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Objectives : To determine the feasibility of a randomized controlled trial (RCT) examining outdoor walking on knee osteoarthritis (KOA) clinical outcomes and magnetic resonance imaging (MRI) structural changes. Method: This was a 24-week parallel two-arm pilot RCT in Tasmania, Australia. KOA participants were randomized to either a walking plus usual care group or a usual care control group. The walking group trained 3 days/week. The primary outcome was feasibility assessed by changes being required to the study design, recruitment, randomization, program adherence, safety, and retention. Exploratory outcomes were changes in symptoms, physical performance/activity, and MRI measures. Results: Forty participants (mean age 66 years (SD 1.4) and 60% female) were randomized to walking (n = 24) or usual care (n = 16). Simple randomization resulted in a difference in numbers randomized to the two groups. During the study, class sizes were reduced from 10 to 8 participants to improve supervision, and exclusion criteria were added to facilitate program adherence. In the walking group, total program adherence was 70.0% and retention 70.8% at 24 weeks. The walking group had a higher number of mild adverse events and experienced clinically important improvements in symptoms (e.g., visual analogue scale (VAS) knee pain change in the walking group: − 38.7 mm [95% CI − 47.1 to − 30.3] versus usual care group: 4.3 mm [− 4.9 to 13.4]). Conclusions: This study supports the feasibility of a full-scale RCT given acceptable adherence, retention, randomization, and safety, and recruitment challenges have been identified. Large symptomatic benefits support the clinical usefulness of a subsequent trial. Trial registration number: 12618001097235. Key Points • This pilot study is the first to investigate the effects of an outdoor walking program on knee osteoarthritis clinical outcomes and MRI joint structure, and it indicates that a full-scale RCT is feasible. • The outdoor walking program (plus usual care) resulted in large improvements in self-reported knee osteoarthritis symptoms compared to usual care alone. • The study identified recruitment challenges, and the manuscript explores these in more details and provides recommendations for future studies. [ABSTRACT FROM AUTHOR]

Approximately 30% of healthy persons aged over 75 years show A[beta] deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between A[beta] burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and cognitive tests were performed on 34 elderly participants (age 73 [plus or minus] 6) from the longitudinal Melbourne Healthy Aging Study (MHAS). Subjects were classified as being cognitively "stable" or "declining" by an independent behavioural neurologist based on clinical assessment and serial word-list recall scores from the preceding 6-10 years. Decline was calculated from the slope of the word-list recall scores. A[beta] burden was quantified using Standardized Uptake Value normalized to cerebellar cortex. Ten subjects were clinically classified as declining. At the time of the PET scans, three of the declining subjects had mild cognitive impairment, one had AD, and six were declining but remained within the normal range for age on cognitive tests. Declining subjects were much more likely to show cortical PiB binding than stable subjects (70% vs. 17%, respectively). Neocortical A[beta] burden correlated with word-list recall slopes (r = -0.78) and memory function (r = -0.85) in the declining group. No correlations were observed in the stable group. A[beta] burden correlated with incident memory impairment and the rate of memory decline in the non-demented ageing population. These observations suggest that neither memory decline nor A[beta] deposition are part of normal ageing and likely represent preclinical AD. Further longitudinal observations are required to confirm this hypothesis. (Contains 4 tables and 4 figures.)

Globally, the impacts of anthropogenic climate change can displace species into more favourable climates. Semi‐arid desert specialists, such as the sandhill dunnart, Sminthopsis psammophila, are typically susceptible to rainfall deficits, wildfires and extreme temperatures caused by anthropogenic climate change. We first used maximum entropy (MaxEnt) species distribution models (SDMs) to predict the current distribution of S. psammophila. Between 2016 and 2018, we ground validated the model's predictions throughout Western Australia, confirming S. psammophila in 18 locations in which it was predicted to occur. The predicted distribution of S. psammophila appears mostly constrained to within its known range. However, S. psammophila was verified 150 km north of its range in Western Australia and connectivity between the South Australian populations was correctly predicted. In 2019, we used updated occurrence data to project SDMs for S. psammophila during the mid‐Holocene, present day and under two future representative concentration pathways (RCPs) of RCP 4.5 (an optimistic emissions scenario) and RCP 8.5 ("business as usual") for 2050 and 2070. By 2050 (RCP 8.5), almost all Western Australian Great Victoria Desert (WAGVD) habitat is predicted to be unsuitable for S. psammophila. By 2070 (RCP 8.5), the climates of the WAGVD and Yellabinna Regional Reserve populations are predicted to become unsuitable, and the species' geographical range is predicted to contract in Australia by 80%. However, the 2070 (RCP 4.5) scenario predicts that this contraction could be halved. As a sandy desert specialist, the distribution of S. psammophila is geographically limited at its southern bounds due to the cessation of suitable spinifex (Triodia spp.) habitats, and so further extension of the range southwards is not possible. Sympatric desert species may be similarly affected, and we suggest that SDMs will be a useful tool in helping to predict the effects of climate change on their distributions. [ABSTRACT FROM AUTHOR]

Objective: Age-related declines in skeletal muscle mass may confer significant metabolic consequences for older adults. Associations of low muscle mass and metabolic syndrome (MetS) in Caucasians, and comparisons with associations observed in Asian populations, have not been reported. We examined associations of low muscle mass and metabolic syndrome (MetS) in Asian and Caucasian middle-aged and older men and women using criteria for low muscle mass. Design, Setting and Participants: Two population-based studies of Australian (Tasmanian Older Adult Cohort Study; TASOAC; N=1005) and Korean (Korean Sarcopenic Obesity Study; KSOS; N=376) community-dwelling adults, mean age 62 and 58 years, respectively. Measurements: Appendicular lean mass (aLM) determined by dual-energy X-ray absorptiometry and normalised to height squared (aLM/Ht2), weight (aLM/Wt) or body mass index (aLM/BMI). Participants in the lowest sex-specific 20% for aLM measures were defined as having low muscle mass. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. Results: Although Australians demonstrated generally unfavourable anthropometric and metabolic characteristics compared to Koreans, prevalence of MetS was similar (29.5% in Australians and 31.4% in Koreans, respectively). Low aLM/Ht2 was associated with significantly reduced likelihood of MetS in both Australians (OR: 0.30, 95% CI 0.19 - 0.46) and Koreans (OR: 0.31, 95% CI 0.16 - 0.62). Conversely, low aLM/BMI was associated with increased odds for MetS in Australians (OR: 1.78, 95% CI 1.12-2.84), but not Koreans (OR: 1.33, 95% CI = 0.67-2.64). Conclusion: Low aLM/BMI is associated with significantly increased likelihood of MetS in Australian adults, but not Koreans, suggesting potential differences in effects of low muscle mass relative to body mass on cardiometabolic health in Caucasian and Asian middle-aged and older adults. Low muscle mass relative to height is associated with reduced likelihood of MetS in both populations. [ABSTRACT FROM AUTHOR]

Aims It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. Methods Indigenous Australians with ( n = 224) or without ( n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). Results The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min−1 1.73 m−2, respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min−1 1.73 m−2, the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min−1 1.73 m−2 in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). Conclusions The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function. [ABSTRACT FROM AUTHOR]

