Medicine (Western Health) - Research Publications

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    Muscle and Bone: An Indissoluble Union
    Kirk, B ; Duque, G (WILEY, 2022-07)
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    Defining terms commonly used in sarcopenia research: a glossary proposed by the Global Leadership in Sarcopenia (GLIS) Steering Committee
    Cawthon, PM ; Visser, M ; Arai, H ; Avila-Funes, JA ; Barazzoni, R ; Bhasin, S ; Binder, E ; Bruyere, O ; Cederholm, T ; Chen, L-K ; Cooper, C ; Duque, G ; Fielding, RA ; Guralnik, J ; Kiel, DP ; Kirk, B ; Landi, F ; Sayer, AA ; Von Haehling, S ; Woo, J ; Cruz-Jentoft, AJ (SPRINGER, 2022-12)
    METHODS: The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings. RESULTS: Several terms that are commonly used in sarcopenia research are defined, including self-reported measures of function and ability; objective physical performance tests; and measures related to muscle function and size. CONCLUSION: As new methods and technologies are developed, these definitions may be expanded or refined over time. Our goal is to promote this common language to describe sarcopenia and its components in clinical and research settings in order to increase clinical awareness and research interest in this important condition. We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.
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    Screening, Diagnosis and Management of Sarcopenia and Frailty in Hospitalized Older Adults: Recommendations from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Expert Working Group
    Daly, RM ; Iuliano, S ; Fyfe, JJ ; Scott, D ; Kirk, B ; Thompson, MQ ; Dent, E ; Fetterplace, K ; Wright, ORL ; Lynch, GS ; Zanker, J ; Yu, S ; Kurrle, S ; Visvanathan, R ; Maier, AB (ELSEVIER SCIENCE INC, 2022-06)
    Sarcopenia and frailty are highly prevalent conditions in older hospitalized patients, which are associated with a myriad of adverse clinical outcomes. This paper, prepared by a multidisciplinary expert working group from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR), provides an up-to-date overview of current evidence and recommendations based on a narrative review of the literature for the screening, diagnosis, and management of sarcopenia and frailty in older patients within the hospital setting. It also includes suggestions on potential pathways to implement change to encourage widespread adoption of these evidence-informed recommendations within hospital settings. The expert working group concluded there was insufficient evidence to support any specific screening tool for sarcopenia and recommends an assessment of probable sarcopenia/sarcopenia using established criteria for all older (≥65 years) hospitalized patients or in younger patients with conditions (e.g., comorbidities) that may increase their risk of sarcopenia. Diagnosis of probable sarcopenia should be based on an assessment of low muscle strength (grip strength or five times sit-to-stand) with sarcopenia diagnosis including low muscle mass quantified from dual energy X-ray absorptiometry, bioelectrical impedance analysis or in the absence of diagnostic devices, calf circumference as a proxy measure. Severe sarcopenia is represented by the addition of impaired physical performance (slow gait speed). All patients with probable sarcopenia or sarcopenia should be investigated for causes (e.g., chronic/acute disease or malnutrition), and treated accordingly. For frailty, it is recommended that all hospitalized patients aged 70 years and older be screened using a validated tool [Clinical Frailty Scale (CFS), Hospital Frailty Risk Score, the FRAIL scale or the Frailty Index]. Patients screened as positive for frailty should undergo further clinical assessment using the Frailty Phenotype, Frailty Index or information collected from a Comprehensive Geriatric Assessment (CGA). All patients identified as frail should receive follow up by a health practitioner(s) for an individualized care plan. To treat older hospitalized patients with probable sarcopenia, sarcopenia, or frailty, it is recommended that a structured and supervised multi-component exercise program incorporating elements of resistance (muscle strengthening), challenging balance, and functional mobility training be prescribed as early as possible combined with nutritional support to optimize energy and protein intake and correct any deficiencies. There is insufficient evidence to recommend pharmacological agents for the treatment of sarcopenia or frailty. Finally, to facilitate integration of these recommendations into hospital settings organization-wide approaches are needed, with the Spread and Sustain framework recommended to facilitate organizational culture change, with the help of 'champions' to drive these changes. A multidisciplinary team approach incorporating awareness and education initiatives for healthcare professionals is recommended to ensure that screening, diagnosis and management approaches for sarcopenia and frailty are embedded and sustained within hospital settings. Finally, patients and caregivers' education should be integrated into the care pathway to facilitate adherence to prescribed management approaches for sarcopenia and frailty.
