Medicine (RMH) - Research Publications
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ItemNo Preview AvailableUnresolved inflammation during hospitalization is associated with post-discharge institutionalization and mortality in geriatric rehabilitation inpatients: The RESORT cohort(PERGAMON-ELSEVIER SCIENCE LTD, 2021-12)BACKGROUND: Inflammation contributes to adverse health outcomes in community-dwelling populations. Little is known about inflammation in hospitalized older adults and its association with adverse outcomes. This study aimed to evaluate the association of the inflammatory markers C-reactive protein (CRP) and albumin measured during acute and geriatric rehabilitation hospitalization with institutionalization and mortality in geriatric rehabilitation inpatients. METHODS: Within the REStORing health of acutely unwell adulTs (RESORT) cohort, CRP and albumin were measured as part of usual care during acute and geriatric rehabilitation hospitalization. Inflammatory markers are presented as median, peak (CRP: maximum; albumin: minimum), variation (interquartile range) and direction of change (increased CRP or decreased albumin: positive or negative difference between last measurement and median of preceding measurements). Logistic regression was used to determine the associations between inflammatory markers and institutionalization at three-month and all-cause mortality at three- and twelve-month post-discharge. RESULTS: Geriatric rehabilitation inpatients (n = 1846) with a median age of 83.3 years (interquartile range 77.6-88.3) and 56.6% of female were included. Increased CRP during geriatric rehabilitation was associated with institutionalization. Higher median, peak and increased levels of CRP during geriatric rehabilitation but not during acute hospitalization were associated with higher mortality. Lower CRP variation during acute hospitalization but higher CRP variation during geriatric rehabilitation was associated with higher mortality. Lower median level of albumin during both hospitalizations were associated with higher mortality. CONCLUSIONS: Inflammation characterized by lower albumin during acute hospitalization and, higher CRP and lower albumin during geriatric rehabilitation was associated with mortality in geriatric rehabilitation inpatients. Increased CRP during geriatric rehabilitation was associated with institutionalization. Unresolved inflammation in geriatric rehabilitation might indicate ongoing disease activity leading to adverse outcomes.
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ItemNo Preview AvailableTargeting impaired nutrient sensing with repurposed therapeutics to prevent or treat age-related cognitive decline and dementia: A systematic review(ELSEVIER IRELAND LTD, 2021-05)BACKGROUND: Dementia is a debilitating syndrome that significantly impacts individuals over the age of 65 years. There are currently no disease-modifying treatments for dementia. Impairment of nutrient sensing pathways has been implicated in the pathogenesis of dementia, and may offer a novel treatment approach for dementia. AIMS: This systematic review collates all available evidence for Food and Drug Administration (FDA)-approved therapeutics that modify nutrient sensing in the context of preventing cognitive decline or improving cognition in ageing, mild cognitive impairment (MCI), and dementia populations. METHODS: PubMed, Embase and Web of Science databases were searched using key search terms focusing on available therapeutics such as 'metformin', 'GLP1', 'insulin' and the dementias including 'Alzheimer's disease' and 'Parkinson's disease'. Articles were screened using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). The risk of bias was assessed using the Cochrane Risk of Bias tool v 2.0 for human studies and SYRCLE's risk of bias tool for animal studies. RESULTS: Out of 2619 articles, 114 were included describing 31 different 'modulation of nutrient sensing pathway' therapeutics, 13 of which specifically were utilized in human interventional trials for normal ageing or dementia. Growth hormone secretagogues improved cognitive outcomes in human mild cognitive impairment, and potentially normal ageing populations. In animals, all investigated therapeutic classes exhibited some cognitive benefits in dementia models. While the risk of bias was relatively low in human studies, this risk in animal studies was largely unclear. CONCLUSIONS: Modulation of nutrient sensing pathway therapeutics, particularly growth hormone secretagogues, have the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.
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ItemNo Preview AvailableSenescence in tissue samples of humans with age-related diseases: A systematic review(ELSEVIER IRELAND LTD, 2021-07)BACKGROUND: Higher numbers of senescent cells have been implicated in age-related disease pathologies. However, whether different diseases have different senescent phenotypes is unknown. Here we provide a systematic overview of the current available evidence of senescent cells in age-related diseases pathologies in humans and the markers currently used to detect senescence levels in humans. METHODS: PubMed, Web of Science and EMBASE were systematically searched from inception to the 29th of September 2019, using keywords related to 'senescence', 'age-related diseases' and 'biopsies'. RESULTS: In total 12,590 articles were retrieved of which 103 articles were included in this review. The role of senescence in age-related disease has been assessed in 9 different human organ system and 27 different age-related diseases of which heart (27/103) and the respiratory systems (18/103) are the most investigated. Overall, 27 different markers of senescence have been used to determine cellular senescence and the cell cycle regulator p16ink4a is most often used (23/27 age-related pathologies). CONCLUSION: This review demonstrates that a higher expression of senescence markers are observed within disease pathologies. However, not all markers to detect senescence have been assessed in all tissue types.
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ItemTrajectories of functional performance recovery after inpatient geriatric rehabilitation: an observational study(WILEY, 2021-08)OBJECTIVE: To identify functional performance trajectories and the characteristics of people who receive inpatient geriatric rehabilitation after hospital admissions. DESIGN, SETTING, PARTICIPANTS: REStORing health of acutely unwell adulTs (RESORT) is an observational, prospective, longitudinal inception cohort study of consecutive patients admitted to geriatric rehabilitation wards at the Royal Melbourne Hospital. Recruitment commenced on 15 October 2017. MAIN OUTCOME MEASURES: Functional performance, assessed with the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales two weeks before acute hospitalisation, on admission to and discharge from geriatric rehabilitation, and three months after discharge from geriatric rehabilitation. RESULTS: A total of 618 rehabilitation patients were included in our analysis. For each of the two scales, three distinct functional performance trajectories were identified by latent class growth modelling: poor at baseline and 3-month follow-up (remained poor: ADL, 6.6% of patients; IADL, 42%), good at baseline but poor recovery (deteriorated: ADL, 33%; IADL, 20%), and good at baseline and good recovery (recovered: ADL, 60%; IADL, 35%). Higher Clinical Frailty Scale (CFS) score (v recovered, per point: odds ratio [OR], 2.51; 95% CI, 1.64-3.84) and cognitive impairment (OR, 6.33; 95% CI, 2.09-19.1) were associated with greater likelihood of remaining poor in ADL, and also with deterioration (CFS score: OR, 1.76; 95% CI, 1.45-2.13; cognitive impairment: OR, 1.87; 95% CI, 1.24-2.82). Higher CFS score (OR, 1.64; 95% CI, 1.37-1.97) and cognitive impairment (OR, 3.60; 95% CI, 2.31-5.61) were associated with remaining poor in IADL, and higher CFS score was also associated with deterioration (OR, 1.63; 95% CI, 1.33-1.99). CONCLUSIONS: Based on ADL assessments, most people who underwent inpatient geriatric rehabilitation regained their baseline functional performance. As higher CFS score and cognitive impairment were associated with poorer functional recovery, assessing frailty and cognition at hospital admission could assist intervention and discharge planning.