This study examined recruitment patterns and microhabitat associations for three carnivorous fishes, Plectropomus maculatus, Lutjanus carponotatus and Epinephelus quoyanus, at the Keppel Islands, southern Great Barrier Reef, Australia. Habitat selectivity was highest for recruits that were found mostly with corymbose Acropora, predominantly on patches of live coral located over loose substrates (sand). Adults were more commonly associated with tabular Acropora. The proportion of P. maculatus (72 %) found with live corals was higher than for L. carponotatus (68 %) and E. quoyanus (44 %). Densities of recruits were highly variable among locations, but this was only partly related to availability of preferred microhabitats. Our findings demonstrate that at least some carnivorous reef fishes, especially during early life-history stages, strongly associate with live corals. Such species will be highly sensitive to increasing degradation of coral reef habitats. [ABSTRACT FROM AUTHOR]

Summary: Sunlight deprivation results in vitamin D deficiency but serum vitamin D levels can be maintained above 50nmol/L when supplemented with 50,000IU at least every alternate month. Introduction: Antarctic expeditioners are exposed to prolonged sunlight deprivation resulting in vitamin D deficiency. We hypothesised that monthly dosing of 50,000 IU vitamin D (~1,600 IU daily) will increase serum 25-hydroxyvitamin D (25(OH)D), suppress parathyroid hormone (PTH) and improve bone mineral density (BMD), 50,000 IU alternate months (~800 IU daily) will maintain these measures, while a single 50,000 IU dose pre-departure (~1,00 IU daily) will not be protective. Methods: This was a randomised double-blind study involving 110 healthy adults: 91 males, mean age 41 years (range 24-65 years) working in Antarctica for up to 12 months, who we administered 50,000 IU vitamin D3 monthly, alternate months or a single dose pre-departure. Serum 25(OH)D, PTH, osteocalcin, CTx and calcium were assessed at baseline, mid- and end of expedition. Proximal femur and lumbar spine BMD were assessed pre- and post-expedition. Results: Baseline 25(OH)D was 59 ± 14 nmol/L. By mid-expedition, 25(OH)D increased by 7 nmol/L in those supplemented monthly ( p < 0.05) and remained unchanged in those supplemented in alternate months. In those given a single dose pre-departure, 25(OH)D decreased by 8 nmol/L ( p < 0.05) and PTH increased by 27% ( p < 0.09). Serum osteocalcin increased by ~22% in all groups but BMD remained unchanged. If serum 25(OH)D was >50 nmol/L at baseline, 25(OH)D was maintained above this level with all regimens. If 25(OH)D was <50 nmol/L at baseline, monthly or alternate month regimens were needed to achieve levels >50 nmol/L, the single pre-departure dose was ineffective. Conclusion: During sunlight deprivation of up to 12 months, serum 25(OH)D levels can be maintained above 50 nmol/L when expeditioners are provided with 50,000 I U at least every alternate month. [ABSTRACT FROM AUTHOR]

Summary: In this large population-based study, walking was assessed twice yearly for a week, each time by pedometer, had consistent clinically important associations with hip areal bone mineral density (aBMD) in both sexes which appears most important in those over 65 years of age suggesting that walking becomes more important with increasing age. Introduction: Walking is advocated as a preventative strategy for osteoporosis but the evidence is conflicting in females and lacking in males. The aim of this population-based longitudinal study in community dwelling older people ( n = 875) was to determine the association between pedometer determined ambulatory activity (PAA) and bone mass. Methods: Bone mass was assessed as aBMD at the hip and spine using dual X-ray absorptiometry. Steps per day were measured using pedometers for 1 week on four occasions at least 6 months apart. Data were analysed using linear mixed models. Results: At baseline, PAA was positively associated with hip aBMD. An age interaction was present with steps having a stronger association for those aged over 65 years. Longitudinally, the effect of steps on hip aBMD was constant, but not additive over time. For those over 65 years, the difference in hip aBMD between the lowest and highest steps quartiles ranged from 3.1% to 9.4%. With regard to the spine, the relationship between daily steps and spine aBMD was modified by sex. For males; there was no significant relationship between steps and spine aBMD. However, for females, higher steps were associated with higher spine aBMD with the effect being constant over time but not additive. There was no evidence of a threshold effect. Conclusion: In conclusion, pedometer-determined ambulatory activity has consistent clinically important associations with hip aBMD in both sexes which appears most important in those over 65 years of age. The associations for spine aBMD were both weaker and inconsistent suggesting site specificity. [ABSTRACT FROM AUTHOR]

Partnerships between scientists and local communities can increase research capacity and data delivery while improving management effectiveness through enhanced community participation. To encourage such collaboration, this study demonstrates how these partnerships can be formed, drawing on two case studies in coral reef ecosystems in very different social settings (Papua New Guinea and Australia). In each case, steps towards successfully engaging communities in research were similar. These included: (1) early engagement by collaborating organizations to build trust, (2) ensuring scientific questions have direct relevance to the community, (3) providing appropriate incentives for participation, and (4) clear and open communication. Community participants engaged in a variety of research activities, including locating and capturing fishes, collecting and recording data (weight, length and sex), applying external tags, and removing otoliths (ear bones) for ageing and elemental analysis. Research partnerships with communities enhanced research capacity, reduced costs and, perhaps more importantly, improved the likelihood of long-term community support for marine protected areas (MPAs). [ABSTRACT FROM AUTHOR]

Background and Aims: This paper describes the changes in temperature-based indices used to classify viticultural climates in Australia for three warming scenarios produced by the Commonwealth Scientific and Industrial Research Organisation: Mk3.0 global climate model for the years 2030, 2050 and 2070. Methods and Results: Temperature indices that describe grapevine growing season temperature (GST), ripening period temperature, accumulated biologically effective degree days and growing season length were calculated to produce maps of Australia for each warming scenario. Summary statistics of each index's median and range are presented for each Australian wine region under each warming scenario. The greatest change in GST (above the 1971–2000 mean) was modelled to occur for the Perth Hills region, increasing by 1.0°C by 2030, 1.9°C by 2050 and 2.7°C by 2070. The least change in GST was modelled to occur for the Kangaroo Island region, increasing by 0.5°C by 2030, 0.9°C by 2050 and 1.3°C by 2070. Conclusion: Of the 61 recognised wine regions, a median GST of over 21°C (an indicator of the limit of quality wine grape production conditions) was found for three regions for the period 1971–2000, for eight regions for the 2030 scenario, 12 regions for the 2050 scenario and 21 regions for the 2070 scenario. Significance of the Study: Without appropriate adaptations, some established viticultural regions of Australia may become less suitable for quality winegrape production, whereas regions that were once considered unsuitable for quality winegrape production may become more suitable. [ABSTRACT FROM AUTHOR]

The author reflects on the database research in Australia. He states the advantages of database research such as being large and cheap to conduct as well as suitable for long-term follow-up. According to the author, Australia has lagged behind the world in database research for reasons such as the lack of national databases that can be easily accessed.

