not available
End Date: End date not available
Funder: National Health and Medical Research Council
View Funded Activity