Iterative Development of Clinician Guides to Support Deprescribing Decisions and Communication for Older Patients in Hospital: A Novel Methodology.

BACKGROUND/OBJECTIVES: Medication review is an important component of the management of older hospital patients. Deprescribing (supervised withdrawal of inappropriate medicines) is one outcome of review. This study aimed to iteratively develop and test the usability of deprescribing guides, which support multidisciplinary clinicians to reduce inappropriate polypharmacy in older inpatients. METHODS: Deprescribing guides for hospital clinicians were developed using a novel mixed-methods, ten-step process. Iterative development and usability testing were applied. This included content development through review of the literature; expert consensus through five rounds of feedback using a modified Delphi approach; and usability testing by 16 multidisciplinary hospital clinicians on hypothetical clinical scenarios involving observations, semi-structured interviews, and administration of the System Usability Scale. RESULTS: This novel process was used to develop deprescribing guides that facilitate implementation of evidence on deprescribing in routine hospital care. The guides present evidence-based information in a format that aligns with workflows of multidisciplinary hospital clinicians. The guides were adapted for various clinical roles to navigate efficiently to suit differing workflow needs. Guides include unique communication support in the form of "preferred language". Clinicians can use the "preferred language" to apply the evidence to the individual patient and relay decisions between health providers and with patients/carers. The total System Usability Scale score was 80.6 ± 2.0 (mean ± standard error of the mean), indicating excellent usability. Guides have been developed using consistent format for nine medication classes that are common targets for deprescribing and are publicly available. CONCLUSION: This study demonstrates a novel approach to the development and implementation of evidence-based recommendations that support deprescribing in routine hospital care.

Costs of potentially inappropriate medication use in residential aged care facilities.

BACKGROUND: The potential harms of some medications may outweigh their potential benefits (inappropriate medication use). Despite recommendations to avoid the use of potentially inappropriate medications (PIMs) in older adults, the prevalence of PIM use is high in different settings including residential aged care. However, it remains unclear what the costs of these medications are in this setting. The main objective of this study was to determine the costs of PIMs in older adults living in residential care. A secondary objective was to examine if there was a difference in costs of PIMs in a home-like model of residential care compared to an Australian standard model of care. METHODS: Participants included 541 participants from the Investigation Services Provided in the Residential Environment for Dementia (INSPIRED) Study. The INSPIRED study is a cross-sectional study of 17 residential aged care facilities in Australia. 12 month medication costs were determined for the participants and PIMs were identified using the 2015 updated Beers Criteria for older adults. RESULTS: Of all of the medications dispensed in 1 year, 15.9% were PIMs and 81.4% of the participants had been exposed to a PIM. Log-linear models showed exposure to a PIM was associated with higher total medication costs (Adjusted ß = 0.307, 95% CI 0.235 to 0.379, p < 0.001). The mean proportion (±SD) of medication costs that were spent on PIMs in 1 year was 17.5% (±17.8) (AUD$410.89 ± 479.45 per participant exposed to a PIM). The largest PIM costs arose from proton-pump inhibitors (34.4%), antipsychotics (21.0%) and benzodiazepines (18.7%). The odds of incurring costs from PIMs were 52% lower for those residing in a home-like model of care compared to a standard model of care. CONCLUSIONS: The use of PIMs for older adults in residential care facilities is high and these medications represent a substantial cost which has the potential to be lowered. Further research should investigate whether medication reviews in this population could lead to potential cost savings and improvement in clinical outcomes. Adopting a home-like model of residential care may be associated with reduced prevalence and costs of PIMs.

Discontinuation of statins in a population of older New Zealanders with limited life expectancy.

Discontinuation of statins may be considered for older individuals with a cancer, multi-morbidity, approaching end-of-life and in primary prevention. The aim of this study is to investigate the relationship between the rates of statin discontinuation in the last 12 months of life and a diagnosis of cancer, and in individuals using statins for primary or secondary prevention. A case-control study of matched cases and controls. Matching was based on age, Charlson comorbidity index scores and socioeconomic status. Prescription and diagnostic data for 20,482 individuals who were aged over 75 years, were in their last 12 months of life and were receiving statins during the study period (1 January 2007 to 31 December 2012). After propensity score matching, we identified 4832 cases with a diagnosis of cancer and 4809 matched controls. We used Cox regression to test the relationship between the relative risk of statin discontinuation and a diagnosis of cancer, and in individuals using statins for primary or secondary prevention. Statins were discontinued in 70.4% of older adults with a diagnosis of cancer and 55.8% of those without cancer (P < 0.05). The Cox regression analysis supports that a diagnosis of cancer can increase the rate of statin discontinuation compared with individuals without a diagnosis of cancer regardless of whether statins were used for primary or secondary prevention (P < 0.05). The findings from this study support that statins are likely to be discontinued in the last year of life in older people with limited life expectancy from cancer, even if statins were indicated for secondary prevention of cardiovascular disease.

