Multisystem physiological perspective of human frailty and its modulation by physical activity.

"Frailty" is a term used to refer to a state characterized by enhanced vulnerability to, and impaired recovery from, stressors compared with a nonfrail state, which is increasingly viewed as a loss of resilience. With increasing life expectancy and the associated rise in years spent with physical frailty, there is a need to understand the clinical and physiological features of frailty and the factors driving it. We describe the clinical definitions of age-related frailty and their limitations in allowing us to understand the pathogenesis of this prevalent condition. Given that age-related frailty manifests in the form of functional declines such as poor balance, falls, and immobility, as an alternative we view frailty from a physiological viewpoint and describe what is known of the organ-based components of frailty, including adiposity, the brain, and neuromuscular, skeletal muscle, immune, and cardiovascular systems, as individual systems and as components in multisystem dysregulation. By doing so we aim to highlight current understanding of the physiological phenotype of frailty and reveal key knowledge gaps and potential mechanistic drivers of the trajectory to frailty. We also review the studies in humans that have intervened with exercise to reduce frailty. We conclude that more longitudinal and interventional clinical studies are required in older adults. Such observational studies should interrogate the progression from a nonfrail to a frail state, assessing individual elements of frailty to produce a deep physiological phenotype of the syndrome. The findings will identify mechanistic drivers of frailty and allow targeted interventions to diminish frailty progression.

Multimodal cell atlas of the ageing human skeletal muscle.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

An open science study of ageing in companion dogs.

The Dog Aging Project is a long-term longitudinal study of ageing in tens of thousands of companion dogs. The domestic dog is among the most variable mammal species in terms of morphology, behaviour, risk of age-related disease and life expectancy. Given that dogs share the human environment and have a sophisticated healthcare system but are much shorter-lived than people, they offer a unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy lifespan. To take advantage of this opportunity, the Dog Aging Project will collect extensive survey data, environmental information, electronic veterinary medical records, genome-wide sequence information, clinicopathology and molecular phenotypes derived from blood cells, plasma and faecal samples. Here, we describe the specific goals and design of the Dog Aging Project and discuss the potential for this open-data, community science study to greatly enhance understanding of ageing in a genetically variable, socially relevant species living in a complex environment.

How I treat multiple myeloma in geriatric patients.

ABSTRACT: Multiple myeloma (MM) is primarily a disease of older patients. Until recently, geriatric aspects in the context of MM have been poorly investigated. Treatment outcomes for geriatric patients with MM are often compromised by comorbidities and an enhanced susceptibility to adverse events from therapy. Assessment of patient frailty has become more frequent and will be useful in the context of significant and continuous advances in therapy. The recent emergence of immunotherapy with CD38 monoclonal antibodies and upcoming immunooncology drugs, such as bispecific antibodies, will lead to additional therapeutic progress. The applicability of these new molecules to older and frail patients is a key clinical question. Here, we present 2 patient cases derived from clinical practice. We review current frailty scores and standards of care for older, newly diagnosed patients with MM, including frail subgroups, and discuss ways to tailor treatment, as well as treatment perspectives in this population.

Brentuximab vedotin with dacarbazine or nivolumab as frontline cHL therapy for older patients ineligible for chemotherapy.

