The Impact of Deprescribing Interventions on the Drug Burden Index and Other Outcomes: A Systematic Review.

OBJECTIVES: The Drug Burden Index (DBI) calculates a person's exposure to anticholinergic and sedative medications. We aimed to review randomized controlled trials (RCTs) of deprescribing interventions that reported the DBI as an outcome, their characteristics, effectiveness in reducing the DBI, and impact on other outcomes. DESIGN: Systematic review with meta-analysis. SETTING AND PARTICIPANTS: RCTs of deprescribing interventions where the DBI was measured as a primary or secondary outcome in humans within any setting were included. METHODS: Electronic databases, citation indexes, and gray literature were searched from April 1, 2007, to September 1, 2023. Quality was assessed using the Cochrane risk-of-bias tool. RESULTS: Of 1721 records identified, 9 met the inclusion criteria. Six interventions were delivered by pharmacists and 3 were delivered by pharmacists/nurses or pharmacists/geriatricians. All interventions required at least intermediate-level skills and involved multiple components and target groups. Studies were conducted in the community (n = 5), nursing homes (n = 2), and hospitals (n = 2). The mean or median age was ≥75 years and most participants were women in all studies. Most (n = 6) studies were underpowered. The follow-up period ranged from 3 to 12 months. Three studies reported a lower DBI in the intervention group compared with control: 1 pharmacist independent prescriber-delivered in nursing homes (adjusted rate ratio, 0.83; 95% CI, 0.74 to 0.92), 1 pharmacist/nurse practitioner-delivered in hospital (adjusted mean difference (MD), -0.28; 95% CI, -0.51 to -0.04), and 1 geriatrician/pharmacist-delivered in hospital (MD, -0.28; 95% CI, -0.52 to -0.04). Meta-analysis showed no difference in the change in DBI between control and intervention groups in the community including nursing homes (MD, -0.03; 95% CI, -0.08 to 0.01) or hospital setting (MD, -0.19; 95% CI, -0.45 to 0.06). Interventions had inconsistent effects on cognition and no effect on other reported outcomes. CONCLUSIONS AND IMPLICATIONS: RCTs of deprescribing interventions had no significant impact on reducing DBI or improving outcomes. Further suitably powered studies are required.

The Drug Burden Index Is Associated With Measures of Cognitive Function Among Older Adults in the Health, Aging, and Body Composition Study.

BACKGROUND: Anticholinergic and sedative medications affect cognition among older adults. The Drug Burden Index (DBI) is a validated measure of exposure to these medications, with higher DBI scores indicating higher drug burden. This ancillary analysis investigated the association between DBI and cognition assessed by the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSST). METHODS: The Health, Aging, and Body Composition Study was a prospective study of community-dwelling adults aged 70-79 years at enrollment. Using data from years 1, 5, and 10, DBI was calculated using medication data per participant. Linear mixed modeling was used to assess cross-sectional and longitudinal effects of DBI on 3MS and DSST. Adjusted models included biological sex, race, education level, APOE status, and death. Sensitivity analyses included testing the strength of the associations for each year and testing attrition due to death as a possible confounding factor via Cox-Proportional Hazard models. RESULTS: After adjustment, DBI was inversely associated with 3MS and DSST scores. These associations became stronger in each subsequent year. Neither DBI at year 1 nor within-person change in DBI were predictive of longitudinal declines in either cognitive measure. Sensitivity analyses indicated that DBI, 3MS, and DSST were associated with a greater risk of attrition due to death. CONCLUSIONS: Results suggest that in years when older adults had a higher DBI scores, they had significantly lower global cognition and slower processing speed. These findings further substantiate the DBI as a useful pharmacological tool for assessing the effect of medication exposure.

The Drug Burden Index and Level of Frailty as Determinants of Healthcare Costs in a Cohort of Older Frail Adults in New Zealand.

OBJECTIVES: Frailty is common in older people and is associated with increased use of healthcare services and ongoing use of multiple medications. This study provides insights into the healthcare cost structure of a frail group of older adults in Aotearoa, New Zealand. Furthermore, we investigated the relationship between participants' anticholinergic and sedative medication burden and their total healthcare costs to explore the viability of deprescribing interventions within this cohort. METHODS: Healthcare cost analysis was conducted using data collected during a randomized controlled trial within a frail, older cohort. The collected information included participant demographics, medications used, frailty, cost of service use of aged residential care and outpatient hospital services, hospital admissions, and dispensed medications. RESULTS: Data from 338 study participants recruited between 25 September 2018 and 30 October 2020 with a mean age of 80 years were analyzed. The total cost of healthcare per participant ranged from New Zealand $15 (US dollar $10) to New Zealand $270 681 (US dollar $175 943) over 6 months postrecruitment into the study. Four individuals accounted for 26% of this cohort's total healthcare cost. We found frailty to be associated with increased healthcare costs, whereas the drug burden was only associated with increased pharmaceutical costs, not overall healthcare costs. CONCLUSIONS: With no relationship found between a patient's anticholinergic and sedative medication burden and their total healthcare costs, more research is required to understand how and where to unlock healthcare cost savings within frail, older populations.