Atrial fibrillation in older inpatients: are there any differences in clinical characteristics and pharmacological treatment between the frail and the non-frail?

BACKGROUND: Frailty is common in patients with atrial fibrillation and may impact on antithrombotic and anti-arrhythmic treatment. AIM: To describe differences in clinical characteristics, prescription of antithrombotic and anti-arrhythmic medications and incidence of haemorrhage and stroke, between frail and non-frail older inpatients. METHODS: Prospective observational study in patients aged ≥65 years with atrial fibrillation admitted to a teaching hospital in Sydney, Australia. Frailty was assessed using the Reported Edmonton Frail Scale, stroke risk with CHA2DS2-VASc score and bleeding risk with HAS-BLED score. Participants were followed after 6 months for haemorrhages and strokes. RESULTS: We recruited 302 patients (mean age 84.7 ± 7.1 years, 53.3% frail, 50% female, mean CHA2DS2-VASc 4.61 ± 1.44, mean HAS-BLED 2.97 ± 1.04). Frail participants were older and had more co-morbidities and higher risk of stroke but not haemorrhage. Upon discharge, 55.7% participants were prescribed with anticoagulants (49.3% frail, 62.6% non-frail, P = 0.02). Thirty-three per cent received antiplatelets only and 11.1% no antithrombotics, with no difference by frailty status. For anti-arrhythmics, 52.6% received rate-control drugs only, 11.8% rhythm-control drugs only and 13.5% both and 22.1% were not prescribed either, with no difference by frailty status. On univariate logistic regression, frailty decreased the likelihood of anticoagulant prescription (odds ratio (OR) 0.58, 95%CI 0.36-0.93), but this was not significant on multivariate analysis (OR 0.66, 95%CI 0.40-1.11). After 6 months, overall incidence of ischaemic stroke was 2.1%, and in patients taking anticoagulants, incidence of major/severe bleeding was 6.3%, with no significant difference between frailty groups. CONCLUSIONS: Frailty status had little impact on antithrombotic prescription and no impact on anti-arrhythmic prescription.

A Review of Frailty in Developing Countries.

BACKGROUND: As the population ages, the prevalence and clinical importance of frailty are increasing. There have been few published studies about frailty in developing world. This study aims to review the evidence from developing countries on the prevalence of frailty, definition of frailty and factors associated with frailty. METHOD: A literature search was conducted via MEDLINE and EMBASE. Keywords included "frail", "frailty", "prevalence", "criteria", "definition", "risk factors", "outcomes", "developing country", "developing world", and names of low and middle income countries according to the classification of the World Bank. RESULT: A total of 14 articles were reviewed from Brazil (n=6), China (n=3), Mexico (n=2), and one each from Russia, India, and Peru. There were 9 articles from community-based studies and 5 articles from hospital-based studies. Fried's phenotype for frailty was used to define frailty in the majority of studies. The prevalence of frailty in community-dwelling older people was 17%-31% in Brazil, 15% in Mexico, 5%-31% in China, and 21%-44% in Russia. The prevalence of frailty was 49% in institutionalized older patients in Brazil and 32% in hospitalized older patients in India. The prevalence of frailty in outpatient clinics was 55%-71% in Brazil and 28% in Peru. Frailty was associated with increased mortality and comorbidities, decreased physical and cognitive function, and poor perceptions of health. CONCLUSION: The limited studies available suggest that frailty occurs frequently in older people in the developing world and it appears to be associated with adverse outcomes. This has implications for policy and health care provision for these ageing populations.

Statin utilisation patterns in older Australians living in residential care: 1-year prevalence study.

Despite controversy over the risks and benefits of statin therapy, statins continue to be commonly used medicines by older people. In a cohort study of participants aged ≥70 years (n = 540) living in residential care, Sydney, we found that the proportion of statin users decreased gradually from the baseline of 33.1% to 31.3% at 6 months (P = 0.13) and to 28.7% over 1 year (P = 0.002). Prevalence of statin use decreased with increasing age, with individuals aged ≥90 years being more likely to discontinue or deprescribe statins. The patterns of statin use did not change according to increasing baseline dose or baseline indication.

