Use of medications with anticholinergic activity and self-reported injurious falls in older community-dwelling adults

Objectives: To assess the association between the use of medications with anticholinergic activity and the subsequent risk of injurious falls in older adults. Design: Prospective, population-based study using data from The Irish Longitudinal Study on Ageing. Setting: Irish population. Participants: Community-dwelling men and women without dementia aged 65 and older (N = 2,696). Measurements: Self-reported injurious falls reported once approximately 2 years after baseline interview. Self-reported regular medication use at baseline interview. Pharmacy dispensing records from the Irish Health Service Executive Primary Care Reimbursement Service in a subset (n = 1,553). Results: Nine percent of men and 17% of women reported injurious falls. In men, the use of medications with definite anticholinergic activity was associated with greater risk of subsequent injurious falls (adjusted relative risk (aRR) = 2.55, 95% confidence interval (CI) = 1.33-4.88), but the risk of having any fall and the number of falls reported were not significantly greater. Greater anticholinergic burden was associated with greater injurious falls risk. No associations were observed for women. Findings were similar using pharmacy dispensing records. The aRR for medications with definite anticholinergic activity dispensed in the month before baseline and subsequent injurious falls in men was 2.53 (95% CI = 1.15-5.54). Conclusion: The regular use of medications with anticholinergic activity is associated with subsequent injurious falls in older men, although falls were self-reported after a 2-year recall and so may have been underreported. Further research is required to validate this finding in men and to consider the effect of duration and dose of anticholinergic medications.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

The impact of anticholinergic burden in Alzheimer's dementia-the LASER-AD study

Objective - to examine the effect of medications with anticholinergic effects on cognitive impairment and deterioration in Alzheimer's dementia (AD). Methods - cognitive function was measured at baseline and at 6- and 18-month follow-up using the Mini-Mental State Exam (MMSE), the Severe Impairment Battery (SIB) and the Alzheimer's Disease Assessment Battery, Cognitive subsection (ADAS-COG) in a cohort study of 224 participants with AD. Baseline anticholinergic Burden score (ABS) was measured using the Anticholinergic Burden scale and included all prescribed and over the counter medication. Results - the sample was 224 patients with Alzheimer's dementia and 71.4% were women. Their mean age was 81.0 years [SD 7.4 (range 55–98)]. The mean number of medications taken was 3.6 (SD 2.4) and the mean anticholinergic load was 1.1 (SD 1.4, range 0–7). The total number of drugs taken and anticholinergic load correlated (rho = 0.44; P < 0.01). There were no differences in MMSE and other cognitive functioning at either 6 or 18 months after adjusting for baseline cognitive function, age, gender and use of cholinesterase inhibitors between those with, and those without high anticholinergenic load. Conclusions - medications with anticholinergic effect in patients with AD were not found to effect deterioration in cognition over the subsequent 18 months. Our study did not support a continuing effect of these medications on people with AD who are established on them.

The cognitive impact of anticholinergics:a clinical review

Context: The cognitive side effects of medications with anticholinergic activity have been documented among older adults in a variety of clinical settings. However, there has been no systematic confirmation that acute or chronic prescribing of such medications lead to transient or permanent adverse cognitive outcomes. Objective: Evaluate the existing evidence regarding the effects of anticholinergic medications on cognition in older adults. Data sources: We searched the MEDLINE, OVID, and CINAHL databases from January, 1966 to January, 2008 for eligible studies. Study selection: Studies were included if the anticholinergic activity was systematically measured and correlated with standard measurements of cognitive performance. Studies were excluded if they reported case studies, case series, editorials, and review articles. Data extraction: We extracted the method used to determine anticholinergic activity of medications and its association with cognitive outcomes. Results: Twenty-seven studies met our inclusion criteria. Serum anticholinergic assay was the main method used to determine anticholinergic activity. All but two studies found an association between the anticholinergic activity of medications and either delirium, cognitive impairment or dementia. Conclusions: Medications with anticholinergic activity negatively affect the cognitive performance of older adults. Recognizing the anticholinergic activity of certain medications may represent a potential tool to improve cognition.

