Vasi Naganathan

Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes

OBJECTIVE This study aimed to determine an optimal discriminating number of concomitant medications associated with geriatric syndromes, functional outcomes, and mortality in community-dwelling older men. STUDY DESIGN AND SETTING Older men aged ≥ 70 years (n=1,705), enrolled in the Concord Health and Aging in Men Project were studied. Receiver operating characteristic curve analysis using the Youden Index and the area under the curve was performed to determine discriminating number of medications in relation to each outcome. RESULTS The highest value of the Youden Index for frailty was obtained for a cutoff point of 6.5 medications compared with a cutoff of 5.5 for disability and 3.5 for cognitive impairment. For mortality and incident falls, the highest value of Youden Index was obtained for a cutoff of 4.5 medications. For every one increase in number of medications, the adjusted odds ratios were 1.13 (95% confidence interval [CI]=1.06-1.21) for frailty, 1.08 (95% CI=1.00-1.15) for disability, 1.09 (95% CI=1.04-1.15) for mortality, and 1.07 (95% CI=1.03-1.12) for incident falls. There was no association between increasing number of medications and cognitive impairment. CONCLUSION The study supports the use of five or more medications in the current definition of polypharmacy to estimate the medication-related adverse effects for frailty, disability, mortality, and falls.

Loss of muscle strength, mass (sarcopenia), and quality (specific force) and its relationship with functional limitation and physical disability: the Concord Health and Ageing in Men Project.

OBJECTIVES: To determine the association between loss of muscle strength, mass, and quality and functional limitation and physical disability in older men.

Medication Withdrawal Trials in People Aged 65 Years and Older A Systematic Review

The objective of this review was to assess the benefits and risks of medication withdrawal in older people as documented in published trials of medication withdrawal. This was done by systematic review of the evidence from clinical trials of withdrawal of specific classes of medications in patient populations with a mean age of ≥65 years. We identified all relevant articles published between 1966 and 2007 initially through electronic searches on PubMed and manual searches of review articles. Numerous search terms related to the withdrawal of medication in older people were utilized. Clinical trials identified were reviewed according to predetermined inclusion/exclusion criteria. Only trials that focused on the withdrawal of specific classes of medication were included. Thirty-one published studies (n = 8972 subjects) met the inclusion criteria, including four randomized and placebo-controlled studies (n = 448 subjects) of diuretic withdrawal, nine open-label and prospective observational studies (n = 7188 subjects) of withdrawal of antihypertensives (including diuretics), 16 studies (n = 1184 patients) of withdrawal of sedative, antidepressant, cholinesterase inhibitor and antipsychotic medications, and 1 study each of withdrawal of nitrates and digoxin. These studies were of heterogeneous study design, patient selection criteria and follow-up. Withdrawal of diuretics was maintained in 51–100% of subjects and was unsuccessful primarily when heart failure was present. Adverse effects from medication withdrawal were infrequently encountered. After withdrawal of antihypertensive therapy, many subjects (20–85%) remained normotensive or did not require reinstatement of therapy for between 6 months and 5 years, and there was no increase in mortality. Withdrawal of psychotropic medications was associated with a reduction in falls and improved cognition. In conclusion, there is some clinical trial evidence for the short-term effectiveness and/or lack of significant harm when medication withdrawal is undertaken for antihypertensive, benzodiazepine and psychotropic agents in older people.

Cluster randomised trial of a targeted multifactorial intervention to prevent falls among older people in hospital

Objective To determine the efficacy of a targeted multifactorial falls prevention programme in elderly care wards with relatively short lengths of stay. Design Cluster randomised trial. Setting 24 elderly care wards in 12 hospitals in Sydney, Australia. Participants 3999 patients, mean age 79 years, with a median hospital stay of seven days. Interventions A nurse and physiotherapist each worked for 25 hours a week for three months in all intervention wards. They provided a targeted multifactorial intervention that included a risk assessment of falls, staff and patient education, drug review, modification of bedside and ward environments, an exercise programme, and alarms for selected patients. Main outcome measure Falls during hospital stay. Results Intervention and control wards were similar at baseline for previous rates of falls and individual patient characteristics. Overall, 381 falls occurred during the study. No difference was found in fall rates during follow-up between intervention and control wards: respectively, 9.26 falls per 1000 bed days and 9.20 falls per 1000 bed days (P=0.96). The incidence rate ratio adjusted for individual lengths of stay and previous fall rates in the ward was 0.96 (95% confidence interval 0.72 to 1.28). Conclusion A targeted multifactorial falls prevention programme was not effective among older people in hospital wards with relatively short lengths of stay. Trial registration Australian New Zealand Clinical Trials Registry ACTRNO 12605000467639.