Teaching Junior Medical Officers safe and effective prescribing.

Medication errors are an iatrogenic threat to patient safety, and recently graduated Junior Medical Officers (JMOs) are a common source of these errors. A ward-based, physician-led, small-group interactive teaching session was developed to improve JMOs competence in prescribing. The ability of JMOs to detect problems in mock medication charts before and after the teaching session was assessed, with the majority improving after the intervention, a result sustained on re-testing later in the year. The teaching sessions were well received by JMOs.

Investigating polypharmacy and drug burden index in hospitalised older people.

AIMS: To investigate the changes in polypharmacy and the drug burden index (DBI) occurring during hospitalisation for older people. The secondary aim was to examine the associations of these two measures with the length of hospital stay and admission for falls or delirium. METHODS: A retrospective analysis of patients' medical records was undertaken at a large university teaching hospital (Sydney, Australia) for patients with the age of ≥ 65 years and admitted under the care of the geriatric medicine or rehabilitation teams. Polypharmacy was defined as the use of more than five regular medications. The DBI measures exposure to drugs with anticholinergic and sedative effects. Logistic regression analysis was conducted to investigate the associations between polypharmacy and DBI with outcome measures. Data are presented using odds ratios with 95% confidence intervals. RESULTS: A total of 329 patients was included in this study. The mean (± standard deviation) age of the population was 84.6 ± 7.0 years, 62% were female and 40% were admitted from residential aged-care facilities. On admission, polypharmacy was observed in 60% of the cohort and DBI exposure for 50%. DBI and polypharmacy exposure decreased during hospitalisation, but only the number of medications taken decreased by a statistically significant margin (P = 0.02). Patients with a high DBI (≥ 1) were approximately three times more likely to be admitted for delirium than those with no DBI exposure (odds ratio, 2.95; 95% confidence interval, 1.34-6.51). CONCLUSIONS: In the present study, DBI was associated with an increased risk of hospital admission for delirium only. Polypharmacy was not associated with any of the clinical measures.

High-risk prescribing and incidence of frailty among older community-dwelling men.

Evidence about the association between treatment with high-risk medicines and frailty in older individuals is limited. We investigated the relationship between high-risk prescribing and frailty at baseline, as well as 2-year incident frailty, in 1,662 men ≥70 years of age. High-risk prescribing was defined as polypharmacy (≥5 medicines), hyperpolypharmacy (≥10 medicines), and by the Drug Burden Index (DBI), a dose-normalized measure of anticholinergic and sedative medicines. At baseline, frail participants had adjusted odds ratios (ORs) of 2.55 (95% confidence interval, CI: 1.69-3.84) for polypharmacy, 5.80 (95% CI: 2.90-11.61) for hyperpolypharmacy, and 2.33 (95% CI: 1.58-3.45) for DBI exposure, as compared with robust participants. Of the 1,242 men who were robust at baseline, 6.2% developed frailty over two years. Adjusted ORs of incident frailty were 2.45 (95% CI: 1.42-4.23) for polypharmacy, 2.50 (95% CI: 0.76-8.26) for hyperpolypharmacy, and 2.14 (95% CI: 1.25-3.64) for DBI exposure. High-risk prescribing may contribute to frailty in community-dwelling older men.

Estimation of lean body weight in older women with hip fracture.

OBJECTIVE: Lean body weight (LBW) decreases with age while total body fat increases, resulting in altered drug pharmacokinetics. A semi-mechanistic equation estimating LBW using height, weight and sex has been developed for potential use across a wide range of body compositions. The aim of this study was to determine the ability of the LBW equation to estimate dual energy x-ray absorptiometry-derived fat free mass (FFM(DXA)) in a population of older women with recent hip fracture. METHODS: Baseline, four and 12 month data obtained from 23 women enrolled in the Sarcopenia and Hip Fracture study were pooled to give 58 measurements. LBW was estimated using the equation: LBW (kg) = (9270 x Wt) / (8780 + (244 x BMI)). Body composition was classified as: 'normal' (BMI <25kg/m(2) and not sarcopenic), 'overweight-obese' (BMI >25kg/m(2) and not sarcopenic), 'sarcopenic' (sarcopenic and BMI <25kg/m(2)), or 'sarcopenic-obese' (sarcopenic and BMI >25kg/m(2)). The ability of the LBW equation to predict FFMDXA was determined graphically using Bland-Altman plots and quantitatively using the method of Sheiner and Beal. RESULTS: The mean ± SD age of female participants women was 83±7 years (n=23). Sarcopenia was frequently observed (65.2%). Bland-Altman plots demonstrated an underestimation by the LBW equation compared to FFMDXA. The bias (95% CI) and precision (95% CI) calculated using the method of Sheiner and Beal was 0.5kg (-0.7, 1.66kg) and 4.4kg (-3.7, 12.4kg) respectively for pooled data. CONCLUSION: This equation can be used to easily calculate LBW. When compared to FFMDXA, the LBW equation resulted in a small underestimation on average in this population of women with recent hip fracture. The degree of bias may not be clinically important although further studies of larger heterogeneous cohorts are needed to investigate and potentially improve the accuracy of this predictive equation in larger clinical cohorts.

