Nutrition shapes development, health and risk of disease over the life course and across generations. The predominant approaches to understanding these relationships have either been to consider the effects of single nutrients, one at a time, or to consider associations with food types and dietary patterns. Although, to date, the single-nutrient approach has defined much of the scientific enquiry and public debate on the macronutrients - carbohydrate, fat and protein - there is an emerging appreciation that their proportions and quality matter more than their individual effects. Growing evidence demonstrates that macronutrient interactions operate at multiple biological levels, and research on dietary protein has proven a particularly productive entry point for characterizing these mixture effects. In this narrative Review, we begin by analysing key issues and introducing a framework for navigating the complexity of macronutrient mixtures (nutritional geometry), then consider the role of macronutrient proportions on food intake, systemic physiology, health and the risk of disease across the life course. Finally, we discuss how human nutritional biology has been subverted within the modern, industrialized food environment, contributing to the global burden of obesity and related diseases of unhealthy ageing.

Ageing is a complex process influenced by modifiable factors such as diet, which may accelerate or decelerate physiological decline. While chronological age increases uniformly, biological ageing varies between individuals, reflecting differences in health status and the resilience of biological systems. The Klemera-Doubal Method (KDM), a composite biomarker-based index often used as an estimate of biological age, has been associated with morbidity and mortality in large cohorts. This study examined whether dietary manipulation of protein source and macronutrient composition affects KDM estimates in older adults. We analysed data from the Nutrition for Healthy Living study, a 2 × 2 factorial dietary intervention trial involving 104 participants aged 65-75 years. Participants were randomised to one of four diets: omnivorous/high-fat (OHF), omnivorous/high-carbohydrate (OHC), semi-vegetarian/high-fat (VHF) or semi-vegetarian/high-carbohydrate (VHC). KDM-derived δAge (the difference between KDM- and chronological-age) was calculated before and after a 4-week intervention. The OHF group, most like participants' baseline diets, showed no meaningful change in δAge. Compared to OHF, participants in the OHC group showed a significant reduction in δAge. The VHF and VHC groups showed similar reductions in δAge, relative to OHF, though not all reached statistical significance. KDM-derived δAge appears responsive to dietary change within 4 weeks and may offer a useful proxy for evaluating shifts in physiological status. Caution is warranted in interpreting such changes as evidence of biological age reversal as observed shifts may reflect acute physiological responsiveness to dietary inputs rather than altered ageing trajectories. Longer-term treatment would be needed to assess changes in age-related disease risks.

Clozapine is the most effective antipsychotic drug, while also causing the most severe metabolic side effects. The underlying mechanisms of these side effects appear multifactorial and are not entirely understood. We hypothesized that liver sinusoidal endothelial cells (LSEC) dysfunction is linked to the metabolic side effects of clozapine, based on known association between reduced LSEC porosity, hypertriglyceridemia and insulin resistance. Accordingly, we conducted a translational study by assessing the porosity of murine LSECs following clozapine exposure in vitro and correlating serum clozapine concentrations with metabolic parameters in routine human blood samples. The patient data showed a correlation for clozapine serum concentrations with both triglycerides (Spearman’s ρ = 0.47, P = 0.00024) and glucose levels (ρ = 0.24, P = 0.034), but no correlation with LDL cholesterol (ρ = −0.04, P = 0.82) or HDL cholesterol (ρ = −0.22, P = 0.088). The in vitro experiments showed a concentration-dependent reduction in murine LSEC porosity (P for trend = 0.00036). Together, these findings support a link between clozapine exposure and reduced LSEC porosity. This represents a promising point of intervention that potentially could expand safe access to clozapine as a highly effective antipsychotic treatment for a broader population, also in individuals at high risk for metabolic and cardiovascular side effects.

