European position paper on polypharmacy and fall-risk-increasing drugs recommendations in the World Guidelines for Falls Prevention and Management: implications and implementation.

Falls prevention and management in older adults is a critical global challenge. One of the key risk factors for falls is the use of certain medications. Therefore, to prevent medication-related falls, the following is recommended in the recent World Guidelines for Falls Prevention and Management: (1) assess for fall history and the risk of falls before prescribing potential fall-risk-increasing drugs (FRIDs), (2) use a validated, structured screening and assessment tool to identify FRIDs when performing a medication review, (3) include medication review and appropriate deprescribing of FRIDs as a part of the multifactorial falls prevention intervention, and (4) in long-term care residents, if multifactorial intervention cannot be conducted due to limited resources, the falls prevention strategy should still always include deprescribing of FRIDs.In the present statement paper, the working group on medication-related falls of the World Guidelines for Falls Prevention and Management, in collaboration with the European Geriatric Medicine Society (EuGMS) Task and Finish group on FRIDs, outlines its position on how to implement and execute these recommendations in clinical practice.Preferably, the medication review should be conducted as part of a comprehensive geriatric assessment to produce a personalized and patient-centered assessment. Furthermore, the major pitfall of the published intervention studies so far is the suboptimal implementation of medication review and deprescribing. For the future, it is important to focus on gaining which elements determine successful implementation and apply the concepts of implementation science to decrease the gap between research and practice.

Involvement of Informal Caregivers in Preventing Falls in Older Adults with Cognitive Impairment: A Rapid Review.

BACKGROUND: The prevalence of falls and related injuries is double in older adults with cognitive impairment compared with cognitively healthy older adults. A growing body of literature shows that falls prevention interventions in the cognitively impaired are difficult to implement and that the feasibility and adherence to interventions depend on a number of factors including informal caregiver involvement. However, no systematic review exists on the topic. OBJECTIVE: Our objective is to determine whether involvement of informal caregivers can reduce falls in older adults with cognitive impairment. METHODS: Rapid review following Cochrane collaboration guidelines. RESULTS: Seven randomized controlled trials were identified involving 2,202 participants. We identified the following areas where informal caregiving may have an important role in fall prevention in older adults with cognitive impairment: 1) enhancing adherence to the exercise program; 2) identifying and recording falls incidents and circumstances; 3) identifying and modifying possible environmental falls risk factors inside patient's home; and 4) playing an active role in modifying lifestyle in terms of diet/nutrition, limiting antipsychotics, and avoiding movements risking falls. However, informal caregiver involvement was identified as an incidental finding in these studies and the level of evidence ranged from low to moderate. CONCLUSION: Informal caregiver involvement in planning and delivering interventions to reduce falls has been found to increase the adherence of individuals with cognitive impairment in falls prevention programs. Future research should address whether involvement of informal caregivers may improve efficacy of prevention programs by reducing the number of falls as a primary outcome.

Reasoning about mental states under uncertainty.

Theory of Mind (ToM), the ability to infer the mental states of others, is integral to facilitating healthy social interactions. People can reason about the mental states of others even with limited or (sometimes) inconsistent information. However, little is known about how people make inferences about the mental states of others under uncertainty, and what features of information are important in aiding mental state reasoning. In the current study, we conducted three unique experiments that alter participant's uncertainty when engaging in ToM tests. In Experiment 1, we simultaneously manipulated both the amount and consistency of information available in social stimuli presented to 59 participants. In Experiments 2 and 3, we aimed to decipher which feature of social stimuli is more conducive to mental state reasoning. Experiment 2 manipulated only the amount of information available to 47 participants, while Experiment 3 manipulated only the consistency of information available to 46 participants. Using both frequentist and Bayesian statistics, results confirmed that manipulating the amount and consistency of information alters ToM performance. Exploratory analysis comparing the effects of the amount and consistency of information suggests that the effects of the consistency of information seem to be stronger than those of the amount of information. Taken together, all three experiments suggest that while both the amount and consistency of information are important features of social stimuli-the consistency of information available is more salient when inferring mental states of others. These findings are discussed in relation to information theory and have important implications for creating enriched social stimuli, which may enhance mental state reasoning in individuals with social deficits.

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. 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, I2 = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70-1.27, I2 = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69-1.14, I2 = 0%, 2 s) for injurious falls. HOSPITAL: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74-1.28, I2 = 15%, 2 s) and in an RR = 0.50 (0.07-3.50, I2 = 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, I2 = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64-1.35, I2 = 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: CRD42020218231.

World guidelines for falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. OBJECTIVES: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. METHODS: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. RECOMMENDATIONS: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. CONCLUSIONS: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

Listening to Trainee Concerns and Suggestions During COVID-19: a Report from the Canadian Consortium on Neurodegeneration in Aging (CCNA).

