Improvement In Frailty Status Research Articles

Efficacy Analysis of Ixazomib-Based Regimens Based on Dynamic Frailty Assessment in Elderly and Frail Patients with Newly Diagnosed Multiple Myeloma

Background: Elderly frail MM patients often lack evidence-based basis due to many comorbidities and poor treatment tolerance, and are often excluded by new drug clinical trials. There are many unsolved problems in clinical practice.There is still variation in the prognosis of frail patients identified using current frailty assessment tools. A potential treatment approach to improve outcomes in this heterogeneous population could involve starting with a well-tolerated low-intensity regimen and adjusting treatment based on ongoing dynamic frailty assessments.Therefore, our center conducted a retrospective study to explore the efficacy and safety of real-world isazomib-based two-drug regimen in the treatment of newly diagnosed elderly frail MM patients by adjusting treatment intensity based on dynamic frailty assessment. Methods: Patients with NDMM who received 2 or more courses of ixazomib-based regimens at the Department of Hematology, Affiliated Hospital of Hebei University from January 1, 2018 to April 1, 2023. All patients were assessed for frailty using the IMWG Geriatric Assessment (IMWG-GA) tool, and a total of 21 patients with frailty assessed as Frail were included, including 11 patients (52.4%) aged 75 years and older and 17 patients (81.0%) with ECOG score ≥ 2.A two-drug regimen of ixazomib combined with dexamethasone (ID) was initiated, and dynamic frailty assessment and efficacy evaluation were performed during the 3-4 courses of treatment. After the frailty status improved, the third drug was used in the following cases: 1) R-ISS high-risk group, and 2) R-ISS intermediate-low risk group with efficacy < PR. The combination of the two drugs was continued in the following cases: 1) R-ISS intermediate-low risk group with improved frailty status with efficacy ≥ PR, and 2) no improvement in frailty status with efficacy ≥ SD. The effectiveness of treatment, discontinuation rate, early death and related adverse effects were assessed. Results: A total of 21 patients were included in this study, of whom 12 patients increased the intensity of treatment after improvement of frail status , the third drug was added with Cyclophosphamide (8 patients) or Lenalidomide (3 patients) or Daratumumab (1 patient) in courses 3-4. 9 patients continued to be treated with ID regimen. The median duration of treatment was 10 (2-19).The ORR was 85.7% (18/21), and the efficacy above MR was 95.2% (20/21). Two patients died, both over 80 years of age, with many underlying complications, including one patient who abandoned treatment and died (17 months), one patient who died (24 months) due to gastrointestinal bleeding, without early death. Four patients experienced disease progression after self-interruption of treatment, 15 patients were still using ixazomib-based therapy, and none discontinued due to adverse reactions. After a follow-up time of 9.0 (2.6-37.0) months, the PFS and OS were not reached. All patients overall tolerated well, mainly grade 1-2 adverse reactions (CTCAE 5.0). Conclusion: This study is a single-center retrospective study that included 21 frail patients with newly diagnosed multiple myeloma and achieved good efficacy with a low discontinuation rate, no serious adverse effects, and no early deaths. This study confirmed that the frail state of the patient was dynamically altered over time and treatment during the remedy period. For elderly frail patients, the two-drug regimen for ID was initiated, the treatment regimen was dynamically adjusted based on frailty assessment, cytogenetic-based stratification (R-ISS) was introduced after frailty assessment was improved, the treatment intensity was increased in patients, and the third drug was added to make up for the lack of treatment; for intermediate-low risk patients with better efficacy, continuous two-drug treatment was performed to avoid adverse reactions caused by excessive treatment, early drug withdrawal and early death. For the heterogeneous population of frail MM in the elderly, the treatment was dynamically adjusted according to frailty assessment and an individualized treatment plan was developed, which achieved the combination of efficacy and safety. However, the benefit of dynamically adjusting treatment regimens according to frailty stratification and the optimal regimen suitable for frailty MM in the elderly still need to be confirmed by evidence-based medical data.

