Medicine (Western Health) - Research Publications

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    A micro-costing analysis of post-fracture care pathways: results from the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS)
    Talevski, J ; Sanders, KM ; Lal, A ; Watts, JJ ; Beauchamp, A ; Duque, G ; Borgstrom, F ; Kanis, JA ; Svedbom, A ; Brennan-Olsen, SL (SPRINGER LONDON LTD, 2022-06-15)
    UNLABELLED: This study identified the costs and health-related quality of life impacts of several post-fracture multidisciplinary care pathways specific to individual skeletal site (hip, distal forearm, vertebrae, humerus). These care pathways may assist healthcare providers in allocating resources for osteoporotic fractures in more effective and cost-efficient ways. INTRODUCTION: This micro-costing study was undertaken to provide the estimated healthcare costs of several fracture site-specific health service use pathways associated with different trajectories of health-related quality of life (HRQoL) 12-months post-fracture. METHODS: The study included 4126 adults aged ≥ 50 years with a fragility fracture (1657 hip, 681 vertebrae, 1354 distal forearm, 434 humerus) from the International Costs & Utilities Related to Osteoporotic fractures Study (ICUROS). ICUROS participants were asked to recall the frequency and duration (where applicable) of their health and community care service use at 4- and 12-month follow-up visits. Patient-level costs were identified and aggregated to determine the average cost of healthcare use related to the fracture in each care pathway (presented in Australian 2021 dollars). Mean cost differences were calculated and analysed using a one-way analysis of variance (ANOVA) and post hoc Bonferroni correction to determine any statistically significant differences. RESULTS: The total direct cost of fractures was estimated at $89564, $38926, $18333, and $38461AUD per patient for hip, vertebral, wrist, and humeral participants, respectively. A Kruskal-Wallis test yielded a statistically significant difference in cost values between most care pathways (p < 0.001). Of the 20 care pathways, those associated with recovery of HRQoL had lower mean costs per patient across each fracture site. CONCLUSIONS: This study identified the costs and HRQoL impacts of several multidisciplinary care pathways for individual fracture sites based on the health service utilization of an international cohort of older adults. These care pathways may assist healthcare providers in allocating resources for fragility fractures in more effective and cost-efficient ways.
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    Tongue muscle mass is associated with total grey matter and hippocampal volumes in Dementia with Lewy Bodies
    Borda, MG ; Castellanos-Perilla, N ; Tovar-Rios, DA ; Ferreira, D ; Duque, G ; Aarsland, D (ELSEVIER IRELAND LTD, 2022-05-01)
    BACKGROUND: Age-related neurodegeneration, sarcopenia, and ectopic fat accumulation are conditions with shared pathways that remain poorly understood. We have measured muscle volume and fat accumulation in masseter and tongue muscle, and aim to explore their association with the total grey matter volume using MRI in older adults recently diagnosed with Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB). METHODS: In this cross-sectional study, people newly diagnosed with mild AD (n=33) and DLB (n=20) underwent structural head MRI. Muscle volume and intramuscular fat (iMAT) of the tongue and masseter were computed using Slice-O-Matic software for segmentation. Total grey volume and hippocampal volumetric segmentation were performed with the FreeSurfer image analysis suite version 6.0. Independent regression models were employed to analyse the associations. RESULTS: Tongue iMAT was higher and total grey volume lower in DLB compared to AD. In the DLB group, tongue muscle was positively associated with total grey matter volume Est 0.92 (SE 0.24 p-value 0.002), left- Est 0.01 (SE 0.0028 p-value 0,002), and right- Est 0.0088 (SE 0.0027 p-value: 0.005) hippocampal volume. There were no statistically significant results for AD. CONCLUSION: Tongue muscle volume was positively associated with hippocampal and total grey volume in DLB. Longitudinal designs are required to explore the extent and significance of this association.
