Medicine (Western Health) - Research Publications
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ItemFragile X syndrome and connective tissue dysregulation(WILEY, 2019-02)Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism spectrum disorders, and it is an X-linked disorder in which there is a deficiency of the fragile X mental retardation 1 protein. This protein is crucial in regulating translation of mRNAs related to dendritic maturation and cognitive development. The phenotype of FXS is characterized by neurobehavioral alterations, social deficits, communication difficulties, and findings which suggest an alteration of connective tissue, especially in the ligaments and muscles, cardiovascular system and genitourinary system. Connective tissue connects and supports all other tissues of the body and is composed of cells and extracellular matrix (ECM). Several proteins have been involved in the connective tissue abnormalities associated with the FXS, such as matrix metalloproteinase 9, which plays an important role in the homeostasis of the ECM, being a potential therapeutic target for certain tetracycline antibiotics that have shown beneficial effects in FXS. Here, we review connective tissue problems described in FXS.
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ItemOsteoporosis in Older Persons: Old and New Players(WILEY, 2019-04)Osteoporosis is the most common bone disease in humans. Older persons are at higher risk of osteoporotic fractures that also result in poor quality of life, disability, loss of independence, institutionalization, and higher mortality. Osteoporosis shares a distinct pathophysiologic relationship with sarcopenia, an age-related disease comprising declines in muscle mass, strength, or function. The combination of these two diseases is known as osteosarcopenia. Understanding the pathophysiology of osteosarcopenia, in addition to its diagnostic and therapeutic approaches, is key in providing older adults with the best falls and fractures prevention strategies. This review provides updated information on new discoveries on the combined pathophysiology of osteoporosis and sarcopenia that have led to the development of novel therapeutic approaches. New recommendations for the use of risk calculators and densitometry are also presented in this review as well as evidence on current and upcoming pharmacologic treatments to prevent falls and fractures in older persons. J Am Geriatr Soc 67:831-840, 2019.
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ItemAssociation between structural changes in brain with muscle function in sarcopenic older women: the women's healthy ageing project (WHAP)(JMNI, 2019-06)OBJECTIVES: The involvement of changes in brain structure in the pathophysiology of muscle loss (sarcopenia) with aging remains unclear. In this study, we investigated the associations between brain structure and muscle strength in a group of older women. We hypothesized that structural changes in brain could correlate with functional changes observed in sarcopenic older women. METHODS: In 150 women (median age of 70 years) of the Women's Healthy Ageing Project (WHAP) Study, brain grey (total and cortex) volumes were calculated using magnetic resonance imaging (MRI) analyses. Grip strength and timed up and go (TUG) were measured. The brain volumes were compared between sarcopenic vs. non-sarcopenic subjects and women with previous falls vs. those without. RESULTS: Based on handgrip strength and TUG results respectively, 27% and 15% of women were classified as sarcopenic; and only 5% were sarcopenic based on both criteria. At least one fall was experienced by 15% of participants. There was no difference in brain volumetric data between those with vs. without sarcopenia (p>0.24) or between women with falls (as a symptom of weakness or imbalance) vs. those without history of falls (p>0.25). CONCLUSIONS: Brain structure was not associated with functional changes or falls in this population of older women.
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ItemEffects of the falls and fractures clinic as an integrated multidisciplinary model of care in Australia: a pre-post study(BMJ PUBLISHING GROUP, 2019-08)OBJECTIVES: Traditionally, the approach to fracture prevention has focused on increasing bone mineral density while typically lacking a combined clinical approach to falls prevention and vice versa. To resolve this gap, we implemented and evaluated a novel combined model of care to the assessment and prevention of osteoporosis and falls in the outpatients setting. SETTING: Falls and Fractures Clinic (FFC) at Nepean Hospital (Penrith, NSW, Australia). PARTICIPANTS: Pre-effects and posteffects assessment of 106 community-dwelling older patients referred from the community. PRIMARY AND SECONDARY OUTCOME MEASURES: Previous falls and fractures were recorded. Clinical, functional and paraclinical evaluations were performed. A comprehensive multidisciplinary care plan was then tailored based on the presence of risk factors. Six-month follow-ups were performed assessing the incidence of falls and fractures, change in risk factors for falls and level of risk, with the recommended plan. RESULTS: We report that 97% of patients had a fall in the preceding 6 months, 47.6% of whom experienced a fracture from the fall. Furthermore, 64% of patients had a marked risk for falling by Physiological Profile Assessment (PPA), 90% had intermediate-high 10-year probability of fracture according to FRAX and 78% had sarcopenia. At 6-month follow-up, we observed more than an 80% reduction in falls and recurrent falls, and 50% reduction in fractures. In addition, 65% of patients had reduced PPA and a 57% reduction in 10-year fracture probability. CONCLUSIONS: In conclusion, we suggest that a multidisciplinary FFC can provide substantial reductions in falls and fractures for high-risk older people, even over a relatively short 6-month time period. The current model of service provision via traditional falls clinics could be significantly improved by encompassing fracture prevention within the multifactorial approach to interventions.