The article provides an overview on the characteristics of the black-band disease in Great Barrier Reef, Queensland. It is stated that the disease is the most common coral diseases in the area. It has a distinctive band that marks the interface between live, healthy tissue and dead coral skeleton. Fishes that fed directly upon the infected area could lessen the extent and progression of the disease.

Background - The Menzies Centre has employed a strategy of including physical and biological measures of exposure in its studies where these might be relevant. The Centre has used such measures not surprisingly where the alternative - questionnaire or direct observation - could not obviously provide the desired information. The Centre has also used physical and biological measures to assist the interpretation of data obtained from questionnaire measures or simpler physical measures. Review - In research on the occurrence of dysplastic naevi, a risk factor for melanoma, three physical/biological measures were used in parallel with two established questionnaire measures. Amid the risk factors of interest, in place of sun exposure questions direct sun exposure using polysulphone badges was undertaken and in conjunction with self reported measures of tendency to burn or tan a non-invasive measure of melanin density using a spectrophotometer was included. Also a measure of the type of melanin each individual was producing was obtained from hair samples. In a cohort study of children where the endpoint of interest was bone density information on diet was obtained and physical activity via questionnaire. In addition, physical activity was measured using pedometers, vitamin D was measured from a serum sample. Both the abovementioned studies were able to obtain valuable extra insights for an inclusion of the biological and physical measures.The relevant results will be presented. The Menzies Centre currently has a large NHMRC grant to follow a cohort of over 8,484 children who had physical and biological measurements made on them between the ages of 7 and 15, as well as having had information on diet and physical activity collected through self report. Both sets of information will be used to estimate childhood exposures in a study which now seeks to re-measure the cohort members at age 25-33. As the first step in a longer process of following them until later life diseases, such as coronary heart disease, occur. Conclusions - The goal of this study will be to separate the effect of childhood exposures from exposures in early adulthood on risk of adult coronary heart disease and some other conditions. [ABSTRACT FROM AUTHOR]

Abstract: Thoroughbred jumps racing jockeys have a fall rate greater than their flat racing counterparts. Previous studies have focused on factors that contribute to falls by horses but, to date, there has not been a study of risk factors for falls to jockeys in jumps races. Data on race-day falls were extracted from stipendiary stewards reports lodged with Principal Racing Authorities following each race meeting. Denominator data were provided by Racing Information Services Australia on races conducted from August 2002 until July 2009. Univariable and multivariable analyses, estimating incidence rate ratios, were conducted using Poisson regression. In multivariable analysis in hurdle racing, important predictors of falls were higher club level, larger field size, greater prize money, provisionally licenced jockeys and older jockeys. There were significant interactions between jockey licence and prize money; jockey age and previous rides this meeting; race grade and race distance; horse age and field size; and club level and field size. In steeplechase racing, important predictors were type of jump with lowest fall rates in races over Mark III jumps compared to standard fences, provisionally licenced jockeys, jockeys having had previous rides at a meeting, and larger field size. There were significant interactions between the number of previous starts by the horse and field size; race distance and prize money; and race distance and previous rides this meeting. This study has identified factors for falls in jumps racing that could form the basis for targeted strategies to improve occupational health and safety standards. [Copyright &y& Elsevier]

This observational study evaluated the impact of a sponsor company-provided Patient Support Program (PSP) on discontinuation of adalimumab in adult Australian patients eligible for Pharmaceutical Benefit Scheme (PBS)-reimbursed adalimumab for Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Crohn's Disease (CD), Ulcerative Colitis (UC), or Hidradenitis Suppurativa (HS). Patients initiating adalimumab between May 2018 and September 2019 were enrolled into two prospective cohorts based on their decision to opt for or decline the PSP (PSP or non-PSP cohorts). In addition, a historical, retrospective Non-PSP cohort was established from the Services Australia 10% PBS dataset by extracting data of patients initiating adalimumab prior to the introduction of adalimumab PSPs and based on adalimumab PBS listing dates (AS: April 2007 to March 2009; PsA/RA: January 2007 to December 2008; CD: January 2009 to December 2010; HS and UC indications not included). Follow-up for all cohorts was 12 months. The primary endpoint was the time to discontinuation, compared between the prospective PSP cohort and the prospective or retrospective Non-PSP cohort. Inverse probability of treatment weighting was used to balance the cohorts. A Cox proportional hazards model indicated no difference in time to discontinuation between the prospective PSP (n = 162) and non-PSP (n = 65) cohorts (HR [95% CI] = 1.256 [0.616-2.563], p = 0.5304). The 12-month adalimumab persistence rates (95% CI) were 78% (69%, 84%) and 82% (67%, 90%), respectively. In contrast, discontinuation was less likely in the prospective PSP (n = 151) compared with the retrospective non-PSP (n = 297) cohort (HR [95% CI] = 0.44 [0.28-0.68], p<0.001). The 12-month persistence rates (95% CI) were 81% (76%, 90%) and 61% (56%, 67%), respectively. Overall, this study suggests that optimal adalimumab persistence can be achieved with either a structured PSP or healthcare support from other sources, but this was not the case more than a decade ago., Competing Interests: There are no patents or products in development associated with this research to declare. A marketed product (HUMIRA® [Adalimumab]) is associated with this research., (Copyright: © 2024 Jones et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To describe the development of a new position statement regarding balancing the risks and benefits of sun exposure for Australian adults., Methods: We conducted a Sun Exposure Summit in March 2021, with presentations from invited experts and a workshop including representation from academic, clinical, policy, and patient stakeholder organisations. The group considered advice about balancing the risks and benefits of sun exposure for Australian adults and developed a revised consensus position statement., Results: The balance of risks and benefits of sun exposure is not the same for everybody. For people at very high risk of skin cancer, the risks of exposure likely outweigh the benefits; sun protection is essential. Conversely, people with deeply pigmented skin are at low risk of skin cancer but at high risk of vitamin D deficiency; routine sun protection is not recommended. For those at intermediate risk of skin cancer, sun protection remains a priority, but individuals may obtain sufficient sun exposure to maintain adequate vitamin D status., Conclusions: The new position statement provides sun exposure advice that explicitly recognises the differing needs of Australia's diverse population., Implications for Public Health: Mass communication campaigns should retain the focus on skin cancer prevention. The new position statement will support the delivery of personalised advice., Competing Interests: Conflicts of interest David Whiteman reports a relationship with Pierre Fabre Australia that includes speaking and lecture fees. Peter Ebeling reports a relationship with Healthy Bones Australia that includes board membership. Peter Ebeling reports a relationship with the American Society for Bone and Mineral Research that includes board membership. Peter Ebeling reports a relationship with International Osteoporosis Foundation that includes: board membership. Peter Ebeling reports a relationship with the Asian Pacific Consortium on Osteoporosis that includes board membership. Craig Sinclair reports a relationship with Cancer Council Victoria that includes employment. Christian Girgis reports a relationship with the Australian and New Zealand Bone and Mineral Society that includes board membership. Christian Girgis reports a relationship with the University of Sydney that includes employment. Stephen Shumack reports a relationship with the Australasian College of Dermatologists that includes non-financial support., (Copyright © 2024. Published by Elsevier B.V.)