Deprescribing electronic case reviews for older veterans at risk for falls: Effects on drug burden and falls.

BACKGROUND: Falls are the most common medication-related safety event in older adults. Deprescribing fall risk-increasing drugs (FRIDs) may mitigate fall risk. This study assesses the effects of an innovative deprescribing program in reducing FRID burden and falls-related acute visits over 1 year. METHODS: The Falls Assessment of Medications in the Elderly (FAME) Program is a pilot deprescribing program designed to improve medication safety in Veterans aged ≥65, screening positive for high fall risk at the Durham Veterans Affairs Health Care System. Central case finding and electronic case reviews with deprescribing recommendations were completed by an interdisciplinary team, forwarded to prescribers for approval, then implemented during follow-up telephone visits by FAME team. Primary outcome was change in FRID burden calculated by modified Drug Burden Index (DBI) at 1 year and an exploratory outcome was 1-year fall-related acute visits. RESULTS: Overall, 472 patients (236 intervention cases, 236 matched controls) were included in the study. Of the 236 patients receiving a FAME deprescribing plan, 147 had recommendations approved by prescriber and patient. In the intention-to-treat analysis, the 1-year change in modified DBI was -0.15 (95% CI -0.23, -0.08) in the intervention cohort and -0.11 (-0.21, -0.00) in the matched control cohort (p = 0.47). The odds of increasing DBI by a clinically important threshold of 0.5 was significantly lower in the FAME cohort (OR 0.37, 0.21, 0.66). Fall-related acute events occurred in 6.3% of patients in the intervention group versus 11.0% in control patients over a one-year period (p = 0.10). CONCLUSIONS: The program was associated with a significantly lower odds of further increasing FRID burden at 1 year compared to matched controls. An electronic case review and telephone counseling program has the potential to reduce drug-related falls in high-risk older adults.

The effect of the anticholinergic burden on mortality following elective cardiac surgery.

OBJECTIVE: The cumulative effect of drugs with anticholinergic properties may pose a significant risk in the post-discharge period of patients who have undergone elective cardiac surgery. The aim of this study was to investigate the association between anticholinergic burden and 6-month postdischarge mortality in older cardiac surgery patients. METHODS: This study performed a retrospective longitudinal analysis of patients undergoing elective cardiac surgery at a tertiary care centre from January 2021 to January 2022. The Deyo-Charlson comorbidity index (D-CCI) was used to estimate the burden of comorbidities. The anticholinergic burden was assessed using the Anticholinergic Cognitive Burden scale (ACB) and Drug Burden Index (DBI) scale. All-cause postdischarge mortality was determined from electronic medical records. RESULTS: A total of 255 older adults who had undergone elective cardiac surgery and had been followed up for at least 6 months were included in this study. Approximately 12.5% (n = 32) of older patients died within 6 months of discharge. In multivariate Cox regression analysis, ACB (HR:1.31, 95%CI:1.10-1.56 p = 0.01) and DBI (HR:2.08, 95%CI:1.27-3.39 p = 0.01) showed significantly increased risk of 6-month postdischarge mortality after adjusting for several possible confounders (age, gender, D-CCl, and American Society of Anaesthesiologists (ASA) score). Overall event-free survival differed significantly between patients undergoing cardiac surgery based on anticholinergic burden according to the group-stratified ACB and DBI scales (χ2: 5.907, log-rank test, p = 0.015 and χ2: 15.389, log-rank test, p < 0.001 respectively). CONCLUSION: The anticholinergic burden is associated with 6-month all-cause post-discharge mortality in older cardiac surgery patients. A deprescribing approach should be considered, especially for older adults in the perioperative period. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov. Identifier: NCT05312684 Registered on 5 April 2022.

Association of the Drug Burden Index (DBI) exposure with outcomes: A systematic review.

BACKGROUND: The Drug Burden Index (DBI) measures an individual's total exposure to anticholinergic and sedative medications. This systematic review aimed to investigate the association of the DBI with clinical and prescribing outcomes in observational pharmaco-epidemiological studies, and the effect of DBI exposure on functional outcomes in pre-clinical models. METHODS: A systematic search of nine electronic databases, citation indexes and gray literature was performed (April 1, 2007-December 31, 2022). Studies that reported primary data on the association of the DBI with clinical or prescribing outcomes conducted in any setting in humans aged ≥18 years or animals were included. Quality assessment was performed using the Joanna Briggs Institute critical appraisal tools and the Systematic Review Centre for Laboratory animal Experimentation risk of bias tool. RESULTS: Of 2382 studies screened, 70 met the inclusion criteria (65 in humans, five in animals). In humans, outcomes reported included function (n = 56), cognition (n = 20), falls (n = 14), frailty (n = 7), mortality (n = 9), quality of life (n = 8), hospitalization (n = 7), length of stay (n = 5), readmission (n = 1), other clinical outcomes (n = 15) and prescribing outcomes (n = 2). A higher DBI was significantly associated with increased falls (11/14, 71%), poorer function (31/56, 55%), and cognition (11/20, 55%) related outcomes. Narrative synthesis was used due to significant heterogeneity in the study population, setting, study type, definition of DBI, and outcome measures. Results could not be pooled due to heterogeneity. In animals, outcomes reported included function (n = 18), frailty (n = 2), and mortality (n = 1). In pre-clinical studies, a higher DBI caused poorer function and frailty. CONCLUSIONS: A higher DBI may be associated with an increased risk of falls and decreased function and cognition. Higher DBI was inconsistently associated with increased mortality, length of stay, frailty, hospitalization or reduced quality of life. Human observational findings with respect to functional outcomes are supported by preclinical interventional studies. The DBI may be used as a tool to identify older adults at higher risk of harm.