Caloric restriction (CR) with fasting extends lifespan but is difficult to maintain in humans. Here, we compared conventional CR with periods of fasting to an ad libitum-fed low-protein, high-carbohydrate (LPHC) diet diluted 25% with non-digestible fibre. Both approaches similarly enhanced longevity and metabolic health in mice relative to a control diet. Proteomic analysis of liver tissue revealed that CR increased proteins associated with energy and mitochondrial pathways. By contrast, the LPHC diet reduced these pathways but increased the abundance of proteins associated with RNA metabolism and spliceosome pathways. These results for LPHC support the "energy-splicing resilience" axis theory of ageing. Our results suggest that ad libitum-fed diets can be designed to replicate, and potentially enhance, the geroprotective benefits of CR, albeit via different mechanisms, potentially offering a more sustainable dietary approach to longevity extension.

BACKGROUND:As the aging population grows, the care provided to patients with dementia at the end of life represents a critical area of geriatric and palliative care. This study aimed to describe the care provided to hospitalized patients with dementia who died during their hospital stay. METHODS:A retrospective cohort study was conducted at a teaching hospital in Sydney, Australia. The study included patients with dementia who died during hospitalization. Data were collected on demographic characteristics, clinical management, and documentation of key care processes, including advance care planning, resuscitation orders, and discussions about oral nutrition and hydration. RESULTS:The study cohort comprised patients with a mean age of 87.2 ± 7.2 years (n = 100), 63% of whom had lived in nursing homes. Geriatric medicine teams cared for a large proportion of patients (63%), and their patients were more likely to be older, from a nursing home, and to die from pneumonia compared to those admitted in palliative care teams. Recommended care processes were implemented in the majority of patients with advance care planning and resuscitation orders being the most frequently documented, and discussions about oral nutrition and hydration the least frequent. CONCLUSION:This study highlights the integral role of geriatrics services in providing end-of-life care for hospitalized patients with dementia, and underscore opportunities to enhance the quality and consistency of care for this population.

Rodents have been the primary model for mammalian nutritional physiology for decades. Despite an extensive body of literature, controversies remain around the effects of specific nutrients and total energy intake on several aspects of nutritional biology, even in this well-studied model. One approach that is helping to bring clarity to the field is the geometric framework for nutrition (GFN). The GFN is a multidimensional paradigm that can be used to conceptualize nutrition and nutritional effects, design experiments, and interpret results. To date, more than 30 publications have applied the GFN to data from rodent models of nutrition. Here we review the major conclusions from these studies. We pay particular attention to the effects of macronutrients on satiety, glucose metabolism, lifespan and the biology of aging, reproductive function, immune function, and the microbiome. We finish by highlighting several knowledge gaps that became evident upon reviewing this literature.

BACKGROUND:Optimal heart failure (HF) pharmacotherapy (guideline-directed medical therapy and diuretics) in older people with frailty is uncertain due to limited evidence. AIMS:To evaluate utilisation of HF pharmacotherapy and prevalence of polypharmacy, adverse drug events (ADEs), falls, delirium, renal impairment and duration of hospitalisation in older inpatients, according to frailty. METHODS:A retrospective cross-sectional study of the TO HOME cohort of 2000 inpatients ≥75 years admitted for ≥48 h to rehabilitation, geriatric or general medicine from 1 July 2016 to 30 June 2017 across six hospitals in Sydney, Australia. Data were collected from electronic medical records. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification identified HF diagnosis, ADEs and frailty using hospital frailty risk score. Outcomes included utilisation of HF pharmacotherapy; polypharmacy; ADEs, falls, delirium, renal and impairment; and duration of hospitalisation. RESULTS:Among 439 (22.0% of TO HOME cohort) patients with undifferentiated HF, 284 (69.5%) had intermediate or high risk of frailty, and 412 (94%) took ≥1 HF pharmacotherapy, with 357 (81.3%) patients on loop diuretics. Patients with high frailty risk frequently continued beta-blockers (70%) and discontinued renin-angiotensin system inhibitors (57%). Most patients experienced polypharmacy (n = 426, 97.0%). Renal impairment prevalence was 67%-76% across frailty groups. Increasing frailty risk (low, intermediate and high) was associated with increasing prevalence of ADEs (31%, 56% and 84%), falls (12%, 25% and 46%) and delirium (8%, 27% and 49%) and longer hospitalisation. CONCLUSIONS:Frailty, HF-pharmacotherapy changes in hospital and ADEs were common among older inpatients with HF. The association of adverse outcomes according to frailty needs further investigation. Poor documentation of HF phenotype may be a barrier to medication optimisation in older inpatients.