ABSTRACT: Older patients with advanced-stage classical Hodgkin lymphoma (cHL) have inferior outcomes compared with younger patients, potentially due to comorbidities and frailty. This noncomparative phase 2 study enrolled patients aged ≥60 years with cHL unfit for conventional chemotherapy to receive frontline brentuximab vedotin (BV; 1.8 mg/kg) with dacarbazine (DTIC; 375 mg/m2) (part B) or nivolumab (part D; 3 mg/kg). In parts B and D, 50% and 38% of patients, respectively, had ≥3 general comorbidities or ≥1 significant comorbidity. Of the 22 patients treated with BV-DTIC, 95% achieved objective response, and 64% achieved complete response (CR). With a median follow-up of 63.6 months, median duration of response (mDOR) was 46.0 months. Median progression-free survival (mPFS) was 47.2 months; median overall survival (mOS) was not reached. Of 21 patients treated with BV-nivolumab, 86% achieved objective response, and 67% achieved CR. With 51.6 months of median follow-up, mDOR, mPFS, and mOS were not reached. Ten patients (45%) with BV-DTIC and 16 patients (76%) with BV-nivolumab experienced grade ≥3 treatment-emergent adverse events; sensory peripheral neuropathy (PN; 27%) and neutropenia (9%) were most common with BV-DTIC, and increased lipase (24%), motor PN (19%), and sensory PN (19%) were most common with BV-nivolumab. Despite high median age, inclusion of patients aged ≤88 years, and frailty, these results demonstrate safety and promising durable efficacy of BV-DTIC and BV-nivolumab combinations as frontline treatment, suggesting potential alternatives for older patients with cHL unfit for initial conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806.

Frailty and survival in the 1918 influenza pandemic.

One of the most well-known yet least understood aspects of the 1918 influenza pandemic is the disproportionately high mortality among young adults. Contemporary accounts further describe the victims as healthy young adults, which is contrary to the understanding of selective mortality, which posits that individuals with the highest frailty within a group are at the greatest risk of death. We use a bioarchaeological approach, combining individual-level information on health and stress gleaned from the skeletal remains of individuals who died in 1918 to determine whether healthy individuals were dying during the 1918 pandemic or whether underlying frailty contributed to an increased risk of mortality. Skeletal data on tibial periosteal new bone formation were obtained from 369 individuals from the Hamann-Todd documented osteological collection in Cleveland, Ohio. Skeletal data were analyzed alongside known age at death using Kaplan-Meier survival and Cox proportional hazards analysis. The results suggest that frail or unhealthy individuals were more likely to die during the pandemic than those who were not frail. During the flu, the estimated hazards for individuals with periosteal lesions that were active at the time of death were over two times higher compared to the control group. The results contradict prior assumptions about selective mortality during the 1918 influenza pandemic. Even among young adults, not everyone was equally likely to die-those with evidence of systemic stress suffered greater mortality. These findings provide time depth to our understanding of how variation in life experiences can impact morbidity and mortality even during a pandemic caused by a novel pathogen.

Social Frailty Index: Development and validation of an index of social attributes predictive of mortality in older adults.

While social characteristics are well-known predictors of mortality, prediction models rely almost exclusively on demographics, medical comorbidities, and function. Lacking an efficient way to summarize the prognostic impact of social factor, many studies exclude social factors altogether. Our objective was to develop and validate a summary measure of social risk and determine its ability to risk-stratify beyond traditional risk models. We examined participants in the Health and Retirement Study, a longitudinal, survey of US older adults. We developed the model from a comprehensive inventory of 183 social characteristics using least absolute shrinkage and selection operator, a penalized regression approach. Then, we assessed the predictive capacity of the model and its ability to improve on traditional prediction models. We studied 8,250 adults aged ≥65 y. Within 4 y of the baseline interview, 22% had died. Drawn from 183 possible predictors, the Social Frailty Index included age, gender, and eight social predictors: neighborhood cleanliness, perceived control over financial situation, meeting with children less than yearly, not working for pay, active with children, volunteering, feeling isolated, and being treated with less courtesy or respect. In the validation cohort, predicted and observed mortality were strongly correlated. Additionally, the Social Frailty Index meaningfully risk-stratified participants beyond the Charlson score (medical comorbidity index) and the Lee Index (comorbidity and function model). The Social Frailty Index includes age, gender, and eight social characteristics and accurately risk-stratifies older adults. The model improves upon commonly used risk prediction tools and has application in clinical, population health, and research settings.

Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial.

BACKGROUND: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC). METHODS: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min-1·1.73 m-2 or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events. RESULTS: Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61). CONCLUSIONS: Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications. REGISTRATION: URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study).

In older patients with AF and frailty, switching from VKA to NOAC therapy increased a composite of major or CRNM bleeding at 12 mo.