Background: The COVID-19 pandemic has caused significant disruption to research activities across Canada. The Training and Capacity Building (T&CB) Program of the Canadian Consortium on Neurodegeneration in Aging (CCNA) conducted a survey between May 11th, 2020 and May 19th, 2020 to identify the challenges faced by CCNA trainees because of the pandemic and how to best support trainees in response to those challenges. Methods: Graduate students and postdoctoral researchers working under the supervision of CCNA investigators (n=113) were invited to complete a web-based survey of 13 questions. Trainees were asked questions about the impact of COVID-19 on their research activities, degree progression, funding status, and suggestions for support from the T&CB Program during the COVID-19 pandemic. Results: A total of 41 trainees responded to the survey (response rate: 36.3%); 83% of respondents reported that they experienced changes to their research activities as a result of COVID-19, and 50% anticipated that their degree completion would be delayed. Respondents requested information from the T&CB Program on funding for non-COVID-19 projects, alternative datasets, and short educational workshops. Conclusion: The majority of CCNA trainees surveyed experienced significant changes to their research activities as a result of the COVID-19 pandemic. The T&CB Program responded by switching to online programming and facilitating remote research. Further engagement with trainees is needed to ensure continued progress of research in age-related neurodegenerative disease in Canada post-pandemic.

Multidomain trials to prevent dementia: addressing methodological challenges.

BACKGROUND: Multidomain trials to prevent dementia by simultaneously targeting multiple risk factors with non-pharmacological lifestyle interventions show promise. Designing trials to evaluate the efficacy of individual interventions and their combinations is methodologically challenging. Determining the efficacy is, nevertheless, important to individuals, payers, and for resource allocations to support intervention implementation. MAIN BODY: The central rationale for seminal trials improving cardiovascular health or reducing falls risk in older adults is that multifactorial conditions may be amenable to improvement by simultaneously targeting multiple modifiable risk factors. Similar reasoning underlies lifestyle interventions to reduce dementia risk using combinations of physical exercise, cognitive training, diet, amelioration of vascular-metabolic risk factors, and improving sleep quality. Randomizing individuals with at least two modifiable risk factors to "standardly tailored" interventions to mitigate their risk factors, versus a comparator arm, will yield an unbiased estimate of the cumulative average effect of modifying more versus fewer risk factors. The between-group difference in the cognitive primary outcome will reflect both the main effects of the mitigated risk factors, as well as their synergistic effects. However, given the positive trial results, there are inherent challenges in quantifying post hoc which components, or combination of components, were responsible for improvements in cognition. Here, we elaborate on these methodological challenges and important considerations in using a standardly tailored design with two arms (one consisting of multidomain interventions tailored to participants' risk profiles and another consisting of active control conditions). We compare this approach to fully factorial designs and highlight the disadvantages and advantages of each. We discuss partial solutions, including analytical strategies such as risk reduction scores that measure reductions in the number or severity of risk factors in each study arm. Positive results can support the causal inference that between-group differences in the primary cognitive outcome were due to risk factor modification. CONCLUSION: Standardly tailored designs are pragmatic and feasible evaluations of multidomain interventions to reduce dementia risk. We propose sensitivity and exploratory analyses of between-group reductions in the severity of risk factors, as a methodology to bolster causal inferences that between-group differences in the primary cognitive outcome are due to the risk factors modified.

Protocol for SYNchronising Exercises, Remedies in GaIt and Cognition at Home (SYNERGIC@Home): feasibility of a home-based double-blind randomised controlled trial to improve gait and cognition in individuals at risk for dementia.

INTRODUCTION: Physical exercise and cognitive training have the potential to enhance cognitive function and mobility in older adults at risk of Alzheimer's disease and related dementia (ADRD), but little is known about the feasibility of delivering multidomain interventions in home settings of older adults at risk of ADRD. This study aims to assess the feasibility of home-based delivery of exercise and cognitive interventions, and to evaluate the relationship between participants' intervention preferences and their subsequent adherence. Secondary objectives include the effect of the interventions on ADRD risk factors, including frailty, mobility, sleep, diet and psychological health. METHODS AND ANALYSIS: The SYNchronising Exercises, Remedies in GaIt and Cognition at Home (SYNERGIC@Home) feasibility trial is a randomised control trial that follows a 2×2 factorial design, with a 16-week home-based intervention programme (3 sessions per week) of physical exercises and cognitive training. Participants will be randomised in blocks of four to one of the following four arms: (1) combined exercise (aerobic and resistance)+cognitive training (NEUROPEAK); (2) combined exercise+control cognitive training (web searching); (3) control exercise (balance and toning)+cognitive training; and (4) control exercise+control cognitive training. SYNERGIC@Home will be implemented through video conferencing. Baseline and post-intervention assessments at 4-month and 10-month follow-up will include measures of cognition, frailty, mobility, sleep, diet and psychological health. Primary feasibility outcome is adherence to the interventions. Primary analytic outcome is the relationship between pre-allocation preference for a given intervention and subsequent adherence to the allocated intervention. A series of secondary analytic outcomes examining the potential effect of the individual and combined interventions on cognitive, mobility and general well-being will be measured at baseline and follow-up. ETHICS AND DISSEMINATION: Ethics approval was granted by the relevant research ethics boards. Findings of the study will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences. TRIAL REGISTRATION NUMBER: NCT04997681, Pre-results.