Drug burden index in people living with HIV over 50 years of age in a real clinical practice cohort.

OBJECTIVES: To determine DBI and its relationship with polypharmacy and pharmacotherapeutic complexity (PC) in a cohort of PLWH over 50 years of age at follow-up of pharmacotherapy in a tertiary hospital. METHODS: Observational and retrospective study that included PLWH in active antiretroviral treatment over 50 years of age who have been followed up in outpatient pharmacy services. Pharmacotherapeutic complexity was estimated through Medication Regimen Complexity Index (MRCI). Collected variables included comorbidities, current prescriptions and its classification according to anticholinergic and sedative activity and associated risk of falls. RESULTS: Studied population included 251 patients (85.7% men; median age: 58 years, interquartile range: 54-61). There was a high prevalence of high DBI scores (49.2%). High DBI was significantly correlated with a high PC, polypharmacy, psychiatric comorbidity and substances abuse (p<0.05). Among sedative drugs, the most prescribed were anxiolytic drugs (N05B) (n=85), antidepressant drugs (N06A) (n=41) and antiepileptic drugs (N03A) (n=29). For anticholinergic drugs, alpha-adrenergic antagonist drugs (G04C) were the most prescribed (n=18). Most frequent drugs associated with risk of falls were anxiolytics (N05B) (n=85), angiotensin-converting enzyme inhibitors (C09A) (n=61) and antidepressants (N06A) (n=41). CONCLUSION: The DBI score in older PLWH is high and it is related to PC, polypharmacy, mental diseases and substance abuse as is the prevalence of fall-related drugs. Control of these parameters as well as the reduction of the sedative and anticholinergic load should be included in the lines of work in the pharmaceutical care of people living with HIV+.

Medication Assessment in an Older Population during Acute Care Hospitalization and Its Effect on the Anticholinergic Burden: A Prospective Cohort Study.

(1) Background: Anticholinergic and sedative drugs (ASDs) contribute to negative health outcomes, especially in the frail population. In this study, we aimed to assess whether frailty increases with anticholinergic burden and to evaluate the effects of medication reviews (MRs) on ASD regimens among patients attending an acute care for the elderly (ACE) unit. (2) Methods: A cohort study was conducted between June 2019 and October 2020 with 150 consecutive patients admitted to our ACE unit. Demographic, clinical, and pharmacological data were assessed. Frailty score was determined using the Frail-VIG index (FI-VIG), and ASD burden was quantified using the drug burden index (DBI). In addition, the MR was performed using the patient-centered prescription (PCP) model. We used a paired T-test to compare the DBI pre- and post-MR and univariate and multivariate regression to identify the factors associated with frailty. (3) Results: Overall, 85.6% (n = 128) of participants showed some degree of frailty (FI-VIG > 0.20) and 84% (n = 126) of patients received treatment with ASDs upon admission (pre-MR). As the degree of frailty increased, so did the DBI (p < 0.001). After the implementation of the MR through the application of the PCP model, a reduction in the DBI was noted (1.06 ± 0.8 versus 0.95 ± 0.7) (p < 0.001). After adjusting for covariates, the association between frailty and the DBI was apparent (OR: 11.42, 95% (CI: 2.77-47.15)). (4) Conclusions: A higher DBI was positively associated with frailty. The DBI decreased significantly in frail patients after a personalized MR. Thus, MRs focusing on ASDs are crucial for frail older patients.