SOURCE CITATION: Joosten LP, van Doorn S, van de Ven PM, et al. Safety of switching from a vitamin K antagonist to a non-vitamin K antagonist oral anticoagulant in frail older patients with atrial fibrillation: results of the FRAIL-AF randomized controlled trial. Circulation. 2024;149:279-289. 37634130.

Changes in frailty and incident cardiovascular disease in three prospective cohorts.

BACKGROUND AND AIMS: Previous studies found that frailty was an important risk factor for cardiovascular disease (CVD). However, previous studies only focused on baseline frailty status, not taking into consideration the changes in frailty status during follow-up. The aim of this study was to investigate the associations of changes in frailty status with incident CVD. METHODS: This study used data of three prospective cohorts: China Health and Retirement Longitudinal Study (CHARLS), English Longitudinal Study of Ageing (ELSA), and Health and Retirement Study (HRS). Frailty status was evaluated by the Rockwood frailty index and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty status at baseline and the second survey which was two years after the baseline. Cardiovascular disease was ascertained by self-reported physician-diagnosed heart disease (including angina, heart attack, congestive heart failure, and other heart problems) or stroke. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders. RESULTS: A total of 7116 participants from CHARLS (female: 48.6%, mean age: 57.4 years), 5303 from ELSA (female: 57.7%, mean age: 63.7 years), and 7266 from HRS (female: 64.9%, mean age: 65.1 years) were included according to inclusion and exclusion criteria. The median follow-up periods were 5.0 years in the CHARLS, 10.7 years in the ELSA, and 9.5 years in the HRS. Compared with stable robust participants, robust participants who progressed to pre-frail or frail status had increased risks of incident CVD (CHARLS, HR = 1.84, 95% CI: 1.54-2.21; ELSA, HR = 1.53, 95% CI: 1.25-1.86; HRS, HR = 1.59, 95% CI: 1.31-1.92). In contrast, frail participants who recovered to robust or pre-frail status presented decreased risks of incident CVD (CHARLS, HR = 0.62, 95% CI: 0.47-0.81; ELSA, HR = 0.49, 95% CI: 0.34-0.69; HRS, HR = 0.70, 95% CI: 0.55-0.89) when compared with stable frail participants. These decreased risks of incident CVD were also observed in pre-frail participants who recovered to robust status (CHARLS, HR = 0.66, 95% CI: 0.52-0.83; ELSA, HR = 0.65, 95% CI: 0.49-0.85; HRS, HR = 0.71, 95% CI: 0.56-0.91) when compared with stable pre-frail participants. CONCLUSIONS: Different changes in frailty status are associated with different risks of incident CVD. Progression of frailty status increases incident CVD risks, while recovery of frailty status decreases incident CVD risks.

The Effect of Frailty on the Efficacy and Safety of Intensive Blood Pressure Control: A Post Hoc Analysis of the SPRINT Trial.

BACKGROUND: Frailty is associated with an increased risk of all-cause death and cardiovascular events. However, it is uncertain whether frailty modifies the efficacy and safety of intensive blood pressure control. METHODS: Data from SPRINT (Systolic Blood Pressure Intervention Trial) were used to construct a frailty index. Subgroup differences in intensive blood pressure control treatment effects and safety outcomes were measured on a relative and an absolute scale in patients with and without frailty (defined as a frailty index >0.21) using Cox proportional hazard models and generalized linear models, respectively. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death. RESULTS: A total of 9306 patients (mean age, 67.9±9.4 years), 2560 (26.7%) of whom had frailty, were included in our study. Over a median follow-up of 3.22 years, 561 primary outcomes were observed. Patients with frailty had a significantly higher risk of primary outcome in both the intensive and standard blood pressure control arms (adjusted hazard ratio, 2.10 [95% CI, 1.59-2.77] and 1.85 [95% CI, 1.46-2.35], respectively). Intensive treatment effects on primary and secondary outcomes were not significantly different on a relative scale (except for cardiovascular death [hazard ratio in patients with and without frailty, 0.91 (95% CI, 0.52-1.60) versus 0.30 (95% CI, 0.16-0.59), respectively; Pinteraction=0.01]) or absolute scale. There was no significant interaction between frailty and risks for serious adverse events with intensive treatment. CONCLUSIONS: Frailty status was a marker of high cardiovascular risk. Patients with frailty benefit similarly to other patients from intensive blood pressure control without an increased risk of serious adverse events.

