Deprescribing

Medicines have adverse effects and the use of multiple medicines, polypharmacy, can be associated with poorer outcomes. Health professionals need to recognise when medicines should be ceased and how to deprescribe. Deprescribing could be considered when there is polypharmacy, adverse drug reactions, ineffective treatment, falls or when treatment goals have changed. If patients are slowly weaned off their medicines, withdrawal and rebound syndromes are usually not serious. A cautious approach to deprescribing includes two principles - stop one drug at a time and wean doses slowly over weeks and months

First year student expectations: Results from a university-wide student survey

Although much has been written on the first-year experience of students at higher education institutions, less attention has been directed to the expectations of students when they enter an institution for the first time. This paper provides additional insights into the expectations of students at an Australian university and highlights areas in which students’ expectations may not necessarily align with the realities of common university practices. By providing opportunities for students to articulate their expectations, staff are able to use the responses for a constructive dialogue and work towards a more positive alignment between perceived expectations and levels of student satisfaction with their experience.Geoffrey Crisp, Edward Palmer, Deborah Turnbull, Ted Nettelbeck, Lynn Ward, Amanda LeCouteur, Aspa Sarris, Peter Strelan, and Luke Schneide

Evaluating Calculated Free Testosterone as a Predictor of Morbidity and Mortality Independent of Testosterone for Cross-sectional and 5-Year Longitudinal Health Outcomes in Older Men: The Concord Health and Ageing in Men Project

To determine whether calculated free testosterone (cFT) provides prognostic information independent of serum T for predicting morbidity and mortality in older men in cross-sectional and 5-year longitudinal analyses. We studied men aged ≥70 years at baseline (n = 1,705), 2-year and 5-year measuring serum T (liquid chromatography-mass spectrometry), SHBG (immunoassay), cFT (an assumption-free empirical formula) together with 24 morbidity and 4 mortality outcomes. For cross-sectional and longitudinal analyses we employed a joint prediction model using generalized estimating equation models adjusted for age, smoking, comorbidities, and body mass index (BMI) with men having both normal T and normal cFT as referent group. Most morbidity and mortality outcomes were predicted by a combination of low T and cFT (LL). By contrast, only a single morbidity outcome in cross-sectional and none in longitudinal analysis was predicted by low T/normal cFT (LN) or normal T/low cFT (NL) without significant LL associations (isolated discordance). While for the few outcomes that predicted morbidity in men with discordances (LN or NL), these predictions only occurred when LL was also significant. Hence, for morbidity or mortality prediction in older men, discordance between cFT and T is unusual and isolated discordance is rare, so that cFT provides minimal independent prognostic information over serum T.NHMRC, Sydney Medical School Foundation, and Ageing and Alzheimer’s Institute

Does combined osteopenia/osteoporosis and sarcopenia confer greater risk of falls and fracture than either condition alone in older men? The Concord Health and Ageing in Men Project

Background It is unclear whether older men with osteopenia/osteoporosis and sarcopenia (so-called osteosarcopenia) are at greater risk of falls and fractures than those with either condition alone. Methods One thousand five hundred seventy-five community-dwelling men aged ≥70 years had appendicular lean mass, total hip and lumbar spine bone mineral density determined by dual-energy x-ray absorptiometry, and completed hand grip strength and gait speed tests. Osteopenia/osteoporosis was defined as a T-score at any site ≤−1.0 SD. Sarcopenia was defined using the European Working Group on Sarcopenia algorithm. Participants were contacted every 4 months for 6 ± 2 years to ascertain incident fractures (confirmed by radiographic reports) and for 2 years for incident falls. Results Prevalence of osteosarcopenia was 8%, while 34% of participants had osteopenia/osteoporosis alone and 7% had sarcopenia alone. Men with osteosarcopenia had significantly increased fall (incidence rate ratio: 1.41; 95% confidence interval [CI]: 1.02 to 1.95) and fracture risk (hazard ratio: 1.87; 95% CI: 1.07 to 3.26) compared with men with neither osteopenia/osteoporosis nor sarcopenia. There was no statistical interaction between osteopenia/osteoporosis and sarcopenia, and falls and fracture risk were not different for osteosarcopenia compared with either condition alone (all p > .05). Conclusions Community-dwelling older men with combined osteopenia/osteoporosis and sarcopenia do not have increased falls and fracture risk compared with those with either condition. Further research is required to clarify whether the term “osteosarcopenia” has any meaning above and beyond either term alone and therefore potential clinical utility for falls and fracture prediction.NHMRC (project grant number 301916) and the Ageing and Alzheimer’s Institute. D.Scott is supported by a NHRMC Career Development Fellowship (GNT1123014