Evaluating the Effectiveness of Risk Adjustment Using Dynamic Frailty Assessment in Treating Newly Diagnosed Multiple Myeloma in Elderly Patients

Background: The treatment of newly diagnosed multiple myeloma (NDMM) in elderly patients is challenging due to various problems. To address these challenges, the European Myeloma Network (EMN) recommends conducting a frailty assessment before NDMM treatment in elderly patients. If the assessment identifies an intermediate fit or frail group, dosage reduction is recommended to avoid excessive treatment. However, as frailty status improves, there may be a risk of insufficient treatment leading to poor outcomes. In order to explore the optimal treatment approach for elderly NDMM patients in real-world settings, a retrospective analysis was conducted on the effectiveness of dynamically adjusting treatments based on frailty assessment in intermediate-fit and frail groups of elderly NDMM patients. Methods: Patients who were initially diagnosed with multiple myeloma and assessed as intermediate fit or frail patients by IMWG-GA frailty assessment at the Department of Hematology, Affiliated Hospital of Hebei University from January 1, 2018 to April 1, 2023 were included in this study.The initial treatment regimen for all patients in this group consisted of a combination of Bortezomib with dexamethasone (BD) or Ixazomib with dexamethasone (ID) .Frailty assessment and efficacy evaluation were conducted every 2-3 courses during the treatment period. In the frail group, treatment in those frailty status improved was adjusted based on prognosis stratification by adding a third drug to high-risk R-ISS patients and subsequently adjusting it according to efficacy evaluation; additionally, a third drug was added to patients who did not reach partial response (<PR). For the intermediate fit group, sequential addition of a third drug occurred during courses 2-3.The options for the third drug included cyclophosphamide, lenalidomide, and thalidomide，and common regimens used were ICD, IRD, VRD, VCD, and VTD.The response rate, discontinuation rate, early death, and adverse drug reactions were observed. Results: A total of 45 patients with newly diagnosed NDMM were included in this study. Among them, 37 patients were assessed as frail .24 /45 patients were treated with the BD regimen and 21/45 patients with the ID regimen. During treatment, dynamic frailty assessment showed significant improvement in frail status during courses 3-4 (see Table 1). Following dynamically adjusted principles, additional drugs were administered to certain patients: 24 /37 frail patients received a third drug; among the intermediate fit patients, all received a third drug. The best ORR achieved throughout the study was at an impressive rate of 82.2% (37/45), with a corresponding best efficacy above VGPR seen in 51.1% (23/45) of cases. Twenty-one patients experienced disease progression for various reasons during treatment, with a median PFS of 14.0 (3.0-96.0) months. During the follow-up period, a total of 17 patients died, while none died within 6 months. The median overall survival (OS) was found to be 18.0 months (ranging from 3.0 to 115.5 months). Safety evaluation was conducted on all 45 patients within the first year and they tolerated the treatment well. Most adverse reactions reported were of grade 1-2 according to CTCAE version 5.0. Conclusion: This study is a retrospective study that the initial treatment involved administering a low-intensity regimen consisting of either BD or ID two-drug combination. Serious adverse reactions, drug withdrawal, and early death decreased in both groups. The treatment intensity was increased for high-risk patients or those with poor efficacy in the frail group after the improvement of frailty status. This new therapeutic strategy which integrates dynamic changes of frailty status, cytogenetic risk factors, efficacy evaluation and dynamic adjustment of treatment, has shown improved efficacy for patients with two different levels of frailty. Additionally, it has been found to reduce early mortality rates. These promising results warrant further investigation through prospective studies.

