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Anticholinergic Burden and Fractures: A Systematic Review with Methodological Appraisal.

ABSTRACT: INTRODUCTION:Medications with anticholinergic activity (MACs) are used to treat diseases common in older adults. Evidence on the association between anticholinergic burden (AB) and increased risk of fractures and osteoporosis or reduced bone mineral density (BMD) is inconsistent. Our aim was to conduct a systematic review of observational studies on AB with fractures and osteoporosis or reduced BMD and provide methodological appraisal of included studies. METHODS:We searched MEDLINE, EMBASE, Science Citation Index and CENTRAL as well as grey literature from database inception up to August 2020. Eligibility criteria were: observational design, AB-exposure measured through a scale, fracture of any type or osteoporosis or reduced BMD as outcome, and reported measure of association between exposure and outcome. No restrictions related to time, language or type of data were applied. Eligibility and risk of bias assessment as well as data extraction were performed independently by two reviewers. Risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale and the RTI Item Bank. RESULTS:The majority of the nine included studies had low risk of bias but heterogeneous methodology. No study used a new user design. Seven studies reported an increased risk of fractures associated with AB. In four studies using the Anticholinergic Risk Scale (ARS), adjusted risk of fractures was increased by 2-61% for ARS?=?1, by 0-97% for ARS?=?2, by 19-84% for ARS?=?3, and by 56-96% for ARS???4; in three studies the ARS was aggregated, risk increased by 39% for ARS?=?1-2 and 17% for ARS?=?2-3. Two studies reported increased risk of fractures of 14 and 52% in the highest AB-category and one study reported that change in ARS of???3 during hospitalization was associated with a 321% increased risk in fractures. Two studies did not find an association between AB and fractures. The association between AB and osteoporosis or reduced BMD could only be assessed in two studies, one reporting increased risk of lower BMD at Ward's triangle, the other reporting no association between AB and BMD T-score change at the femoral neck. DISCUSSION:Our study suggests an association between AB and increased risk of fractures with possible dose-exposure gradient in studies using the ARS. The low number of studies and heterogeneity of methods calls for the conduct of more studies. We conducted a study investigating the risk of fractures associated with anticholinergic burden, which is the result of taking one or more medication with anticholinergic activity. The results of our study suggest that persons who experience anticholinergic burden might have a higher risk of fractures. However, since we were only able to include nine studies, more studies conducted in a similar way are needed.

SUBMITTER: Reinold J

PROVIDER: S-EPMC7704512 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Anticholinergic Burden and Fractures: A Systematic Review with Methodological Appraisal.

Reinold Jonas J Schäfer Wiebke W Christianson Lara L Barone-Adesi Francesco F Riedel Oliver O Pisa Federica Edith FE

Drugs & aging 20201023 12

<h4>Introduction</h4>Medications with anticholinergic activity (MACs) are used to treat diseases common in older adults. Evidence on the association between anticholinergic burden (AB) and increased risk of fractures and osteoporosis or reduced bone mineral density (BMD) is inconsistent. Our aim was to conduct a systematic review of observational studies on AB with fractures and osteoporosis or reduced BMD and provide methodological appraisal of included studies.<h4>Methods</h4>We searched MEDLI ...[more]

PMID: 33094444

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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:BackgroundFalls impose significant health and economic burdens on community-dwelling older persons. Decision modelling can inform commissioning of alternative falls prevention strategies. Several methodological challenges arise when modelling public health interventions including community-based falls prevention. This study aims to conduct a systematic review (SR) to: systematically identify community-based falls prevention economic models; synthesise and critically appraise how the models handled key methodological challenges associated with public health modelling; and suggest areas for further methodological research.MethodsThe SR followed the 2021 PRISMA reporting guideline and covered the period 2003-2020 and 12 academic databases and grey literature. The extracted methodological features of included models were synthesised by their relevance to the following challenges: (1) capturing non-health outcomes and societal intervention costs; (2) considering heterogeneity and dynamic complexity; (3) considering theories of human behaviour and implementation; and (4) considering equity issues. The critical appraisal assessed the prevalence of each feature across models, then appraised the methods used to incorporate the feature. The methodological strengths and limitations stated by the modellers were used as indicators of desirable modelling practice and scope for improvement, respectively. The methods were also compared against those suggested in the broader empirical and methodological literature. Areas of further methodological research were suggested based on appraisal results.Results46 models were identified. Comprehensive incorporation of non-health outcomes and societal intervention costs was infrequent. The assessments of heterogeneity and dynamic complexity were limited; subgroup delineation was confined primarily to demographics and binary disease/physical status. Few models incorporated heterogeneity in intervention implementation level, efficacy and cost. Few dynamic variables other than age and falls history were incorporated to characterise the trajectories of falls risk and general health/frailty. Intervention sustainability was frequently based on assumptions; few models estimated the economic/health returns from improved implementation. Seven models incorporated ethnicity- and severity-based subgroups but did not estimate the equity-efficiency trade-offs. Sixteen methodological research suggestions were made.ConclusionExisting community-based falls prevention models contain methodological limitations spanning four challenge areas relevant for public health modelling. There is scope for further methodological research to inform the development of falls prevention and other public health models.