Net Clinical Benefit of Oral Anticoagulation Among Frail Patients With Atrial Fibrillation: Nationwide Cohort Study.

BACKGROUND: Frail people with atrial fibrillation are often undertreated with oral anticoagulants (OACs), and evidence for the net clinical benefit (NCB) of OAC is sparse. We, therefore, examined the risk of thromboembolic events, major bleeding, and NCB of anticoagulation treatment. METHODS: This was a nationwide cohort study including frail patients aged with incident atrial fibrillation between 2013 and 2018. Patients were categorized according to OAC treatment exposure. One-year risks of thromboembolic events and major bleeding were ascertained where death was treated as a competing risk. The NCB of anticoagulation was assessed by a bivariate trade-off between thromboembolism and bleeding. RESULTS: We identified 36 223 frail patients with atrial fibrillation (median age, 79 years; 50.5% female), of whom 61.8% started OAC therapy, while 38.2% were untreated despite indication for stroke prevention. At 1 year, the risk of thromboembolic events was 2.1% (95% CI, 1.8%-2.3%) among patients not receiving OAC versus 1.5% (95% CI, 1.4%-1.7%) in patients with OAC. The bleeding risk was 3.2% (95% CI, 2.9%-3.5%) among patients without OAC versus 3.5% (95% CI, 3.2%-3.8%) among anticoagulated patients. The NCB was 0.70% (95% CI, 0.32%-1.08%), suggesting a benefit of OAC treatment; however, the NCB declined with age and increasing frailty and was lowest among patients >75 years of age or with high frailty level. CONCLUSIONS: Frail patients with atrial fibrillation are often untreated with OAC in routine clinical care despite an indication for stroke prevention. The NCB balancing thromboembolic events and major bleeding was in favor of anticoagulation but decreased with advancing age and increasing frailty.

Pathophysiology of Acute Kidney Frailty.

Acute kidney frailty is a premorbid condition of diminished renal functional reserve that predisposes to acute kidney injury; this condition results from subclinical wear or distortion of renal homeostatic responses that protect the renal excretory function. Knowledge of its pathophysiological basis is critical for the development of diagnostic and therapeutic strategies that allow for prophylactic intervention and disease prevention.

A Segmented Regression Analysis of Household Income and Recurrent Falls Among Adults in a National Cohort Study.

Falls can have life-altering consequences for older adults, including extended recovery periods and compromised independence. Higher household income may mitigate the risk of falls by providing financial resources for mobility tools, remediation of environmental hazards, and needed supports, or it may buffer the impact of an initial fall on subsequent risk through improved assistance and care. Household income has not had a consistently observed association with falls in older adults; however, a segmented association may exist such that associations are attenuated above a certain income threshold. In this study, we utilized segmented negative binomial regression analysis to examine the association between household income and recurrent falls among 2,302 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study recruited between 2003 and 2007. Income-fall association segments separated by changes in slope were considered. Model results indicated a 2-segment association between household income and recurrent falls in the past year. In the range below the breakpoint, household income was negatively associated with the rate of recurrent falls across all age groups examined; in a higher income range (from $20,000-$49,999 to ≥$150,000), the association was attenuated (weaker negative trend) or reversed (positive trend). These findings point to potential benefits of ensuring that incomes for lower-income adults exceed the threshold needed to confer a reduced risk of recurrent falls.

Frailty in patients on dialysis.

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.

The association between food access and frailty among older adults with gastrointestinal malignancies-The CARE Registry.