Background: To compare persistence of disease-modifying antirheumatic (DMARDs), with a focus on Janus kinase (JAK) inhibitors in Australian rheumatoid arthritis (RA) patients., Methods: A retrospective observational study was conducted among 4,521 RA patients (females n=3,181 [70.4%]), using data from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset, aged ≥18 years and initiating a DMARD between 2011 to 2021. Kaplan-Meier analysis was used to estimate persistence rates, defined as occurrence of 6 months gap after the end of a drug dispensing., Results: Twelve-month persistence rates were 72% for upadacitinib, 61% for baricitinib, 58% for subcutaneous tumor necrosis factor-alpha inhibitors (TNFi), 55% for tocilizumab, 53% for tofacitinib, and 49% for abatacept. Median treatment persistence was not reached for upadacitinib (n=574) and baricitinib (n=553); and was 15.0 months for tofacitinib (95% CI 13.5-19.5), 20.5 months for TNFi (95% CI 19.0-22.4), 19.1 months for tocilizumab (95% CI 17.9-23.6), and 12.5 months for abatacept (95% CI 10.4-14.9). Persistence rates on first-line JAK inhibitors were 68% for upadacitinib and baricitinib and 55% for tofacitinib, and 49% for TNFi, 55% for abatacept, and 57% for tocilizumab; rates were sustained for upadacitinib, TNFi, and tocilizumab but dropped to 59% for baricitinib and 47% for abatacept in the second-line treatment. For each b/tsDMARD, persistence rates were higher when combined with methotrexate or other conventional synthetic DMARDs. The median oral glucocorticoid dose decreased from 4.3 mg/day (range:0-40) to 2.3 mg/day (range:0-22) over 2 years. Changes were significant for all RA DMARDs, tofacitinib and baricitinib combined (1-2 years post initiation only), TNFi, abatacept, and tocilizumab., Conclusions: In a real-world setting, we showed highest persistence rates on upadacitinib, followed by baricitinib and then TNFi therapy and was improved by co-therapy. All agents appeared to be corticosteroid sparing., Competing Interests: Declaration of Competing Interest This work was supported by Pfizer (ASPIRE Rheumatology Grant 2020) and Dr. Scheepers received a fellowship from The Trustee for Farrell Foundation (2020-2021). All authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis., Methods: In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40-75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381)., Findings: Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was -15·2 mm (SD 24·0) in the methotrexate group and -7·7 mm (25·3) in the placebo group, with a mean between-group difference of -9·9 (95% CI -19·3 to -0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group., Interpretation: Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype., Funding: National Health and Medical Research Council of Australia., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To improve birth outcomes, all pregnant women without known diabetes are recommended for an oral glucose tolerance test (OGTT) to screen for hyperglycaemia in pregnancy (diabetes in pregnancy or gestational diabetes mellitus (GDM)). This narrative review presents contemporary approaches to minimise preanalytical glycolysis in OGTT samples with a focus on GDM diagnosis using criteria derived from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The challenges of implementing each approach across a diverse Australian healthcare setting were explored. Many Australian sites currently collect and transport OGTT samples at ambient temperature in sodium fluoride (NaF) tubes which is likely to lead to missed diagnosis of GDM in a significant proportion of cases. Alternative preanalytical solutions should be pragmatic and tailored to individual settings and as close as possible to the preanalytical conditions of the HAPO study for correct interpretation of OGTT results. Rapid centrifugation of barrier tubes to separate plasma could be suitable in urban settings provided time to centrifugation is strictly controlled. Tubes containing NaF and citrate could be useful for remote or resource poor settings with long delays to analysis but the impact on the interpretation of OGTT results should be carefully considered. Testing venous blood glucose at the point-of-care bypasses the need for glycolytic inhibition but requires careful selection of devices with robust analytical performance. Studies to evaluate the potential error of each solution compared to the HAPO protocol are required to assess the magnitude of misdiagnosis and inform clinicians regarding the potential impact on patient safety and healthcare costs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis., Methods: We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0-3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses., Discussion: This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype., Trial Registration: Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018., (© 2022. The Author(s).)

We aimed to describe associations between diet quality in adolescence and adulthood and knee symptoms in adulthood. Two hundred seventy-five participants had adolescent diet measurements, 399 had adult diet measurements and 240 had diet measurements in both time points. Diet quality was assessed by Dietary Guidelines Index (DGI), reflecting adherence to Australian Dietary Guidelines. Knee symptoms were collected using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Data were analysed using zero-inflated negative binomial regressions. The overall adolescent DGI was not associated with adult knee symptoms, although lower intake of discretionary foods (e.g. cream, alcohol, bacon and cake) in adolescence was associated with lower pain (mean ratio (MR) 0·96) and dysfunction (MR 0·94). The overall adult DGI was not associated with knee symptoms; however, limiting saturated fat was associated with lower WOMAC (Pain: MR 0·93; stiffness: MR 0·93; dysfunction: MR 0·91), drinking water was associated with lower stiffness (MR 0·90) and fruit intake was associated with lower dysfunction (MR 0·90). Higher DGI for dairy products in adulthood was associated with higher WOMAC (Pain: MR 1·07; stiffness: MR 1·13; dysfunction: MR 1·11). Additionally, the score increases from adolescence to adulthood were not associated with adult knee symptoms, except for associations between score increase in limiting saturated fat and lower stiffness (MR 0·89) and between score increase in fruit intake and lower dysfunction (MR 0·92). In conclusion, the overall diet quality in adolescence and adulthood was not associated with knee symptoms in adulthood. However, some diet components may affect later knee symptoms.

Background: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown., Aim: To describe the association between SES and time to THR and TKR., Methods: One thousand and seventy-two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area-level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group; and (ii) the cohort dichotomised at the quartile 1 cut-point., Results: The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2-13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR; hazard ratio (HR): 0.56; 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90; 95% CI 0.53, 1.54). However, the former became non-significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors., Conclusions: The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES., (© 2020 Royal Australasian College of Physicians.)

Background: Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms., Methods: MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05)., Discussion: Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design., Trial Registration: Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018., (© 2021. The Author(s).)

Background: Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis., Methods: Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups., Discussion: This study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124., (© 2021. The Author(s).)