Community-dwelling men with dementia are at high risk of hip but not any other fracture: The Concord Health and Ageing in Men Project

Aim The aim of the present longitudinal study of community‐dwelling older men was to examine the association between cognitive status at baseline, and falls, fractures and bone loss over time. Methods In the Concord Health and Aging in Men Project, 1705 community‐dwelling men aged 70–97 years had detailed baseline clinical assessment of cognitive status (dementia, mild cognitive impairment [MCI] and normal cognition), as well as depression, physical activity, neuromuscular function, health status, sociodemographics, comorbidities, medication use and serum 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D and parathyroid hormone levels. During a mean follow‐up period of 6 years, participants were contacted 4‐monthly to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Bone mineral density was measured by dual X‐ray absorptiometry at multiple time‐points. Results At baseline, 120 men were assessed to have MCI and 93 men to have dementia. Over time, there were 162 first incident fractures, including 43 hip and 32 vertebral fractures. In univariate models, baseline dementia, but not MCI, predicted an increased incidence of hip fracture (HR 6.95, 95% CI 3.47–13.96), but not vertebral (HR 2.26, 95% CI 0.79–6.46) or non‐hip non‐vertebral fracture (HR 0.73, 95% CI 0.27–1.99). The strong risk of hip fractures associated with dementia remained after accounting for potential confounders (HR 4.44, 95% CI 1.97–9.98). In multivariate analyses, dementia (incidence rate ratio 2.26, 95% CI 1.70–2.99), but not MCI, was associated with an increased risk of falls compared with normal cognition. There was no association between baseline dementia and change in bone mineral density. Conclusions Older men with dementia, but not MCI, have a greater tendency to fall and sustain hip fractures, but not any other types of fractures.NHMRC, Ageing and Alzheimer's Institute, Sydney Medical School Foundatio

The Effects of Old Age on Hepatic Stellate Cells

Aging is associated with marked changes in the hepatic sinusoid, yet the effect of old age on hepatic stellate cells (HSC) has not been well described. Transmission electron microscopy and immunohistochemistry were used to study the effects of aging on HSC in livers from rats (3-4 mths versus 24–27 mths) and mice (2-3 mths versus 20–22 mths). Desmin-positive HSC doubled in old age in both mice and rats. Alpha-smooth muscle actin- (αSMA-) positive cells did not increase significantly and remained only a small percentage of desmin-positive cells. Electron microscopy revealed that old age is associated with HSC that have a substantial increase in the number of lipid droplets which are larger in diameter. There was also a marked increase of HSC that protruded into the sinusoidal lumen in old mice. In conclusion, old age is associated with hyperplasia of HSC that are not activated and are engorged with lipid droplets

High risk prescribing in older adults: Prevalence, clinical and economic implications and potential for intervention at the population level

Background: High risk prescribing can compromise independent wellbeing and quality of life in older adults. The aims of this project are to determine the prevalence, risk factors, clinical consequences, and costs of high risk prescribing, and to assess the impact of interventions on high risk prescribing in older people. Methods. The proposed project will utilise data from the 45 and Up Study, a large scale cohort of 267,153 men and women aged 45 and over recruited during 2006-2009 from the state of New South Wales, Australia linked to a range of administrative health datasets. High risk prescribing will be assessed using three indicators: polypharmacy (use of five or more medicines); Beers Criteria (an explicit measure of potentially inappropriate medication use); and Drug Burden Index (a pharmacologic dose-dependent measure of cumulative exposure to anticholinergic and sedative medicines). Individual risk factors from the 45 and Up Study questionnaire, and health system characteristics from health datasets that are associated with the likelihood of high risk prescribing will be identified. The main outcome measures will include hospitalisation (first admission to hospital, total days in hospital, cause-specific hospitalisation); admission to institutionalised care; all-cause mortality, and, where possible, cause-specific mortality. Economic costs to the health care system and implications of high risk prescribing will be also investigated. In addition, changes in high risk prescribing will be evaluated in relation to certain routine medicines-related interventions. The statistical analysis will be conducted using standard pharmaco-epidemiological methods including descriptive analysis, univariate and multivariate regression analysis, controlling for relevant confounding factors, using a number of different approaches. Discussion. The availability of large-scale data is useful to identify opportunities for improving prescribing, and health in older adults. The size of the 45 and Up Study, along with linkage to health databases provides an important opportunity to investigate the relationship between high risk prescribing and adverse outcomes in a real-world population of older adults. © 2013 Gnjidic et al.; licensee BioMed Central Ltd

