Search

The International Union of Basic and Clinical Pharmacology (IUPHAR) Geriatric Committee aims to improve the use of drugs in older adults and develop new therapeutic approaches for the syndromes and diseases of old age through advocacy, education, and research. In the present paper, we propose strategies relevant to drug development and evaluation, spanning preclinical and the full range of clinical studies. Drugs for older adults need to consider not only age, but also other characteristics common in geriatric patients, such as multimorbidity, polypharmacy, falls, cognitive impairment, and frailty. The IUPHAR Geriatric Committee's position statement on 'Measurement of Frailty in Drug Development and Evaluation' is included, highlighting 12 key principles that cover the spectrum of translational research. We propose that where older adults are likely to be major users of a drug, that frailty is measured at baseline and as an outcome. Preclinical models that replicate the age, frailty, duration of exposure, comorbidities, and co‐medications of the proposed patients may improve translation. We highlight the potential application of recent technologies, such as physiologically based pharmacokinetic–pharmacodynamic modeling informed by frailty biology, and Artificial Intelligence, to inform personalized medicine for older patients. Considerations for the rapidly aging populations in low‐ and middle‐income countries related to health‐care and clinical trials are outlined. Involving older adults, their caregivers and health‐care providers in all phases of research should improve drug development, evaluation, and outcomes for older adults internationally. [ABSTRACT FROM AUTHOR]

Objective(s): To understand Australian health professionals' perceptions of their knowledge and previous training about frailty, as well as barriers to frailty assessment and management in their practice. Methods: A cross‐sectional online survey was developed and distributed to health professionals (medical, nursing and allied health) engaged in clinical practice in Australia through convenience and snowball sampling techniques from March to May 2022. The survey consisted of five sections: frailty training and knowledge; confidence in recognising and managing adults with frailty; the importance and relevance of frailty; barriers to assessing and managing frailty in practice; and interest in further frailty training. Responses were analysed using descriptive statistics. Results: The survey was taken by 736 health professionals. Less than half of respondents (44%, 321/733) reported receiving any training on frailty, with 14% (105/733) receiving training specifically focussed on frailty. Most respondents (78%, 556/712) reported 'good' or 'fair' understanding of frailty. The majority (64%, 448/694) reported being 'fairly' or 'somewhat' confident with identifying frailty. Almost all respondents (>90%) recognised frailty as having an important impact on outcomes and believed that there are beneficial interventions for frailty. Commonly reported barriers to frailty assessment in practice included 'lack of defined protocol for managing frailty' and 'lack of consensus about which frailty assessment tool to use'. Most respondents (88%, 521/595) were interested in receiving further education on frailty, with a high preference for online training. Conclusions: The findings suggest frailty is important to health professionals in Australia, and there is a need for and interest in further frailty education. [ABSTRACT FROM AUTHOR]

Background: Ageing, sex and polypharmacy affect physical function. Objectives: This mouse study investigates how ageing, sex and polypharmacy interact and affect grip strength, balance beam and wire hang, correlating and comparing the different test results between and within subgroups. Methods: Young (2.5 months) and old (21.5 months) C57BL/6 J male and female mice (n = 10–6/group) were assessed for physical function at baseline on grip strength, balance beam and wire hang with three trials of 60 s (WH60s) and one trial of 300 s (WH300s). Mice were randomised to control or diet containing a high Drug Burden Index (DBI, total anticholinergic and sedative drug exposure) polypharmacy regimen (metoprolol, simvastatin, citalopram, oxycodone and oxybutynin at therapeutic oral doses). Following 6–8 weeks of treatment, mice were reassessed. Results: High DBI polypharmacy and control mice both showed age group differences on all tests (p < 0.05). Only control mice showed sex differences, with females outperforming males on the WH60s and balance beam for old mice, WH300s for young mice (p < 0.05). Polypharmacy reduced grip strength in all subgroups (p < 0.05) and only in old females reduced wire hang time and cumulative behaviour and balance beam time and %walked (p < 0.05). Physical function assessments were all correlated with each other, with differences between subgroups (p < 0.05), and mice within subgroups showed interindividual variability in performance. Conclusion: Age, sex and polypharmacy have variable effects on different tests, and behavioural measures are useful adjuvants to assessing performance. There was considerable within‐group variability in change in measures over time. These findings can inform design and sample size of future studies. [ABSTRACT FROM AUTHOR]

The impact of age on mesenchymal stromal cell (MSC) characteristics has been well researched. However, increased age is concomitant with increased prevalence of polypharmacy. This adjustable factor may have further implications for the functionality of MSCs and the effectiveness of autologous MSC procedures. We applied hyperspectral microscopy of cell autofluorescence—a non-invasive imaging technique used to characterise cytometabolic heterogeneity—to identify changes in the autofluorescence signals of MSCs from (1) young mice, (2) old mice, (3) young mice randomised to receive polypharmacy (9–10 weeks of oral therapeutic doses of simvastatin, metoprolol, oxycodone, oxybutynin and citalopram), and (4) old mice randomised to receive polypharmacy. Principal Component Analysis and Logistic Regression Analysis were used to assess alterations in spectral and associated metabolic characteristics. Modelling demonstrated that cells from young mice receiving polypharmacy had less NAD(P)H and increased porphyrin relative to cells from old control mice, allowing for effective separation of the two groups (AUC of ROC curve > 0.94). Similarly, cells from old polypharmacy mice were accurately separated from those from young controls due to lower levels of NAD(P)H (p < 0.001) and higher porphyrin (p < 0.001), allowing for an extremely accurate logistic regression (AUC of ROC curve = 0.99). This polypharmacy regimen may have a more profound impact on MSCs than ageing, and can simultaneously reduce optical redox ratio (ORR) and increase porphyrin levels. This has implications for the use of autologous MSCs for older patients with chronic disease. [ABSTRACT FROM AUTHOR]