Medication reviews and deprescribing as a single intervention in falls prevention: a systematic review and meta-analysis

BACKGROUND: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. METHODS:   DESIGN: systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. ELIGIBILITY CRITERIA: randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome. STUDY RECORDS: title/abstract and full-text screening by two reviewers. RISK OF BIAS: Cochrane Collaboration revised tool. DATA SYNTHESIS: results reported separately for different settings and sufficiently comparable studies meta-analysed. RESULTS: forty-nine heterogeneous studies were included. COMMUNITY: meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85–1.29, I(2) = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70–1.27, I(2) = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69–1.14, I(2) = 0%, 2 s) for injurious falls. HOSPITAL: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74–1.28, I(2) = 15%, 2 s) and in an RR = 0.50 (0.07–3.50, I(2) = 72% %, 2 s) for number of fallers after and during admission, respectively. LONG-TERM CARE: meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72–1.02, I(2) = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64–1.35, I(2) = 92%, 7 s) for number of falls. CONCLUSIONS: the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls. PROSPERO registration number: CRD4202021823

Genetic basis of falling risk susceptibility in the UK Biobank Study

Abstract: Both extrinsic and intrinsic factors predispose older people to fall. We performed a genome-wide association analysis to investigate how much of an individual’s fall susceptibility can be attributed to genetics in 89,076 cases and 362,103 controls from the UK Biobank Study. The analysis revealed a small, but significant SNP-based heritability (2.7%) and identified three novel fall-associated loci (Pcombined ≤ 5 × 10−8). Polygenic risk scores in two independent settings showed patterns of polygenic inheritance. Risk of falling had positive genetic correlations with fractures, identifying for the first time a pathway independent of bone mineral density. There were also positive genetic correlations with insomnia, neuroticism, depressive symptoms, and different medications. Negative genetic correlations were identified with muscle strength, intelligence and subjective well-being. Brain, and in particular cerebellum tissue, showed the highest gene expression enrichment for fall-associated variants. Overall, despite the highly heterogenic nature underlying fall risk, a proportion of the susceptibility can be attributed to genetics

STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. Methods: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. Results: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. Conclusion: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies. Keywords: accidental falls; adverse effects; aged; deprescribing; fall-risk-increasing drugs; older people.Amsterdam Public Health Aging and Later Life Innovation Price and Clementine Brigitta Maria Dalderup fund Amsterdam University fun

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs

Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the associations between cardiovascular medications and fall risk in older adults. Design: A systematic review and meta-analysis. Medline, Embase, and PsycINFO. Key search concepts were "fall," "aged," "causality," and "medication." Studies that investigated cardiovascular medications as risk factors for falls in participants ≥60 years old or participants with a mean age of 70 or older were included. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratios (ORs) separately. In total, 131 studies were included in the qualitative synthesis. Meta-analysis using adjusted ORs showed significant results (pooled OR [95% confidence interval]) for loop diuretics, OR 1.36 (1.17, 1.57), and beta-blocking agents, OR 0.88 (0.80, 0.97). Meta-analysis using unadjusted ORs showed significant results for digitalis, OR 1.60 (1.08, 2.36); digoxin, OR 2.06 (1.56, 2.74); and statins, OR 0.80 (0.65, 0.98). Most of the meta-analyses resulted in substantial heterogeneity that mostly did not disappear after stratification for population and setting. In a descriptive synthesis, consistent associations were not observed. Loop diuretics were significantly associated with increased fall risk, whereas beta-blockers were significantly associated with decreased fall risk. Digitalis and digoxin may increase the risk of falling, and statins may reduce it. For the majority of cardiovascular medication groups, outcomes were inconsistent. Furthermore, recent studies indicate that specific drug properties, such as selectivity of beta-blockers, may affect fall risk, and drug-disease interaction also may play a role. Thus, studies addressing these issues are warranted to obtain a better understanding of drug-related fall

Protocol for a systematic review and meta-analysis assessing the effectiveness of deprescribing in falls prevention in older people

Introduction One of the known risk factors for fall incidents is the use of specific medications, fall-risk-increasing drugs (FRIDs). However, to date, there is uncertainty related to the effectiveness of deprescribing as a single intervention in falls prevention. Thus, a comprehensive update of the literature focusing on all settings in which older people receive healthcare and all deprescribing interventions is warranted to enhance the current knowledge. Methods and analysis This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search was performed in Cochrane Central Register of Controlled Trials, MEDLINE, Embase and PsycINFO (2 November 2020). We will also search in trial registers. We will include randomised controlled trials, in which any deprescribing intervention is compared with usual care and reports falls as an outcome. Both title and abstract screening and full-text screening will be done by two reviewers. The Cochrane Collaboration revised tool of Risk of Bias will be applied to perform risk of bias assessment. We will categorise the results separately for every setting. If a group of sufficiently comparable studies will be identified, we will perform a meta-analysis applying random effects model. We will investigate heterogeneity using a combination of visual inspection of the forest plot along with consideration of the chi(2) test and the I-2 statistic results. We have prespecified several subgroup and sensitivity analyses. Ethics and dissemination Ethics approval is not applicable for this study since no original data will be collected. The results will be disseminated through peer-reviewed publication and conference presentations. Furthermore, this systematic review will inform the recommendations of working group of polypharmacy and FRIDs of the anticipated World's Falls Guidelines. PROSPERO registration number CRD42020218231

