Mohammed Saji Salahudeen

Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review

BackgroundThe cumulative effect of taking multiple medicines with anticholinergic properties termed as anticholinergic burden can adversely impact cognition, physical function and increase the risk of mortality. Expert opinion derived risk scales are routinely used in research and clinical practice to quantify anticholinergic burden. These scales rank the anticholinergic activity of medicines into four categories, ranging from no anticholinergic activity (= 0) to definite/high anticholinergic activity (= 3). The aim of this systematic review was to compare anticholinergic burden quantified by the anticholinergic risk scales and evaluate associations with adverse outcomes in older people.MethodsWe conducted a literature search in Ovid MEDLINE, EMBASE and PsycINFO from 1984-2014 to identify expert opinion derived anticholinergic risk scales. In addition to this, a citation analysis was performed in Web of Science and Google Scholar to track prospective citing of references of selected articles for assessment of individual scales for adverse anticholinergic outcomes. The primary outcomes of interest were functional and cognitive outcomes associated with anticholinergic burden in older people. The critical appraisals of the included studies were performed by two independent reviewers and the data were extracted onto standardised forms.ResultsThe primary electronic literature search identified a total of 1250 records in the 3 different databases. On the basis of full-text analysis, we identified 7 expert-based anticholinergic rating scales that met the inclusion criteria. The rating of anticholinergic activity for medicines among these rating scales was inconsistent. For example, quetiapine was rated as having high anticholinergic activity in one scale (n = 1), moderate in another scale (n = 1) and low in two other scales (n = 2). Citation analysis of the individual scales showed that the Anticholinergic Cognitive Burden (ACB) scale was the most frequently validated expert based anticholinergic scale for adverse outcomes (N = 13).ConclusionsIn conclusion, there is not one standardised tool for measuring anticholinergic burden. Cohort studies have shown that higher anticholinergic burden is associated with negative brain effects, poorer cognitive and functional outcomes.

Comparison of anticholinergic risk scales and associations with adverse health outcomes in older people

To investigate whether anticholinergic burden scores from nine published anticholinergic scales are associated with adverse health outcomes, including hospital admissions, hospitalizations for falls, hospital length of stay (LOS), and more visits to general practitioners (GPs).

Temporal Trends in Polypharmacy and Hyperpolypharmacy in Older New Zealanders over a 9-Year Period: 2005-2013

Background: Polypharmacy and hyperpolypharmacy are proxy indicators for inappropriate medicine use. Inappropriate medicine use in older people leads to adverse clinical outcomes. Objective: The objectives of this study were to investigate the prevalence and trends of polypharmacy and hyperpolypharmacy in older people in New Zealand from 2005 to 2013, analyzing the pharmaceutical collections maintained by the Ministry of Health. Methods: A repeated cross-sectional analysis of population-level dispensing data was conducted from January 1, 2005 to December 31, 2013. Polypharmacy and hyperpolypharmacy in individuals were defined as the use of 5-9 medicines and ≥10 medicines, respectively, dispensed concurrently for a period of ≥90 days. Differences in polypharmacy and hyperpolypharmacy between 2005 and 2013 were examined. A multinomial regression model was used to predict sociodemographic characteristics associated with polypharmacy and hyperpolypharmacy. Results: Polypharmacy and hyperpolypharmacy were found to be higher in 2013 compared to 2005 (polypharmacy: 29.5 vs. 23.4%, p < 0.001; hyperpolypharmacy: 2.1 vs. 1.3%, p < 0.001). The risk of polypharmacy and hyperpolypharmacy was higher in females, in those aged 80-84 years, in the Māori population (for polypharmacy) and the Middle Eastern, Latin American, or African population (for hyperpolypharmacy), in people living in the Southern-district health board, and in individuals with increasing deprivation. Conclusion: The population of New Zealand is aging and the number of older people with multiple chronic conditions is increasing. The proportion of older people exposed to polypharmacy and hyperpolypharmacy has increased in 2013 compared to 2005. Our study provides important information to alert health policy makers, researchers, and clinicians about the dire need to reduce the medication burden in older New Zealanders.