Objectives: Health state utilities (HSUs) are an input metric for estimating quality-adjusted life-years (QALY) in cost-utility analyses. Currently, there is a paucity of data on association of knee symptoms with HSUs for middle-aged populations. We aimed to describe the association of knee symptoms and change in knee symptoms with SF-6D HSUs and described the distribution of HSUs against knee symptoms' severity., Methods: Participants (36-49-years) were selected from the third follow-up (completed 2019) of Australian Childhood Determinants of Adult Health study. SF-6D HSUs were generated from the participant-reported SF-12. Association between participant-reported WOMAC knee symptoms' severity, change in knee symptoms over 6-9 years, and HSUs were evaluated using linear regression models., Results: For the cross-sectional analysis, 1,567 participants were included; mean age 43.5 years, female 54%, BMI ± SD 27.18 ± 5.31 kg/m 2 . Mean ± SD HSUs for normal, moderate, and severe WOMAC scores were 0.820 ± 0.120, 0.800 ± 0.120, and 0.740 ± 0.130, respectively. A significant association was observed between worsening knee symptoms and HSUs in univariable and multivariable analyses after adjustment (age and sex). HSU decrement for normal-to-severe total-WOMAC and WOMAC-pain was - 0.080 (95% CI - 0.100 to - 0.060, p < 0.01) and - 0.067 (- 0.085 to - 0.048, p < 0.01), exceeding the mean minimal clinically important difference (0.04). Increase in knee pain over 6-9 years was associated with a significant reduction in HSU., Conclusion: In a middle-aged population-based sample, there was an independent negative association between worse knee symptoms and SF-6D HSUs. Our findings may be used by decision-makers to define more realistic and conservative baseline and ongoing HSU values when assessing QALY changes associated with osteoarthritis interventions., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To describe the impact of OA on health-related quality of life (HRQoL) in the forms of health state utilities (HSUs) and health-dimension scores, and to compare the longitudinal changes in HRQoL for people with and without OA, using an Australian population-based longitudinal cohort., Methods: Participants of the Tasmanian Older Adult Cohort with data on OA diagnosis and HRQoL were included [interviewed at baseline (n = 1093), 2.5 years (n = 871), 5 years (n = 760) and 10 years (n = 562)]. HRQoL was assessed using the Assessment of Quality of Life four-dimensions and analysed using multivariable linear mixed regressions., Results: Compared with participants without OA, HSUs for those with OA were 0.07 (95% confidence interval: 0.09, 0.05) units lower on average over 10 years. HSUs for participants with knee and/or hip OA were similar to those with other types of OA at the 2.5 year follow-up and then diverged, with HSUs of the former being up to 0.09 units lower than the latter. Those with OA had lower scores for psychological wellness, independent living and social relationships compared with those without OA. Independent living and social relationships were mainly impacted by knee and/or hip OA, with the effect on the former increasing over time., Conclusion: Interventions to improve HRQoL should be tailored to specific OA types, health dimensions, and times. Support for maintaining psychological wellness should be provided, irrespective of OA type and duration. However, support for maintaining independent living could be more relevant to knee and/or hip OA patients living with the disease for longer., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To examine associations of education and occupation with handgrip strength (HGS), lower limb strength (LLS) and appendicular lean mass (ALM)., Methods: Measures of HGS, LLS and ALM (dual-energy X-ray absorptiometry) were ascertained at baseline in 1090 adults (50-80 years, 51% women), ~3 and 5 years. Education and occupation were self-reported, the latter categorised as high-skilled white collar (HSWC), low-skilled white collar (LSWC) or blue collar. Separate general estimating equations were performed., Results: The highest education group had greater HGS than the middle (0.33 psi) and lowest (0.48 psi) education groups, and 0.34 kg greater ALM than the lowest education group. HGS was 0.46 psi greater for HSWC than LSWC groups. Compared to LSWC groups, LLS was 5.38 and 7.08 kg greater in HSWC and blue-collar groups. Blue-collar and HSWC groups each had ~ 0.60-0.80kg greater ALM than LSWC., Conclusion: Progressive muscle loss can be prevented by targeted intervention; thus, we suggest clinical attention be directed towards specific social groups., (© 2020 AJA Inc.)

Objectives: To identify subgroups of community-dwelling older adults and to assess their longitudinal associations with long-term osteoarthritis (OA) outcomes., Methods: 1046 older adults aged 50-80 years were studied. At baseline, body mass index (BMI), pedometer-measured ambulatory activity (AA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) determined knee pain and information on comorbidities were obtained. Tibial cartilage volume and bone-marrow lesions (BMLs) were assessed using MRI at baseline and 10 years and total knee replacements (TKR) by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Latent class analysis was used to determine participant subgroups, considering baseline BMI, AA, pain and comorbidities, and linear mixed-effects or log-binomial models were used to assess the associations., Results: Three subgroups/classes were identified: subgroup 1 (43%): Normal/overweight participants with higher AA, lower pain and lower comorbidities; subgroup 2 (32%): Overweight participants with lower AA, mild pain and higher comorbidities; subgroup 3 (25%): Obese participants with lower AA, mild pain and higher comorbidities. Subgroup 3 had greater cartilage volume loss (β - 60.56 mm 3 , 95% CI - 105.91, - 15.21) and a higher risk of TKR (RR 3.19, 95% CI 1.75, 5.81), compared to subgroup 1. Subgroup 2 was not associated with cartilage volume change (β 13.06 mm 3 , 95% CI - 30.87, 57.00) or risk of TKR (RR 1.16, 95% CI 0.56, 2.36), compared to subgroup 1. Subgroup membership was not associated with worsening BMLs., Conclusions: Our findings suggest the existence of homogeneous subgroups of participants and support the utility of identifying patterns of characteristics/risk factors that may cluster together and using them to identify subgroups of people who may be at a higher risk of developing and/or progressing OA. Key Points • Complex interplay among characteristics/factors leads to conflicting evidence between ambulatory activity and knee osteoarthritis. • Distinct subgroups are identifiable based on ambulatory activity, body mass index, knee pain, and comorbidities. • Identifying subgroups can be used to determine those who are at risk of developing/progressing osteoarthritis.

Objective: To evaluate the effects of the updated version of an evidence-based osteoarthritis (OA) resource and consumer hub, 'My Joint Pain' website, on health education and quality of care over 12 months., Methods: Using a classic quasi-experimental design, participants with symptomatic hip or knee OA were recruited across Australia to evaluate the 'My Joint Pain' website, compared to a control group of non-users from 12 to 24 months. Outcome measures included the Health Education Impact Questionnaire (HEIQ) and the OA Quality Indicator (OAQI) questionnaire. The changes from 12 to 24 months in the HEIQ were evaluated using a generalised linear model. The differences between users and non-users in the OAQI were evaluated using a chi-square test., Results: A total of 277 eligible participants with symptomatic hip or knee OA were recruited at baseline, and 122 participants completed the 24-month surveys (users: n = 35, non-users: n = 87). There was no significant difference between users and non-users for the HEIQ scores at 24 months after adjustments for age, sex and body mass index (BMI). Users had higher emotional distress scores than non-users in univariable analysis. When compared with non-users in the OAQI, users showed favourable changes in receiving information about "self-management" and "acetaminophen" and "non-steroidal anti-inflammatory drugs (NSAIDs)" from 12 to 24 months., Conclusion: The evaluation of the updated 'My Joint Pain' website didn't find significant improvements in terms of health education, but it may help delivering useful information about self-management and appropriate use of pharmacological treatments. More strategies are needed to facilitate the uptake of evidence-based self-management and education online resources for OA consumers.