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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)
    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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    The prevention of osteoporosis and sarcopenia in older adults
    Coll, PP ; Phu, S ; Hajjar, SH ; Kirk, B ; Duque, G ; Taxel, P (WILEY, 2021-05)
    Osteoporosis and sarcopenia are common in older adults. Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Bone fractures can result in changes in posture, pain, the need for surgical repair and functional impairment. Sarcopenia is the progressive and generalized loss of skeletal muscle mass, strength and/or physical performance. Older adults with sarcopenia experience increased risk of frailty, disability, hospitalizations, mortality, and a reduced quality of life. In this narrative review we provide guidance regarding the prevention of both osteoporosis and sarcopenia, including interventions that prevent both conditions from occurring, recommended screening and treatment to prevent progression.
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    Leucine-enriched whey protein supplementation, resistance-based exercise, and cardiometabolic health in older adults: a randomized controlled trial
    Kirk, B ; Mooney, K ; Vogrin, S ; Jackson, M ; Duque, G ; Khaiyat, O ; Amirabdollahian, F (WILEY, 2021-12)
    BACKGROUND: Increasing protein intake (above the Recommended Dietary Amount) alone or with resistance-based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. METHODS: The Liverpool Hope University-Sarcopenia Aging Trial (LHU-SAT) was a 16 week RCT (ClinicalTrials.gov Identifier: NCT02912130) of 100 community-dwelling older adults [mean age: 68.73 ± 5.80 years, body mass index: 27.06 ± 5.18 kg/m2 (52% women)] who were randomized to four independent groups [Control (C), Exercise (E), Exercise + Protein (EP), Protein (P)]. E and EP completed supervised and progressive resistance-based exercise (resistance exercise: two times per week, functional circuit exercise: once per week), while EP and P were supplemented with a leucine-enriched whey protein drink (three times per day) based on individual body weight (0.50 g/kg/meal, 1.50 g/kg/day). Outcome measures including arterial stiffness (pulse wave velocity), fasting plasma/serum biomarkers [glucose/glycated haemoglobin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, insulin, resistin, leptin, adiponectin, C-reactive protein, tumour necrosis factor-alpha, interleukin-6, cystatin-C, & ferritin], insulin resistance (HOMA-IR), and kidney function (eGFR) were measured before and after intervention. RESULTS: Total protein intake (habitual diet plus supplementation) increased to 1.55 ± 0.69 g/kg/day in EP and to 1.93 ± 0.72 g/kg/day in P, and remained significantly lower (P < 0.001) in unsupplemented groups (E: 1.08 ± 0.33 g/kg/day, C: 1.00 ± 0.26 g/kg/day). At 16 weeks, there was a group-by-time interaction whereby absolute changes in LDL-cholesterol were lower in EP [mean difference: -0.79 mmol/L, 95% confidence interval (CI): -1.29, -0.28, P = 0.002] and P (mean difference: -0.76 mmol/L, 95% CI: -1.26, -0.26, P = 0.003) vs. C. Serum insulin also showed group-by-time interactions at 16 weeks whereby fold changes were lower in EP (mean difference: -0.40, 95% CI: -0.65, -0.16, P = 0.001) and P (mean difference: -0.32, 95% CI: -0.56, -0.08, P = 0.009) vs. C, and fold changes in HOMA-IR improved in EP (mean difference: -0.37, 95% CI: -0.64, -0.10, P = 0.007) and P (mean difference: -0.27, 95% CI: -0.53, -0.00, P = 0.048) vs. C. Serum resistin declined in P only (group-by-time interaction at 16 weeks: P = 0.009). No other interactions were observed in outcome measures (P > 0.05), and kidney function (eGFR) remained unaltered. CONCLUSIONS: Sixteen weeks of leucine-enriched whey protein supplementation alone and combined with resistance-based exercise improved cardiometabolic health markers in older adults.