BACKGROUND: Food access is associated with higher gastrointestinal (GI) cancer mortality; however, its association with frailty, which is a predictor of premature mortality among older adults with cancer, is less understood. METHODS: The authors included 880 adults aged 60 years and older who were recently diagnosed with GI cancers and were undergoing self-reported geriatric assessment at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. Food access was measured using the 2019 US Department of Agriculture Economic Research Service designation low-income, low-access (LILA), classifying census tracts based on income and/or access to food stores at various distances. The primary outcome was frailty on the CARE (Cancer and Aging Resilience Evaluation) Frailty Index, a composite of the proportion of impaired geriatric assessment measures. The authors examined the LILA-frailty association with modified Poisson regression accounting for census-tract clustering. RESULTS: The median patient age was 69 years, 58.1% were men, 22.5% were non-Hispanic Black, 29.2% had colorectal cancer, 28.0% had pancreatic cancer, 70.1% presented with stage III/IV disease, and 34.9% were frail. A higher proportion in LILA areas were non-Hispanic Black (44.1% vs. 10.8%; p < .001) and had less education (high school or less: 48.1% vs. 37.9%; p = .020). Adjusting for age, race and ethnicity, sex, cancer type and stage, and education, an LILA designation was associated with 58% greater odds of worsening frailty status (95% confidence interval, 1.18-2.12). An analysis of LILA subcategories revealed that associations were maintained across all LILA measures. CONCLUSIONS: Poor food access was associated with a greater risk of frailty among newly diagnosed older adults with GI cancers before they received systemic treatment. Intervening on local food access, particularly in LILA areas, may be a target for improving rates of frailty and promoting health equity in this population.

Goal setting as part of a holistic intervention to promote independence in older people with mild frailty: a process evaluation alongside a randomised controlled trial.

BACKGROUND: Frailty is a condition resulting from a decline in physiological reserves caused by an accumulation of several deficits, which progressively impairs the ability to recover from health adverse events. Following a promising feasibility study, the HomeHealth trial assessed a holistic tailored intervention for older adults with mild frailty to promote independence in their own homes, compared with usual care. We aimed to understand how goal setting worked among older people with mild frailty. METHODS: This study was a process evaluation alongside the HomeHealth randomised trial in older adults with mild frailty. The intervention was delivered at participants' homes, either in person or by telephone or videoconferencing. We carried out semi-structured interviews with older participants who had received the intervention (between three and six appointments), on average 233 days (range 68-465) after their last appointment, purposively sampled according to age, gender, number of sessions attended, adverse events, ethnicity, Index of Multiple Deprivation, Montreal Cognitive Assessment (MoCA) and Barthel scores, research site, and HomeHealth worker. We also conducted interviews with HomeHealth workers who delivered the intervention (n=7). Interviews explored the experience and process of goal setting, benefits and challenges, perceived progress, and behaviour change maintenance after the service had finished. Ethics approval was obtained, and all participants gave informed consent. Interviews were thematically analysed. HomeHealth workers kept formal records of goals set and assessed progress towards goals (0-2 rating scale) during six monthly-sessions, which were descriptively summarised. FINDINGS: 56 interviews were completed between July 15, 2022, and May 18, 2023. Study participants (n=49) had a mean age of 80 years (range 66-94), including 32 (65%) women and 17 (35%) men. Participants self-identified as White (n=42), Asian (n=3), Black (n=2), Mixed (n=1), and other ethnic (n=1) backgrounds. Findings suggested goal setting could be both a challenge and a motivator for older participants with mild frailty. Goal setting worked well when the older person could identify a clear need and set realistic goals linked to functioning, which led to a positive sense of achievement. Challenges occurred when older people were already accessing multiple resources and health services, or where the terminology of "goals" was off-putting due to work or school connotations. Average progress towards goals was 1·15/2. Most participants set goals around improving mobility (or a combination of mobility and another goal type such as socialising), and there was evidence of participants sustaining these behaviour changes after the intervention. INTERPRETATION: Older people with mild frailty can engage well with goal setting to promote independence. The lapse between receiving the intervention and being interviewed limited recall for some participants. However, the acceptability and adherence to the intervention for older people with mild frailty, and their moderate progress towards goals, should encourage further tailored and person-centred practices to promote their independence. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment.