Sums of hermitian squares and the BMV conjecture

Recently Lieb and Seiringer showed that the Bessis-Moussa-Villani conjecture from quantum physics can be restated in the following purely algebraic way: The sum of all words in two positive semidefinite matrices where the number of each of the two letters is fixed is always a matrix with nonnegative trace. We show that this statement holds if the words are of length at most 13. This has previously been known only up to length 7. In our proof, we establish a connection to sums of hermitian squares of polynomials in noncommuting variables and to semidefinite programming. As a by-product we obtain an example of a real polynomial in two noncommuting variables having nonnegative trace on all symmetric matrices of the same size, yet not being a sum of hermitian squares and commutators.Comment: 21 pages; minor changes; a companion Mathematica notebook is now available in the source fil

Association between pain and the frailty phenotype in older men: longitudinal results from the Concord Health and Ageing in Men Project (CHAMP)

Objectives to determine whether pain increases the risk of developing the frailty phenotype and whether frailty increases the risk of developing chronic or intrusive pain, using longitudinal data. Design/Setting longitudinal data from the Concord Health and Ageing in Men Project (CHAMP), a prospective population based cohort study. Participants a total of 1,705 men aged 70 years or older, living in an urban area of New South Wales, Australia. Measurements data on the presence of chronic pain (daily pain for at least 3 months), intrusive pain (pain causing moderate to severe interference with activities) and the criteria for the Cardiovascular Health Study (CHS) frailty phenotype were collected in three waves, from January 2005 to October 2013. Data on age, living arrangements, education, smoking status, alcohol consumption, body mass index, comorbidities, cognitive function, depressive symptoms and history of vertebral or hip fracture were also collected and included as covariates in the analyses. Results a total of 1,705 participants were included at baseline, of whom 1,332 provided data at the 2-year follow-up and 940 at the 5-year follow-up. Non-frail (robust and pre-frail) men who reported chronic pain were 1.60 (95% confidence interval (CI): 1.02–2.51, P = 0.039) times more likely to develop frailty at follow-up, compared to those with no pain. Intrusive pain did not significantly increase the risk of future frailty. Likewise, the frailty status was not associated with future chronic or intrusive pain in the adjusted analysis. Conclusions the presence of chronic pain increases the risk of developing the frailty phenotype in community-dwelling older men.NHMRC, The Ageing and Alzheimer's Institut

Adequacy of nutritional intake among older men living in Sydney, Australia: findings from the Concord Health and Ageing in Men Project (CHAMP)

Previous research shows that older men tend to have lower nutritional intakes and higher risk of under-nutrition compared with younger men. The objectives of this study were to describe energy and nutrient intakes, assess nutritional risk and investigate factors associated with poor intake of energy and key nutrients in community-dwelling men aged 75 years participating in the Concord Health and Ageing in Men Project - a longitudinal cohort study on older men in Sydney, Australia. A total of 794 men (mean age 81.4 years) had a detailed diet history interview, which was carried out by a dietitian. Dietary adequacy was assessed by comparing median intakes with nutrient reference values (NRV): estimated average requirement, adequate intake or upper level of intake. Attainment of NRV of total energy and key nutrients in older age (protein, Fe, Zn, riboflavin, Ca and vitamin D) was incorporated into a "key nutrients" variable dichotomised as "good" (5) or "poor" (4). Using logistic regression modelling, we examined associations between key nutrients with factors known to affect food intake. Median energy intake was 8728 kJ (P5=5762 kJ, P95=12 303 kJ), and mean BMI was 27.7 (sd 4.0) kg/m(2). Men met their NRV for most nutrients. However, only 1 % of men met their NRV for vitamin D, only 19 % for Ca, only 30 % for K and only 33 % for dietary fibre. Multivariate logistic regression analysis showed that only country of birth was significantly associated with poor nutritional intake. Dietary intakes were adequate for most nutrients; however, only half of the participants met the NRV of 5 key nutrients