Falls prevention interventions for community-dwelling older adults: systematic review and meta-analysis of benefits, harms, and patient values and preferences.
About 20-30% of older adults (≥ 65 years old) experience one or more falls each year, and falls are associated with substantial burden to the health care system, individuals, and families from resulting injuries, fractures, and reduced functioning and quality of life. Many interventions for preventing falls have been studied, and their effectiveness, factors relevant to their implementation, and patient preferences may determine which interventions to use in primary care. The aim of this set of reviews was to inform recommendations by the Canadian Task Force on Preventive Health Care (task force) on fall prevention interventions. We undertook three systematic reviews to address questions about the following: (i) the benefits and harms of interventions, (ii) how patients weigh the potential outcomes (outcome valuation), and (iii) patient preferences for different types of interventions, and their attributes, shown to offer benefit (intervention preferences).
We searched four databases for benefits and harms (MEDLINE, Embase, AgeLine, CENTRAL, to August 25, 2023) and three for outcome valuation and intervention preferences (MEDLINE, PsycINFO, CINAHL, to June 9, 2023). For benefits and harms, we relied heavily on a previous review for studies published until 2016. We also searched trial registries, references of included studies, and recent reviews. Two reviewers independently screened studies. The population of interest was community-dwelling adults ≥ 65 years old. We did not limit eligibility by participant fall history. The task force rated several outcomes, decided on their eligibility, and provided input on the effect thresholds to apply for each outcome (fallers, falls, injurious fallers, fractures, hip fractures, functional status, health-related quality of life, long-term care admissions, adverse effects, serious adverse effects). For benefits and harms, we included a broad range of non-pharmacological interventions relevant to primary care. Although usual care was the main comparator of interest, we included studies comparing interventions head-to-head and conducted a network meta-analysis (NMAs) for each outcome, enabling analysis of interventions lacking direct comparisons to usual care. For benefits and harms, we included randomized controlled trials with a minimum 3-month follow-up and reporting on one of our fall outcomes (fallers, falls, injurious fallers); for the other questions, we preferred quantitative data but considered qualitative findings to fill gaps in evidence. No date limits were applied for benefits and harms, whereas for outcome valuation and intervention preferences we included studies published in 2000 or later. All data were extracted by one trained reviewer and verified for accuracy and completeness. For benefits and harms, we relied on the previous review team's risk-of-bias assessments for benefit outcomes, but otherwise, two reviewers independently assessed the risk of bias (within and across study). For the other questions, one reviewer verified another's assessments. Consensus was used, with adjudication by a lead author when necessary. A coding framework, modified from the ProFANE taxonomy, classified interventions and their attributes (e.g., supervision, delivery format, duration/intensity). For benefit outcomes, we employed random-effects NMA using a frequentist approach and a consistency model. Transitivity and coherence were assessed using meta-regressions and global and local coherence tests, as well as through graphical display and descriptive data on the composition of the nodes with respect to major pre-planned effect modifiers. We assessed heterogeneity using prediction intervals. For intervention-related adverse effects, we pooled proportions except for vitamin D for which we considered data in the control groups and undertook random-effects pairwise meta-analysis using a relative risk (any adverse effects) or risk difference (serious adverse effects). For outcome valuation, we pooled disutilities (representing the impact of a negative event, e.g. fall, on one's usual quality of life, with 0 = no impact and 1 = death and ~ 0.05 indicating important disutility) from the EQ-5D utility measurement using the inverse variance method and a random-effects model and explored heterogeneity. When studies only reported other data, we compared the findings with our main analysis. For intervention preferences, we used a coding schema identifying whether there were strong, clear, no, or variable preferences within, and then across, studies. We assessed the certainty of evidence for each outcome using CINeMA for benefit outcomes and GRADE for all other outcomes.