Hepatotoxicity of therapeutic short-course paracetamol in hospital inpatients: impact of ageing and frailty.

BACKGROUND: Paracetamol, a commonly used simple analgesic, can be fatal in overdose. Case reports suggest liver damage may occur at therapeutic doses. In older and particularly frail patients, dose reduction of therapeutic paracetamol is recommended due to concerns of an increased risk of hepatotoxicity. AIMS: This study aimed to investigate the effects of ageing and frailty on the safety of paracetamol in hospital inpatients commenced on short courses of the drug. METHODS: An observational cohort study of young (18-55 years, n = 19), older (≥ 70 years) fit (n = 24) and older frail (n = 28) hospital inpatients. Treatment group participants commenced regular paracetamol (3-4 g/day) during their hospital admission, whereas the control group was not exposed to paracetamol. In both groups, plasma alanine aminotransferase (ALT) was measured at baseline and day 5, and risk factors for raised ALT were recorded. A random serum paracetamol concentration was measured at day 5 in the treatment group. RESULTS: No older frail treatment participants had an abnormal day 5 ALT. Odds ratios for having a day 5 ALT above the upper limit of normal (ULN) with paracetamol use, compared with unexposed controls, were 3·7 [95% confidence intervals (CI): 0·32, 41·59] for older not frail participants and 2·5 (95% CI: 0·34, 18·3) for younger participants. Decreasing frailty score independently predicted a day 5 ALT above the ULN (P < 0·05). Day 5 serum paracetamol concentrations were highest in older frail participants (P < 0·005). CONCLUSION: Higher paracetamol concentrations observed in frail older patients after 5 days of therapeutic paracetamol do not necessarily indicate an increased risk of hepatotoxicity.

Do medical courses adequately prepare interns for safe and effective prescribing in New South Wales public hospitals?

AIMS: To assess ability of interns immediately before starting clinical practice in New South Wales (NSW) teaching hospitals to prescribe medications safely and appropriately and to describe their impressions of the adequacy of their clinical pharmacology training in medical school. METHODS: A cross-sectional study was performed on all interns (n= 191) who attended intern orientation programmes at four NSW hospitals in January 2008. A clinical case scenario that tested prescribing ability and a survey investigating impressions of clinical pharmacology training in medical school were administered to the interns in exam format. Outcome measures were: (i) ability to prescribe medications safely and appropriately for the clinical case scenario and (ii) interns' impressions of their training in clinical pharmacology at medical school. RESULTS: No intern completed all prescribing tasks correctly. No intern charted the patient's usual medications on admission completely correctly, only six wrote an accurate discharge medication list, and none wrote both an accurate discharge medication list and a legal Schedule 8 discharge script. None of the respondents strongly agreed that they felt adequately trained to prescribe medications in their intern year and 84% would have liked to have more training in pharmacology as medical students. CONCLUSIONS: Interns about to commence clinical practice in NSW teaching hospitals demonstrated significant deficits in prescribing of regular medications, initiation of new therapies, prescribing of discharge medications, and particularly prescribing of Schedule 8 medications. Most interns recognized these deficits and would have liked more clinical pharmacology training at medical school.

Physical and cognitive performance and burden of anticholinergics, sedatives, and ACE inhibitors in older women.