How does the environment in and around the home affect social care and health outcomes for older people? A national longitudinal dynamic cohort study.

BACKGROUND: Reducing the burden of falls and fall-related admissions to hospital and care homes is an important policy area because falls cause significant injury leading to a reduced quality of life. We investigated the effect of the environment around people's homes on the risk of falls for older people in Wales. METHODS: In this longitudinal cohort study, we created a dynamic national e-cohort of individuals aged 60 years or older living in Wales between Jan 1, 2010, and Dec 31, 2019. Using the Secure Anonymised Information Linkage Databank, we linked routinely collected, anonymised health-data on general practitioner (GP) appointments; hospital and emergency admissions; and longitudinal individual-level demographic data to metrics detailing the built environment and deprivation as determined by the Welsh Index of Multiple Deprivation. Using adjusted cox regression models, we assessed how the risk of a fall changed with sex, age, deprivation quintile, urban or rural classification, household occupancy, care status, frailty, dementia diagnosis, and built environment metrics. Built environments of urban and rural areas are very different, so we stratified our analysis by urbanicity to compare these associations in each setting. FINDINGS: We analysed 5 536 444 person-years of data from 931 830 individuals (sex: 51·5% female, 48·5% male; age: 69·2% aged 60-64 years, 12·3% aged 65-69 years, 13·3% aged 70-79 years, 4·4% aged 80-89 years, and 0·7% aged ≥90 years). 154 060 (16·5%) had a fall between joining the cohort and Dec 31, 2019. Men had a lower risk of falling than women (adjusted hazard ratio [aHR] 0·736 [0·729-0·742]), and the risk increased with age compared with individuals aged 60-64 years (1·395 [1·378-1·412] for 65-69 years, 1·892 [1·871-1·913] for 70-79 years, 2·668 [2·623-2·713] for 80-89 years, 3·196 [3·063-3·335] for ≥90 years) and with frailty compared with fit individuals (1·609 [1·593-1·624] for mild frailty, 2·263 [2·234-2·293] for moderate frailty, and 2·833 [2·770-2·897] for severe frailty). Those living in rural areas were less likely to fall than those in urban areas (0·711 [0·702-0·720]). All p values were less than 0·0001. INTERPRETATION: Although preliminary, these results corroborate current knowledge that as we age and become frailer, the risk of falling increases. The effect of urbanicity on risk of fall suggests that the built environment could be associated with fall risk. We only detected falls that caused emergency or hospital admission, leading to potential selection bias. Nevertheless, this research could help guide policy to reduce the incidence of injuries caused by falls in older people. FUNDING: Health and Care Research Wales.

Gait retraining to reduce falls: an experimental study toward scalable and personalised use in the home.

BACKGROUND: Age-related neurological conditions can result in poor mobility typified by gait abnormalities and falls, increasing risk of frailty and lowering quality of life. In the UK, the expense and inaccessibility of services to improve mobility through gait training (eg, auditory cueing) is a public health issue. Contemporary and scalable pervasive technologies for widespread public use could provide an affordable and accessible solution. We aimed to show the preliminary efficacy of a novel smartphone app that provides a personalised approach to mobility and gait assessment while facilitating gait training. METHODS: In this experimental study, we recruited participants aged 22-46 years with no physical functional impairments (ie, no age-related neurological condition and who could walk unaided) from Northumbria University staff (Newcastle upon Tyne, UK) between April 19, and May 26. Participants wore a smartphone on their lower back. Inertial data from the smartphone were recorded during two walks, one at a self-selected pace and the other with a personalised auditory cue via headphones (+10% pace on walk 1). Smartphone app functionality enabled the measurement of clinically relevant gait characteristics via a Python-based Cloud server. We compared smartphone-based mobility or gait characteristics with a gold-standard reference (Opal Mobility Lab, APDM). We used Pearson and intraclass correlation coefficients (ICC2,1) to examine agreement between the novel app and reference. The study ran from April 4 to July 21, 2023. This study received ethics approval from the Northumbria University Ethics committee, and all participants provided written informed consent. FINDINGS: Ten adults were recruited (six women and four men; mean age 27·4 years [SD 6·2], mean weight 79·6 kg [SD 12·7], mean height 174·7 cm [SD 7·9]). High levels of agreement were found between the smartphone app and reference, quantified by Pearson (≥0·858) and ICC values (≥0·911). The personalised cueing intervention increased the mean cadence by an average of 11%, which shows good participant adherence to cueing via an app. INTERPRETATION: Here, we propose a contemporary approach to increase the accessibility to a health-based intervention. Preliminary findings suggest the smartphone app is a suitable tool for personalised mobility or gait assessment while facilitating gait training. Use of a scalable app could be an accessible and affordable method for improving mobility to reduce falls in the home. Here, current limitations are the lack of investigation with the smartphone app for neurological gait assessment on older adults and the lack of information on participants app experience, but this will be included in future work. The pervasive use of smartphones enables a decentralised approach to overcoming issues such as frailty and logistical challenges of travelling to bespoke clinics. FUNDING: National Institute of Health and Care Research (NIHR) Applied Research Collaboration (ARC) North-East and North Cumbria (NENC); Faculty of Engineering and Environment at Northumbria University.