A total of 290 studies were included across the reviews, with two studies included in multiple questions. For benefits and harms, we included 219 trials reporting on 167,864 participants and created 59 interventions (nodes). Transitivity and coherence were assessed as adequate. Across eight NMAs, the number of contributing trials ranged between 19 and 173, and the number of interventions ranged from 19 to 57. Approximately, half of the interventions in each network had at least low certainty for benefit. The fallers outcome had the highest number of interventions with moderate certainty for benefit (18/57). For the non-fall outcomes (fractures, hip fracture, long-term care [LTC] admission, functional status, health-related quality of life), many interventions had very low certainty evidence, often from lack of data. We prioritized findings from 21 interventions where there was moderate certainty for at least some benefit. Fourteen of these had a focus on exercise, the majority being supervised (for > 2 sessions) and of long duration (> 3 months), and with balance/resistance and group Tai Chi interventions generally having the most outcomes with at least low certainty for benefit. None of the interventions having moderate certainty evidence focused on walking. Whole-body vibration or home-hazard assessment (HHA) plus exercise provided to everyone showed moderate certainty for some benefit. No multifactorial intervention alone showed moderate certainty for any benefit. Six interventions only had very-low certainty evidence for the benefit outcomes. Two interventions had moderate certainty of harmful effects for at least one benefit outcome, though the populations across studies were at high risk for falls. Vitamin D and most single-component exercise interventions are probably associated with minimal adverse effects. Some uncertainty exists about possible adverse effects from other interventions. For outcome valuation, we included 44 studies of which 34 reported EQ-5D disutilities. Admission to long-term care had the highest disutility (1.0), but the evidence was rated as low certainty. Both fall-related hip (moderate certainty) and non-hip (low certainty) fracture may result in substantial disutility (0.53 and 0.57) in the first 3 months after injury. Disutility for both hip and non-hip fractures is probably lower 12 months after injury (0.16 and 0.19, with high and moderate certainty, respectively) compared to within the first 3 months. No study measured the disutility of an injurious fall. Fractures are probably more important than either falls (0.09 over 12 months) or functional status (0.12). Functional status may be somewhat more important than falls. For intervention preferences, 29 studies (9 qualitative) reported on 17 comparisons among single-component interventions showing benefit. Exercise interventions focusing on balance and/or resistance training appear to be clearly preferred over Tai Chi and other forms of exercise (e.g., yoga, aerobic). For exercise programs in general, there is probably variability among people in whether they prefer group or individual delivery, though there was high certainty that individual was preferred over group delivery of balance/resistance programs. Balance/resistance exercise may be preferred over education, though the evidence was low certainty. There was low certainty for a slight preference for education over cognitive-behavioral therapy, and group education may be preferred over individual education.
To prevent falls among community-dwelling older adults, evidence is most certain for benefit, at least over 1-2 years, from supervised, long-duration balance/resistance and group Tai Chi interventions, whole-body vibration, high-intensity/dose education or cognitive-behavioral therapy, and interventions of comprehensive multifactorial assessment with targeted treatment plus HHA, HHA plus exercise, or education provided to everyone. Adding other interventions to exercise does not appear to substantially increase benefits. Overall, effects appear most applicable to those with elevated fall risk. Choice among effective interventions that are available may best depend on individual patient preferences, though when implementing new balance/resistance programs delivering individual over group sessions when feasible may be most acceptable. Data on more patient-important outcomes including fall-related fractures and adverse effects would be beneficial, as would studies focusing on equity-deserving populations and on programs delivered virtually.
Not registered.
Pillay J
，Gaudet LA
，Saba S
，Vandermeer B
，Ashiq AR
，Wingert A
，Hartling L
... -
《Systematic Reviews》
Galantamine for dementia due to Alzheimer's disease and mild cognitive impairment.
Dementia leads to progressive cognitive decline, and represents a significant health and societal burden. Its prevalence is growing, with Alzheimer's disease as the leading cause. There is no cure for Alzheimer's disease, but there are regulatory-approved pharmacological interventions, such as galantamine, for symptomatic relief. This review updates the 2006 version.
To assess the clinical effects, including adverse effects, of galantamine in people with probable or possible Alzheimer's disease or mild cognitive impairment, and to investigate potential moderators of effect.
We systematically searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register on 14 December 2022 using the term 'galantamine'. The Register contains records of clinical trials identified from major electronic databases (including CENTRAL, MEDLINE, and Embase), trial registries, grey literature sources, and conference proceedings. We manually searched reference lists and collected information from US Food and Drug Administration documents and unpublished trial reports. We imposed no language restrictions.
We included double-blind, parallel-group, randomised controlled trials comparing oral galantamine with placebo for a treatment duration exceeding four weeks in people with dementia due to Alzheimer's disease or with mild cognitive impairment.
Working independently, two review authors selected studies for inclusion, assessed their quality, and extracted data. Outcomes of interest included cognitive function, change in global function, activities of daily living, functional disability, behavioural function, and adverse events. We used a fixed-effect model for meta-analytic synthesis, and presented results as Peto odds ratios (OR) or weighted mean differences (MD) with 95% confidence intervals. We used Cochrane's original risk of bias tool (RoB 1) to assess the risk of bias in the included studies.