Background & Aims: Aging is characterized by progressive decline in physiologic reserves and functions as well as prolonged inflammation, increasing susceptibility to disease. Diet plays an important role in maintaining health, and reducing morbidity and mortality, especially in older populations. This study was designed to determine prospective associations between dietary inflammatory index (DII®) scores and bone health, sarcopenia-related outcomes, falls risk and incident fractures in community-dwelling Australian older adults., Methods: A total of 1098 [51% male; age (mean ± SD) 63.0 ± 7.5 years] non-institutionalized older adults who participated in the Tasmanian Older Adult Cohort Study (TASOAC) at baseline, 768 at 5 years, and 566 at 10 years follow-up were included in this analysis. Baseline energy-adjusted DII (E-DII) scores were calculated using a validated Food Frequency Questionnaire. Changes in bone mineral density (BMD) and appendicular lean mass (ALM) were measured over ten years using dual-energy x-ray absorptiometry. Ten-year changes in hand grip, knee extensor and whole lower-limb muscle strength and quality were assessed by dynamometers and change in falls risk score using the Physical Profile Assessment (PPA). Incident fractures at any site and non-vertebral fractures over 10 years were self-reported., Results: The E-DII range was -3.48 to +3.23 in men and -3.80 to +2.74 in women. Higher E-DII score (indicating a more pro-inflammatory diet) was associated with lower total hip (B: -0.009; 95% CI: -0.017, 0.000) and lumbar spine BMD (B: -0.013; 95% CI: -0.024, -0.002), and higher falls risk score (B: 0.040; 95% CI: 0.002, 0.078) over 10 years in men. Women with higher E-DII scores had higher whole lower-limb muscle quality over 10 years (B: 0.109; 95% CI: 0.002, 0.215). For every unit increase in E-DII score, incident fracture rates increased by 9.0% in men (IRR: 1.090; 95% CI: 1.011, 1.175) and decreased by 12.2% in women (IRR: 0.878; 95% CI: 0.800, 0.964) in a fully adjusted model., Conclusion: Higher E-DII scores were associated with lower bone density, higher falls risk, and increased incidence of fractures in community-dwelling older men, but decreased fracture incidence in women, over 10 years. This suggests pro-inflammatory diets may be more detrimental to musculoskeletal health in older men than in women. Additional studies are warranted to elucidate these sex differences., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Knee osteoarthritis (OA) is a common and important cause of pain and disability, but interventions aimed at modifying structures visible on imaging have been disappointing. While OA affects the whole joint, synovitis and effusion have been recognised as having a role in the pathogenesis of OA. Krill oil reduces knee pain and systemic inflammation and could be used for targeting inflammatory mechanisms of OA., Methods/design: We will recruit 260 patients with clinical knee OA, significant knee pain and effusion-synovitis present on MRI in five Australian cities (Hobart, Melbourne, Sydney, Adelaide and Perth). These patients will be randomly allocated to the two arms of the study, receiving 2 g/day krill oil or inert placebo daily for 6 months. MRI of the study knee will be performed at screening and after 6 months. Knee symptoms, function and MRI structural abnormalities will be assessed using validated methods. Safety data will be recorded. Primary outcomes are absolute change in knee pain (assessed by visual analog score) and change in size of knee effusion-synovitis over 24 weeks. Secondary outcomes include improvement in knee pain over 4, 8, 12, 16 and 20 weeks. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses adjusting for missing data and for treatment compliance will be performed as the secondary analyses., Discussion: This study will provide high-quality evidence to assess whether krill oil 2 g/day reduces pain and effusion-synovitis size in older adults with clinical knee OA and knee effusion-synovitis. If krill oil is effective and confirmed to be safe, we will provide compelling evidence that krill oil improves pain and function, changes disease trajectory and slows disease progression in OA. Given the lack of approved therapies for slowing disease progression in OA, and moderate cost of krill oil, these findings will be readily translated into clinical practice., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12616000726459. Registered on 02 June 2016. Universal Trial Number (UTN) U1111-1181-7087.

Objectives: To determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depressive symptoms in patients with knee osteoarthritis (OA) and vitamin D deficiency., Design: A prespecified secondary analysis of a multicentre, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive oral vitamin D 3 (50,000 IU, n = 209) or placebo (n = 204) monthly for 24 months. In addition, participants who completed the trial were classified into 2 groups according to their serum 25(OH)D levels at month 3 and 24 as follows: not consistently sufficient (serum 25(OH)D ≤ 50 nmol/L at month 3 and/or 24), and consistently sufficient (serum 25(OH)D > 50 nmol/L at both month 3 and 24). Multilevel mixed-effect models were used to compare differences of change in PHQ-9 scores between groups., Setting and Participants: This clinical trial was conducted in participants with symptomatic knee OA and vitamin D deficiency from June 2010 to December 2013 in Tasmania and Victoria, Australia., Measures: The primary outcome was the depressive symptoms change over 24 months, which was measured using the Patient Health Questionnaire (PHQ-9, 0-27)., Results: Of 599 participants who were screened for eligibility, 413 participants were enrolled (mean age: 63.2 years; 50.3% female) and 340 participants (intervention n = 181, placebo n = 159, 82.3% retention rate) completed the study. The baseline prevalence of depression (PHQ-9 score ≥5) was 25.4%. Depressive symptoms improved more in the vitamin D supplementation group compared to the placebo group [β: -0.66, 95% confidence interval (CI): -1.22 to -0.11, P for difference = .02] and in the participants who maintained vitamin D sufficiency compared to those who did not (β: -0.73, 95% CI: -1.41 to -0.05, P for difference = .04) over 24 months., Conclusions/implications: These findings suggest that vitamin D supplementation and maintaining adequate vitamin D levels over 24 months may be beneficial for depressive symptoms in patients with knee OA., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the associations of childhood and adulthood adiposity measures with knee cartilage thickness, volume and bone area in young adults., Methods: Childhood and adulthood adiposity measures (weight, height, waist circumference and hip circumference) of 186 participants were collected in 1985 (aged 7-15 years) and during 2004-2006 (aged 26-36 years). Knee magnetic resonance imaging was conducted during 2008-2010 (aged 31-41 years) and cartilage thickness, volume and bone area were measured using a quantitative approach (Chondrometrics, Germany). Linear regressions were used to examine the above associations., Results: The prevalence of overweight was 7.6% in childhood and 42.1% in adulthood. Childhood weight (β = - 5.57 mm 2 /kg) and body mass index (BMI) (β = - 11.55 mm 2 /kg/m 2 ) were negatively associated with adult patellar bone area, whereas adult weight was positively associated with bone area in medial femorotibial compartment (MFTC) (β = 3.37 mm 2 /kg) and lateral femorotibial compartment (LFTC) (β = 2.08 mm 2 /kg). Adult waist-hip ratio (WHR) was negatively associated with cartilage thickness (MFTC: β = - 0.011; LFTC: β = - 0.012 mm/0.01 unit), volume (Patella: β = - 20.97; LFTC: β = - 21.71 mm 3 /0.01 unit) and bone area (Patella: β = - 4.39 mm 2 /0.01 unit). The change in WHR z-scores from childhood to adulthood was negatively associated with cartilage thickness (MFTC: β = - 0.056 mm), volume (patella: - 89.95; LFTC: - 93.98 mm 3 ), and bone area (patella: - 20.74 mm 2 ). All p-values < 0.05., Conclusions: Childhood weight and BMI were negatively but adult weight was positively associated with adult bone area. Adult WHR and the change in WHR from childhood to adulthood were negatively associated with cartilage thickness, volume, and bone area. These suggest early-life adiposity measures may affect knee structures in young adults.