Potentially inappropriate medications and anticholinergic and sedative burden in older community-dwelling patients with advanced chronic kidney disease

Objective: Regarding older patients, multiple chronic conditions lead to the intake of multiple medications, involving a higher risk of adverse drug events. In older patients with advanced chronic kidney disease, the medication exposure was poorly explored. The aim of this study was to describe the use of potentially inappropriate medications and medications with anticholinergic and sedative properties in older community-dwelling patients with advanced chronic kidney disease. Methods: An observational study was conducted in a geriatric day-care unit. All patients aged over 65 years with advanced chronic kidney disease, defined by estimated glomerular filtration rate < 20 mL/min/1.73 m2 or estimated glomerular filtration rate > 20 mL/min/1.73 m2 with rapid progression, and referred by nephrologist for pretransplant comprehensive geriatric assessment, were included in the study. Potentially inappropriate medications were identified using the EU(7)-PIM list, and he anticholinergic and sedative drug exposure was measured using the Drug Burden Index. Results: Overall, 139 patients were included in the study (mean age 74.4 ± 3.3 years, 32.4% females, 61.9% on dialysis). Potentially inappropriate medications were used by 74.1% (103/139) of patients and were mainly represented by proton pump inhibitors, alpha-1-blockers and central antihypertensive drugs. Regarding anticholinergic and / or sedative medications, 79.9% (111/139) of older patients were exposed. Conclusion: In older community-dwelling patients with advanced chronic kidney disease, the prevalence of potentially inappropriate medication exposure and anticholinergic and sedative exposure was high. Interventions focusing on deprescription of these inappropriate medications should be conducted in this specific population.

Objectif: Chez le patient âgé, la polypathologie est souvent associée à la prise de plusieurs médicaments, impliquant un risque élevé d'iatrogénie médicamenteuse. L'exposition médicamenteuse a été peu explorée chez les patients âgés atteints d'insuffisance rénale chronique. L'objectif de cette étude est de décrire l'exposition aux médicaments potentiellement inappropriés et aux médicaments présentant des propriétés anticholinergiques et sédatives chez ces patients. Méthodes: Il s'agit d'une étude observationnelle conduite au sein d'un hôpital de jour gériatrique. Tous les patients âgés de plus de 65 ans avec une maladie rénale chronique avancée, définie par un débit de filtration glomérulaire estimé inférieur à 20 mL/min/1,73 m² ou supérieur à 20 mL/min/1,73 m² avec une progression rapide, et adressés par un néphrologue pour la réalisation d'une évaluation gériatrique standardisée pré-transplantation rénale, ont été inclus dans l'étude. Les médicaments potentiellement inappropriés ont été identifiés à partir de la liste EU(7)-PIM, et l'exposition aux médicaments anticholinergiques et sédatifs a été mesurée à partir du Drug Burden Index. Résultats: Un total de 139 patients a été inclus dans l'étude (74,4 ± 3,3 ans, 32,4 % de femmes, 61,9 % dialysés). Des médicaments potentiellement inappropriés ont été retrouvés chez 74,1 % (103/139) des patients. Ils étaient principalement représentés par les inhibiteurs de la pompe à protons, les alpha-1-bloquants et les antihypertenseurs centraux. Concernant les médicaments anticholinergiques et/ou sédatifs, 79,9 % (111/139) des patients âgés étaient exposés. Conclusion: L'étude montre que la prévalence de l'exposition aux médicaments potentiellement inappropriés et aux médicaments anticholinergiques et/ou sédatifs est élevée chez les patients âgés atteints de maladie rénale chronique avancée. Des interventions portant sur la déprescription de ces médicaments devraient être menées auprès de cette population spécifique.

Association of drug burden index with delirium in community-dwelling older adults with dementia: a longitudinal observational study.

BACKGROUND: The Drug Burden Index (DBI) is a validated tool for assessing the dose-dependent cumulative exposure to sedative and anticholinergic medications. However, the increased risk of delirium superimposed dementia (DSD) with high DBI levels has not yet been investigated. AIM: This study aimed to examine the potential association between DBI scores and delirium in community-dwelling older adults with dementia. METHOD: A total of 1105 participants with cognitive impairment underwent a comprehensive geriatric assessment. Experienced geriatricians made the final diagnosis of delirium based on DSM-IV-TR and DSM-V. We calculated the DBI as the sum of all sedatives and anticholinergics taken continuously for at least four weeks before admission. Polypharmacy was defined as regular use of five or more medications. We classified the participants as having no exposure (DBI = 0), low exposure (0 < DBI < 1), and high exposure (DBI ≥ 1). RESULTS: Of the 721 patients with dementia, the mean age was 78.3 ± 6.7 years, and the majority were female (64.4%). In the whole sample, low and high exposures to anticholinergic and sedative medications at admission were 34.1% (n = 246) and 38.1% (n = 275), respectively. Patients in the high-exposure group had higher physical impairment (p = 0.01), higher polypharmacy (p = 0.01), and higher DBI scores (p = 0.01). In the multivariate Cox regression analysis, high exposure to anticholinergic and sedative medications increased the risk of delirium 4.09-fold compared to the no exposure group (HR = 4.09, CI: 1.63-10.27, p = 0.01). CONCLUSION: High exposure to drugs with sedative and anticholinergic properties was common in community-dwelling older adults. A high DBI was associated with DSD, highlighting the need for an optimal prescription in this vulnerable population. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov. Identifier: NCT04973709 Registered on 22 July 2021.

Towards Optimizing Hospitalized Older adults' MEdications (TO HOME): Multi-centre study of medication use and outcomes in routine care.