We included 21 studies with a total of 10,990 participants. The average age of participants was 74 years, and 37% were male. The studies' durations ranged from eight weeks to two years, with 24 weeks being the most common duration. One newly included study assessed the effects of galantamine at two years, and another newly included study involved participants with severe Alzheimer's disease. Nineteen studies with 10,497 participants contributed data to the meta-analysis. All studies had low to unclear risk of bias for randomisation, allocation concealment, and blinding. We judged four studies to be at high risk of bias due to attrition and two due to selective outcome reporting. Galantamine for dementia due to Alzheimer's disease We summarise only the results for galantamine given at 8 to 12 mg twice daily (total galantamine 16 mg to 24 mg/day), assessed at six months. See the full review for results of other dosing regimens and assessment time points. There is high-certainty evidence that, compared to placebo, galantamine improves: cognitive function, as assessed with the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) (MD-2.86, 95% CI -3.29 to -2.43; 6 studies, 3049 participants; minimum clinically important effect (MCID) = 2.6- to 4-point change); functional disability, as assessed with the Disability Assessment for Dementia (DAD) scale (MD 2.12, 95% CI 0.75 to 3.49; 3 studies, 1275 participants); and behavioural function, as assessed with the Neuropsychiatric Inventory (NPI) (MD -1.63, 95% CI -3.07 to -0.20; 2 studies, 1043 participants) at six months. Galantamine may improve global function at six months, as assessed with the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus) (OR 1.58, 95% CI 1.36 to 1.84; 6 studies, 3002 participants; low-certainty evidence). Participants who received galantamine were more likely than placebo-treated participants to discontinue prematurely (22.7% versus 17.2%) (OR 1.41, 95% CI 1.19 to 1.68; 6 studies, 3336 participants; high-certainty evidence), and experience nausea (20.9% versus 8.4%) (OR 2.89, 95% CI 2.40 to 3.49; 7 studies, 3616 participants; high-certainty evidence) during the studies. Galantamine reduced death rates at six months: 1.3% of participants in the galantamine groups had died compared to 2.3% in the placebo groups (OR 0.56, 95% CI 0.33 to 0.96; 6 studies, 3493 participants; high-certainty evidence). Galantamine for mild cognitive impairment We summarise results, assessed at two years, from two studies that gave participants galantamine at 8 to 12 mg twice daily (total galantamine 16 mg to 24 mg/day). Compared to placebo, galantamine may not improve cognitive function, as assessed with the expanded ADAS-cog for mild cognitive impairment (MD -0.21, 95% CI -0.78 to 0.37; 2 studies, 1901 participants; low-certainty evidence) or activities of daily living, assessed with the Alzheimer's Disease Cooperative Study - Activities of Daily Living scale for mild cognitive impairment (MD 0.30, 95% CI -0.26 to 0.86; 2 studies, 1901 participants; low-certainty evidence). Participants who received galantamine were probably more likely to discontinue prematurely than placebo-treated participants (40.7% versus 28.6%) (OR 1.71, 95% CI 1.42 to 2.05; 2 studies, 2057 participants) and to experience nausea (29.4% versus 10.7%) (OR 3.49, 95% CI 2.75 to 4.44; 2 studies, 2057 participants), both with moderate-certainty evidence. Galantamine may not reduce death rates at 24 months compared to placebo (0.5% versus 0.1%) (OR 5.03, 95% CI 0.87 to 29.10; 2 studies, 2057 participants; low-certainty evidence). Results from subgroup analysis and meta-regression suggest that an imbalance in discontinuation rates between galantamine and placebo groups, together with the use of the 'last observation carried forward' approach to outcome assessment, may potentially bias cognitive outcomes in favour of galantamine.
Compared to placebo, galantamine (when given at a total dose of 16 mg to 24 mg/day) slows the decline in cognitive function, functional ability, and behaviour at six months in people with dementia due to Alzheimer's disease. Galantamine probably also slows declines in global function at six months. The changes observed in cognition, assessed with the ADAS-cog scale, were clinically meaningful. Gastrointestinal-related adverse events are the primary concerns associated with galantamine use in people with dementia, which may limit its tolerability. Although death rates were generally low, participants in the galantamine groups had a reduced risk of death compared to those in the placebo groups. There is no evidence to support the use of galantamine in people with mild cognitive impairment.
Lim AWY
，Schneider L
，Loy C
《Cochrane Database of Systematic Reviews》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