The Association Between Habitual Tea Consumption and Frailty Transition in Community-Dwelling Older Adults: A Prospective Cohort Study

ObjectivesTo investigate the association between habitual tea consumption and transitions between frailty states among older adults in China. DesignA prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study. Setting and ParticipantsA total of 23,720 older adults aged ≥65 years with complete data regarding frailty status and tea consumption were recruited. MethodsThe frequency and consistency of tea consumption were introduced to evaluate levels of tea consumption. The frailty index was used to define frailty status (frail and nonfrail). Frailty transition was classified into remaining nonfrail, improvement, worsening, and remaining frail groups. Logistic regression models were applied. ResultsThe overall frailty prevalence at baseline was 19.1%, being lower among consistent daily tea drinkers (12.5%) and higher among non-tea drinkers (21.9%). Logistic regression analyses showed that the risk of frailty was significantly reduced among consistent daily tea drinkers after adjusting for all confounders [odds ratio (OR), 0.81; 95% CI, 0.67–0.98]. During the 3-year follow-up, improvement in frailty status was more common among consistent daily tea drinkers (50.9%) than non-tea drinkers (40.9%), and this trend was opposite in participants with worsened frailty status (consistent daily tea drinkers: 12.2%) vs non-tea drinkers: 19.2%). Further analysis showed that consistent daily tea drinkers were significantly associated with improvement in frailty status (OR, 3.24; 95% CI, 1.02–10.31) and remaining in a nonfrail state (OR, 1.35; 95% CI, 1.00–1.83). In addition, daily tea consumption was observed to be positively associated with remaining in a nonfrail state and inversely associated with worsened frailty status in men, but not in women. Conclusions and ImplicationsOlder people consuming tea daily tend to have an improved frailty status in the future. Men with daily tea consumption were less likely to have a worsened frailty status. Advocating for the traditional lifestyle of drinking tea could be a promising way to advance healthy aging for older adults.

Association between physical performance during sit-to-stand motion and frailty in older adults with cardiometabolic diseases: a cross-sectional, longitudinal study

BackgroundAlthough physical performance tests of the lower extremities are used to assess sarcopenia and frailty, little is known about the mechanisms by which the parameters of ground reaction force (GRF) measured during sit-to-stand motion affect the frailty status in older adults. We aimed to examine the association between GRF parameters during sit-to-stand motion and the incidence of frailty in older adults.MethodsThis longitudinal study evaluated 319 outpatients aged ≥ 65 years with cardiometabolic diseases. The GRF parameters were measured using a motor function analyzer, in which the power, speed, and balance scores were calculated. Frailty was diagnosed using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). The independent associations between scores and frailty indices were assessed using multivariate binomial logistic regression analyses. Cox regression analysis was used to examine whether power and speed scores were associated with the incidence of frailty after adjusting for covariates.ResultsLogistic regression analyses adjusted for covariates showed that the power and speed scores were associated with frailty according to the mCHS criteria (power: OR = 0.37, 95% CI = 0.22–0.63; speed: OR = 0.64, 95% CI = 0.52–0.79) and KCL criteria (power: OR = 0.40, 95% CI = 0.26–0.62; speed: OR = 0.81, 95% CI = 0.69–0.96) at baseline. Receiver operating characteristic analyses revealed that the area under the curve values of power and speed scores for discriminating mCHS-defined frailty were 0.72 and 0.73. The Cox regression analysis showed that the speed score predicted the incidence of mCHS-defined (HR = 0.45, 95% CI = 0.22–0.92, P = 0.029) and KCL-defined (HR = 0.77, 95% CI = 0.60–0.99, P = 0.039) frailty, whereas the power score was associated with the incidence of KCL-defined frailty (HR = 0.72, 95% CI = 0.55–0.95, P = 0.02) after adjusting for covariates.ConclusionsThe speed and power scores measured during sit-to-stand motion are predictive of frailty in older adults with cardiometabolic disease. Therefore, the GRF parameters measured during sit-to-stand motion could be an important indicator of frailty. Further studies are necessary to examine whether the GRF parameters can be improved by exercise or whether the changes in these parameters are associated with the improvement of frailty status.