A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly.

What factors influence concordance with medications? Findings from the UK Asian Diabetes study

Aims: To investigate concordance with medication, as assessed at baseline and at 1- and 2-year follow-up, and to examine factors associated with non-concordance in a UK-resident South-Asian population. Methods: Data from the UK Asian Diabetes Study were analysed. Concordance with medications was assessed and recorded at three time points during the study. Multiple logistic regression was used to investigate the factors associated with non-concordance; the associations of baseline factors with year 1 concordance and baseline plus year 1 factors with year 2 concordance. Results: Data for 403 patients from seven practices participating in the UK Asian Diabetes Study were analysed. The numbers of patients who were non-concordant were: 63 (16%) at baseline 101 (25%) at year 1; and 122 (30%) at year 2. The baseline-measured variables that were significantly associated with year 1 non-concordance included diabetes duration, history of cardiovascular disease, components of the EuroQol quality of life questionnaire, the EQ-5D score, and number of medications prescribed. In multivariable analyses, the most important determinant of year 1 non-concordance was baseline non-concordance: odds ratio 13.6 (95% confidence limits 4.7, 39.9). Number of medications prescribed for blood pressure control was also significant: odds ratio 1.8 (95% confidence limits 1.4, 2.4). Similar results were observed for year 2 non-concordance. Conclusions: Non-concordance with medications was common and more likely in people prescribed more medications. The current target-driven management of risk factor levels may lead to increasing numbers and doses of medications. Considering the high cost of medications and the implications of poor health behaviours on morbidity and mortality, further investigation of prescribing behaviours and the factors affecting patient concordance are required.

Understanding the risk of hypoglycaemia in older individuals with diabetes

Introduction: Although older individuals are more prone to hypoglycaemia, it is not known if they have sufficient understanding of the risks of hypoglycaemia or the factors that predispose to it. We evaluated the effectiveness of hypoglycaemia education and examined the factors that increased susceptibility to hypoglycaemia among older people with diabetes. Methods: Forty-five patients (male/female) aged >65 years and known to have diabetes were identified through outpatient clinics at a secondary care hospital. Information relating to education received, awareness of hypoglycaemia and associated risk factors was collected using a standard questionnaire. Additionally, data regarding demographics, treatment regimes, patient attitudes, hypoglycaemic awareness and risks and barriers to self-management of diabetes was collected. Patients were categorised as low, moderate and high risk based on their responses. Independent sample t-tests and Analysis of Variance were carried out to identify factors contributing to high hypoglycaemic risk. Results: Overall, 70% of the patients reported receiving education about hypoglycaemia from health professionals and 95% of them reported good understanding of hypoglycaemia and were able to self-test. Proportion of women receiving education was, however, lower than men (52% women versus 88% men). Compared with men, women were less likely to recognise (59 versus 73%), or act appropriately to a hypoglycaemic episode (59 versus 78%). The mean number of hypoglycaemic episodes per year (41 versus 12) and the duration of hypoglycaemia (9.9 versus 6.3 min) was also greater among women compared with men. The duration of diabetes (P = 0.018), female gender, type 1 diabetes (0.002) and lack awareness of medications causing hypos (P = 0.006) were strong predictors of hypoglycaemia risk. Conclusions: There are significant gaps in education around hypoglycaemia in older people with diabetes. Women, people with longer duration and type 1 diabetes in particular, need additional attention and future educational initiatives need to address these issues.  