Fall risk-increasing drugs and gait performance in community-dwelling older adults: A systematic review.

PURPOSE: Medication use, and gait impairment are two major risk factors for falls in older adults. There are several mechanisms linking fall risk-increasing drugs (FRIDs) and increased fall risk. One pathway involves gait performance as an intermediate variable. It is plausible that FRIDs indirectly increase fall risk by causing gait impairment. The purpose of this review was to systematically review the existing evidence on the association between FRIDs and gait performance in community-dwelling older adults without neurological movement disorders. METHODS: Two searches were performed using MeSH terms and keywords in the electronic databases MEDLINE, EMBASE, PsycINFO, CINAHL and grey literature. We included clinical trials and observational studies that assessed the association between a FRID class and any quantitative measure of gait performance. Quality assessment was performed using the Newcastle-Ottawa scale for observational studies and the Cochrane risk-of-bias tool for clinical trials. Study characteristics and findings were summarized in a descriptive approach for each drug class. RESULTS: A total of 11,197 studies were retrieved from both searches at the first step and a total of 23 studies met the final inclusion criteria. Fourteen studies assessed the association between psychotropic FRIDs and gait performance and nine assessed cardiovascular FRIDs. Four out of five studies found that drugs with sedative properties are associated with reduced gait speed in older adults. Three out of four studies found no association between statin use and gait speed. There is insufficient evidence on the association between FRIDs and other gait performance measures. CONCLUSION: Caution should be taken when prescribing drugs with sedative properties to older adults at risk of falls. Further research is required to assess the impact of the use FRIDs on gait performance measures other than gait speed.

Evaluation of Clinical Practice Guidelines on Fall Prevention and Management for Older Adults: A Systematic Review.

Importance: With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking. Objectives: To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps. Evidence Review: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic. Findings: Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations. Conclusions and Relevance: This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.

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 χ2 test and the I2 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.

New horizons in falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects both on quality of life and functional independence and are associated with increased morbidity, mortality and health care costs. Current clinical approaches and advice from falls guidelines vary substantially between countries and settings, warranting a standardised approach. At the first World Congress on Falls and Postural Instability in Kuala Lumpur, Malaysia, in December 2019, a worldwide task force of experts in falls in older adults, committed to achieving a global consensus on updating clinical practice guidelines for falls prevention and management by incorporating current and emerging evidence in falls research. Moreover, the importance of taking a person-centred approach and including perspectives from patients, caregivers and other stakeholders was recognised as important components of this endeavour. Finally, the need to specifically include recent developments in e-health was acknowledged, as well as the importance of addressing differences between settings and including developing countries. METHODS: a steering committee was assembled and 10 working Groups were created to provide preliminary evidence-based recommendations. A cross-cutting theme on patient's perspective was also created. In addition, a worldwide multidisciplinary group of experts and stakeholders, to review the proposed recommendations and to participate in a Delphi process to achieve consensus for the final recommendations, was brought together. CONCLUSION: in this New Horizons article, the global challenges in falls prevention are depicted, the goals of the worldwide task force are summarised and the conceptual framework for development of a global falls prevention and management guideline is presented.

The role of physical exercise in modulating peripheral inflammatory and neurotrophic biomarkers in older adults: A systematic review and meta-analysis.

BACKGROUND: Physiological cascades of neurotrophic factors and inflammatory cytokines may mediate the exercise-induced amelioration of cognition in older adults. However, there is limited understanding on how different exercise modalities improving cognition alter biomarkers. Our aim was to evaluate the effects of different exercise modalities on blood biomarker concentrations in cognitive clinical trials of older adults. METHODS: A systematic review (SR) and meta-analysis (MA) were performed using the databases PubMed, EMBASE, and SCOPUS. After exclusions, 17 trials with 18 distinct exercise interventions were included. RESULTS: Aerobic training increased (n = 2) or did not significantly change BDNF (n = 5), and resistance training increased (n = 2) or did not significantly change (n = 2) IGF-1. Multimodal training significantly increased (n = 1) or did not change (n = 3) BDNF. Interventions that recruited sex-specific cohorts showed an advantage in males for blood marker concentrations and cognitive performance outcomes (n = 3) compared to females (n = 3). Only one of three interventions decreased concentrations of CRP. Eight studies examining BDNF changes were suited for MA and showed that higher BDNF concentrations were reached post intervention, although not reaching statistical significance (p = .26, I2 = 44 %). DISCUSSION: Our results suggest that exercise has potential to ameliorate cognitive decline in older adults with divergent, modality-specific, neurotrophic mechanisms.