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ItemChanges in Nutritional Status and Musculoskeletal Health in a Geriatric Post-Fall Care Plan Setting(MDPI, 2019-07)Understanding how changes in nutritional status influence musculoskeletal recovery after falling remains unclear. We explored associations between changes in nutritional status and musculoskeletal health in 106 community-dwelling older adults aged ≥65 years, who attended the Falls and Fractures Clinic at Sunshine Hospital in St Albans, Australia after falling. At baseline and after 6 months, individuals were assessed for Mini Nutritional Assessment (MNA®), grip strength, gait speed, Timed Up and Go (TUG) test, Short Physical Performance Battery (SPPB), and bone turnover marker levels. Associations were examined using multiple linear regression, adjusted for baseline covariates and post-fall care plans. Over 6 months, the prevalence of malnutrition or risk thereof decreased from 29% to 15% using MNA <24/30. Specifically, 20 individuals (19%) improved, 7 (7%) deteriorated, and 73 (69%) maintained nutritional status, including 65 (61%) who remained well-nourished and 8 (8%) who remained malnourished/at risk. A 1-point increase in MNA score over 6 months was associated with an increase of 0.20 points (95% confidence interval 0.10, 0.31, p < 0.001) in SPPB score. Improvement in nutritional status was associated with improvement in physical performance, providing a basis for interventional studies to ascertain causality and evaluate nutritional models of care for post-fall functional recovery in older adults.
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ItemExercise interveNtion outdoor proJect in the cOmmunitY for older people - the ENJOY Senior Exercise Park project translation research protocol(BMC, 2019-07-11)BACKGROUND: Creating inclusive and accessible outdoor environments that provide and encourage opportunities for older adults to engage in physical activity and social interaction is important for healthy ageing. The Senior Exercise Park is outdoor exercise equipment designed specifically for use by older people that provides physical and social benefits for older people in the community, and has the potential to be used widely as a sustainable mode of physical activity. The aim of this study is to implement and evaluate the effects of sustained engagement through the use of a community-based novel outdoor physical activity program (purpose-built exercise park) for older people on physical, mental and social health and physical activity outcomes (the ENJOY project). METHODS: This is a prospective pre-post design study with 12 months follow up. Adults aged ≥60 years will be recruited from the general community from the suburbs close to the Senior Exercise Parks locations in Melbourne. Participants will undergo a 12 week structured supervised physical activity program using the outdoor Senior Exercise Park equipment followed by 6 months unstructured physical activity program. Participants will be assessed at baseline, 3, 9, and 12 months. The following outcomes will be assessed: physical activity, physical function, psychosocial and mental health outcomes, falls risk and falls occurrence, participants' feedback and satisfaction, and health care resource use. DISCUSSION: The ENJOY trial is designed to operate in a community setting with local government engagement to maximise the usage of the exercise park and provide an outdoor space for older people to be physically active. This project will evaluate the effectiveness and sustainability of the outdoor exercise park on a range of health outcomes and its long-term usability in the community. TRIAL REGISTRATION: This trial is prospectively registered with the Australian New Zealand Clinical Trials Registry. Trial registration number ACTRN12618001727235 registered 18th of October 2018.
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ItemCurrent and emerging biomarkers of frailty in the elderly(DOVE MEDICAL PRESS LTD, 2019)The term "frailty" is used to describe a subset of older adults who appear weaker and more vulnerable than their age-matched counterparts, despite having similar comorbidities, demography, sex, and age. The diagnosis of frailty is usually clinical and based on specific criteria, which are sometimes inconsistent. Therefore, there is an increasing need to identify and validate robust biomarkers for this condition. In this review, we summarize current evidence on the validity and practicality of the most commonly used biomarkers for frailty, while also comparing them with new upcoming strategies to identify this condition.
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ItemOsteosarcopenia: A case of geroscience.(Wiley, 2019-09)Many older persons lose their mobility and independence due to multiple diseases occurring simultaneously. Geroscience is aimed at developing innovative approaches to better identify relationships among the biological processes of aging. Osteoporosis and sarcopenia are two of the most prevalent chronic diseases in older people, with both conditions sharing overlapping risk factors and pathogenesis. When occurring together, these diseases form a geriatric syndrome termed "osteosarcopenia," which increases the risk of frailty, hospitalizations, and death. Findings from basic and clinical sciences aiming to understand osteosarcopenia have provided evidence of this syndrome as a case of geroscience. Genetic, endocrine, and mechanical stimuli, in addition to fat infiltration, sedentarism, and nutritional deficiencies, affect muscle and bone homeostasis to characterize this syndrome. However, research is in its infancy regarding accurate diagnostic markers and effective treatments with dual effects on muscle and bone. To date, resistance exercise remains the most promising strategy to increase muscle and bone mass, while sufficient quantities of protein, vitamin D, calcium, and creatine may preserve these tissues with aging. More recent findings, from rodent models, suggest treating ectopic fat in muscle and bone marrow as a possible avenue to curb osteosarcopenia, although this needs testing in human clinical trials.