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    Validation of a Semiautomatic Image Analysis Software for the Quantification of Musculoskeletal Tissues
    Imani, M ; Bani Hassan, E ; Vogrin, S ; Ch'Ng, ASTN ; Lane, NE ; Cauley, JA ; Duque, G (SPRINGER, 2021-09-13)
    Accurate quantification of bone, muscle, and their components is still an unmet need in the musculoskeletal field. Current methods to quantify tissue volumes in 3D images are expensive, labor-intensive, and time-consuming; thus, a reliable, valid, and quick application is highly needed. Tissue Compass is a standalone software for semiautomatic segmentation and automatic quantification of musculoskeletal organs. To validate the software, cross-sectional micro-CT scans images of rat femur (n = 19), and CT images of hip and abdomen (n = 100) from the Osteoporotic Fractures in Men (MrOS) Study were used to quantify bone, hematopoietic marrow (HBM), and marrow adipose tissue (MAT) using commercial manual software as a comparator. Also, abdominal CT scans (n = 100) were used to quantify psoas muscle volumes and intermuscular adipose tissue (IMAT) using the same software. We calculated Pearson's correlation coefficients, individual intra-class correlation coefficients (ICC), and Bland-Altman limits of agreement together with Bland-Altman plots to show the inter- and intra-observer agreement between Tissue Compass and commercially available software. In the animal study, the agreement between Tissue Compass and commercial software was r > 0.93 and ICC > 0.93 for rat femur measurements. Bland-Altman limits of agreement was - 720.89 (- 1.5e+04, 13,074.00) for MAT, 4421.11 (- 1.8e+04, 27,149.73) for HBM and - 6073.32 (- 2.9e+04, 16,388.37) for bone. The inter-observer agreement for QCT human study between two observers was r > 0.99 and ICC > 0.99. Bland-Altman limits of agreement was 0.01 (- 0.07, 0.10) for MAT in hip, 0.02 (- 0.08, 0.12) for HBM in hip, 0.05 (- 0.15, 0.25) for bone in hip, 0.02 (- 0.18, 0.22) for MAT in L1, 0.00 (- 0.16, 0.16) for HBM in L1, and 0.02 (- 0.23, 0.27) for bone in L1. The intra-observer agreement for QCT human study between the two applications was r > 0.997 and ICC > 0.99. Bland-Altman limits of agreement was 0.03 (- 0.13, 0.20) for MAT in hip, 0.05 (- 0.08, 0.18) for HBM in hip, 0.05 (- 0.24, 0.34) for bone in hip, - 0.02 (- 0.34, 0.31) for MAT in L1, - 0.14 (- 0.44, 0.17) for HBM in L1, - 0.29 (- 0.62, 0.05) for bone in L1, 0.03 (- 0.08, 0.15) for IMAT in psoas, and 0.02 (- 0.35, 0.38) for muscle in psoas. Compared to a conventional application, Tissue Compass demonstrated high accuracy and non-inferiority while also facilitating easier analyses. Tissue Compass could become the tool of choice to diagnose tissue loss/gain syndromes in the future by requiring a small number of CT sections to detect tissue volumes and fat infiltration.
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    New horizons in falls prevention and management for older adults: a global initiative
    Montero-Odasso, M ; van der Velde, N ; Alexander, NB ; Becker, C ; Blain, H ; Camicioli, R ; Close, J ; Duan, L ; Duque, G ; Ganz, DA ; Gomez, F ; Hausdorff, JM ; Hogan, DB ; Jauregui, JR ; Kenny, RA ; Lipsitz, LA ; Logan, PA ; Lord, SR ; Mallet, L ; Marsh, DR ; Martin, FC ; Milisen, K ; Nieuwboer, A ; Petrovic, M ; Ryg, J ; Sejdic, E ; Sherrington, C ; Skelton, DA ; Speechley, M ; Tan, MP ; Todd, C ; van der Cammen, T ; Verghese, J ; Kamkar, N ; Sarquis-Adamson, Y ; Masud, T (OXFORD UNIV PRESS, 2021-05-26)
    BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects both on quality of life and functional independence and are associated with increased morbidity, mortality and health care costs. Current clinical approaches and advice from falls guidelines vary substantially between countries and settings, warranting a standardised approach. At the first World Congress on Falls and Postural Instability in Kuala Lumpur, Malaysia, in December 2019, a worldwide task force of experts in falls in older adults, committed to achieving a global consensus on updating clinical practice guidelines for falls prevention and management by incorporating current and emerging evidence in falls research. Moreover, the importance of taking a person-centred approach and including perspectives from patients, caregivers and other stakeholders was recognised as important components of this endeavour. Finally, the need to specifically include recent developments in e-health was acknowledged, as well as the importance of addressing differences between settings and including developing countries. METHODS: a steering committee was assembled and 10 working Groups were created to provide preliminary evidence-based recommendations. A cross-cutting theme on patient's perspective was also created. In addition, a worldwide multidisciplinary group of experts and stakeholders, to review the proposed recommendations and to participate in a Delphi process to achieve consensus for the final recommendations, was brought together. CONCLUSION: in this New Horizons article, the global challenges in falls prevention are depicted, the goals of the worldwide task force are summarised and the conceptual framework for development of a global falls prevention and management guideline is presented.