AIMS: Comprehensively investigate prescribing in usual care of hospitalized older people with respect to polypharmacy; potentially inappropriate medications (PIMs) according to Beers criteria; and cumulative anticholinergic and sedative medication exposure calculated with Drug Burden Index (DBI). Specifically, to quantify exposure to these measures on admission, changes between admission and discharge, associations with adverse outcomes and medication costs. METHODS: Established new retrospective inpatient cohort of 2000 adults aged ≥75 years, consecutively admitted to 6 hospitals in Sydney, Australia, with detailed information on medications, clinical characteristics and outcomes. Conducted cross-sectional analyses of index admission data from cohort. RESULTS: Cohort had mean (standard deviation) age 86.0 (5.8) years, 59% female, 21% from residential aged care. On admission, prevalence of polypharmacy was 77%, PIMs 34% and DBI > 0 in 53%. From admission to discharge, mean difference (95% confidence interval) in total number of medications increased 1.05 (0.92, 1.18); while prevalence of exposure to PIMs (-3.8% [-5.4, -2.1]) and mean DBI score (-0.02 [-0.04, -0.01]) decreased. PIMs and DBI score were associated with increased risks (adjusted odds ratio [95% confidence interval]) of falls (PIMs 1.63 [1.28, 2.08]; DBI score 1.21[1.00, 1.46]) and delirium (PIMs 1.76 [1.38, 1.46]; DBI score 1.42 [1.19, 1.71]). Each measure was associated with increased risk of adverse drug reactions (polypharmacy 1.42 [1.19, 1.71]; PIMs 1.87 [1.40, 2.49]; DBI score 1.90 [1.55, 2.15]). Cost (AU$/patient/hospital day) of medications contributing to PIMs and DBI was low ($0.29 and $0.88). CONCLUSION: In this large cohort of older inpatients, usual hospital care results in an increase in number of medications and small reductions in PIMs and DBI, with variable associations with adverse outcomes.

Exposure to anticholinergic and sedative medication is associated with impaired functioning in older people with vertigo, dizziness and balance disorders-Results from the longitudinal multicenter study MobilE-TRA.

Introduction: Anticholinergic and sedative medication is prescribed for various conditions in older patients. While the general association between anticholinergic and sedative medication and impaired functioning is well established, its specific role in older individuals with vertigo, dizziness, and balance disorders (VDB) is still incompletely understood. The objective of this study was to investigate, whether an exposure to anticholinergic and sedative medication is associated with lower generic and lower vertigo-specific functioning in older patients with VDB. Methods: Data originates from the longitudinal multicenter study MobilE-TRA with two follow-ups, conducted from 2017 to 2019 in two German federal states. Exposure to anticholinergic and sedative medication was quantified using the drug burden index (DBI). Generic functioning was assessed by the Health Assessment Questionnaire Disability Index, appraising the amount of difficulties in performing activities of daily living (ADL). Vertigo-specific functioning was measured using the Vestibular Activities and Participation (VAP) questionnaire, assessing patient-reported functioning regarding activities of daily living that are difficult to perform because of their propensity to provoke VDB (Scale 1) as well as immediate consequences of VDB on activities and participation related to mobility (Scale 2). Longitudinal linear mixed models were applied to assess the association of exposure to anticholinergic and sedative medication at baseline and the level of generic and vertigo-specific functioning status over time. Results: An overall of 19 (7 from Bavaria) primary care physicians (mean age = 54 years, 29% female) recruited 158 (59% from Bavaria) patients with VDB (median age = 78 years, 70% female). Anticholinergic and sedative medication at baseline was present in 56 (35%) patients. An exposure to anticholinergic and sedative medication at baseline was significantly associated with lower generic functioning [Beta = 0.40, 95%-CI (0.18; 0.61)] and lower vertigo-specific functioning [VAP Scale 1: Beta = 2.47, 95%-CI (0.92; 4.02)], and VAP Scale 2: Beta = 3.74, 95%-CI [2.23; 5.24]). Conclusion: Our results highlight the importance of a close monitoring of anticholinergic and sedative medication use in older patients with VDB. When feasible, anticholinergic and sedative medication should be replaced by equivalent alternative therapies in order to potentially reduce the burden of VDB.

Deprescribing Anticholinergic and Sedative Drugs to Reduce Polypharmacy in Frail Older Adults Living in the Community: A Randomized Controlled Trial.