1323 VOLUNTEER-LED ONLINE GROUP EXERCISE FOR OLDER ADULTS: A FEASIBILITY AND ACCEPTABILITY STUDY

Abstract Introduction The health benefits of physical activity for older people are well recognised and include reduction in falls, improvement in frailty status and physical function. Nonetheless, physical inactivity remains a significant problem among older adults. This study aimed to determine the feasibility and acceptability of implementing online volunteer-led group exercise for community-dwelling older adults. Methods This pre-post mixed methods study was conducted among older adults attending community social clubs. Eligible participants were aged ≥ 65 years, able to walk independently, and able to provide written consent. The intervention consisted of a once weekly volunteer-led online group chair-based exercise. The primary outcomes were the feasibility and acceptability of the intervention. Secondary outcomes included physical activity levels measured using the Community Health Model Activities Program for Seniors (CHAMPS) questionnaire, functional status (Barthel Index), and health-related quality of life (EQ-5D-5L). Outcomes were measured at baseline and at 6 months. Trials registration: NCT04672200. Results Nineteen volunteers were recruited, 15 completed training and 9 were retained (mean age 68 years, 7 female). Thirty participants (mean age 77 years, 27 female) received the intervention and attended 54% (IQR 37-67) of exercise sessions. One minor adverse event was reported. Participants had no significant changes in secondary outcome measures, with a trend towards improvement in physical activity levels. The intervention was acceptable to volunteers, participants, and staff. The seated exercises were perceived as safe, manageable and enjoyable. Volunteers were relatable role models providing positive vicarious experiences that improved participants confidence to exercise within a friendly, non-judgmental environment. Technological issues, or reluctance to learn how to use technology were barriers to the intervention. The social interactions and sense of belonging motivated participation. Conclusions Trained volunteers can safely deliver online group exercise for community-dwelling older adults and the intervention was feasible and acceptable to older adults, volunteers and club staff.

Transitions of self-management behaviors and frailty status among community-dwelling older adults: a national longitudinal population-based cohort study

BackgroundFrailty in older adults is a common geriatric syndrome that could be prevented; thus, coping strategies for the aging population are essential. Self-management behaviors may represent cost-effective strategies to prevent physical frailty in community-dwelling older adults. This study aimed to describe the changes in frailty status among community-dwelling older adults in Taiwan and investigate the association between transitions of self-management behaviors and frailty status over 4 years of follow-up (2007 to 2011).MethodsData were retrieved from the Taiwan Longitudinal Study of Aging (TLSA), years 2007 and 2011. In this prospective cohort study, 1283 community-dwelling older adults aged 65 years and older without cognitive impairment were recruited. Frailty was defined based on Fried’s frailty phenotype. Self-management behaviors (maintaining body weight, quitting smoking or no smoking, drinking less or no drinking, exercising, keeping diet control, and maintaining a regular lifestyle) were assessed using a questionnaire. Multinomial logistic regression analyses were used to investigate the associations between changes in self-management behaviors and in frailty status. The age group was further stratified to examine the moderation effect in the relationship between changes in self-management behaviors and in frailty status among older adults.ResultsThe prevalence of frailty was 8.7% at baseline and 14.9% after 4 years of follow-up, with 196 (15.3%) deaths. Overall, 514 (40.1%) participants maintained their frailty status, 424 (33.0%) worsened, and only 149 (11.6%) improved. Being aged ≥75 years old, having chronic diseases, and an absence of self-management behaviors were associated with frailty at baseline and after follow-up. Among individuals aged 65–74, compared to those who maintained no self-management behaviors, those who decreased the exercise behaviors (yes-to-no) had a higher risk of worsening (RRR = 2.518), while increasing (no-to-yes) and maintaining (yes-to-yes) frequent physical exercise were associated with a lower risk of worsening (RRR = 0.466 and 0.572, respectively) than stable frailty; those who maintained body weight (yes-to-yes) were associated with a lower risk of worsening (RRR = 0.327) than stable frailty after controlling for individual covariates and chronic diseases. Among individuals over 75 years old, compared to no exerciser, older old who decreased their physical exercise had a higher risk of frailty worsening (RRR = 3.255), and increasing frequent physical exercise (no-to-yes) was associated with an improvement in frailty status (RRR = 3.684). Age was a moderator between the effects of maintaining body weight on frailty worsening. There were no associations between the behavioral transitions of smoking, drinking, diet control, or regular lifestyle on the frailty status changes.ConclusionsMaintaining body weight and frequent physical exercise increased the ratio of frailty stability among individuals 65–74 years old. Increasing exercise behavior is the only factor to improve their frailty status among older adults aged 75 years and over. Older adults should be encouraged to perform adequate physical exercise and maintain a healthy body weight to maintain the frailty status in younger old aged 65–74 years, and especially perform more frequent exercise to improve frailty status in older old over 75 years.