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    The effects of acute exercise on bone turnover markers in middle-aged and older adults: A systematic review
    Smith, C ; Tacey, A ; Mesinovic, J ; Scott, D ; Lin, X ; Brennan-Speranza, TC ; Lewis, JR ; Duque, G ; Levinger, I (ELSEVIER SCIENCE INC, 2021-02-01)
    BACKGROUND: Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs. OBJECTIVES: This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex. METHODS: We searched PubMed, SCOPUS, Web of Science and EMBASE up to 22nd April 2020. Eligibility criteria included randomised controlled trials (RCTs) and single-arm studies that included middle-aged (50 to 65 years) and older adults (>65 years) and, a single-bout, acute-exercise (aerobic, resistance, impact) intervention with measurement of BTMs. PROSPERO registration number CRD42020145359. RESULTS: Thirteen studies were included; 8 in middle-aged (n = 275, 212 women/63 men, mean age = 57.9 ± 1.5 years) and 5 in older adults (n = 93, 50 women/43 men, mean age = 68.2 ± 2.2 years). Eleven studies included aerobic exercise (AE, 7 middle-aged/4 older adults), and two included resistance exercise (RE, both middle-aged). AE significantly increased C-terminal telopeptide (CTX), alkaline phosphatase (ALP) and bone-ALP in middle-aged and older adults. AE also significantly increased total osteocalcin (tOC) in middle-aged men and Procollagen I Carboxyterminal Propeptide and Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in older women. RE alone decreased ALP in older adults. In middle-aged adults, RE with impact had no effect on tOC or BALP, but significantly decreased CTX. Impact (jumping) exercise alone increased Procollagen Type 1 N Propeptide and tOC in middle-aged women. CONCLUSION: Acute exercise is an effective tool to modify BTMs, however, the response appears to be exercise modality-, intensity-, age- and sex-specific. There is further need for higher quality and larger RCTs in this area.
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    Progressive Resistance Training for Concomitant Increases in Muscle Strength and Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis
    O'Bryan, SJ ; Giuliano, C ; Woessner, MN ; Vogrin, S ; Smith, C ; Duque, G ; Levinger, I (ADIS INT LTD, 2022-05-24)
    BACKGROUND: Older adults experience considerable muscle and bone loss that are closely interconnected. The efficacy of progressive resistance training programs to concurrently reverse/slow the age-related decline in muscle strength and bone mineral density (BMD) in older adults remains unclear. OBJECTIVES: We aimed to quantify concomitant changes in lower-body muscle strength and BMD in older adults following a progressive resistance training program and to determine how these changes are influenced by mode (resistance only vs. combined resistance and weight-bearing exercises), frequency, volume, load, and program length. METHODS: MEDLINE/PubMed and Embase databases were searched for articles published in English before 1 June, 2021. Randomized controlled trials reporting changes in leg press or knee extension one repetition maximum and femur/hip or lumbar spine BMD following progressive resistance training in men and/or women ≥ 65 years of age were included. A random-effects meta-analysis and meta-regression determined the effects of resistance training and the individual training characteristics on the percent change (∆%) in muscle strength (standardized mean difference) and BMD (mean difference). The quality of the evidence was assessed using the Cochrane risk-of-bias tool (version 2.0) and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Seven hundred and eighty studies were identified and 14 were included. Progressive resistance training increased muscle strength (∆ standardized mean difference = 1.1%; 95% confidence interval 0.73, 1.47; p ≤ 0.001) and femur/hip BMD (∆ mean difference = 2.77%; 95% confidence interval 0.44, 5.10; p = 0.02), but not BMD of the lumbar spine (∆ mean difference = 1.60%; 95% confidence interval - 1.44, 4.63; p = 0.30). The certainty for improvement was greater for muscle strength compared with BMD, evidenced by less heterogeneity (I2 = 78.1% vs 98.6%) and a higher overall quality of evidence. No training characteristic significantly affected both outcomes (p > 0.05), although concomitant increases in strength and BMD were favored by higher training frequencies, increases in strength were favored by resistance only and higher volumes, and increases in BMD were favored by combined resistance plus weight-bearing exercises, lower volumes, and higher loads. CONCLUSIONS: Progressive resistance training programs concomitantly increase lower-limb muscle strength and femur/hip bone mineral density in older adults, with greater certainty for strength improvement. Thus, to maximize the efficacy of progressive resistance training programs to concurrently prevent muscle and bone loss in older adults, it is recommended to incorporate training characteristics more likely to improve BMD.
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    Evaluation of Clinical Practice Guidelines on Fall Prevention and Management for Older Adults A Systematic Review
    Montero-Odasso, MM ; Kamkar, N ; Pieruccini-Faria, F ; Osman, A ; Sarquis-Adamson, Y ; Close, J ; Hogan, DB ; Hunter, SW ; Kenny, RA ; Lipsitz, LA ; Lord, SR ; Madden, KM ; Petrovic, M ; Ryg, J ; Speechley, M ; Sultana, M ; Tan, MP ; van der Velde, N ; Verghese, J ; Masud, T (AMER MEDICAL ASSOC, 2021-12-15)
    IMPORTANCE: With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking. OBJECTIVES: To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps. EVIDENCE REVIEW: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic. FINDINGS: Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations. CONCLUSIONS AND RELEVANCE: This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.