A telephone survey to determine the experiences of children and their parents/carers, following the initiation of a new medicine

Objective: To determine what issues are experienced during the first few weeks of therapy by patients, and their parents/carers, when a child/young person has been prescribed a new medicine. Method: One hundred patients aged ≤18 years of age prescribed a new medicine for ≥6 weeks were recruited from a single UK National Health Service specialist paediatric hospital outpatient pharmacy. Six weeks after the first dispensing of their new medicine the patient or their parent/carer received telephone follow-up by a researcher and verbally completed a questionnaire containing both open and closed questions. Patient or parent/carer experiences were identified and analysed using thematic analysis and descriptive statistics. Results: Eighty-six participants were available for telephone follow-up. Six (7%) had not started their medicine. Paediatric patients and their parents/carers experienced a range of issues during the first few weeks after starting a new medicine. These included additional concerns/questions (24/80, 30%), administration issues (21/80, 26.3%), adverse effects (29/80, 36.3%) and obtaining repeat supplies (12/80, 15%). The Morisky Medication Adherence Scale indicated that 34/78 (43.6%) participants had a high adherence rating, 35/78 (44.9%) medium and 9/78 (11.5%) a low rating. Conclusions: Paediatric patients and their parents/carers experience a range of issues during the first few weeks after starting a new medicine. Further research is required to determine the type of interventions that may further support medicines use in this group of patients.

Anticholinergic medication use and cognitive impairment in the older population:the Medical Research Council cognitive function and ageing study

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993. SETTING: Community-dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=-0.14–0.11, P=.79). Two-year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics. CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.

Medication reconciliation by a pharmacy technician in a mental health assessment unit

Background: Medication discrepancies are common when patients cross organisational boundaries. However, little is known about the frequency of discrepancies within mental health and the efficacy of interventions to reduce discrepancies. Objective: To evaluate the impact of a pharmacy-led reconciliation service on medication discrepancies on admissions to a secondary care mental health trust. Setting: In-patient mental health services. Methods: Prospective evaluation of pharmacy technician led medication reconciliation for admissions to a UK Mental Health NHS Trust. From March to June 2012 information on any unintentional discrepancies (dose, frequency and name of medication); patient demographics; and type and cause of the discrepancy was collected. The potential for harm was assessed based on two scenarios; the discrepancy was continued into primary care, and the discrepancy was corrected during admission. Logistic regression identified factors associated with discrepancies. Main outcome measure: Mean number of discrepancies per admission corrected by the pharmacy technician. Results Unintentional medication discrepancies occurred in 212 of 377 admissions (56.2 %). Discrepancies involving 569 medicines (mean 1.5 medicines per admission) were corrected. The most common discrepancy was omission (n = 464). Severity was assessed for 114 discrepancies. If the discrepancy was corrected within 16 days the potential harm was minor in 71 (62.3 %) cases and moderate in 43 (37.7 %) cases whereas if the discrepancy was not corrected the potential harm was minor in 27 (23.7 %) cases and moderate in 87 (76.3 %) cases. Discrepancies were associated with both age and number of medications; the stronger association was age. Conclusions: Medication discrepancies are common within mental health services with potentially significant consequences for patients. Trained pharmacy technicians are able to reduce the frequency of discrepancies, improving safety. © 2013 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie.

The 2012 update to the anticholinergic cognitive burden scale

Background: In 2008, the Anticholinergic Cognitive Burden (ACB) scale was generated through a combination of laboratory data, literature review, and expert opinion. This scale identified an increased risk in mortality and worsening cognitive function in multiple populations, including 13,000 older adults in the United Kingdom. We present an updated scale based on new information and new medications available to the market. Methods: We conducted a systematic review for publications recognizing medications with adverse cognitive effects due to anti-cholinergic properties and found no new medications since 2008.Therefore we identified medications from a review of newly ap-proved medications since 2008 and medications identified throughthe clinical experience of the authors. To be included in the updatedACB scale, medications must have met the following criteria; ACBscore of 1: evidence from in vitro data that the medication has antag-onist activity at muscarinic receptors; ACB score of 2: evidence fromliterature, prescriber’s information, or expert opinion of clinical anti-cholinergic effect; ACB score of 3: evidence from literature, pre-scriber’s information, or expert opinion of the medication causingdelirium. Results: The reviewer panel included two geriatric pharmacists,one geriatric psychiatrist, one geriatrician, and one hospitalist.Twenty-three medications were eligible for review and possible inclu-sion in the updated ACB scale. Of these, seven medications were ex-cluded due to a lack of evidence for anticholinergic activity. Of the re-maining 16 medications, ten had laboratory evidence ofanticholinergic activity and added to the ACB list with a score of one.One medication was added with a score of two. Five medicationswere included in the ACB scale with a score of three.Conclusions: The revised ACB scale provides an update of med-ications with anticholinergic effects that may increase the risk of cog-nitive impairment. Future updates will be routinely conducted tomaintain an applicable library of medications for use in clinical andresearch environments.