Wearable-Based Assessment of Frailty Trajectories During Cardiac Rehabilitation After Open-Heart Surgery.

Frailty in patients after open-heart surgery influences the type and intensity of a cardiac rehabilitation program. The response to tailored exercise training can be different, requiring convenient tools to assess the effectiveness of a training program routinely. The study aims to investigate whether kinematic measures extracted from the acceleration signals can provide information about frailty trajectories during rehabilitation. One hundred patients after open-heart surgery, assigned to the equal-sized intervention and control groups, participated in exercise training during inpatient rehabilitation. After rehabilitation, the intervention group continued exercise training at home, whereas the control group was asked to maintain the usual physical activity regimen. Stride time, cadence, movement vigor, gait asymmetry, Lissajous index, and postural sway were estimated during the clinical walk and stair-climbing tests before and after inpatient rehabilitation as well as after home-based exercise training. Frailty was assessed using the Edmonton frail scale. Most kinematic measures estimated during walking improved after rehabilitation along with the improvement in frailty status, i.e., stride time, cadence, postural sway, and movement vigor improved in 71%, 77%, 81%, and 83% of patients, respectively. Meanwhile, kinematic measures during stair-climbing improved to a lesser extent compared to walking. Home-based exercise training did not result in a notable change in kinematic measures which agrees well with only a negligible deterioration in frailty status. The study demonstrates the feasibility to follow frailty trajectories during inpatient rehabilitation after open-heart surgery based on kinematic measures extracted using a single wearable sensor.

Physical fitness and frailty status of frail older adults in long-term care facilities after acupunch exercises: A cluster-randomized controlled trial.

Frailty is a complex geriatric syndrome and serves as an indicator for functional degradation in older adults. Regular exercise intervention could reduce the level of frailty and improve general physical fitness. The aim of this study was to test the effects of the Vitality Acupunch (VA) exercise on the promotion of physical fitness and the improvement of frailty status among frail older adults in long-term care facilities. This study was a cluster-randomized controlled trial adopted a pretest-posttest design. Using convenience sampling, 81 frail adults older than 65years of age from 10 long-term care facilities participated in this study. The older adults were cluster-randomized by facility into an intervention group (5 long-term care facilities, n=40) and a control group (5 long-term care facilities, n=41). The intervention group engaged in the VA exercise 3 times a week, each lasting 40min, for 24weeks. The control group maintained regular activities of daily living. The outcome measures for physical fitness were assessed before study began (pretest), at the 12th week (posttest 1), and at the 24th week (posttest 2) in the study. After a 24-week intervention, the frail older adults who engaged in the VA exercise program showed significant improvements in handgrip strength, upper-limb muscle endurance, lung function, shoulder flexibility, forward flexion, shoulder joint flexion, and shoulder joint abduction (all p<0.05) but not in lower-limb muscle endurance (p=0.502) compared against their pretest data. The intervention group had significantly better physical fitness and positive changes in frailty status than the control group (all p<0.001), except for the lower-limb muscle endurance (p=0.557). Regular engagement in the VA exercise program for 24weeks significantly improved the physical fitness and frailty status of frail older adults in long-term care facilities.

A pilot randomized controlled trial using Baduanjin qigong to reverse frailty status among post-treatment older cancer survivors