Prevention and treatment of glucocorticoid-induced osteoporosis: A comparison of calcitriol, vitamin D plus calcium, and alendronate plus calcium

High‐dose corticosteroids, used for many medical conditions, are associated with rapid bone loss from sites such as the vertebrae, and compression fractures can be observed within months. Recent trials suggest treatment with bisphosphonates or active vitamin D analogs can reduce bone loss and the risk of fracture associated with glucocorticoids, but few studies have directly compared such agents. We conducted a randomized, multicenter, open‐label trial to compare the efficacy of alendronate, calcitriol, and simple vitamin D in prevention and treatment of glucocorticoid‐induced bone loss. A total of 195 subjects (134 females and 61 males) commencing or already taking glucocorticoids were randomized to one of three groups: calcitriol, 0.5 to 0.75 μg/day; simple vitamin D (ergocalciferol, 30,000 IU weekly) plus calcium carbonate (600 mg daily); or alendronate, 10 mg/day plus calcium carbonate (600 mg daily). Over 2 years, mean lumbar bone mineral density change was +5.9% with alendronate, −0.5% with ergocalciferol, and −0.7% with calcitriol (p < 0.001). At the femoral neck, there was no significant difference in bone mineral density change between the treatments over 2 years: alendronate (+0.9%), ergocalciferol (−3.2%), and calcitriol (−2.2%). Lumbar bone loss varied according to whether patients were starting or receiving chronic glucocorticoids, and there was a significant treatment × prior glucocorticoid use interaction effect. Six of 66 calcitriol subjects, 1 of 61 ergocalciferol subjects, and 0 of 64 alendronate subjects sustained new vertebral fractures. These data do not suggest any difference between simple vitamin D and calcitriol but do show that alendronate was superior to either treatment for glucocorticoid induced bone loss.

Cohort Profile: The Concord Health and Ageing in Men Project (CHAMP)

Epidemiological studies on ageing have tended to focus on women, a phenomenon recognized by sociologists as the feminization of ageing. However, a large percentage of older people are men. For example, in Australia, 44% of those aged 65 and over are male, as are 39% of those aged 75 years and over. Furthermore, the 5–7 year shorter life expectancy for men than women and higher death rates at all ages, including older ages, suggest that more detailed study of the health of older men is essential. Probably the best known study of the health of ageing in men is the Massachusetts Male Aging Study. However, at baseline, men in the Massachusetts Male Aging Study were relatively young, with a mean age of 58 years (range: 40–70 years). The recently established European Male Ageing Study also involves mostly younger men (range: 45–79 years). The Concord Health and Ageing in Men Project (CHAMP) was established to investigate health in old men, defined as age 70 years and over. There is no upper age limit for recruitment into CHAMP. CHAMP is funded by the National Health and Medical Research Council of Australia. Current funding is for baseline assessments and a two-year followup assessment. Additional funding will be sought to allow biennial assessments for at least 10 years. Recruitment of study subjects mainly occurred during 2005 and 2006, with the first follow-up assessments in early 2007. What does it cover?

Drug Burden Index and physical function in older Australian men.

AIMS This study evaluated the associations of physical performance and functional status measures with the Drug Burden Index in older Australian men. The Drug Burden Index is a measure of total exposure to anticholinergic and sedative medications that incorporates the principles of dose-response and maximal effect. METHODS A cross-sectional survey was performed on community-dwelling older men enrolled in The Concord Health and Ageing in Men Project, Sydney, Australia. Outcomes included chair stands, walking speed over 6 m, 20-cm narrow walk speed, balance, grip strength and Instrumental Activities of Daily Living score (IADLs). RESULTS The study population consisted of 1705 men (age 76.9 +/- 5.5 years). Of the 1527 (90%) participants who reported taking medications, 21% were exposed to anticholinergic and 13% to sedative drugs. The average Drug Burden Index in the study population was 0.18 +/- 0.35. After adjusting for confounders (sociodemographics, comorbidities, cognitive impairment, depression), Drug Burden Index was associated with slower walking speed (P < 0.05), slower narrow walk speed (P < 0.05), balance difficulty (P < 0.01), grip weakness (P < 0.01) and poorer performance on IADLs (P < 0.05). Associations with physical performance and function were stronger for the sedative than for the anticholinergic component of the Drug Burden Index. CONCLUSIONS Higher Drug Burden Index is associated with poorer physical performance and functional status in community-dwelling older Australian men. The Drug Burden Index has broad applicability as a tool for assessing the impact of medications on functions that determine independence in older people.

Clinical pharmacology of analgesic medicines in older people: impact of frailty and cognitive impairment

Pain is highly prevalent in frail older people who often have multiple co-morbidities and multiple medicines. Rational prescribing of analgesics in frail older people is complex due to heterogeneity in drug disposition, comorbid medical conditions, polypharmacy and variability in analgesic response in this population. A critical issue in managing older people with pain is the need for judicious choice of analgesics based on a comprehensive medical and medication history. Care is needed in the selection of analgesic medicine to avoid drug-drug or drug-disease interactions. People living with dementia and cognitive impairment have suboptimal pain relief which in part may be related to altered pharmacodynamics of analgesics and challenges in the systematic assessment of pain intensity in this patient group. In the absence of rigorously controlled trials in frail older people and those with cognitive impairment a pharmacologically-guided approach can be used to optimize pain management which requires a systematic understanding of the pharmacokinetics and pharmacodynamics of analgesics in frail older people with or without changes in cognition.

Gender differences in plasma ghrelin and its relations to body composition and bone – an opposite‐sex twin study

Background  Ghrelin, a peptide hormone that plays a role in the regulation of appetite and body adiposity, may also play a role in bone metabolism.

Relationship between pretreatment bone resorption and vertebral fracture incidence in postmenopausal osteoporotic women treated with risedronate.

It is unclear whether the antifracture efficacy of bisphosphonates depends on pretreatment bone turnover. We analyzed the risedronate phase III clinical programs using the urinary excretion of deoxypyridinoline (uDPD) as an index of pretreatment bone resorption rates. Risedronate reduced incident vertebral fractures in women with postmenopausal osteoporosis independent from pretreatment bone resorption.