The clearance of peripheral beta amyloid (Aβ) is a potential target for the treatment of Alzheimer’s disease (AD). The liver has been implicated in the elimination of Aβ from the peripheral circulation. Here, the single-pass uptake of Aβ40 in perfused livers from young and old rats (6 to 10 rats per group) was investigated with the multiple indicator dilution technique. Aβ40 had volumes of distribution between those of the vascular marker Evans Blue and the extracellular marker sucrose. The hepatic extraction of Aβ40 was negligible, explained in part by the small permeability surface area products consistent with a high endothelial barrier to liver uptake. There were no substantial effects of age on any of these results. In vitro experiments with isolated hepatocytes and liver sinusoidal endothelial cells showed only very small amounts of Aβ uptake consistent with low intrinsic clearance. These results indicate that the hepatic clearance of Aβ is capacity-limited, explained by the low-permeability surface area products and hepatocyte uptake. However, this does not preclude an effect of aging in longer-term in vivo studies where age-related changes in liver blood flow and protein binding influence liver clearance.

BACKGROUND:Diet is associated with major adverse cardiovascular events (MACE). OBJECTIVE:We evaluated the associations between empirically derived dietary patterns and MACE. DESIGN:Prospective cohort study. SETTING:The Concord Health and Ageing in Men Project, Sydney, Australia. PARTICIPANTS:539 community-dwelling older Australian men aged 75 years and older. METHODS:Men underwent dietary assessment using a validated dietitian-administered diet history questionnaire. Cox regression analyses were conducted between MACE and the three dietary patterns identified from factor analysis. Five-point MACE comprised of all-cause mortality, myocardial infarction (MI), congestive cardiac failure (CCF), coronary revascularisation, and/or ischaemic stroke. Four-point MACE included the four endpoints of MI, CCF, coronary revascularisation, and/or ischaemic stroke, and excluded all-cause mortality. RESULTS:At a median of 5.3 (IQR 4.6-6.3) years of follow-up, the incidences were: five-point MACE 31.2% (n = 168); four-point MACE excluding all-cause mortality 17.8% (n = 96); all-cause mortality 20.1% (n = 111); CCF 11.3% (n = 61); MI 3.7% (n = 20); stroke 3.2% (n = 17); and coronary revascularisation 3.1% (n = 15). In fully adjusted analyses, compared to the bottom tertile, the middle tertile of 'vegetables-legumes-seafood' dietary pattern was associated with reduced five-point MACE (HR 0.67 [95% CI: 0.45, 0.99, P = .047]), and CCF (HR 0.31 [95% CI: 0.15, 0.65, P = .002]), whilst the middle tertile of 'wholegrains-milk-other fruits' dietary pattern was associated with increased five-point MACE (HR 1.78 [95% CI: 1.17, 2.70, P = .007]), four-point MACE (HR 1.92 [95% CI: 1.12, 3.30, P = .018]), and CCF (HR 2.33 [95% CI: 1.17, 4.65, P = .016]). For the 'discretionary-starchy vegetables-processed meats' dietary pattern, a higher score was associated with increased five-point MACE (HR 1.33 [95% CI: 1.09, 1.62, P = .004]), and all-cause mortality (HR 1.63 [95% CI: 1.26, 2.12, P < .001]), and compared to the bottom tertile, the top tertile was associated with increased all-cause mortality (HR 2.26 [95% CI: 1.27, 4.00, P = .005]). CONCLUSION:Older men may benefit from consuming a 'vegetables-legumes-seafood' dietary pattern rather than 'discretionary-starchy vegetables-processed meats' and 'wholegrains-milk-other fruits' dietary patterns for the prevention of MACE.