ObjectivesTo evaluate the feasibility and potential effects of qigong Baduanjin for reversing frailty status among older cancer survivors. Materials and MethodsTwenty-eight older cancer survivors screened as pre-frail or frail were recruited. They were randomly assigned (1:1) to receive a sixteen-week Baduanjin intervention or an active control condition (light flexibility exercise). Frailty status (primary outcome) and secondary outcomes (physical performance, activities of daily living performance, psychological well-being, and health-related quality of life) were measured by physical performance tests and questionnaires. Qualitative interviews were conducted to explore participants' perspectives on the intervention. ResultsTwenty-one participants (75%) completed the study, with reasons of withdrawal mainly relating to the COVID-19 pandemic. Attendance at Baduanjin sessions and adherence to self-practice were satisfactory, with all retained participants attending all sessions and 81.8% practicing Baduanjin for more than 90 min per week. Qualitative findings demonstrated that participants accepted Baduanjin. The proportion of improvement in frailty status at post-intervention appeared to be higher in the intervention group (26.7%; 95% confidence interval [CI], 10.1% to 54.0%) than the control group (15.4%; 95% CI, 3.7% to 46.0%); yet the difference was not statistically significant (p = 0.461). ConclusionsBaduanjin qigong appears to be feasible and acceptable among older cancer survivors. To confirm the intervention effect, an adequately powered trial is warranted. Trial RegistrationClinicalTrials.gov, NCT04694066. Retrospectively registered 5 January 2021, https://clinicaltrials.gov/ct2/show/NCT04694066.

Frailty Status and Patient-Reported Outcomes in Octogenarians Following Transcatheter or Surgical Aortic Valve Replacement

Frailty status and patient-reported outcomes are especially pertinent in octogenarians following transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) to guide treatment decisions and promote patient-centred care. We aimed to determine if frailty changed 6 months after aortic valve replacement (AVR) in octogenarians, and to describe changes in self-rated health according to frailty status in patients who underwent TAVI or SAVR. In a prospective cohort study, frailty and self-rated health were measured one day prior to and 6 months after AVR. Frailty status was measured with the Study of Osteoporotic Fracture index. Self-rated health was measured comprehensively with the disease-specific Minnesota Living with Heart Failure Questionnaire, the generic Medical Outcomes Study Short Form-12 questionnaire (SF-12), and two global questions from The World Health Organization Quality of Life Instrument Abbreviated. Data were available for 143 consecutive patients (mean age 83±2.7 years, 57% women; 45% underwent TAVI). At baseline, 34% were robust, 27% prefrail, and 39% frail. Overall, there was no change in the distribution of frailty status 6 months after baseline (p=0.13). However, on an individual level 65 patients changed frailty status after AVR (40 patients improved and 25 declined). Improvement in frailty status was common in prefrail (33%; n=13) and frail patients (48%; n=27). Patients had improved self-rated health after AVR, with significant differences between frailty states both at baseline (SF-12 physical: 37.4 [robust], 33.1 [prefrail], 31.6 [frail], p=0.03); SF-12 mental: 51.9 [robust], 50.8 [prefrail], 44.5 [frail], p<0.001); and at the 6-month follow-up (SF-12 physical: 45.4 [robust], 38.3 [prefrail], 32.1 [frail], p<0.001); SF-12 mental: 54.9 [robust], 49.6 [prefrail], 46.8 [frail], p=0.002). Advanced treatment performed in a high-risk population allowed people to improve their self-rated health. Although frailty is associated with poor self-rated health, frailty status does not equal negative outcomes. The frail patients were those who improved most in self-rated physical and mental health. They had the lowest baseline self-rated health scores and had therefore the most to gain.

Community-Based Peer-Led Intervention for Healthy Ageing and Evaluation of the 'HAPPY' Program.