Polypharmacy, common in older people, confers both risk of adverse outcomes and benefits. We assessed the relationship of commonly prescribed medications with anticholinergic and sedative effects to physical and cognitive performance in older individuals. The study population comprised 932 moderately to severely disabled community-resident women aged 65 years or older who were participants in the Women's Health and Aging Study I. A scale based on pharmacodynamic principles was developed and utilized as a measure of drug burden. This was related to measures of physical and cognitive function. After adjusting for demographics and comorbidities, anticholinergic drug burden was independently associated with greater difficulty in four physical function domains with adjusted odds ratios (95% confidence interval (CI)) of 4.9 (2.0-12.0) for balance difficulty; 3.2 (1.5-6.9) for mobility difficulty; 3.6 (1.6-8.0) for slow gait; 4.2 (2.0-8.7) for chair stands difficulty; 2.4 (1.1-5.3) for weak grip strength; 2.7 (1.3-5.4) for upper extremity limitations; 3.4 (1.7-6.9) for difficulty in activities of daily living; and 2.4 (95% CI, 1.1-5.1) for poor performance on the Mini-Mental State Examination. Sedative burden was associated only with impaired grip strength (3.3 (1.5-7.3)) and mobility difficulty (2.4 (1.1-5.3)). The burden of multiple drugs can be quantified by incorporating the recommended dose regimen and the actual dose and frequency of drug taken. Anticholinergic drug burden is strongly associated with limitations in physical and cognitive function. Sedative burden is associated with impaired functioning in more limited domains. The risk associated with exposure of vulnerable older women to drugs with anticholinergic properties, and to a lesser extent those with sedative properties, implies that such drugs should not be used in this patient group without compelling clinical indication.

Failure to weigh patients in hospital: a medication safety risk.

Often patients are not weighed in hospital. Failure to weigh patients prescribed renally excreted drugs may correlate to adverse drug events. We carried out a cross-sectional study of patients prescribed common renally excreted drugs (heparin, enoxaparin and gentamicin), admitted to two wards at Royal North Shore Hospital, Sydney over 3 months. Of all patients surveyed, 28% (22/78) in the orthopaedic ward and 22% (27/124) in the medical ward were weighed. Among those prescribed therapeutic doses of the study drugs, 25% (3/12) in the orthopaedic ward and 27% (7/26) in the medical ward were weighed. Patients prescribed therapeutic anticoagulation who were not weighed experienced more haemorrhagic complications than patients who were weighed (P = 0.03). Patients prescribed renally excreted drugs in hospital are frequently not weighed. This is associated with reduced medication safety.

Alterations in liver sinusoidal endothelium in a baboon model of type 1 diabetes.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with extensive vascular pathology, yet little is known about its long-term effects on liver sinusoidal endothelial cells (LSECs). Potential diabetic changes in LSECs are important because of the role played by fenestrations in the LSECs in hepatic disposition of lipoproteins. MATERIALS AND METHODS: Surgical liver biopsies for electron microscopy and immunohistochemistry were obtained from baboons with long-standing streptozotocin-induced, insulin-treated diabetes mellitus and compared with those from age-matched control animals. RESULTS: There was an increase in the thickness of LSECs (170 +/- 17 vs 123 +/- 10 nm, p < 0.01). Fenestrations in LSECs, as determined by overall porosity, were markedly reduced (1.4 +/- 0.1% vs 2.6 +/- 0.2%, p < 0.01). Increased numbers of stellate cells were seen on electron microscopy, and this finding was corroborated by increased smooth muscle actin expression. Diabetes mellitus was also associated with increased endothelial production of von Willebrand factor and caveolin-1. CONCLUSIONS/INTERPRETATION: Diabetes mellitus in the non-human primate is associated with marked changes in LSECs, including a reduction in fenestrations. Such changes provide an additional and novel mechanism for impaired hepatic lipoprotein clearance and post-prandial hyperlipidaemia in diabetes mellitus.

The effect of aging on the immunohistochemistry of apolipoprotein E in the liver.

Apolipoprotein E (apoE) is involved in hepatic disposition of chylomicron remnants, which is impaired in old age. Isoforms of apoE have been implicated in age-related diseases and possibly the aging process itself. Because the effects of old age on expression and distribution of apoE in the liver have not been reported, we studied the effect of old age on the immunohistochemistry of apoE in the livers of humans and the non-human primate, Papio hamadryas. Overall, old age was not associated with marked changes in the expression of apoE between adult (48+/-19 years) and old (82+/-5 years) humans. However, there was a change in the distribution of apoE staining. The livers of older humans displayed increased hepatocyte cytoplasmic staining and reduced peri-sinusoidal staining. Similar trends were noted in the livers from the baboons. Such findings are suggestive of altered apoE recycling in old age and have implications for age-related dyslipidaemia.