Plant-based diets reduces the risk of chronic conditions. The interaction between protein source and other macronutrients-fat (F) and carbohydrate (C)-has yet to be investigated. The aim was to assess the main and interactive effects of protein-source (plant vs. animal) and F:C (high or low) and the transition from an Australian diet to a whole food diet on various health markers in older individuals. This single-blinded, parallel, randomised experimental trial used a 2 × 2 factorial design to compare pro-vegetarian (70:30 plant to animal) versus omnivorous (50:50 plant to animal) diets at 14% protein and varying fat-to-carbohydrate ratios (high fat ~40% vs. low fat ~30%) over 4 weeks. Study foods were provided, alcohol consumption was discouraged, and dietary intake was determined through food records. Analysis included both RCT and observational data. Changes in appetite, palatability of diets, and dietary intake were assessed. Body composition, muscle strength, function, gut microbiome, and cardiometabolic health parameters were measured. Data from 113 (of the 128 randomised) individuals aged 65-75 years were analysed. Pro-vegetarian diets reduced diastolic blood pressure, total cholesterol and glucose levels. Moreover, the overall sample exhibited increased short-chain fatty acids and FGF21 levels, as well as improvements in body composition, function, and cardio-metabolic parameters irrespective of dietary treatment. Transitioning to a diet rich in fruit, vegetables, fibre, and moderate protein was associated with improved health markers in older age, with added benefits from pro-vegetarian diets. Further research on long-term effects is needed.

Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years (n 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy. The Energy-adjusted Dietary Inflammatory Index (E-DIITM) was used to assess the inflammatory potential of the diet. Physical performance data were collected via handgrip strength and walking speed tests, and activities of daily living (ADL) and instrumental activities of daily living (IADL) questionnaires, at baseline and 3-year follow-up (n 616). Logistic regression analysis was used to identify associations between diet and incident poor physical function and disability. Both poor antioxidant intake and high E-DII scores at baseline were significantly associated with poor grip strength and ADL disability at 3-year follow-up. No significant associations with walking speed or IADL disability were observed. Individual micronutrient analysis revealed a significant association between the lowest two quartiles of vitamin C intake and poor grip strength. The lowest quartiles of intake for vitamins A, C, E and Zn were significantly associated with incident ADL disability. The study observed that poor antioxidant and anti-inflammatory food intake were associated with odds of developing disability and declining muscle strength in older men. Further interventional research is necessary to clarify the causality of these associations.

Background: Diet may be associated with frailty. Objective: We aimed to evaluate the associations between empirically derived dietary patterns and frailty in older men. Design: Prospective cohort study. Setting: The Concord Health and Ageing in Men Project, Sydney, Australia. Participants: 785 community-dwelling older Australian men aged 75 years and older. Methods: Men underwent dietary assessment using a validated dietitian-administered diet history questionnaire. Factor analysis identified three dietary patterns. Multinomial logistic regression was conducted between frailty and dietary patterns for cross-sectional analyses and longitudinal analyses over a 3-year follow-up. Frailty was defined by the Fried frailty phenotype. Results: Of the 785 men, pre-frailty was prevalent in 47.1% (n = 370), and frailty in 8.3% (n = 65). In fully adjusted cross-sectional analyses, the top tertile and a higher ‘vegetables-legumes-seafood’ dietary pattern score were associated with reduced prevalence of frailty (OR 0.34 [95% CI: 0.12, 0.93, P = .036]) and OR 0.50 [95% CI: 0.30, 0.83, P = .007] respectively). The top tertile of the ‘discretionary-starchy vegetables-processed meats’ dietary pattern was also associated cross-sectionally with increased prevalence of pre-frailty (OR 1.75 [95% CI: 1.08, 2.83, P = .022]). Of the 296 robust men in fully adjusted longitudinal analyses, the incidence of pre-frailty was 52.4% (n = 155), and frailty was 5.4% (n = 16) over a 3-year follow-up. The middle tertile of the ‘vegetables-legumes-seafood’ dietary pattern had a non-significant trend towards reduced incident pre-frailty (OR 0.52 [95% CI: 0.27, 1.00, P = .050]). Conclusion: Consumption of a ‘vegetables-legumes-seafood’ dietary pattern appears to be less favoured by frail older men.