Project description:BackgroundAs people age, they accumulate several health conditions, requiring the use of multiple medications (polypharmacy) to treat them. One of the challenges with polypharmacy is the associated increase in anticholinergic exposure to older adults. In addition, several studies suggest an association between anticholinergic burden and declining physical function in older adults.Objective/purposeThis systematic review aimed to synthesise data from published studies regarding the association between anticholinergic burden and mobility. The studies were critically appraised for the strength of their evidence.MethodsA systematic literature search was conducted across five electronic databases, EMBASE, CINAHL, PSYCHINFO, Cochrane CENTRAL and MEDLINE, from inception to December 2021, to identify studies on the association of anticholinergic burden with mobility. The search was performed following a strategy that converted concepts in the PECO elements into search terms, focusing on terms most likely to be found in the title and abstracts of the studies. For observational studies, the risk of bias was assessed using the Newcastle Ottawa Scale, and the Cochrane risk of bias tool was used for randomised trials. The GRADE criteria was used to rate confidence in evidence and conclusions. For the meta-analyses, we explored the heterogeneity using the Q test and I2 test and the publication bias using the funnel plot and Egger's regression test. The meta-analyses were performed using Jeffreys's Amazing Statistics Program (JASP).ResultsSixteen studies satisfied the inclusion criteria from an initial 496 studies. Fifteen studies identified a significant negative association of anticholinergic burden with mobility measures. One study did not find an association between anticholinergic intervention and mobility measures. Five studies included in the meta-analyses showed that anticholinergic burden significantly decreased walking speed (0.079 m/s ± 0.035 MD ± SE,95% CI: 0.010 to 0.149, p = 0.026), whilst a meta-analysis of four studies showed that anticholinergic burden significantly decreased physical function as measured by three variations of the Instrumental Activities of Daily Living (IADL) instrument 0.27 ± 0.12 (SMD ± SE,95% CI: 0.03 to 0.52), p = 0.027. The results of both meta-analyses had an I2 statistic of 99% for study heterogeneity. Egger's test did not reveal publication bias.ConclusionThere is consensus in published literature suggesting a clear association between anticholinergic burden and mobility. Consideration of cognitive anticholinergic effects may be important in interpreting results regarding the association of anticholinergic burden and mobility as anticholinergic drugs may affect mobility through cognitive effects.

Project description:BackgroundFoodborne and zoonotic diseases such as brucellosis present many challenges to public health and economic welfare. Increasingly, researchers and public health institutes use disability-adjusted life years (DALYs) to generate a comprehensive comparison of the population health impact of these conditions. DALYs calculations, however, entail a number of methodological choices and assumptions, with data gaps and uncertainties to accommodate. Thisreview identifies existing brucellosis burden of disease studies and analyzes their methodological choices, assumptions, and uncertainties. It supports the Global Burden of Animal Diseases programme in the development of a systematic methodology to describe the impact of animal diseases on society, including human health.Methods/principal findingsA systematic search for brucellosis burden of disease calculations was conducted in pre-selected international and grey literature databases. Using a standardized reporting framework, we evaluated each estimate on a variety of key methodological assumptions necessary to compute a DALY. Fourteen studies satisfied the inclusion criteria (human brucellosis and quantification of DALYs). One study reported estimates at the global level, the rest were national or subnational assessments. Data regarding different methodological choices were extracted, including detailed assessments of the adopted disease models. Most studies retrieved brucellosis epidemiological data from administrative registries. Incidence data were often estimated on the basis of laboratory-confirmed tests. Not all studies included mortality estimates (Years of Life Lost) in their assessments due to lack of data or the assumption that brucellosis is not a fatal disease. Only two studies used a model with variable health states and corresponding disability weights. The rest used a simplified singular health state approach. Wide variation was seen in the duration chosen for brucellosis, ranging from 2 weeks to 4.5 years, irrespective of the whether a chronic state was included.ConclusionAvailable brucellosis burden of disease assessments vary widely in their methodology and assumptions. Further research is needed to better characterize the clinical course of brucellosis and to estimate case-fatality rates. Additionally, reporting of methodological choices should be improved to enhance transparency and comparability of estimates. These steps will increase the value of these estimates for policy makers.

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Anticholinergic Burden and Fractures: A Systematic Review with Methodological Appraisal.

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Anticholinergic Burden and Fractures: A Systematic Review with Methodological Appraisal.

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