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The Prognostic Value of Anticholinergic Burden Measures in Relation to Mortality in Older Individuals: A Systematic Review and Meta-Analysis.

ABSTRACT: Background:Greater anticholinergic burden (ACB) increases the risk of mortality in older individuals, yet the strength of this association varies between studies. One possible explanation for this variance is the use of different approaches to quantify ACB. This systematic review (PROSPERO number CRD42019115918) assessed the prognostic utility of ACB-specific measures on mortality in older individuals. Methods:Multiple cross-disciplinary databases were searched from 2006-2018. Observational studies assessing the association between ACB and mortality utilizing ?1 ACB measure, involving persons aged ?65 years were included. Screening and data extraction were performed by two independent reviewers, with disagreements resolved by a third independent reviewer. Risk of bias and quality of evidence were assessed using Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Meta-analysis was conducted where appropriate. Results:Of 19,224 titles, 20 articles describing 18 cohort studies involving 498,056 older individuals were eligible. Eight anticholinergic-specific measures were identified; the Anticholinergic Cognitive Burden Scale (ACBS, n=9) and Anticholinergic Risk scale (ARS, n=8) were most frequently reported. The evidence base was of poor quality, with moderate to high risk of bias. Meta-analysis showed increased mortality risk. Conclusions:There was a modest association between some ACB measures and mortality, with most evidence derived from the ACBS. Studies comparing different measures within the same population were lacking. Analysis was limited by poor generalizability between studies, specifically regarding heterogeneity in methodology and reporting, as well as high risk of bias for most studies in the evidence base.

SUBMITTER: Graves-Morris K

PROVIDER: S-EPMC7201087 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Prognostic Value of Anticholinergic Burden Measures in Relation to Mortality in Older Individuals: A Systematic Review and Meta-Analysis.

Graves-Morris Katherine K Stewart Carrie C Soiza Roy L RL Taylor-Rowan Martin M Quinn Terence J TJ Loke Yoon K YK Myint Phyo Kyaw PK

Frontiers in pharmacology 20200429

<h4>Background</h4>Greater anticholinergic burden (ACB) increases the risk of mortality in older individuals, yet the strength of this association varies between studies. One possible explanation for this variance is the use of different approaches to quantify ACB. This systematic review (PROSPERO number CRD42019115918) assessed the prognostic utility of ACB-specific measures on mortality in older individuals.<h4>Methods</h4>Multiple cross-disciplinary databases were searched from 2006-2018. Obs ...[more]

PMID: 32411001

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Project description:IntroductionSeveral adverse outcomes have been associated with anticholinergic burden (ACB), and these risks increase with age. Several approaches to measuring this burden are available but, to date, no comparison of their prognostic abilities has been conducted. This PROSPERO-registered systematic review (CRD42019115918) compared the evidence behind ACB measures in relation to their ability to predict risk of falling in older people.MethodsMedline (OVID), EMBASE (OVID), CINAHL (EMBSCO) and PsycINFO (OVID) were searched using comprehensive search terms and a validated search filter for prognostic studies. Inclusion criteria included: participants aged 65 years and older, use of one or more ACB measure(s) as a prognostic factor, cohort or case-control in design, and reporting falls as an outcome. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool.ResultsEight studies reporting temporal associations between ACB and falls were included. All studies were rated high risk of bias in ⩾1 QUIPS tool categories, with five rated high risk ⩾3 categories. All studies (274,647 participants) showed some degree of association between anticholinergic score and increased risk of falls. Findings were most significant with moderate to high levels of ACB. Most studies (6/8) utilised the anticholinergic cognitive burden scale. No studies directly compared two or more ACB measures and there was variation in how falls were measured for analysis.ConclusionThe evidence supports an association between moderate to high ACB and risk of falling in older people, but no conclusion can be made regarding which ACB scale offers best prognostic value in older people.Plain language summaryA review of published studies to explore which anticholinergic burden scale is best at predicting the risk of falls in older people Introduction: One third of older people will experience a fall. Falls have many consequences including fractures, a loss of independence and being unable to enjoy life. Many things can increase the chances of having a fall. This includes some medications. One type of medication, known as anticholinergic medication, may increase the risk of falls. These medications are used to treat common health issues including depression and bladder problems. Anticholinergic burden is the term used to describe the total effects from taking these medications. Some people may use more than one of these medications. This would increase their anticholinergic burden. It is possible that reducing the use of these medications could reduce the risk of falls. We need to carry out studies to see if this is possible. To do this, we need to be able to measure anticholinergic burden. There are several scales available, but we do not know which is best.Methods: We wanted to answer: 'Which anticholinergic scale is best at predicting the risk of falling in older people?'. We reviewed studies that could answer this. We did this in a systematic way to capture all published studies. We restricted the search in several ways. We only included studies relevant to our question.Results: We found eight studies. We learned that people who are moderate to high users of these medications (often people who will use more than one of these medications) had a higher risk of falling. It was less clear if people who have a lower burden (often people who only use one of these medications) had an increased risk of falling. The low number of studies prevented us from determining if one scale was better than another.Conclusion: These findings suggest that we should reduce use of these medications. This could reduce the number falls and improve the well-being of older people.