Enabling health and maintaining independence for older people at home (HomeHealth trial): a multicentre randomised controlled trial.

BACKGROUND: NHS frailty services commonly target more severely frail older people, despite evidence suggesting frailty can be prevented or reversed when addressed at an earlier stage. HomeHealth is a new home-based, manualised voluntary sector service supporting older people with mild frailty to maintain their independence through behaviour change. Over six appointments, a trained HomeHealth worker discusses what matters to the older person and supports them to set and achieve goals around mobility, nutrition, socialising and/or psychological wellbeing. The service showed promising effects in a feasibility trial. We aimed to test the clinical and cost-effectiveness of HomeHealth for maintaining independence in older people with mild frailty compared with treatment as usual. METHODS: In this single-blind multicentre randomised controlled trial, we recruited community-dwelling older people aged 65 years or older with mild frailty from 27 general practices, community groups and sheltered housing in London, Yorkshire, and Hertfordshire. Participants were randomly assigned (1:1) to receive either HomeHealth monthly for 6 months or treatment as usual (usual GP and outpatient care, no specific frailty services). Our primary outcome was independence in activities of daily living, measured by blinded outcome assessors using the modified Barthel Index, and analysed using linear mixed models, including 6-month and 12-month data and controlling for baseline Barthel score and site. The study was approved by the Social Care Research Ethics Committee, and all participants provided written or orally recorded informed consent. This study is registered with the ISRCTN registry, ISRCTN54268283. FINDINGS: This trial took place between Jan 18, 2021, and July 4, 2023. We recruited 388 participants (mean age 81·4 years; 64% female [n=250], 94% White British/European [n=364], 2·5% Asian [n=10], 1·5% Black [n=6], 2·0% other [n=8]). We achieved high retention for 6-month follow-up (89%, 345/388), 12-month follow-up (86%, 334/388), and medical notes data (89%, 347/388). 182 (93%) of 195 participants in the intervention group completed the intervention, attending a mean of 5·6 appointments. HomeHealth had no effect on Barthel Index scores at 12 months (mean difference 0·250, 95% CI -0·932 to 1·432). At 6 months, there was a small reduction in psychological distress (-1·237, -2·127 to -0·348) and frailty (-0·124, -0·232 to -0·017), and at 12 months, we found small positive effects on wellbeing (1·449, 0·124 to 2·775) in those receiving HomeHealth. Other outcomes in analysis to date showed no significant difference. Health economic outcomes (including quality of life, capability, health services use and care needs or burden) are pending. INTERPRETATION: This high-quality trial showed that HomeHealth did not maintain independence in older people with mild frailty, and had limited effects upon secondary outcomes. Future studies need to explore different ways to promote health in this population. FUNDING: National Institute for Health and Care Research Health Technology Assessment (NIHR HTA).