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Scott I.A.,Princess Alexandra Hospital | Scott I.A.,University of Queensland | Le Couteur D.G.,Ageing and Alzheimers Institute | Le Couteur D.G.,University of Sydney
Internal Medicine Journal

Inappropriate polypharmacy and its associated harm pose a significant threat to older patients. The prescribing decisions of physicians greatly influence what other practitioners prescribe. Minimising medication-related harm requires physicians to adopt a systematic approach to the deliberate and judicious deprescribing of potentially inappropriate medicines in at-risk individuals. © 2015 Royal Australasian College of Physicians. Source

Huizer-Pajkos A.,Kolling Institute of Medical Research | Kane A.E.,Kolling Institute of Medical Research | Kane A.E.,University of Sydney | Howlett S.E.,Dalhousie University | And 8 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences

We aimed to develop a mouse model of polypharmacy, primarily to establish whether short-term exposure to polypharmacy causes adverse geriatric outcomes. We also investigated whether old age increased susceptibility to any adverse geriatric outcomes of polypharmacy. Young (n = 10) and old (n = 21) male C57BL/6 mice were administered control diet or polypharmacy diet containing therapeutic doses of five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen, and citalopram). Mice were assessed before and after the 2- to 4-week intervention. Over the intervention period, we observed no mortality and no change in food intake, body weight, or serum biochemistry in any age or treatment group. In old mice, polypharmacy caused significant declines in locomotor activity (pre minus postintervention values in control 2±13 counts, polypharmacy 32±7 counts, p <.05) and front paw wire holding impulse (control -2.45±1.02 N s, polypharmacy +1.99±1.19 N s, p <.05), loss of improvement in rotarod latency (control -59±11 s, polypharmacy -1.7±17 s, p <.05), and lowered blood pressure (control -0.2±3 mmHg, polypharmacy 11±4 mmHg, p <.05). In young mice, changes in outcomes over the intervention period did not differ between control and polypharmacy groups. This novel model of polypharmacy is feasible. Even short-term polypharmacy impairs mobility, balance, and strength in old male mice. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. Source

Le Couteur D.G.,Ageing and Alzheimers Institute | Le Couteur D.G.,Center for Education and Research on Ageing | Le Couteur D.G.,University of Sydney | McLachlan A.J.,Center for Education and Research on Ageing | And 4 more authors.
Medicine Today

Nearly two-thirds of people aged 75 years or over take five or more medicines. Polypharmacy is associated with adverse outcomes, including geriatric syndromes (e.g. falls and confusion), institutionalisation and mortality. An individualised patient-centred approach that takes into account multimorbidity can help prioritise medicines and identify when deprescribing is indicated. © MedicineToday 2016. Source

Mach J.,Kolling Institute of Medical Research | Mach J.,University of Sydney | Huizer-Pajkos A.,Kolling Institute of Medical Research | Kane A.,Kolling Institute of Medical Research | And 14 more authors.
Experimental Gerontology

Apoptosis is increased in the liver in old age and is a common pathological feature of liver disease. The mitochondria play a key role in regulating apoptosis via the intrinsic death pathway. As the effect of aging on this pathway is unclear, we aimed to characterize the impact of aging on the hepatic intrinsic death pathway and apoptosis. Livers from young adult (6.6. ±. 0.3. months, n. =. 9) and old (25.4. ±. 0.7. months, n. =. 9) male Fischer 344 rats were extracted for cellular fractionation and immunobloting. In old age there were lower mitochondrial protein levels of pro-apoptotic BAK, BID, tBID and VDAC1 (. p<. 0.05) and of anti-apoptotic Bcl-2. Compared to young, old rats had lower cytosolic protein levels of pro-apoptotic BAX, BAK, BID, tBID and anti-apoptotic Bcl-xL (. p<. 0.05). BAK, Bcl-2 and Bcl-xL were found in the cytosol. Furthermore with old age, cytosolic protein levels of cytochrome C, AIF and cleaved caspase-9 did not change but activation of caspase-3, -6 and -7 increased (. p<. 0.05) and DNA fragmentation trended to increase. Our results suggest an age-related decline in the levels of a number of proteins involved in the intrinsic death pathway, an uncoupling of intermediate apoptosis signaling and increased cellular apoptosis in the liver in old age. © 2015 Elsevier Inc. Source

Gnjidic D.,University of Sydney | Gnjidic D.,Ageing and Alzheimers Institute | Bennett A.,University of Sydney | Bennett A.,Kolling Institute of Medical Research | And 15 more authors.
International Journal of Cardiology

Background Guideline recommended management of ischemic heart disease (IHD) suggests the concomitant use of antiplatelet, beta-blocker, renin angiotensin system blocker and statin therapy. In older people exposure to multiple medications has been associated with adverse events and geriatric syndromes. The study aimed to investigate the use of medications for IHD in older men with and without geriatric syndromes, and whether adherence to medication guidelines impacts on adverse outcomes. Methods Community-dwelling men, aged ≥ 70 years and enrolled in the Concord Health and Ageing in Men Project were studied. Data on self-reported IHD, number of guideline recommended medications (use of four guideline medications considered optimal medical therapy) and geriatric syndromes (frailty, falls, cognitive impairment and urinary incontinence) were obtained. Cox regression was used to assess the relationship between optimal medical therapy and adverse outcomes (mortality and institutionalization), stratifying by geriatric syndromes. Results At baseline, 462 (27%) men self-reported a history of IHD and of these, 226 (49%) had at least one geriatric syndrome. Among men with IHD, no significant difference was observed in patterns of prescribing between those with and without geriatric syndromes. Compared to zero medications, optimal medical therapy among men with IHD was associated with lower mortality [hazard ratio, HR = 0.40 (95% CI: 0.21-0.95)] and institutionalization risk (HR = 0.31; 95% CI: 0.09-0.81). The presence of geriatric syndromes did not modify the association of increasing use of guideline recommended medications and clinical outcomes. Conclusion In older men with IHD, greater adherence to medication guidelines appears to be positively associated with better clinical outcomes, independent of geriatric syndromes. © 2015 Elsevier Ireland Ltd. All rights reserved. Source

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