BACKGROUND: Polypharmacy is associated with poor outcomes in older adults. Targeted deprescribing of anticholinergic and sedative medications may improve health outcomes for frail older adults. Our pharmacist-led deprescribing intervention was a pragmatic 2-arm randomized controlled trial stratified by frailty. We compared usual care (control) with the intervention of pharmacists providing deprescribing recommendations to general practitioners. METHODS: Community-based older adults (≥65 years) from 2 New Zealand district health boards were recruited following a standardized interRAI needs assessment. The Drug Burden Index (DBI) was used to quantify the use of sedative and anticholinergic medications for each participant. The trial was stratified into low, medium, and high-frailty. We hypothesized that the intervention would increase the proportion of participants with a reduction in DBI ≥ 0.5 within 6 months. RESULTS: Of 363 participants, 21 (12.7%) in the control group and 21 (12.2%) in the intervention group had a reduction in DBI ≥ 0.5. The difference in the proportion of -0.4% (95% confidence interval [CI]: -7.9% to 7.0%) provided no evidence of efficacy for the intervention. Similarly, there was no evidence to suggest the effectiveness of this intervention for participants of any frailty level. CONCLUSION: Our pharmacist-led medication review of frail older participants did not reduce the anticholinergic/sedative load within 6 months. Coronavirus disease 2019 (COVID-19) lockdown measures required modification of the intervention. Subgroup analyses pre- and post-lockdown showed no impact on outcomes. Reviewing this and other deprescribing trials through the lens of implementation science may aid an understanding of the contextual determinants preventing or enabling successful deprescribing implementation strategies.

Is anticholinergic and sedative drug burden associated with postdischarge institutionalization in community-dwelling older patients acutely admitted to hospital? A Norwegian registry-based study.

PURPOSE: Investigate the association between anticholinergic (AC) and sedative (SED) drug burden before hospitalization and postdischarge institutionalization (PDI) in community-dwelling older patients acutely admitted to hospital. METHODS: A cross-sectional study using data from the Norwegian Patient Registry and the Norwegian Prescription Database. We studied acutely hospitalized community-dwelling patients ≥70 years during 2013 (N = 86 509). Patients acutely admitted to geriatric wards underwent subgroup analyses (n = 1715). We calculated drug burden by the Drug Burden Index (DBI), use of AC/SED drugs, and the number of AC/SED drugs. Piecewise linearity of DBI versus PDI and a knot point (DBI = 2.45) was identified. Statistical analyses included an adjusted multivariable logistic regression model. RESULTS: In the total population, 45.4% were exposed to at least one AC/SED drug, compared to 52.5% in the geriatric subgroup. AC/SED drugs were significantly associated with PDI. The DBI with odds ratios (ORs) of 1.11 (95% CI 1.07-1.15) for DBI < 2.45 and 1.08 (95% CI 1.04-1.13) for DBI ≥ 2.45. The number of AC/SED drugs with OR of 1.07 (95% CI 1.05-1.09). The AC component of DBI with OR 1.23 and the number of AC drugs with OR 1.13. In the subgroup, ORs were closer to 1 for AC drugs. CONCLUSIONS: The use of AC/SED drugs was highly prevalent in older patients before acute hospital admissions, and significantly associated with PDI. The number, or just using AC/SED drugs, gave similar associations with PDI compared to applying the DBI. Using AC drugs showed higher sensitivity, indicating that to reduce the risk of PDI, a clinical approach could be to reduce the number of AC drugs.

Comparing Effects of Polypharmacy on Inflammatory Profiles in Older Adults and Mice: Implications for Translational Aging Research.

Aging and multimorbidity are associated with inflammation. Polypharmacy is common in older people with multimorbidity. Given the potential for interactions between polypharmacy and inflammation, the relationship between inflammation and polypharmacy were studied in older adults with multimorbidity and in healthy aging mice. A cross-sectional analysis of data from the 5-year wave of the Concord Health and Ageing in Men Project, a population-based study of community-dwelling men aged ≥70 years. Serum concentrations of 27 cytokines were measured using a multiplex immunoassay. Associations between polypharmacy (≥5 medications) and cytokines were evaluated using multivariable linear regression adjusting for age, frailty, comorbidities, and individual drug classes. Interaction between polypharmacy and Drug Burden Index (DBI-drugs with anticholinergic and sedative effects) was analyzed. Effects of polypharmacy and DBI on serum levels of 23 cytokines were determined in aging male mice treated with chronic polypharmacy or control. Compared to the nonpolypharmacy group (n = 495), CHAMP participants with polypharmacy (n = 409) had significantly higher concentrations of IL-8, IL-6, CCL3, Eotaxin, IL-1ra, IL-1ß, IP-10, and lower concentrations of anti-inflammatory cytokine IL-4. In fully-adjusted multivariable models, polypharmacy was positively associated with concentrations of IL-8 and CCL3. There were no significant differences in inflammatory profiles between control and polypharmacy-treated mice. The relationship was not influenced by DBI in men or in mice. Inflammatory markers associated with polypharmacy in older adults were not seen in healthy aged mice administered polypharmacy, and may be related to underlying diseases. The polypharmacy mouse model provides opportunities for mechanistic investigations in translational research.

An Increased Anticholinergic Drug Burden Index Score Negatively Affect Nutritional Status in Older Patients Without Dementia.