Impact of Anticholinergic Discontinuation on Cognitive Outcomes in Older People: A Systematic Review

BackgroundMedicines with anticholinergic properties increase the risks of functional and cognitive decline, morbidity and mortality, institutionalization and length of hospital stay in older people. It is postulated that minimizing anticholinergic burden should result in improved short-term memory, confusion and delirium, and may improve the quality of life and daily functioning of older people.ObjectiveThe objective of this systematic review was to investigate the impact of discontinuing medicines with anticholinergic properties on cognitive outcomes in older people.DesignA comprehensive systematic search was performed to identify relevant studies, using Medline, Embase, International Pharmaceutical Abstracts (IPA), PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials, from 1946 to July 2013. The critical appraisal was performed by two independent reviewers, and the data were extracted onto standardized forms. The primary outcome of interest was evaluation of cognitive changes in older people after anticholinergic discontinuation, measured using cognitive assessment scales. Meta-analysis was not conducted, because of the heterogeneity of the study designs, interventions and outcome measures.ResultsThe primary electronic literature search identified a total of 475 records in the six different databases. On the basis of full-text analysis, only four studies met the inclusion criteria. The review found two randomized control trials and two prospective cohort studies that met the inclusion criteria. Only the cohort studies demonstrated improvement of cognitive performance after discontinuation of anticholinergic medicines.ConclusionsThe impact of anticholinergic discontinuation on cognitive function remains poorly researched and poorly understood. A larger sample size, longer duration of follow-up and better methods of assessing anticholinergic-induced cognitive impairment are warranted.

Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature.

Introduction Studies have reported associations between serum anticholinergic activity (SAA) and decline in cognitive performance, delirium, and functional impairment. The aim of this meta-analysis was to explore and quantify associations between SAA and adverse cognitive and functional outcomes in older people. Materials and Methods A literature search in Ovid MEDLINE, EMBASE, PsycINFO and IPA from 1946–2014 was completed. The primary outcomes of interest were cognitive and functional adverse outcomes associated with SAA in older people aged 55 years and above. The Cochrane Risk-Bias assessment tool was used to assess bias in randomised controlled trials (RCTs). The Newcastle-Ottawa Scale was used to assess the quality of non-RCTs. Meta-analyses were conducted for RCTs and cohort studies separately. Heterogeneity was assessed using I2 tests. Results The primary electronic literature search identified a total of 1559 records in the 4 different databases. On the basis of full-text analysis, 33 studies that met the inclusion criteria. The review included 4 RCTs, 5 prospective cohort studies, 3 longitudinal cohort studies, 17 cross-sectional studies, and 4 case-control studies. Twenty-four of the retrieved studies examined an association between SAA and cognitive outcomes, 2 studies examined an association with SAA and functional outcomes and 8 studies examined associations between SAA and both cognitive, and functional outcomes. The meta-analysis on 4 RCTs showed no association with higher SAA and cognitive performance (I2 = 89.38%, H2 = 25.53 and p-value = <0.05) however, the pooled data from 4 observational studies showed elevated SAA was associated with reduced cognitive performance (I2 = 0.00%, H2 = 3.37 and p-value = 0.34). Conclusion This systematic review summarises the limitations of the SAA on predicting cognitive and functional outcomes in older people. SAA measured by receptor bioassay is flawed and its use in older people with multimorbidity and polypharmacy is questionable.

The Influence of Patient Characteristics on Anticholinergic Events in Older People

Aims: To examine patient characteristics that predict adverse anticholinergic-type events in older people. Methods: This retrospective population-level study included 2,248 hospitalised patients. Individual data on medicines that are commonly associated with anticholinergic events (delirium, constipation and urinary retention) were identified. Patient characteristics examined were medicines with anticholinergic effects (ACh burden), age, sex, non-anticholinergic medicines (non-ACM), Charlson comorbidity index scores and ethnicity. The Akaike information criterion was used for model selection. The data were analysed using logistic regression models for anticholinergic events using the software NONMEM. Results: ACh burden was found to be a significant independent predictor for developing an anticholinergic event [adjusted odds ratio (aOR): 3.21, 95% CI: 1.23-5.81] for those taking an average of 5 anticholinergic medicines compared to those taking 1. Both non-ACM and age were also independent risk factors (aOR: 1.41, 95% CI: 1.31-1.51 and aOR: 1.08, 95% CI: 1.05-1.10, respectively). Conclusion: To our knowledge, this is the first study that has examined population-level data in a nonlinear model framework to predict anticholinergic-type adverse events. This study evaluated the relationship between important patient characteristics and the occurrence of anticholinergic-type events. These findings reinforce the clinical significance of reviewing anticholinergic medicines in older people.