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    International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines
    Izquierdo, M ; Merchant, RA ; Morley, JE ; Anker, SD ; Aprahamian, I ; Arai, H ; Aubertin-Leheudre, M ; Bernabei, R ; Cadore, EL ; Cesari, M ; Chen, L-K ; de Souto Barreto, P ; Duque, G ; Ferrucci, L ; Fielding, RA ; Garcia-Hermoso, A ; Gutierrez-Robledo, LM ; Harridge, SDR ; Kirk, B ; Kritchevsky, S ; Landi, F ; Lazarus, N ; Martin, FC ; Marzetti, E ; Pahor, M ; Ramirez-Velez, R ; Rodriguez-Manas, L ; Rolland, Y ; Ruiz, JG ; Theou, O ; Villareal, DT ; Waters, DL ; Won, CW ; Woo, J ; Vellas, B ; Singh, MF (SPRINGER FRANCE, 2021-07)
    The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.
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    Diagnostic Power of Circulatory Metabolic Biomarkers as Metabolic Syndrome Risk Predictors in Community-Dwelling Older Adults in Northwest of England (A Feasibility Study)
    Hassannejad, R ; Sharrouf, H ; Haghighatdoost, F ; Kirk, B ; Amirabdollahian, F (MDPI, 2021-07)
    BACKGROUND: Metabolic Syndrome (MetS) is a cluster of risk factors for diabetes and cardiovascular diseases with pathophysiology strongly linked to aging. A range of circulatory metabolic biomarkers such as inflammatory adipokines have been associated with MetS; however, the diagnostic power of these markers as MetS risk correlates in elderly has yet to be elucidated. This cross-sectional study investigated the diagnostic power of circulatory metabolic biomarkers as MetS risk correlates in older adults. METHODS: Hundred community dwelling older adults (mean age: 68.7 years) were recruited in a study, where their blood pressure, body composition and Pulse Wave Velocity (PWV) were measured; and their fasting capillary and venous blood were collected. The components of the MetS; and the serum concentrations of Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Plasminogen Activator Inhibitor-I (PAI-I), Leptin, Adiponectin, Resistin, Cystatin-C, C-Reactive Protein (CRP), insulin and ferritin were measured within the laboratory, and the HOMA1-IR and Atherogenic Index of Plasma (AIP) were calculated. RESULTS: Apart from other markers which were related with some cardiometabolic (CM) risk, after Bonferroni correction insulin had significant association with all components of Mets and AIP. These associations also remained significant in multivariate regression. The multivariate odds ratio (OR with 95% confidence interval (CI)) showed a statistically significant association between IL-6 (OR: 1.32 (1.06-1.64)), TNF-α (OR: 1.37 (1.02-1.84)), Resistin (OR: 1.27 (1.04-1.54)) and CRP (OR: 1.29 (1.09-1.54)) with MetS risk; however, these associations were not found when the model was adjusted for age, dietary intake and adiposity. In unadjusted models, insulin was consistently statistically associated with at least two CM risk factors (OR: 1.33 (1.16-1.53)) and MetS risk (OR: 1.24 (1.12-1.37)) and in adjusted models it was found to be associated with at least two CM risk factors and MetS risk (OR: 1.87 (1.24-2.83) and OR: 1.25 (1.09-1.43)) respectively. Area under curve (AUC) for receiver operating characteristics (ROC) demonstrated a good discriminatory diagnostics power of insulin with AUC: 0.775 (0.683-0.866) and 0.785 by cross validation and bootstrapping samples for at least two CM risk factors and AUC: 0.773 (0.653-0.893) and 0.783 by cross validation and bootstrapping samples for MetS risk. This was superior to all other AUC reported from the ROC analysis of other biomarkers. Area under precision-recall curve for insulin was also superior to all other markers (0.839 and 0.586 for at least two CM risk factors and MetS, respectively). CONCLUSION: Fasting serum insulin concentration was statistically linked with MetS and its risk, and this link is stronger than all other biomarkers. Our ROC analysis confirmed the discriminatory diagnostic power of insulin as CM and MetS risk correlate in older adults.