INTRODUCTION/AIM: Anticholinergic drugs, which have severe central and peripheric side effects, are frequently prescribed to older adults. Increased anticholinergic drug burden is associated with poor physical and cognitive functions. On the other side, the impact of anticholinergics on nutritional status is not elaborated in the literature. Therefore, this study was aimed to investigate the effect of the anticholinergic burden on nutrition. MATERIALS AND METHODS: Patients who underwent comprehensive geriatric assessment (CGA) 6 months apart were included in the study. Patients diagnosed with dementia were excluded because of the difference in the course of cognition, physical performance and nutrition. Nutritional status and global cognition were evaluated using Mini Nutritional Assessment-short form (MNA-SF), Mini-Mental State Examination (MMSE). Anticholinergic drug burden was assessed with the Drug Burden Index (DBI), enabling a precise dose-related cumulative exposure. Patients were divided into three groups according to DBI score: 0, no DBI exposure; 0-1, low risk; and ≥1, high risk. Regression analysis was performed to show the relationship between the difference in CGA parameters and the change in DBI score at the sixth month. RESULTS: A total of 423 patients were included in the study. Participants' mean age was 79.40 ± 7.50, and 68.6% were female. The DBI 0 score group has better MMSE and MNA-SF scores and a lower rate of falls, polypharmacy, malnutrition, and risk of malnutrition in the baseline. Having malnutrition or risk of malnutrition is 2.21 times higher for every one-unit increase in DBI score. Additionally, during the 6-month follow-up, increased DBI score was associated with decreased MNA-SF and MMSE score, albumin. CONCLUSIONS: The harmful effects of anticholinergics may be prevented because anticholinergic activity is a potentially reversible factor. Therefore, reducing exposure to drugs with anticholinergic activity has particular importance in geriatric practice.

Potentially inappropriate medications and anticholinergic and sedative burden in older patients with haemophilia or von Willebrand disease: The M'HEMORRH-AGE study.

WHAT IS KNOWN AND OBJECTIVE: In older patients, multiple chronic conditions lead to the intake of multiple medications and a higher risk of adverse drug events. The exposure to inappropriate medications in older patients with bleeding disorders is poorly explored. The aim of this study was to describe the exposure to potentially inappropriate medications (PIMs) and medications with anticholinergic and sedative properties in older community-dwelling patients with haemophilia or von Willebrand Disease (VWD). METHODS: The M'HEMORRH-AGE study (Medication in AGEd patients with HAEMORRHagic disease) is a multicentre prospective observational study. Community-dwelling patients over 65 years with haemophilia or VWD were included in the study. PIMs were identified using the EU(7)-PIM list, and the anticholinergic and sedative drug exposure was measured using the Drug Burden Index. RESULTS AND DISCUSSION: 142 older community-dwelling patients with haemophilia (n = 89) or VWD (n = 53) were included (mean age: 72.8 ± 5.8 years). PIMs were used by 45.8% of older patients and were mainly represented by cardiovascular (34.9%), nervous systems (26.7%) and alimentary tract and metabolism PIMs (25.6%). Regarding anticholinergic and/or sedative medications, 37.3% of older patients were exposed mainly due to nervous system medications (68.3%), for example analgesics. WHAT IS NEW AND CONCLUSION: The M'HEMORRH-AGE study showed the exposure to PIMs and anticholinergic/sedative medications was high in older community-dwelling patients with haemophilia or VWD. Interventions focusing on deprescription of these inappropriate medications should be conducted in this specific population.

Preclinical frailty assessments: Phenotype and frailty index identify frailty in different mice and are variably affected by chronic medications.

Use of different objective frailty assessment tools may improve understanding of the biology of frailty and allow evaluation of effects of interventions on frailty. Polypharmacy is associated with increased risk of frailty in epidemiologic studies, regardless of frailty definition, but the pathophysiology of the association is not well understood. This study aims to (1) assess and compare the prevalence of frailty from middle to old age following control, chronic polypharmacy or monotherapy treatment, when measured using the clinical frailty index assessment and the mouse frailty phenotype tools; and (2) to evaluate and compare the effects of chronic polypharmacy regimens with zero, low and high Drug Burden Index (DBI) and monotherapies from middle to old age on the rate of deficit accumulation on the frailty index, mean number of phenotype criteria, odds of being frail assessed by the frailty index or phenotype, and the time to onset of frailty assessed by the frailty index or phenotype. In a longitudinal study, middle-aged (12 months) male C57BL/6J(B6) mice were administered non medicated control feed and water, or therapeutic doses of different polypharmacy combinations or monotherapies in feed and/or water. Frailty assessments were performed at 12, 15, 18, 21 and 24 months. There was limited overlap between animals identified as frail using different frailty assessments. Polypharmacy has measurable and different effects on each frailty assessment. Long-term chronic administration of some polypharmacy and monotherapy therapeutic drug regimens increased the number of frailty deficits (clinical frailty index: low DBI polypharmacy (15 and 21 months), high DBI polypharmacy (15-21 months), oxycodone (15-18 months), oxybutynin (15-18 months), citalopram (15-21 months) and metoprolol monotherapy (15 months) and modified frailty phenotype assessment (over the whole duration of treatment, low DBI polypharmacy (adjusted Risk Ratio(aRR) = 1.97, 95% confidence interval (CI) 1.43-2.72), high DBI polypharmacy (aRR = 1.88; 95% CI 1.36-2.60), oxybutynin (aRR = 1.48; 95% CI 1.01-2.16) and citalopram monotherapy (aRR = 1.96; 95% CI 1.41-2.74), p < 0.05) . The odds of developing frailty measured with the clinical frailty index increased with high DBI polypharmacy (adjusted odds ratio (aOR) = 3.13; 95% CI 1.01-9.66) and when measured with the frailty phenotype assessment increased with low DBI polypharmacy (aOR = 4.38, 95% CI 1.40-13.74), high DBI polypharmacy (aOR = 3.43; 95% CI 1.12-10.50) and citalopram monotherapy (aOR = 4.63; 95% CI 1.39-15.54)). No treatment affected time to frailty using either frailty assessment. Analysis of the number of deficits on the frailty index or number of positive criteria on the frailty phenotype allows analysis of rate of change and provides greater sensitivity, while the odds of being frail analysis provided a clinically relevant indicator of whether mice had greater chance of reaching a cut-off for becoming frail with medication exposure than without. Our results are consistent with clinical studies, demonstrating that certain polypharmacy regimens induce frailty, with different relationships observed when using different frailty assessments and analyses.