Nutrition profoundly influences the risk for many age-related diseases. Whether nutrition influences human aging biology directly is less clear. Studies in different animal species indicate that reducing food intake ("caloric restriction" [CR]) can increase lifespan and delay the onset of diseases and the biological hallmarks of aging. Obesity has been described as "accelerated aging" and therefore the lifespan and health benefits generated by CR in both aging and obesity may occur via similar mechanisms. Beyond calorie intake, studies based on nutritional geometry have shown that protein intake and the interaction between dietary protein and carbohydrates influence age-related health and lifespan. Studies where animals are calorically restricted by providing free access to diluted diets have had less impact on lifespan than those studies where animals are given a reduced aliquot of food each day and are fasting between meals. This has drawn attention to the role of fasting in health and aging, and exploration of the health effects of various fasting regimes. Although definitive human clinical trials of nutrition and aging would need to be unfeasibly long and unrealistically controlled, there is good evidence from animal experiments that some nutritional interventions based on CR, manipulating dietary macronutrients, and fasting can influence aging biology and lifespan.

Poor nutrition is a risk factor for dental decay in younger people. However, except for sugar, it is unclear if this is true in older age groups. The aim of this study was to analyze the possible associations between overall dietary intake of nutrients and diet quality and the presence of dental decay in community-dwelling older men. A cross-sectional analysis of a longitudinal study with a standardized validated diet history assessment and comprehensive oral health examination in 520 community-dwelling men (mean age: 84 years) participating in the Concord Health and Ageing in Men Project. Nutrient reference values were used to determine if individual micronutrients and macronutrients were meeting recommendations. Acceptable macronutrient distribution ranges (AMDRs) were attained for fat and carbohydrate intakes and were incorporated into a dichotomous variable to determine if the participants were consuming a high fat-low carbohydrate diet. Diagnosis of coronal caries was based on visual criteria and inspection and was completed on each of the five coronal surfaces. Root surface caries was textual changes across four root surfaces. This diagnosis was used to categorize participants by the presence and severity of coronal and root caries. The adjusted logistic regression showed not meeting the recommended intakes for thiamin (odds ratio [OR]: 2.32 95% confidence interval [CI] 1.15-4.67), and zinc (OR: 3.33, 95% CI: 1.71-6.48) were associated with presence of severe root decay. Adjusted analysis also showed that participants who were outside the recommended AMDR for fat (OR: 0.61, 95% CI: 0.38-0.98) and those who consumed a high fat and low carbohydrate diet (OR: 0.56, 95% CI: 0.35-0.91) were less likely to have coronal tooth decay. Our study shows associations between micronutrients and macronutrients and coronal and root surface decay. Although this study cannot prescribe causality or be generalized to all older adults, diet has a possible association with dental decay in older men.

Unraveling the complex interplay between nutrients and drugs via their effects on "omics" features could revolutionize our fundamental understanding of nutritional physiology, personalized nutrition, and, ultimately, human health span. Experimental studies in nutrition are starting to use large-scale "omics" experiments to pick apart the effects of such interacting factors. However, the high dimensionality of the omics features, coupled with complex fully factorial experimental designs, poses a challenge to the analysis. Current strategies for analyzing such types of data are based on between-feature correlations. However, these techniques risk overlooking important signals that arise from the experimental design and produce clusters that are hard to interpret. We present a novel approach for analyzing high-dimensional outcomes in nutriomics experiments, termed experiment-guided NutriOmics DatA cLustering ('eNODAL'). This three-step hybrid framework takes advantage of both Analysis of Variance (ANOVA)-type analyses and unsupervised learning methods to extract maximum information from experimental nutriomics studies. First, eNODAL categorizes the omics features into interpretable groups based on the significance of response to the different experimental variables using an ANOVA-like test. Such groups may include the main effects of a nutritional intervention and drug exposure or their interaction. Second, consensus clustering is performed within each interpretable group to further identify subclusters of features with similar response profiles to these experimental factors. Third, eNODAL annotates these subclusters based on their experimental responses and biological pathways enriched within the subcluster. We validate eNODAL using data from a mouse experiment to test for the interaction effects of macronutrient intake and drugs that target aging mechanisms in mice.

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.