Anticholinergics: theoretical and clinical overview

ABSTRACT Introduction: Anticholinergics are a class of medicines that block the neurotransmitter, acetylcholine, in the brain and peripheral tissues. Medicines with anticholinergic activity are widely prescribed for and used by older people for various medical conditions. One-third to one-half of the medicines commonly prescribed for older people have anticholinergic activity. Several studies have reported anticholinergic burden to be a predictor of cognitive and functional impairments in older people. Areas covered: This article exemplifies the theoretical and clinical aspects of medicines with anticholinergic activity, including pharmacology (definition of medicines that possess anticholinergic activity, antimuscarinic receptors, therapeutic and adverse effects), epidemiology, measures and effects of cumulative anticholinergic burden in older adults, and clinical recommendations. In addition, the gaps in the literature have been identified for future research. Expert opinion: Many medicines that are commonly prescribed to older people have a degree of anticholinergic activity that can contribute to anticholinergic burden. Anticholinergic burden, measured in several ways that consider number, dose and/or degree of anticholinergic activity of medicines, has shown to be a predictor of adverse health and functional outcomes. The anticholinergic burden on older people should be minimised by avoiding, reducing dose and deprescribing medicines with anticholinergic activity where clinically possible.

Examination and Estimation of Anticholinergic Burden: Current Trends and Implications for Future Research

It is postulated that minimizing anticholinergic burden in older people may result in improved short-term memory and behavior, reduced confusion and delirium, and enhanced quality of life and daily functioning. The purpose of this opinion article was to investigate the current trends and future implications relating to the examination and estimation of anticholinergic burden in older people. Current evidence linking medicines with anticholinergic activity and cognitive impairment is derived mostly from observational data. Further research with larger trials or cohort studies with adequate power and appropriate follow-up periods is required to confirm associations between anticholinergic burden and adverse outcomes. This article provides insights into different approaches for the estimation of anticholinergic burden. Network-based systems pharmacology models could be an effective way of understanding anticholinergic drug-induced adverse effects. The emphasis on mechanistic models may open new opportunities for researchers to understand adverse drug effects in clinical practice. In the interim, medicines with high anticholinergic activity should be avoided in older people, unless considered clinically essential. In this instance, they should be used at a low/titrated dose and for the shortest duration possible. It is therefore important to reinforce the clinical significance of reviewing anticholinergic medicines in older people.

An overview of pharmacodynamic modelling, ligand-binding approach and its application in clinical practice

The study of the magnitude and variation of drug response is defined as pharmacodynamics (PDs). PD models examine plasma concentration and effect relationship. It can predict the archetypal effect (E) of a drug as a function of the drug concentration (C) and estimate an unknown PD parameter (θpd). The PD models have been described as fixed, linear, log-linear, Emax, sigmoid Emax, and indirect PD response. Ligand binding model is an example of a PD model that works on the underpinning PD principle of a drug, eliciting its pharmacological effect at the receptor site. The pharmacological effect is produced by the drug binding to the receptor to either activate or antagonise the receptor. Ligand binding models describe a system of interacting components, i.e. the interaction of one or more ligands with one or more binding sites. The Emax model is the central method that provides an empirical justification for the concentration/dose-effect relationship. However, for ligand binding models justification is provided by theory of receptor occupancy. In essence, for ligand binding models, the term fractionaloccupancy is best used to describe the fraction of receptors occupied at a particular ligand concentration. It is stated that the fractionaloccupancy=occupiedbindingsites/totalbindingsites, which means the effect of a drug should depend on the fraction of receptors that are occupied. In the future, network-based systems pharmacology models using ligand binding principles could be an effective way of understanding drug-related adverse effects. This will facilitate and strengthen the development of rational drug therapy in clinical practice.

Residential medication management reviews of antithrombotic therapy in aged care residents with atrial fibrillation: assessment of stroke and bleeding risk

Antithrombotics reduce the risk of stroke in individuals with atrial fibrillation (AF). However, optimal prescribing of antithrombotics in older people remains a challenge. The objective of this study was to assess the risk of stroke for aged care home residents with AF and to examine the pharmacist‐led medication reviews on the utilization of antithrombotic therapy.