Development, validation and evaluation of the Goal-directed Medication review Electronic Decision Support System (G-MEDSS)©.

OBJECTIVES: 1) To understand and investigate the experiences of accredited clinical pharmacists (ACP) using computerised clinical decision support systems (CCDSS) during medication reviews for older people, including those living with dementia; 2) To design, develop, validate, and evaluate a CCDSS that incorporates pharmacological and other deprescribing tools to aid person-centred management of high-risk medications in older adults living with and without dementia. METHODS: This study consisted of three phases and was designed on scenario-based methodology: a) the development phase, which included an exploratory survey and prototype building; b) the validation phase, which included qualitative data collection and usability testing with ACPs, general practitioners (GPs) and carers for people living with dementia; and c) the evaluation phase, using mixed-methods analyses. RESULTS: The exploratory survey found that ACPs required a flexible, and reliable CCDSS to support them with clinical decisions regarding high-risk medication use in older adults. The Goal-directed Medication review Electronic Decision Support System (G-MEDSS)© was developed and validated using quantitative and qualitative feedback received from ACPs, GPs and carers for people with dementia. The mean (SD) System Usability Scale score was 69.0 (12.9), which indicated fair-good usability. DISCUSSION AND CONCLUSIONS: Involving end-users in the design process refined and improved the design of G-MEDSS, allowing for a person-centred and goal-directed delivery of pharmaceutical care. G-MEDSS allows healthcare practitioners conducting medication reviews for older adults living with and without dementia to tailor pharmaceutical care to meet their goals and preferences. Future studies may explore integration of G-MEDSS with prescribing or dispensing software.

Deprescribing to reduce polypharmacy: study protocol for a randomised controlled trial assessing deprescribing of anticholinergic and sedative drugs in a cohort of frail older people living in the community.

BACKGROUND: Targeted deprescribing of anticholinergic and sedative medications in older people may improve their health outcomes. This trial will determine if pharmacist-led reviews lead to general practitioners deprescribing anticholinergic and sedative medications in older people living in the community. METHODS AND ANALYSIS: The standard protocol items: Recommendations for Interventional Trials (SPIRIT) checklist was used to develop and report the protocol. The trial will involve older adults stratified by frailty (low, medium, and high). This will be a pragmatic two-arm randomized controlled trial to test general practitioner uptake of pharmacist recommendations to deprescribe anticholinergic and sedative medications that are causing adverse side effects in patients. STUDY POPULATION: Community-dwelling frail adults, 65 years or older, living in the Canterbury region of New Zealand, seeking publicly funded home support services or admission to aged residential care and taking at least one anticholinergic or sedative medication regularly. INTERVENTION: New Zealand registered pharmacists using peer-reviewed deprescribing guidelines will visit participants at home in the community, review their medications, and recommend anticholinergic and sedative medications that could be deprescribed to the participant's general practitioner. The total use of anticholinergic and sedative medications will be quantified using the Drug Burden Index (DBI). OUTCOMES: The primary outcome will be the change in total DBI between baseline and 6-month follow-up. Secondary outcomes will include entry into aged residential care, prolonged hospitalization, and death. DATA COLLECTION POINTS: Data will be collected at the time of interRAI assessments (T0), at the time of the baseline review (T1), at 6 months following the baseline review (T2), and at the end of the study period, or end of study participation for participants admitted into aged residential care, or who died (T3). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human, Disability and Ethics Committee: ethical number (17CEN265). TRIAL REGISTRATION: ClinicalTrials.gov ACTRN12618000729224 . Registered on May 2, 2018, with the Australian New Zealand Clinical Trials Registry.