Danijela Gnjidic

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.

Reducing Inappropriate Polypharmacy: The Process of Deprescribing

Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application.

The Effects of Polypharmacy in Older Adults

An assessment of the safety and efficacy of multiple medications in older adults requires clinically relevant objective outcomes and pharmacological measures of medication exposure. Important outcomes include geriatric syndromes and objective measures of physical function. Measurements of medication exposure have evolved from merely counting the drugs to a consideration of pharmacologic principles such as drug class, dose response, and maximal effect. Emerging evidence regarding the effects of cumulative medication exposure on functions critical for independence may provide guidance for prescribers.

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.

Deprescribing trials: methods to reduce polypharmacy and the impact on prescribing and clinical outcomes.

Different styles of interventions can reduce medication exposure in older adults. However, the evidence for their clinical effectiveness and sustainability is conflicting and lacking. There are some data to guide clinicians on which medicines are more likely to be inappropriate in older people, which medicines are more likely to cause ADWEs, and which medicines should be tapered slowly rather than stopped. To reduce the likelihood of clinically significant adverse events, clinicians should undertake a step-wise approach to discontinuing medications and do so under appropriate supervision. Further research to determine the most effective ways to discontinue medications, and to provide a better understanding of the clinical benefits of various interventions is required. Large RCTs evaluating multidisciplinary interventions and clinical outcomes of changes in medicines regimen across different settings are required to confirm the findings of the studies performed so far.

Investigating polypharmacy and drug burden index in hospitalised older people.

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.

How fast does the Grim Reaper walk? Receiver operating characteristics curve analysis in healthy men aged 70 and over

Objective To determine the speed at which the Grim Reaper (or Death) walks. Design Population based prospective study. Setting Older community dwelling men living in Sydney, Australia. Participants 1705 men aged 70 or more participating in CHAMP (Concord Health and Ageing in Men Project). Main outcome measures Walking speed (m/s) and mortality. Receiver operating characteristics curve analysis was used to calculate the area under the curve for walking speed and determine the walking speed of the Grim Reaper. The optimal walking speed was estimated using the Youden index (sensitivity+specificity−1), a common summary measure of the receiver operating characteristics curve, and represents the maximum potential effectiveness of a marker. Results The mean walking speed was 0.88 (range 0.15-1.60) m/s. The highest Youden index (0.293) was observed at a walking speed of 0.82 m/s (2 miles (about 3 km) per hour), corresponding to a sensitivity of 63% and a specificity of 70% for mortality. Survival analysis showed that older men who walked faster than 0.82 m/s were 1.23 times less likely to die (95% confidence interval 1.10 to 1.37) than those who walked slower (P=0.0003). A sensitivity of 1.0 was obtained when a walking speed of 1.36 m/s (3 miles (about 5 km) per hour) or greater was used, indicating that no men with walking speeds of 1.36 m/s or greater had contact with Death. Conclusion The Grim Reaper’s preferred walking speed is 0.82 m/s (2 miles (about 3 km) per hour) under working conditions. As none of the men in the study with walking speeds of 1.36 m/s (3 miles (about 5 km) per hour) or greater had contact with Death, this seems to be the Grim Reaper’s most likely maximum speed; for those wishing to avoid their allotted fate, this would be the advised walking speed.

Impact of high risk drug use on hospitalization and mortality in older people with and without Alzheimer's disease: a national population cohort study.

Background Evidence is lacking about outcomes associated with the cumulative use of anticholinergic and sedative drugs in people with Alzheimer’s disease (AD). This retrospective cohort study investigated the relationship between cumulative exposure to anticholinergic and sedative drugs and hospitalization and mortality in people with and without AD in Finland. Methods Community-dwelling people aged 65 years and over, with AD on December 31st 2005 (n = 16,603) and individually matched (n = 16,603) comparison persons (age, sex, region of residence) were identified by the Social Insurance Institution of Finland. Drug utilization data were extracted from the Finnish National Prescription Register. Exposure to anticholinergic and sedative drugs was defined using the Drug Burden Index (DBI). Hospitalization and mortality data were extracted from national registers. Cox and zero-inflated negative binomial analyses were used to investigate the relationship between DBI and hospitalization and mortality over a one-year follow-up. Results In total, 5.8% of people with AD and 3.7% without AD died during 2006. For every unit increase in DBI, the adjusted hazard ratio for mortality was 1.21 (95% confidence intervals [CI]: 1.09–1.33) among people with AD, and 1.37 (95%CI: 1.20–1.56) among people without AD. Overall, 44.3% of people with AD and 33.4% without AD were hospitalized. When using no DBI exposure as the reference group, the adjusted incidence rate ratio for length of hospital stay among high DBI group (≥1) in people with AD was 1.15 (95%CI: 1.05–1.26) and 1.63 (95%CI: 1.41–1.88) in people without AD. Conclusion There is a dose-response relationship between cumulative anticholinergic and sedative drug use and hospitalization and mortality in people with and without AD.

Pharmacoepidemiology in the Postmarketing Assessment of the Safety and Efficacy of Drugs in Older Adults

Much of the information on safety and efficacy of drugs in older people is obtained after marketing. Pharmacoepidemiologic studies play an increasing role in obtaining this information. Pharmacoepidemiologic studies contribute significantly to knowledge of risks associated with medicines in older people and less so to that of benefits. Recent improvements in methodology in both pharmacoepidemiology and geriatric medicine have improved the validity and reduced the bias of these studies. Pharmacoepidemiologic studies are a critical component of assessing the risks of medicines in older people. Where possible, findings of pharmacoepidemiologic studies should be tested with well-conducted interventional randomized trials in relevant populations of older people.

Prescription and Administration of Opioids to Hospital In-patients, and Barriers to Effective Use

OBJECTIVE This study aimed to describe prescribing and administration of opioids in a tertiary referral teaching hospital. Secondary aims were assessment of staff knowledge of opioid pharmacology and available preparations, and of perceived barriers limiting opioid use. DESIGN A cross-sectional survey of in-patients requiring opioid analgesia was performed. An anonymous semi-structured questionnaire was administered to medical and nursing staff. SETTING Australian tertiary referral teaching hospital. PATIENTS All patients prescribed opioids on study wards over 3 months (N = 190). RESULTS Oxycodone was the most frequently prescribed opioid (51.4%). The majority (64.7%) of participants had incomplete pain relief, which was significantly associated with having opioid related side effects. There was no association between pain relief and prescribed daily dose or received daily dose of opioids. Limited understanding of opioid preparations, tolerance, and dependence was demonstrated by staff. The most common perceived barriers to opioid use included difficulties in identifying the right dose, staff time required to prescribe and monitor, and large numbers of preparations. While prescription of inadequate doses was perceived as a barrier, this study identified that submaximal doses were administered. An opioid educational session improved knowledge of opioid formulations. CONCLUSION The majority of participants had incomplete pain relief and the maximum prescribed doses of opioids were not administered. Reported barriers included staff knowledge of opioid dose titration and opioid preparations, and time constraints. Identified barriers included poor knowledge of opioid preparations.