Prevalence of potentially preventable unplanned hospitalizations caused by therapeutic failures and adverse drug withdrawal events among older veterans.

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Background: Older people carry a high burden of illness for which medications are indicated, along with increased risk of adverse drug reactions. We developed an index to determine drug burden based on pharmacologic principles. We evaluated the relationship of this index to physical and cognitive performance apart from disease indication. Methods: Data from the Health, Aging, and Body Composition Study on 3075 well-functioning communitydwelling persons aged 70 to 79 years were analyzed by multiple linear regression to assess the cross-sectional association of drug burden index with a validated composite continuous measure for physical function, and with the Digit Symbol Substitution Test for cognitive performance. Results: Use of anticholinergic and sedative medications was associated with poorer physical performance score (anticholinergic exposure, 2.08 vs 2.21, PϽ.001; sedative exposure, 2.09 vs 2.19, PϽ.

Age-related accumulation of cellular damage and death has been linked to oxidative stress. Calorie restriction (CR) is the most robust, nongenetic intervention that increases lifespan and reduces the rate of aging in a variety of species. Mechanisms responsible for the antiaging effects of CR remain uncertain, but reduction of oxidative stress within mitochondria remains a major focus of research. CR is hypothesized to decrease mitochondrial electron flow and proton leaks to attenuate damage caused by reactive oxygen species. We have focused our research on a related, but different, antiaging mechanism of CR. Specifically, using both in vivo and in vitro analyses, we report that CR reduces oxidative stress at the same time that it stimulates the proliferation of mitochondria through a peroxisome proliferation-activated receptor coactivator 1␣ signaling pathway. Moreover, mitochondria under CR conditions show less oxygen consumption, reduce membrane potential, and generate less reactive oxygen species than controls, but remarkably they are able to maintain their critical ATP production. In effect, CR can induce a peroxisome proliferationactivated receptor coactivator 1␣-dependent increase in mitochondria capable of efficient and balanced bioenergetics to reduce oxidative stress and attenuate age-dependent endogenous oxidative damage.aging ͉ peroxisome proliferation-activated receptor coactivator 1 ͉ reactive oxygen species O ne of the major hypotheses directing gerontological research over several decades is that aging results from the accumulation of macromolecules damaged by oxidative stress and that the major loci of this damage is the mitochondrion (1-4). This hypothesis has been proposed as one explanation of how calorie restriction (CR) in various animal models works so effectively to increase lifespan and stress resistance, reduce susceptibility to chronic disease, and attenuate age-related functional decline (5, 6). Past studies have demonstrated that CR decreases mitochondrial electron and proton leak in mammalian cells and attenuates damage resulting from intracellular oxidative stress (4, 6-9).Mitochondria provide an integrated functional network, many components of which are vulnerable to oxidative stress that can impair cellular function and increase the chance of cell death. Age-related accumulation of cellular damage and death ultimately leads to impaired organ function generating further physiological dysfunction (1, 2). The mitochondrial theory of aging proposes that somatic mutations of mtDNA induced by reactive oxygen species (ROS) are the primary cause of cellular energy decline with complex I being particularly affected by decreasing its rate of electron transport (3).CR is the most robust, nongenetic intervention that increases lifespan and reduces the rate of aging in mammals and other organisms (5, 7). The mechanisms responsible for the antiaging effects of CR remain unknown and likely involve several processes. Results from many different laboratories support that both the activation of c...

Aims The aim of this study was to identify what definitions have been published for the term ‘deprescribing’, and determine whether a unifying definition could be reached. A secondary aim was to uncover patterns between the published definitions which could explain any variation. Methods Systematic literature searches were performed (earliest records to February 2014) in MEDLINE, Embase, CINAHL, Informit, Scopus and Google Scholar. The terms deprescrib* or de‐prescrib* were employed as a keyword search in all fields. Conventional content analysis and word frequencies were used to identify characteristics of the definitions. Network analysis was conducted to visualize characteristic distribution across authors and articles. Results Following removal of duplicates, 231 articles were retrieved, 37 of which included a definition. Eight characteristics of the definitions were identified: use of the term stop/withdraw/cease/discontinue (35 articles), aspect of prescribing included e.g. long term therapy/inappropriate medications (n = 18), use of the term ‘process’ or ‘structured’ (n = 13), withdrawal is planned/supervised/judicious (n = 11), involving multiple steps (n = 7), includes dose reduction/substitution (n = 7), desired goals/outcomes described (n = 5) and involves tapering (n = 4). Network analysis did not reveal patterns responsible for variations in previously used definitions. Conclusions These findings show that there is lack of consensus on the definition of deprescribing. This article proposes the following definition: ‘Deprescribing is the process of withdrawal of an inappropriate medication, supervised by a health care professional with the goal of managing polypharmacy and improving outcomes’. This definition has not yet been externally validated and further work is required to develop an internationally accepted and appropriate definition.

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.

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. Clinical Pharmacology & Therapeutics (2008); 85, 1, 86–88 doi:

The revised PATD questionnaire had acceptable validity and reliability. This newly validated questionnaire may provide insight into individuals' willingness for/barriers to deprescribing, with applications in practice and research.