Anticholinergic burden in older adults with intellectual disability; relationships with multimorbidity and adverse effects

Background: Anticholinergic medications may be associated with adverse clinical outcomes, including acute impairments in cognition and anticholinergic side effects, the risk of adverse outcomes increasing with increasing anticholinergic exposure. Older people with intellectual disability may be at increased risk of exposure to anticholinergic medicines due to their higher prevalence of comorbidities. We sought to determine anticholinergic burden in ageing people with intellectual disability. Methods: Medication data (self-report/proxy-report) was drawn from Wave 1 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a study on the ageing of 753nationally representative people with an IDC40 years randomly selected from the National Intellectual Disability Database. Each individual’s cumulative exposure to anticholinergic medications was calculated using the Anticholinergic Cognitive Burden Scale (ACB) amended by a multi-disciplinary group with independent advice to account for the range of medicines in use in this population. Results: Overall, 70.1 % (527) reported taking medications with possible or definite anticholinergic properties (ACBC1), with a mean (±SD) ACB score of 4.5 (±3.0) (maximum 16). Of those reporting anticholinergic exposure (n=527), 41.3 % (217) reported an ACB score o fC5. Antipsychotics accounted for 36.4 % of the total cumulative ACB score followed by anticholinergics (16 %) and antidepressants (10.8 %). The most frequently reported medicine with anticholinergic activity was carbamazepine 16.8 % (127). The most frequently reported medicine with high anticholinergic activity (ACB 3) was olanzapine13.4 % (101). There was a significant association between higher anti-cholinergic exposure and multimorbidity, particularly mental health morbidity, and some anticholinergic adverse effects such as constipation and day-time drowsiness but not self-rated health. Conclusion: Using simple cumulative measures proved an effective means to capture total burden and helped establish that anticholinergic exposure in the study population was high. The finding highlights the need for comprehensive reviews of medications.

Type 2 diabetes:assessing the relative risks and benefits of glucose-lowering medications

The selection of appropriate pharmacologic therapy for any disease requires a careful assessment of benefit and risk. In the case of type 2 diabetes, this decision typically balances the benefits accrued from improved glycemic control with the risks inherent in glucose-lowering medications. This review is intended to assist therapeutic decision-making by carefully assessing the potential benefit from improved metabolic control relative to the potential risks of a wide array of currently prescribed glucose-lowering agents. Wherever possible, risks and benefits have been expressed in terms of absolute rates (events per 1000 patient-years) to facilitate cross-study comparisons. The review incorporates data from new studies (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, Action to Control Cardiovascular Risk in Diabetes, and the Veterans Affairs Diabetes Trial), as well as safety issues associated with newer glucose-lowering medications. © 2010 Elsevier Inc. All rights reserved.

Financial consequences of one-stop dispensing at Birmingham Children's Hospital

Poster session - Costs for one stop dispensing and the use of patients’ own drugs (PODs) were compared with traditional dispensing costs - It was found that operating a one-stop dispensing scheme, with the use of PODs where applicable, could save an average of £4.35 per patient per day on ward A and £5.19 per patient per day on ward B - These saving would equate to annual savings of £24,000 on ward A and £34,000 on ward B - Additional savings can be made to the secondary care budget as no in-patient drugs would be wasted upon patient discharge - These additional savings are an average £25.19 per patient on ward A and £13.42 per patient on ward B