Background & aims: The potential for older adults with obesity to also have sarcopenia, and the health consequences of 'sarcopenic obesity', may be underappreciated by health professionals. The primary aim of this secondary analysis of a prospective cohort study of older men was to explore the prevalence and functional outcomes of sarcopenic obesity based on different consensus definitions.Methods: 1416 community-dwelling men aged & GE;70 years were classified into sarcopenia categories according to the European Working Group on Sarcopenia in Older People (EWGSOP2) definition, and sarcopenic obesity categories according to the European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity (ESPEN-EASO) definition. Descriptive analyses determined prevalence of sarcopenia in obese and non-obese older men. Multivariable analyses compared associations with functional outcomes including activity of daily living (ADL) and instrumental activity of daily living (IADL) disability and 12-month incident falls.Results: According to the EWGSOP2 definition, 12.6% of men had confirmed sarcopenia but only 0.3% of men had sarcopenia and obesity (BMI & GE;30 kg/m2). Conversely, 9.6% of men had sarcopenic obesity according to the ESPEN-EASO definition. Notably, no men with a BMI & GE;32 kg/m2 were classified as having EWGSOP2-confirmed sarcopenia, despite the fact that 60.8% of all men with BMI & GE;32 kg/m2 had low muscle strength. Due to low numbers (N = 4) of obese older men with EWGSOP2-confirmed sarcopenia, associations with functional outcomes were not assessed. Men with sarcopenic obesity according to the ESPEN-EASO definition had significantly lower hand grip strength, higher chair-stands time and slower gait speed (all P < 0.05), increased odds for ADL (odds ratio: 5.02, 95% CI: 1.85-13.58) and IADL (2.18, 1.38 -3.45) disability, and higher 12-month incident falls rates (incident rate ratio: 1.59, 95% CI: 1.03-2.4 4) than men with neither sarcopenia nor obesity. Conclusion: Low muscle strength is common in older men with obesity, but the prevalence of sarcopenia is likely to be underestimated when the EWGSOP2 operational definition is applied in this population. The ESPEN-EASO operational definition of sarcopenic obesity appears to provide a valid approach for identifying older men with obesity who are at risk of poor functional outcomes related to sarcopenia.& COPY; 2023 The Author(s). Published by Elsevier Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Aims Comprehensively investigate prescribing in usual care of hospitalized older people with respect to polypharmacy; potentially inappropriate medications (PIMs) according to Beers criteria; and cumulative anticholinergic and sedative medication exposure calculated with Drug Burden Index (DBI). Specifically, to quantify exposure to these measures on admission, changes between admission and discharge, associations with adverse outcomes and medication costs.Methods Established new retrospective inpatient cohort of 2000 adults aged >= 75 years, consecutively admitted to 6 hospitals in Sydney, Australia, with detailed information on medications, clinical characteristics and outcomes. Conducted cross-sectional analyses of index admission data from cohort.Results Cohort had mean (standard deviation) age 86.0 (5.8) years, 59% female, 21% from residential aged care. On admission, prevalence of polypharmacy was 77%, PIMs 34% and DBI > 0 in 53%. From admission to discharge, mean difference (95% confidence interval) in total number of medications increased 1.05 (0.92, 1.18); while prevalence of exposure to PIMs (-3.8% [-5.4, -2.1]) and mean DBI score (-0.02 [-0.04, -0.01]) decreased. PIMs and DBI score were associated with increased risks (adjusted odds ratio [95% confidence interval]) of falls (PIMs 1.63 [1.28, 2.08]; DBI score 1.21[1.00, 1.46]) and delirium (PIMs 1.76 [1.38, 1.46]; DBI score 1.42 [1.19, 1.71]). Each measure was associated with increased risk of adverse drug reactions (polypharmacy 1.42 [1.19, 1.71]; PIMs 1.87 [1.40, 2.49]; DBI score 1.90 [1.55, 2.15]). Cost (AU$/patient/hospital day) of medications contributing to PIMs and DBI was low ($0.29 and $0.88).Conclusion In this large cohort of older inpatients, usual hospital care results in an increase in number of medications and small reductions in PIMs and DBI, with variable associations with adverse outcomes.