Background Diagnostic testing provides integral information for the prevention, diagnosis, treatment and management of disease. Inadequate test result reporting and follow-up is a major risk to patient safety. Factors contributing to failure to follow-up test results include unclear delineation of responsibility about who is meant to act on a test result; poor coordination across different levels of care; and the absence of integrated health information systems for the efficient information communication. Methods A 2016 Australian Stakeholder Forum brought together over 30 representatives from 14 different consumer, clinical and management stakeholder organisations to discuss safe and effective test result communication, management and follow-up. Thematic analysis was conducted drawing on multimodal data collected in the form of observational fieldnotes and document artefacts produced by participants. Results The forum identified major challenges which pose immediate risks to patient safety. Participants recommended priorities for addressing issues relating to: (i) the governance of test result management processes; (ii) integration of health care processes through the utilisation of effective digital health solutions; and (iii) involving patients as key partners in the decision-making and care process. Conclusions Stakeholder groups diverged slightly in their priorities. Consumers highlighted the lack of patient involvement in the test result management process but were less concerned about standardisation of reports and critical result thresholds than pathologists. The forum foregrounded the need for a systems approach, capable of identifying and addressing interconnections and multiple factors that contribute to poor test result follow-up, with a strong emphasis on enhancing the contribution of patients.

Objective: Fear of cancer recurrence (FCR) is a common concern among cancer survivors. Identifying survivors with clinically significant FCR requires validated screening measures and clinical cut-offs. We evaluated the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) clinical cut-off in 2 samples., Methods: Level of FCR in study 1 participants (from an Australian randomized controlled trial: ConquerFear) was compared with FCRI-SF scores. Based on a biopsychosocial interview, clinicians rated participants as having nonclinical, subclinical, or clinical FCR. Study 2 participants (from a Canadian FCRI-English validation study) were classified as having clinical or nonclinical FCR by using the semistructured clinical interview for FCR (SIFCR). Receiver operating characteristic analyses evaluated the screening ability of the FCRI-SF against clinician ratings (study 1) and the SIFCR (study 2)., Results: In study 1, 167 cancer survivors (mean age: 53 years, SD = 10.1) participated. Clinicians rated 43% as having clinical FCR. In study 2, 40 cancer survivors (mean age: 68 years, SD = 7.0) participated; 25% met criteria for clinical FCR according to the SIFCR. For both studies 1 and 2, receiver operating characteristic analyses suggested a cut-off ≥22 on the FCRI-SF identified cancer survivors with clinical levels of FCR with adequate sensitivity and specificity., Conclusions: Establishing clinical cut-offs on FCR screening measures is crucial to tailoring individual care and conducting rigorous research. Our results suggest using a higher cut-off on the FCRI-SF than previously reported to identify clinically significant FCR. Continued evaluation and validation of the FCRI-SF cut-off is required across diverse cancer populations., (Copyright © 2017 John Wiley & Sons, Ltd.)

Introduction: This study aimed to determine if beneficial effects of individualized feedback of fracture risk on osteoporosis preventive behaviors and bone mineral density observed in a 2-year trial were sustained long-term., Methods: This was a 10-year follow-up of a 2-year RCT in 470 premenopausal women aged 25-44 years, who were randomized to one of two educational interventions (the Osteoporosis Prevention and Self-Management Course [OPSMC] or an osteoporosis information leaflet) and received tailored feedback of their relative risk of fracture in later life (high versus normal risk groups). Bone mineral density of lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical activity, dietary calcium intake, calcium and vitamin D supplements, and smoking status were measured by questionnaires., Results: From 2 to 12 years, the high-risk group had a smaller decrease in femoral neck bone mineral density (β=0.023, 95% CI=0.005, 0.041 g/cm 2 ) but similar lumbar spine bone mineral density change as the normal-risk group. They were more likely to use calcium (relative risk=1.66, 95% CI=1.22, 2.24) and vitamin D supplements (1.99, 95% CI=1.27, 3.11). The OPSMC had no effects on bone mineral density change. Both high-risk (versus normal-risk) and the OPSMC groups (versus leaflet) had a more favorable pattern of smoking behavior change (relative risk=1.85, 95% CI=0.70, 4.89 and relative risk=2.27, 95% CI=0.86, 6.01 for smoking cessation; relative risk=0.33, 95% CI=0.13, 0.80 and relative risk=0.28, 95% CI=0.10, 0.79 for commenced or persistent smoking)., Conclusions: Feedback of high fracture risk to younger women was associated with long-term improvements in osteoporosis preventive behaviors and attenuated femoral neck bone mineral density loss. Therefore, this could be considered as a strategy to prevent osteoporosis., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) NCT00273260., (Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management., Methods: A cross-sectional analysis of Indigenous participants of the eGFR Study., Measures: Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR., Results: 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m 2 , WHR 0.94, eGFR 99.2 ml/min/1.73m 2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse)., Conclusion: Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required., (© 2016 Asian Pacific Society of Nephrology.)

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD)., Hypothesis: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians., Method: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c≥6.5% or ≥48mmol/mol. Anaemia was defined as Hb<130g/L or <120g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed., Results: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR>3mg/mmol and 18.2% with eGFR<60mL/min/1.73m 2 . Median bilirubin concentration was lower in females than males (6 v 8μmol/L, p<0.001) and in Aboriginal than TSI participants (6 v 9.5μmol/L, p<0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related)., Conclusion: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the associations between body composition and hormonal and inflammatory factors measured 5 years prior and tibial cartilage volume in young adults, and to explore if these factors contribute to the sex difference in tibial cartilage volume., Methods: Subjects broadly representative of the young adult Australian population (n = 328, ages 31-41 years, 47.3% women) were selected. They underwent T1-weighted fat-suppressed magnetic resonance imaging (MRI) of their knees. Tibial cartilage volume was measured from MRI. Sex hormone binding globulin (SHBG) and testosterone in a subset of women and C-reactive protein (CRP) level and fibrinogen in both sexes were measured 5 years prior. Body mass index (BMI), fat mass, and lean mass were calculated from height, weight, and skinfolds., Results: In multivariable analyses, correlates of tibial cartilage volume included lean body mass (β = 26.4 mm(3) ; 95% confidence interval [95% CI] 13.6, 39.1), fat mass (β = -11.8 mm(3) ; 95% CI -22.2, -1.4), and fibrinogen (β = -146.4 mm(3) ; 95% CI -276.4, -16.4), but not BMI, testosterone, or CRP level. In women, SHBG was positively associated with tibial cartilage volume (β = 0.67 mm(3) ; 95% CI 0.14, 1.20) and Free Androgen Index was negatively associated with lateral tibial cartilage volume (β = -0.04 mm(3) ; 95% CI -0.07, 0.00). Men had 13% more tibial cartilage volume (500 mm(3) ) than women. The magnitude of this association decreased by 38%, 20%, and 37% after adjustment for lean body mass, fat mass, and fibrinogen, respectively., Conclusion: Body composition, sex hormones, and fibrinogen correlate with knee cartilage volume in young adult life. Sex difference in knee cartilage volume is contributed largely by variations in body composition and/or fibrinogen., (© 2016, American College of Rheumatology.)