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    Effects of 3 months of multi-nutrient supplementation on the immune system and muscle and respiratory function of older adults in aged care (The Pomerium Study): protocol for a randomised controlled trial
    Al Saedi, A ; Kirk, B ; Iuliano, S ; Zanker, J ; Vogrin, S ; Jayaram, L ; Thomas, S ; Golding, C ; Navarro-Perez, D ; Marusic, P ; Leng, S ; Nanan, R ; Duque, G (BMJ PUBLISHING GROUP, 2022-05-01)
    INTRODUCTION: Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with SARS-CoV-2 (COVID-19), which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intakes associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the impact of inadequate nutrition can be reversed using multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections and improving respiratory and muscle function. METHODS AND ANALYSIS: The Pomerium Study is a 3-month, single-blind, randomised, controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20 g protein, 1.5 g calcium 3-hydroxy-3-methylbutyrate monohydrate (CaHMB), 449 mg calcium, 500 IU vitamin D3 and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). The primary outcome is a change in T-cell subsets CD8 + and CD28null counts at months 1 and 3. Secondary outcomes measured at baseline and month 3 are multiple markers of immunosenescence (also at 1 month), body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry) and quality of life (EQ-5D-5L). Incidence and complications of COVID-19 and/or viral infections (ie, hospitalisation, complications or death) will be recorded throughout the trial, including 3 months after supplementation is ceased. ETHICS AND DISSEMINATION: This study was approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115). Written informed consent will be obtained from participants. Results will be published in peer-reviewed journals and made available to key aged care stakeholders, including providers, residents, and government bodies. TRIAL REGISTRATION NUMBER: ACTRN12621000420842.
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    COP CELLS AND TISSUE LOSS SYNDROMES: FRAILTY, SARCOPENIA, AND OSTEOPOROSIS
    Duque, G (OXFORD UNIV PRESS, 2021-01-01)
    Abstract COP cells have been identified as having a potential role in the pathogenesis of tissue loss syndromes such as osteoporosis and frailty. This is based on the hypothesis that their dysregulation may cause a decrease in bone and muscle formation, which also increase the risk of adverse outcomes such as frailty and disability. Whereas high numbers of COP cells have been associated with osteoporosis and fracture healing, a low percentage of COP (%COP) cells have been associated with frailty and disability. In addition, low expression of lamin A (a protein of the inner nuclear envelope) in COP cells has also been associated with frailty and disability in older persons. In this session, the evidence on quantification methods for COP cells in clinical settings and the potential clinical use of COP cells in tissue loss syndromes will be discussed. This discussion will include current evidence supporting the use of COP cells as a biomarker or as a novel therapeutic approach to these age-related conditions.
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    Association Between Tryptophan Metabolites, Physical Performance, and Frailty in Older Persons
    Al Saedi, A ; Chow, S ; Vogrin, S ; Guillemin, GJ ; Duque, G (SAGE PUBLICATIONS LTD, 2022-01-01)
    Frailty is defined as a syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes. A robust biomarker for frailty is still lacking. Tryptophan (TRP) metabolism through the kynurenine pathway (KP) plays essential roles in aging, the musculoskeletal system, and physical performance. In this study, we quantified 7 KP metabolites, including kynurenine (KYN), kynurenine acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), and anthranilic acid (AA) using ultra-high-performance liquid chromatography and gas chromatography-mass spectrometry in the serum of 85 participants (median age 75; 65% female; 28 non-frail, 29 pre-frail, and 28 frail) at the Nepean Osteoporosis and Frailty (NOF) Study. We looked at the association between TRP metabolites and physical performance, sarcopenia, and frailty. After adjusting for age and sex, our results showed that KYN and KYN/TRP were associated with higher interleukin (IL)-6 levels (r = .324 and r = .390, respectively). KYNA and its ratios to other products (mainly KYNA/KYN, KYNA/QUIN, and KYNA/PIC) were associated with a lower likelihood of frailty by Fried's criteria (OR 0.93 [0.88, 0.98], P = .009) and Rockwood index (r = -.241, P = .028) as well as a lower likelihood of sarcopenia (OR 0.88 [0.78, 1.00], P = .049). QUIN and QUIN/KYN showed an association with increased IL-6 (r = .293 and .204 respectively), higher likelihood of frailty (OR 1.02 [1.00, 1.04], P = .029 and OR 6.43 [2.23, 18.51], P = .001 respectively) and lower physical function (r = -.205 and r = -.292). In conclusion, different TRP metabolites have various associations with physical performance, frailty, and sarcopenia. Defining the underlying mechanisms may permit the development and validation of new biomarkers and therapeutics for frailty and musculoskeletal conditions targeting specific metabolites of the TRP catabolic pathway.