Project description:BackgroundAnticholinergic burden has been associated with adverse outcomes such as falls. To date, no gold standard measure has been identified to assess anticholinergic burden, and no conclusion has been drawn on which of the different measure algorithms best predicts falls in older patients from general practice. This study compared the ability of five measures of anticholinergic burden to predict falls. To account for patients' individual susceptibility to medications, the added predictive value of typical anticholinergic symptoms was further quantified in this context.Methods and findingsTo predict falls, models were developed and validated based on logistic regression models created using data from two German cluster-randomized controlled trials. The outcome was defined as "≥ 1 fall" vs. "no fall" within a 6-month follow-up period. Data from the RIME study (n = 1,197) were used in model development, and from PRIMUM (n = 502) for external validation. The models were developed step-wise in order to quantify the predictive ability of anticholinergic burden measures, and anticholinergic symptoms. In the development set, 1,015 patients had complete data and 188 (18.5%) experienced ≥ 1 fall within the 6-month follow-up period. The overall predictive value of the five anticholinergic measures was limited, with neither the employed anticholinergic variable (binary / count / burden), nor dose-dependent or dose-independent measures differing significantly in their ability to predict falls. The highest c-statistic was obtained using the German Anticholinergic Burden Score (0.73), whereby the optimism-corrected c-statistic was 0.71 after interval validation using bootstrapping and 0.63 in the external validation. Previous falls and dizziness / vertigo had the strongest prognostic value in all models.ConclusionsThe ability of anticholinergic burden measures to predict falls does not appear to differ significantly, and the added value they contribute to risk classification in fall-prediction models is limited. Previous falls and dizziness / vertigo contributed most to model performance.

Project description:ObjectivesThe Drug Burden Index (DBI) tool quantifies individual exposure to anticholinergic and sedative medications. The DBI has been internationally validated against adverse health outcomes in older people. DBI exposure has not been reported in the Irish older population. This study aimed to: (1) develop a list of drugs with clinically significant anticholinergic and/or sedative effects (DBI medications) relevant to Ireland; (2) examine, using the DBI formula, the prevalence of exposure to DBI medications in Irish older people and (3) explore patient factors associated DBI exposure.DesignA cross-sectional national pharmacy claims database study.SettingCommunity setting using the General Medical Services (GMS) scheme pharmacy claims database maintained by the Health Service Executive Primary Care Reimbursement Services.ParticipantsIrish older individuals (aged ≥65 years) enrolled in the GMS scheme and dispensed at least one prescription item in 2016 (n=428 516).Main outcome measuresPrevalence of exposure to DBI medications and patient factors associated with DBI exposure.Results282 874 (66%) of the GMS population aged ≥65 years were exposed to at least one DBI medication in 2016. Prevalence of exposure to DBI medications was significantly higher in females than males (females 71.6% vs males 58.7%, adjusted OR 1.65, 95% CI 1.63 to 1.68). Prevalence of DBI exposure increased progressively with the number of chronic drugs used, rising from 42.7% of those prescribed 0-4 chronic drugs to 95.4% of those on ≥12 chronic drugs (adjusted OR 27.8, 95% CI 26.7 to 29.0). The most frequently used DBI medications were codeine/paracetamol combination products (20.1% of patients), tramadol (11.5%), zopiclone (9.5%), zolpidem (8.5%), pregabalin (7.9%) and alprazolam (7.8%).ConclusionsThe majority of older people in Ireland are exposed to medications with anticholinergic and/or sedative effects, particularly females and those with multiple comorbidities. The high use of low-dose codeine/paracetamol combination products, Z-drugs and benzodiazepines, suggests there are opportunities for deprescribing.

Project description:BackgroundAnticholinergic burden potentially increases the risk of fracture. Although there are various anticholinergic burden scales, little is known about the inter-scale compatibility regarding the relationship of anticholinergic burden with fracture risk. We performed meta-analysis to examine the association of fracture risk with anticholinergic burden measured using various scales.MethodsPrimary literature was retrieved from PubMed (1966 to March, 2021), the Cochrane Library (1974 to March, 2021), Scopus (1970 to March, 2021), and Ichushi-web (1983 to March, 2021). Cohort and case-control studies that evaluated the association between any fracture and anticholinergic drugs were included. Additionally, we included studies in which patients were administered anticholinergic drugs included on the anticholinergic risk scale (ARS), anticholinergic cognitive burden (ACB), anticholinergic drug scale, or drug burden index-anticholinergic component. Random effects models were used to calculate pooled relative risk (RR) and 95% confidence interval (CI) due to heterogeneity among the studies. Publication bias was examined by funnel plots and the Begg's test.ResultsA total of 49 datasets from 10 studies were included in the meta-analysis. Six of the 10 studies included only patients aged over 65 years, who accounted for 93% of the total study population (453,186/487,247). Meta-analysis indicated a positive relationship between use of anticholinergic drugs and fracture risk, regardless of the anticholinergic burden scale used. However, the relationship between anticholinergic burden and fracture risk varied depending on the scale used. Fracture risk increased linearly with increasing anticholinergic burden measured using ARS. ARS 1 point was associated with 28% increase in fracture risk, ARS 1-2 point(s) with 39%, ARS 2 points with 54%, ARS 3 points with 66%, and ARS ≥ 4 points with 77%. On the other hand, ACB 1 point and ACB 2 points were associated with similar fracture risk (pooled RR [95% CI]: overall; 1.28 [1.18-1.39], 1 point; 1.12 [1.06-1.18], 2 points; 1.15 [1.08-1.23]).ConclusionsThis result suggests that the relationship between anticholinergic drug burden and fracture risk may differ depending on the anticholinergic burden scale used.

Dataset Information

The Prognostic Value of Anticholinergic Burden Measures in Relation to Mortality in Older Individuals: A Systematic Review and Meta-Analysis.

Publications

The Prognostic Value of Anticholinergic Burden Measures in Relation to Mortality in Older Individuals: A Systematic Review and Meta-Analysis.

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