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: II. Psychotropics

Falls are a major public health problem in older adults. Earlier studies showed that psychotropic medication use increases the risk of falls. The aim of this study is to update the current knowledge by providing a comprehensive systematic review and meta-analysis on psychotropic medication use and falls in older adults. This study is a systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated psychotropics (antipsychotics, antidepressants, anxiolytics, sedatives, and hypnotics) as risk factors for falls in participants ≥60 years of age or participants with a mean age of ≥70 years. Meta-analyses were performed using generic inverse variance method pooling unadjusted and adjusted odds ratio (OR) estimates separately. In total, 248 studies met the inclusion criteria for qualitative synthesis. Meta-analyses using adjusted data showed the following pooled ORs: antipsychotics 1.54 [95% confidence interval (CI) 1.28-1.85], antidepressants 1.57 (95% Cl 1.43-1.74), tricyclic antidepressants 1.41 (95% CI 1.07-1.86), selective serotonin reuptake inhibitors 2.02 (95% CI 1.85-2.20), benzodiazepines 1.42 (95%, CI 1.22-1.65), long-acting benzodiazepines 1.81 (95%, CI 1.05-3.16), and short-acting benzodiazepines 1.27 (95%, CI 1.04-1.56) Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and healthcare setting. Antipsychotics, antidepressants, and benzodiazepines are consistently associated with a higher risk of falls. It is unclear whether specific subgroups such as short-acting benzodiazepines and selective serotonin reuptake inhibitors are safer in terms of fall risk. Prescription bias could not be accounted for. Future studies need to address pharmacologic subgroups as fall risk may differ depending on specific medication properties. Precise and uniform classification of target medication (Anatomical Therapeutic Chemical Classification) is essential for valid comparisons between studie

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others

The use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication classes are still under debate as potential risk factors for falls in the older population. The aim of this systematic review and meta-analysis is to evaluate the associations between fall risk and nonpsychotropic and noncardiovascular medications. A systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated nonpsychotropic and noncardiovascular medications as risk factors for falls in participants ≥60 years or participants with a mean age ≥70 years. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratio (OR) estimates separately. In a qualitative synthesis, 281 studies were included. The results of meta-analysis using adjusted data were as follows (a pooled OR [95% confidence interval]): analgesics, 1.42 (0.91-2.23); nonsteroidal anti-inflammatory drugs (NSAIDs), 1.09 (0.96-1.23); opioids, 1.60 (1.35-1.91); anti-Parkinson drugs, 1.54 (0.99-2.39); antiepileptics, 1.55 (1.25-1.92); and polypharmacy, 1.75 (1.27-2.41). Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and setting in most cases. In a descriptive synthesis, consistent associations with falls were observed for long-term proton pump inhibitor use and opioid initiation. Laxatives showed inconsistent associations with falls (7/20 studies showing a positive association). Opioid and antiepileptic use and polypharmacy were significantly associated with increased risk of falling in the meta-analyses. Long-term use of proton pump inhibitors and opioid initiation might increase the fall risk. Future research is necessary because the causal role of some medication classes as fall-risk-increasing drugs remains unclear, and the existing literature contains significant limitation

Genetic basis of falling risk susceptibility in the UK Biobank Study.

Both extrinsic and intrinsic factors predispose older people to fall. We performed a genome-wide association analysis to investigate how much of an individual's fall susceptibility can be attributed to genetics in 89,076 cases and 362,103 controls from the UK Biobank Study. The analysis revealed a small, but significant SNP-based heritability (2.7%) and identified three novel fall-associated loci (Pcombined ≤ 5 × 10-8). Polygenic risk scores in two independent settings showed patterns of polygenic inheritance. Risk of falling had positive genetic correlations with fractures, identifying for the first time a pathway independent of bone mineral density. There were also positive genetic correlations with insomnia, neuroticism, depressive symptoms, and different medications. Negative genetic correlations were identified with muscle strength, intelligence and subjective well-being. Brain, and in particular cerebellum tissue, showed the highest gene expression enrichment for fall-associated variants. Overall, despite the highly heterogenic nature underlying fall risk, a proportion of the susceptibility can be attributed to genetics

A Propensity Score Matched Approach to Assess the Associations of Commonly Prescribed Medications with Fall Risk in a Large Harmonized Cohort of Older Ambulatory Persons

Introduction: Several medication classes are considered to present risk factors for falls. However, the evidence is mainly based on observational studies that often lack adequate adjustment for confounders. Therefore, we aimed to assess the associations of medication classes with fall risk by carefully selecting confounders and by applying propensity score matching (PSM). Methods: Data from several European cohorts, harmonized into the ADFICE_IT cohort, was used. Our primary outcome was time until the first fall within 1-year follow-up. The secondary outcome was a fall in the past year. Our exposure variables were commonly prescribed medications. We used 1:1 PSM to match the participants with reported intake of specific medication classes with participants without. We constructed Cox regression models stratified by the pairs matched on the propensity score for our primary outcome and conditional logistic regression models for our secondary outcome. Results: In total, 32.6% of participants fell in the 1-year follow-up and 24.4% reported falling in the past year. ACE inhibitor users (prevalence of use 15.3%) had a lower fall risk during follow-up when matched to non-users, with a hazard ratio (HR) of 0.82 (95% CI 0.68–0.98). Also, statin users (prevalence of use 20.1%) had a lower risk, with an HR of 0.76 (95% CI 0.65–0.90). Other medication classes showed no association with risk of first fall. Also, in our secondary outcome analyses, statin users had a significantly lower risk. Furthermore, β-blocker users had a lower fall risk and proton pump inhibitor use was associated with a higher risk in our secondary outcome analysis. Conclusion: Many commonly prescribed medication classes showed no associations with fall risk in a relatively healthy population of community-dwelling older persons. However, the treatment effects and risks can be heterogeneous between individuals. Therefore, focusing on identification of individuals at risk is warranted to optimize personalized falls prevention.</p