CCCDTD5 recommendations on early non cognitive markers of dementia: A Canadian consensus.

INTRODUCTION: Cognitive impairment is the hallmark of Alzheimer's disease (AD) and related dementias. However, motor decline has been recently described as a prodromal state that can help to detect at-risk individuals. Similarly, sensory changes, sleep and behavior disturbances, and frailty have been associated with higher risk of developing dementia. These clinical findings, together with the recognition that AD pathology precedes the diagnosis by many years, raises the possibility that non-cognitive changes may be early and non-invasive markers for AD or, even more provocatively, that treating non-cognitive aspects may help to prevent or treat AD and related dementias. METHODS: A subcommittee of the Canadian Consensus Conference on Diagnosis and Treatment of Dementia reviewed areas of emerging evidence for non-cognitive markers of dementia. We examined the literature for five non-cognitive domains associated with future dementia: motor, sensory (hearing, vision, olfaction), neuro-behavioral, frailty, and sleep. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assign the strength of the evidence and quality of the recommendations. We provide recommendations to primary care clinics and to specialized memory clinics, answering the following main questions: (1) What are the non-cognitive and functional changes associated with risk of developing dementia? and (2) What is the evidence that sensory, motor, behavioral, sleep, and frailty markers can serve as potential predictors of dementia? RESULTS: Evidence supported that gait speed, dual-task gait speed, grip strength, frailty, neuropsychiatric symptoms, sleep measures, and hearing loss are predictors of dementia. There was insufficient evidence for recommending assessing olfactory and vision impairments as a predictor of dementia. CONCLUSIONS: Non-cognitive markers can assist in identifying people at risk for cognitive decline or dementia. These non-cognitive markers may represent prodromal symptoms and several of them are potentially amenable to treatment that might delay the onset of cognitive decline.

Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.

BACKGROUND: An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors. METHODS: HCV-uninfected organ recipients without pre-existing liver disease were treated with ezetimibe (10 mg; an HCV entry inhibitor) and glecaprevir-pibrentasvir (300 mg/120 mg) before and after transplantation from HCV-infected donors aged younger than 70 years without co-infection with HIV, hepatitis B virus, or human T-cell leukaemia virus 1 or 2. Recipients received a single dose 6-12 h before transplant and once a day for 7 days after surgery (eight doses in total). HCV RNA was assessed once a day for 14 days and then once a week until 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection, as evidenced by undetectable serum HCV RNA at 12 weeks after transplant, and assessed in the intention-to-treat population. Safety monitoring was according to routine post-transplant practice. 12-week data are reported for the first 30 patients. The trial is registered on ClinicalTrials.gov, NCT04017338. The trial is closed to recruitment but follow-up is ongoing. FINDINGS: 30 patients (23 men and seven women; median age 61 years (IQR 48-66) received transplants (13 lung, ten kidney, six heart, and one kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5·11 log10IU/mL (IQR 4·55-5·63) and at least three HCV genotypes were represented (nine [50%] donors with genotype 1, two [11%] with genotype 2, five [28%] with genotype 3, and two [11%] with unknown genotype). All 30 (100%) transplant recipients met the primary endpoint of undetectable HCV RNA at 12 weeks post-transplant, and were HCV RNA-negative at last follow-up (median 36 weeks post-transplant [IQR 25-47]). Low-level viraemia was transiently detectable in 21 (67%) of 30 recipients in the early post-transplant period but not after day 14. Treatment was well tolerated with no dose reductions or treatment discontinuations; 32 serious adverse events occurred in 20 (67%) recipients, with one grade 3 elevation in alanine aminotransferase (ALT) possibly related to treatment. Non-serious transient elevations in ALT and creatine kinase during the study dosing period resolved with treatment completion. Among the serious adverse events were two recipient deaths due to causes unrelated to study drug treatment (sepsis at 49 days and subarachnoid haemorrhage at 109 days post-transplant), with neither patient ever being viraemic for HCV. INTERPRETATION: Ezetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors. FUNDING: Canadian Institutes of Health Research; the Organ Transplant Program, University Health Network.