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    Body composition reference ranges in community-dwelling adults using dual-energy X-ray absorptiometry: the Australian Body Composition (ABC) Study
    Kirk, B ; Bani Hassan, E ; Brennan-Olsen, S ; Vogrin, S ; Bird, S ; Zanker, J ; Phu, S ; Meerkin, JD ; Heymsfield, SB ; Duque, G (WILEY, 2021-08)
    BACKGROUND: Reference ranges for lean mass (LM) and fat mass (FM) are essential in identifying soft tissue disorders; however, no such reference ranges exist for the most commonly used Hologic dual-energy X-ray absorptiometry (DXA) machine in Australia. METHODS: Cross-sectional study of community-dwelling adults (aged 18-88 years) who underwent a Hologic DXA scan at one of three commercialized densitometry centres in Australia. Age-specific and sex-specific percentile curves were generated for LM [LM, appendicular lean mass (ALM), ALM adjusted for height squared (ALM/h2 ), and ALM adjusted for body mass index (ALM/BMI)] and FM [FM, FM adjusted for height squared (FM/h2 ), appendicular fat mass, and android and gynoid fat] parameters using the LMS statistical method. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations below the young mean reference group (20-29 years) were also generated for LM parameters. RESULTS: A total of 15 479 community-dwelling adults (54% men) with a median age of 33 years (interquartile range: 28, 42) were included. LM, ALM, and ALM/h2 remained stable until age 50, after which these parameters started to decline in both sexes. Compared with age 50, median percentiles of LM, ALM, and ALM/h2 declined by -5.9 kg, -3.7 kg, and -0.86 kg/m2 in men and by -2.5 kg, -1.8 kg, and -0.10 kg/m2 in women at age 70, respectively. Adjusting ALM for BMI (rather than height squared) resulted in different trends, with ALM/BMI decreasing from as early as age 20. Compared with age 20, median percentiles of ALM/BMI at age 40 declined by -0.10 kg/kg/m2 in men and by -0.06 kg/kg/m2 in women; and at age 70, ALM/BMI declined by -0.25 kg/kg/m2 in men and by -0.20 kg/kg/m2 in women. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations for ALM/BMI were 1.01, 0.86, and 0.77 kg/kg/m2 in men and 0.70, 0.59, and 0.53 kg/kg/m2 in women, respectively. All FM parameters progressively increased from age 20 and continued up until age 70. CONCLUSIONS: We developed reference ranges for LM and FM parameters from Hologic DXA machines in a large cohort of Australian adults, which will assist researchers and clinicians in identifying soft tissue disorders such as obesity, sarcopenia, and cachexia.
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    Current Evidence and Possible Future Applications of Creatine Supplementation for Older Adults
    Candow, DG ; Forbes, SC ; Kirk, B ; Duque, G (MDPI, 2021-03)
    Sarcopenia, defined as age-related reduction in muscle mass, strength, and physical performance, is associated with other age-related health conditions such as osteoporosis, osteosarcopenia, sarcopenic obesity, physical frailty, and cachexia. From a healthy aging perspective, lifestyle interventions that may help overcome characteristics and associated comorbidities of sarcopenia are clinically important. One possible intervention is creatine supplementation (CR). Accumulating research over the past few decades shows that CR, primarily when combined with resistance training (RT), has favourable effects on aging muscle, bone and fat mass, muscle and bone strength, and tasks of physical performance in healthy older adults. However, research is very limited regarding the efficacy of CR in older adults with sarcopenia or osteoporosis and no research exists in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia. Therefore, the purpose of this narrative review is (1) to evaluate and summarize current research involving CR, with and without RT, on properties of muscle and bone in older adults and (2) to provide a rationale and justification for future research involving CR in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia.