Anticholinergic and Sedative Medications and Dynamic Gait Parameters in Older Patients.

BACKGROUND: Anticholinergic and sedative medications are associated with poorer physical function in older age. Gait and physical function have traditionally been assessed with the time needed to execute objective function tests. Accelerometer-based gait parameters provide a precise capturing of gait dynamics and patterns and as such have added value. OBJECTIVES: This study examined the associations between cumulative exposure to anticholinergic and sedative medications and gait dimensions as assessed with accelerometer-based dynamic gait parameters. METHODS: Data were collected from outpatients of a diagnostic geriatric day clinic who underwent a comprehensive geriatric assessment (CGA). Cumulative exposure to anticholinergic and sedative medications was quantified with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. From a total of 22 dynamic gait parameters, the gait dimensions 'Regularity', 'Complexity', 'Stability', 'Pace', and 'Postural Control' were derived using factor analysis (and standardized total scores for these dimensions were calculated accordingly). Data were analyzed with multivariable linear regression analysis, in which adjustment was made for the covariates age, gender, body mass index (BMI), Mini Mental State Examination (MMSE) score, Charlson Comorbidity Index (CCI) including dementia, and number of medications not included in the DBI. RESULTS: A total of 184 patients participated, whose mean age was 79.8 years (± SD 5.8), of whom 110 (60%) were women and of whom 88 (48%) had polypharmacy (i.e., received treatment with ≥5 medications). Of the 893 medications that were prescribed in total, 157 medications (17.6%) had anticholinergic and/or sedative properties. Of the patients, 100 (54%) had no exposure (DBI = 0), 42 (23%) had moderate exposure (0 > DBI ≤ 1), while another 42 (23%) had high exposure (DBI >1) to anticholinergic and sedative medications. Findings showed that high cumulative exposure to anticholinergic and sedative medications was related with poorer function on the Regularity and Pace dimensions. Furthermore, moderate and high exposure were associated with poorer function on the Complexity dimension. CONCLUSIONS: These findings show that in older patients with comorbidities, cumulative anticholinergic and sedative exposure is associated with poorer function on multiple gait dimensions.

Drug Burden Index and Cognitive and Physical Function in Aged Care Residents: A Longitudinal Study.

OBJECTIVES: Anticholinergic/antimuscarinic and sedative medications (eg, benzodiazepines) have been found to be associated with poorer cognitive and physical function and mobility impairment in older age. However, previous studies were mostly conducted among community-dwelling older individuals and had often a cross-sectional design. Accordingly, our aim was to examine longitudinal associations between cumulative exposure to anticholinergic and sedative medications and cognitive and physical function among residents from aged care homes. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: A total of 4624 residents of Dutch aged care homes of whom data were collected between June 2005 and April 2014. METHODS: Outcome measures were collected with the Long-Term Care Facilities assessment from the international Residential Assessment Instrument (interRAI-LTCF) and included the Cognitive Performance Scale, the Activities of Daily Living (ADL) Hierarchy scale, a timed 4-meter walk test, distance walked, hours of physical activity, and days being outside. Cumulative exposure to anticholinergic and sedative medications was calculated with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. Associations were examined with linear mixed models to take the potential dependence of observations into account (ie, data were collected at repeated assessment occasions of residents who were clustered in aged care homes). Analyses were adjusted for sex, age, dementia, comorbidity (neurological, psychiatric, cardiovascular, oncological, and pulmonary), fractures, depressive symptoms, and medications excluded from the DBI. RESULTS: We observed significant longitudinal associations between a higher DBI and poorer ADLs, fewer hours of physical activity, and fewer days being outside. We found no significant longitudinal association between a higher DBI and poorer cognitive function. CONCLUSIONS AND IMPLICATIONS: Over time, cumulative exposure to anticholinergic and sedative medications is associated with poorer physical but not cognitive function in aged care residents. Careful monitoring of aged care residents with high cumulative anticholinergic and sedative medication exposure is needed.

Long-Term Exposure to Anticholinergic and Sedative Medications and Cognitive and Physical Function in Later Life.

BACKGROUND: Anticholinergic and sedative medications are frequently prescribed to older individuals. These medications are associated with short-term cognitive and physical impairment, but less is known about long-term associations. We therefore examined whether over 20 years cumulative exposure to these medications was related to poorer cognitive and physical functioning. METHODS: Older adult participants of the Longitudinal Aging Study Amsterdam (LASA) were followed from 1992 to 2012. On seven measurement occasions, cumulative exposure to anticholinergic and sedative medications was quantified with the drug burden index (DBI), a linear additive pharmacological dose-response model. Cognitive functioning was assessed with the Mini-Mental State Examination (MMSE), Alphabet Coding Task (ACT, three trials), Auditory Verbal Learning Test (AVLT, learning and retention condition), and Raven Colored Progressive Matrices (RCPM, two trials). Physical functioning was assessed with the Walking Test (WT), Cardigan Test (CT), Chair Stands Test (CST), Balance Test (BT), and self-reported Functional Independence (FI). Data were analyzed with linear mixed models adjusted for age, education, sex, living with a partner, BMI, depressive symptoms, comorbidities (cardiovascular disease, diabetes, cancer, COPD, osteoarthritis, CNS diseases), and prescribed medications. RESULTS: Longitudinal associations were found of the DBI with poorer cognitive functioning (less items correct on the three ACT trials, AVLT learning condition, and the two RCPM trials) and with poorer physical functioning (longer completion time on the CT, CST, and lower self-reported FI). CONCLUSIONS: This longitudinal analysis of data collected over 20 years, showed that higher long-term cumulative exposure to anticholinergic and sedative medications was associated with poorer cognitive and physical functioning.

Feasibility, acceptability and potential effectiveness of an information technology-based, pharmacist-led intervention to prevent an increase in anticholinergic and sedative load among older community-dwelling individuals.

BACKGROUND: Anticholinergic/sedative medications are frequently used by older people, despite their negative impacts on cognitive and physical function. We explore the feasibility, acceptability and potential effectiveness of an innovative information technology (IT)-based intervention to prevent an increase in anticholinergic/sedative load in older people. METHODS: This was a prospective study in 51 Dutch community pharmacies. Pharmacists used an IT-based tool to identify patients aged ⩾65 years, with existing high anticholinergic/sedative loads (drug burden index ⩾2) and a newly initiated anticholinergic/sedative medication. We determined the following. Feasibility: number of eligible patients identified. Acceptability: pharmacists' satisfaction with the intervention, pharmacists' time investment and patients' willingness to reduce medication use. Potential effectiveness: number of recommendations, rate of agreement of general practitioners (GPs) with proposed recommendations and factors associated with agreement. To evaluate the latter, pharmacists conducted medication reviews and proposed recommendations to GPs for 5-10 patients selected by the IT-based tool. RESULTS: We included 305 patients from 47 pharmacies. Feasibility: a mean of 17.0 (standard deviation, 8.8) patients were identified per pharmacy. Acceptability: 43 pharmacists (91.5%) were satisfied with the intervention. The median time investment per patient was 33 min (range 6.5-210). Of 35 patients, 30 (85.7%) were willing to reduce medication use. Potential effectiveness: pharmacists proposed 351 recommendations for 212 patients (69.5%). GPs agreed with recommendations for 108 patients (35.4%). Agreement to stop a medication was reached in 19.8% of recommendations for newly initiated medications (37 of 187) and for 15.2% of recommendations for existing medications (25 of 164). Agreement was more likely for recommendations on codeine [odds ratio (OR) 3.30; 95% confidence interval (CI) 1.14-9.57] or medications initiated by a specialist (OR 2.85; 95% CI 1.19-6.84) and less likely for pharmacies with lower level of collaboration with GPs (OR 0.15; 95% CI 0.02-0.97). CONCLUSION: This innovative IT-based intervention was feasible, acceptable and potentially effective. In one-third of patients an increase in anticholinergic/sedative load was prevented within reasonable time investment.

Anticholinergic and sedative medication use in older community-dwelling people: A national population study in the Netherlands.

PURPOSE: To identify the proportion of older adults with a high anticholinergic/sedative load and to identify patient subgroups based on type of central nervous system (CNS)-active medication used. METHODS: A cross-sectional study of a nationwide sample of patients with anticholinergic/sedative medications dispensed by 1779 community pharmacies in the Netherlands (90% of all community pharmacies) in November 2016 was conducted. Patients aged older than 65 years with a high anticholinergic/sedative load defined as having a drug burden index (DBI) greater than 1 were included. Proportion of patients with a high anticholinergic/sedative load was calculated by dividing the number of individuals in our study population by the 2.4 million older patients using medications dispensed from study pharmacies. Patient subgroups based on type of CNS-active medications used were identified with latent class analysis. RESULTS: Overall, 8.7% (209 472 individuals) of older adults using medications had a DBI greater than 1. Latent class analysis identified four patient subgroups (classes) based on the following types of CNS-active medications used: "combined psycholeptic/psychoanaleptic medication" (class 1, 57.9%), "analgesics" (class 2, 17.9%), "antiepileptic medication" (class 3, 17.8%), and "anti-Parkinson medication" (class 4, 6.3%). CONCLUSIONS: A large proportion of older adults in the Netherlands had a high anticholinergic/sedative load. Four distinct subgroups using specific CNS-active medication were identified. Interventions aiming at reducing the overall anticholinergic/sedative load should be tailored to these subgroups.

Reducing the anticholinergic and sedative load in older patients on polypharmacy by pharmacist-led medication review: a randomised controlled trial.

OBJECTIVE: To evaluate if a pharmacist-led medication review is effective at reducing the anticholinergic/sedative load, as measured by the Drug Burden Index (DBI). DESIGN: Randomised controlled single blind trial. SETTING: 15 community pharmacies in the Northern Netherlands. PARTICIPANTS: 157 community-dwelling patients aged ≥65 years who used ≥5 medicines for ≥3 months, including at least one psycholeptic/psychoanaleptic medication and who had a DBI≥1. INTERVENTION: A medication review by the community pharmacist in collaboration with the patient's general practitioner and patient. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary outcome was the proportion of patients whose DBI decreased by at least 0.5. Secondary outcomes were the presence of anticholinergic/sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission and mortality. Data were collected at baseline and 3 months follow-up. RESULTS: Mean participant age was 75.7 (SD, 6.9) years in the intervention arm and 76.6 (SD, 6.7) years in the control arm, the majority were female (respectively 69.3% and 72.0%). Logistic regression analysis showed no difference in the proportion of patients with a≥0.5 decrease in DBI between intervention arm (17.3%) and control arm (15.9%), (OR 1.04, CI 0.47 to 2.64, p=0.927). Intervention patients scored higher on the Digit Symbol Substitution Test, measure of cognitive function (OR 2.02, CI 1.11 to 3.67, p=0.021) and reported fewer sedative side effects (OR 0.61, CI 0.40 to 0.94, p=0.024) at follow-up. No significant difference was found for other secondary outcomes. CONCLUSIONS: Pharmacist-led medication review as currently performed in the Netherlands was not effective in reducing the anticholinergic/sedative load, measured with the DBI, within the time frame of 3 months. Preventive strategies, signalling a rising load and taking action before chronic use of anticholinergic/sedative medication is established may be more successful. TRIAL REGISTRATION NUMBER: NCT02317666.

Discontinuing Inappropriate Medication Use in Nursing Home Residents: A Cluster Randomized Controlled Trial.

BACKGROUND: Inappropriate prescribing is a well-known clinical problem in nursing home residents, but few interventions have focused on reducing inappropriate medication use. OBJECTIVE: To examine successful discontinuation of inappropriate medication use and to improve prescribing in nursing home residents. DESIGN: Pragmatic cluster randomized controlled trial, with clustering by elder care physicians and their wards. (ClinicalTrials.gov: NCT01876095). SETTING: 59 Dutch nursing home wards for long-term care. PATIENTS: Residents with a life expectancy greater than 4 weeks who consented to treatment with medication. INTERVENTION: Multidisciplinary Multistep Medication Review (3MR) consisting of an assessment of the patient perspective, medical history, critical appraisal of medications, a meeting between the treating elder care physician and the pharmacist, and implementation of medication changes. MEASUREMENTS: Successful discontinuation of use of at least 1 inappropriate drug (that is, without relapse or severe withdrawal symptoms) and clinical outcomes (neuropsychiatric symptoms, cognitive function, and quality of life) after 4 months of follow-up. RESULTS: Nineteen elder care physicians (33 wards) performed the 3MR, and 16 elder care physicians (26 wards) followed standard procedures. A total of 426 nursing home residents (233 in the intervention group and 193 in the control group) were followed for an average of 144 days (SD, 21). In an analysis of all participants, use of at least 1 inappropriate medication was successfully discontinued for 91 (39.1%) residents in the intervention group versus 57 (29.5%) in the control group (adjusted relative risk, 1.37 [95% CI, 1.02 to 1.75]). Clinical outcomes did not deteriorate between baseline and follow-up. LIMITATIONS: The 3MR was done only once. Some withdrawal symptoms or relapses may have been missed. CONCLUSION: The 3MR is effective in discontinuing inappropriate medication use in frail nursing home residents without a decline in their well-being. PRIMARY FUNDING SOURCE: Netherlands Organisation for Health Research and Development.

Quantification of anticholinergic and sedative drug load with the Drug Burden Index: a review of outcomes and methodological quality of studies.

PURPOSE: The Drug Burden Index (DBI) is a non-invasive method to quantify patients' anticholinergic and sedative drug burden from their prescriptions. This systematic review aimed to summarise the evidence on the associations between the DBI and clinical outcomes and methodological quality of studies. METHODS: A search in PubMed and Embase (search terms: 'drug', 'burden', and 'index') was performed and experts were contacted. We excluded publications that did not report empirical results or clinical outcomes. Methodological quality was assessed using the Newcastle-Ottawa Scale. Potential omissions of relevant clinical outcomes and populations were studied. RESULTS: Of the 2998 identified publications, 21 were eligible. Overall, methodological quality of studies was good. In all but one study, adjustment was made for prevalent co-morbidity. The DBI was examined in diverse older individuals, i.e. both males and females from different settings and countries. However, no studies were conducted in other relevant patient groups, e.g. psychiatric patients. Exposure to anticholinergic and sedative drugs was thoroughly ascertained, though the specific calculation of the DBI differed across studies. Outcomes were assessed from medical records, record linkage or validated objective tests or questionnaires. Many studies found associations between the DBI and outcomes including hospitalisation, physical and cognitive function. Cognitive function and quality of life were understudied and the number and scope of longitudinal studies was limited. CONCLUSIONS: An accumulating body of evidence supports the validity of the DBI. Longitudinal studies of cognitive function and quality of life and in other patient groups, e.g. psychiatric patients, are warranted.

Changes in Prescribing Symptomatic and Preventive Medications in the Last Year of Life in Older Nursing Home Residents.

Background: At the end of life goals of care change from disease prevention to symptomatic control, however, little is known about the patterns of medication prescribing at this stage. Objectives: To explore changes in prescribing of symptomatic and preventive medication in the last year of life in older nursing home residents. Methods: A retrospective cohort study was conducted using pharmacy medication supply data of 553 residents from 16 nursing home facilities around Sydney, Australia. Residents received 24-h nursing care, were aged ≥ 65 years, died between June 2008 and June 2010 and were using at least one medication 1 year before death. Medications were classified as symptomatic, preventive, or other. A linear mixed model was used to compare changes in prescribing in the last year of life. Results: 68.1% of residents were female, mean age was 88.0 (SD: 7.5) years and residents used a mean of 9.1 (SD: 4.1) medications 1 year before death. The mean number of symptomatic medications per resident increased from 4.6 medications 1 year before death to 5.1 medications at death [95% CI 4.4-4.7 to 5.9-5.2, P = 0.000], while preventive medication decreased from 2.0 to 1.4 medications [95% CI 1.9-2.1 to 1.3-1.5, P = 0.000]. Symptomatic medications were used longer in the last year of life, compared to preventive medications (336.3 days [95% CI 331.8-340.8] versus 310.9 days [95% CI 305.2-316.7], P = 0.000). Conclusion: Use of medications for symptom relief increased throughout the last year of life, while medications for prevention of long-term complications decreased. But changes were slight and clinical relevance can be questioned.

Decreasing the load? Is a Multidisciplinary Multistep Medication Review in older people an effective intervention to reduce a patient's Drug Burden Index? Protocol of a randomised controlled trial.

INTRODUCTION: Older people often use medications with anticholinergic or sedative side effects which increase the risk of falling and worsen cognitive impairment. The Drug Burden Index (DBI) is a measure of the burden of anticholinergic and sedative medications. Medication reviews are typically done by a pharmacist in collaboration with a general practitioner to optimise the medication use and reduce these adverse drug events. We will evaluate whether a Multidisciplinary Multistep Medication Review (3MR) is an effective intervention to reduce a patient's DBI. METHODS: A randomised controlled trial including 160 patients from 15 community pharmacies will be conducted. Per pharmacy, 1 pharmacist will perform a structured 3MR in close collaboration with the general practitioner, including the objective to reduce the DBI. ANALYSIS: Primary outcome--the difference in proportion of patients having a decrease in DBI ≥ 0.5 in the intervention and control groups at follow-up. Secondary outcomes--anticholinergic and sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission, and mortality. ETHICS AND DISSEMINATION: The burden of patients will be kept at a minimum. The 3MR can be considered as usual care by the pharmacist and general practitioner. Medical specialists will be consulted, if necessary. The intervention is specifically aimed at older community-dwelling patients in an attempt to optimise prescribing, in particular, to reduce medication with anticholinergic and sedative properties. Study results will be published in peer-reviewed journals and will be distributed through information channels targeting professionals. TRIAL REGISTRATION NUMBER: NCT02317666; Pre-results.