Objective: To describe the associations between overweight measures in childhood and knee pain, stiffness and dysfunction among adults 25 years later., Methods: Subjects broadly representative of the Australian population (n=449, aged 31-41 years, female 48%) were selected from the Australian Schools Health and Fitness Survey of 1985. Height, weight and knee injury were recorded and knee pain was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Childhood height, weight and knee injury had been measured according to standard protocols 25 years earlier and body mass index (BMI) and percentage overweight were calculated., Results: The prevalence of knee pain was 34% and overweight in childhood and adulthood was 7% and 48%, respectively. Overall, there were no significant associations between childhood overweight measures and total WOMAC knee pain, stiffness and dysfunction scores in adulthood. However, in men, overweight in childhood was associated with adulthood WOMAC pain (relative risk (RR) 1.72, 95% CI 1.11 to 2.69) and childhood weight and BMI were associated with WOMAC stiffness and dysfunction. Childhood weight, BMI and overweight were all associated with the presence of adulthood walking knee pain in men and the whole sample. Most of these associations were independent of adult overweight measures. Subjects who were overweight in both childhood and adult life had a significant increase in the risk and prevalence of adulthood walking pain (RR=2.42, 95% CI 1.06 to 5.53)., Conclusions: Childhood overweight measures were significantly associated with adulthood knee mechanical joint pain, stiffness and dysfunction among men, independent of adult overweight, suggesting that childhood overweight may lead to later knee symptoms in men., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: This article is facilitated by the Australian Cochrane Musculoskeletal Group (CMSG) editorial base. The CMSG is one of the largest Cochrane review groups and produces reliable, up-to-date systematic reviews of interventions for the prevention, treatment or rehabilitation of musculoskeletal disorders., Objective: Our aim is to place the findings of recent Cochrane musculoskeletal reviews in a context immediately relevant to general practitioners (GPs) by summarising the findings of a review of interventions to improve adherence to exercise for adults with chronic musculoskeletal pain (CMP)., Discussion: The findings indicate that there are various strategies that may be effective in increasing adherence to exercise and physical activity in patients suffering from CMP. These strategies are discussed in detail and general practice scenarios are presented to show how the results can be applied in practice.

We examine patient socioeconomic status, the strength of the patient-doctor relationship and local area competition as determinants of the quality and price of GP services. We exploit a large-sample patient data set in Australia and its linkage to administrative databases. The sample contains over 260,000 patients and over 12,600 GPs, observed between 2005 and 2010. Controlling for GP fixed effects and patient health, we find no strong evidence that quality differs by patient age, gender, country of origin, health concession card status and income, but quality is increased by stronger patient-doctor relationship. Using a competition measure that is defined at the individual GP level and not restricted to a local market, we find that competition lowers quality. Price is increasing in patient income, whereas competition has a small impact on price., (Copyright © 2014 John Wiley & Sons, Ltd.)

Although mutualisms are ubiquitous in nature, our understanding of the potential impacts of climate change on these important ecological interactions is deficient. Here, we report on a thermal stress-related shift from cooperation to antagonism between members of a mutualistic coral-dwelling community. Increased mortality of coral-defending crustacean symbionts Trapezia cymodoce (coral crab) and Alpheus lottini (snapping shrimp) was observed in response to experimentally elevated temperatures and reduced coral-host (Pocillopora damicornis) condition. However, strong differential numerical effects occurred among crustaceans as a function of species and sex, with shrimp (75%), and female crabs (55%), exhibiting the fastest and greatest declines in numbers. These declines were due to forceful eviction from the coral-host by male crabs. Furthermore, surviving female crabs were impacted by a dramatic decline (85%) in egg production, which could have deleterious consequences for population sustainability. Our results suggest that elevated temperature switches the fundamental nature of this interaction from cooperation to competition, leading to asymmetrical effects on species and/or sexes. Our study illustrates the importance of evaluating not only individual responses to climate change, but also potentially fragile interactions within and among susceptible species.

Clinical laboratories need to test patient samples precisely, accurately, and efficiently. The latest member of the Roche cobas modular platform family, the cobas 8000 modular analyzer series allows compact and convenient consolidation of clinical chemistry and immunochemistry assays in high-workload laboratories with a throughput of 3 to 15 million tests annually. Here we present the results of studies designed to test the overall system performance under routine-like conditions that were conducted at 14 laboratories over 2 y. Experiments that test analytical performance of the new module were integrated with overall system functionality testing of all modules in different configurations. More than two million results were generated and evaluated for ~100 applications using serum/plasma, urine, or EDTA blood samples. During the workflow studies, eight configurations of the possible 38 combinations were used, covering all available analytical modules. The versatility of the module combinations makes the system customizable to fit the needs of diverse laboratories, allowing precise and accurate analysis of a broad spectrum of clinical chemistry and immunochemistry parameters with short turnaround times. This new system will contribute to the ability of clinical laboratories to offer better service to their customers and support vital clinical decision making.

Ethnopharmacological Significance: Eremophila longifolia is one of the most respected of the traditional medicines used by Australian Aboriginal people. Customary use involves smoldering the leaves over hot embers of a fire to produce an acrid smoke, believed to have therapeutic effects broadly consistent with antimicrobial, antifungal and anti-inflammatory capacity., Aim of the Study: The current study aims to examine the contribution of partially pyrolysed and non-pyrolysed essential oils in traditional usage of Eremophila longifolia., Materials and Methods: Non-pyrolysed and partially pyrolysed essential oils were produced by hydrodistillation and part-wet/part-dry distillation, respectively. All samples were tested for antimicrobial activity by broth dilution. Some of these samples were further treated to an incrementally stepped temperature profile in a novel procedure employing a commercial thermocycler in an attempt to mimic the effect of temperature gradients produced during smoking ceremonies. Components from the pyrodistilled oils were compared with the non-pyrodistilled oils, using GC-MS, GC-FID and HPLC-PAD. The 2,2-diphenyl-1-picrylhydrazyl method, was used to compare free radical scavenging ability., Results: Partially pyrolysed oils had approximately three or more times greater antimicrobial activity, enhanced in cultures warmed incrementally to 60°C and held for 30s and further enhanced if held for 2 min. Partially pyrolysed oils showed a radical scavenging capacity 30-700 times greater than the corresponding non-pyrolysed oils. HPLC-PAD revealed the presence of additional constituents not present in the fresh essential oil., Conclusion: These results, by showing enhanced antimicrobial and antioxidant activities, provide the first known Western scientific justification for the smoking ceremonies involving leaves of Eremophila longifolia. During customary use, both partially pyrolysed as well as non-pyrolysed essential oils may contribute significantly to the overall intended medicinal effect., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)