ObjectivesPopulation ageing impacts many areas of society from health and social care cost to housing and future workforce, and whole-of-society approach is required to promote healthy ageing. The Decade of Healthy Ageing report has called upon multi-sectoral collaboration to promote age-friendly communities. The Healthy Ageing Promotion Program for You (HAPPY) is a community-based dual-task exercise program for older adults led by health coaches (HC) or trained volunteers (HAPPY leaders) to promote healthy ageing. The primary objective was to observe improvement in cognition. The secondary objective was to observe improvement in frailty status, functional status, perceived health and reduction of social isolation. We also aim to evaluate the effectiveness and describe the implementation of the HAPPY program.DesignTo engage older adults with prefrailty, frailty and/or cognitive impairment in dual-task exercise program. Recruitment and publicity were through country-wide multisectoral collaboration.SettingCommunity settingParticipantsMore than 700 older adults participated in ≥ 50 different sites including senior activity centres. Five hundred and sixty-nine participants attended phase 1 screening. Pre-frail or frail ambulant participants or those with underlying cognitive impairment were invited to participate in phase 2 screening. Among them 296 participants enrolled in phase 2 with 66.6% follow up rate at 3 months.MeasurementsPhase 1 and 2 screening consisted of screening for frailty (FRAIL), cognition (Montreal Cognitive Assessment [MoCA]), falls, vision, grip strength, perceived health (EuroQol vertical visual analogue scale), depression (geriatric depression scale), social network (6-item Lubben Social Network Scale), gait speed and physical function (Short physical performance battery [SPPB]).ResultsHC led 61.7% of the participants, and HAPPY was conducted twice weekly for 64% of the participants. There was significant improvement in the MoCA scores both in the HC and HAPPY leaders’ led groups. Overall physical function, chair-stand and balance domain improved significantly especially in the groups led by HC and those participating in twice-weekly exercises. There was significant improvement in perceived health, reduction in social isolation, improvement in frailty status and reduction of falls at 3 months.ConclusionCommunity embedded peer-led program to promote healthy ageing like HAPPY can improve cognition, physical function, and frailty status, reduce social isolation, and improve perceived health. It takes a “village” to promote healthy ageing, and the need to have a life course approach to healthy longevity which must involve local government and ministerial organisations, non-profit organisations, industries, academia, and community to redesign health.

P0958THE EX-FRAIL CKD TRIAL: A PILOT RANDOMISED CONTROLLED TRIAL OF A HOME-BASED EXERCISE PROGRAMME FOR PRE-FRAIL AND FRAIL, OLDER ADULTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Frailty is highly prevalent in adults with chronic kidney disease (CKD) and is associated with adverse health outcomes. However, exercise training may improve physical function leading to associated improvements in outcomes. The EX-FRAIL CKD trial (ISRCTN87708989) aimed to inform the design of a randomised controlled trial (RCT) that investigates the efficacy of a progressive home-based exercise programme in pre-frail and frail older adults with CKD. Methods Patients aged ≥65 years with CKD G3b-5 and a Clinical Frailty Scale score ≥4 were eligible for participation. Participants categorised as pre-frail or frail, following Frailty Phenotype (FP) assessment, were randomised to receive a tailored 12-week home-based exercise programme or usual care (UC). Primary outcome measures included recruitment, intervention adherence, outcome measure completion and participant attrition rate. Secondary outcome measures included frailty status (FP), physical function (walking speed, handgrip strength and Short Physical Performance Battery [SPPB]), fall concern (Falls Efficacy Scale-International tool [FESI]), symptom-burden (Palliative Care Outcome Scale-Symptoms RENAL [POS-S RENAL]) and health-related quality of life (Short Form-12v2 [SF-12]). Outcome measures are reported descriptively with 95% confidence intervals (CI) as recommended for pilot trials. Progression criteria to RCT stage were defined as: (1) eligibility: STOP &amp;lt;5%, GO &amp;gt;10%; (2) recruitment: STOP &amp;lt;10%, GO &amp;gt;30%; (3) exercise adherence: STOP: &amp;lt;30%, GO &amp;gt;70%; (4) outcome measure completion: STOP &amp;lt;70%, GO &amp;gt;80%; and (5) loss to follow-up: STOP &amp;gt;50%, GO &amp;lt;25%. Results Six hundred and sixty-five participants had an eligibility assessment with 201 (30% [95% CI 27-34]) patients eligible for enrolment. Thirty-five (17% [95% CI 12-23]) participants were recruited. Six participants were categorised as robust and therefore withdrawn prior to randomisation. Fifteen participants were randomised to exercise (mean age 77.0±8.3 years; mean eGFR 18.9±7.0 ml/min/1.73m2) and 14 to UC (mean age 78.8±7.0 years; mean eGFR 20.4±7.2 ml/min/1.73m2). Eleven (73% [95% CI 45-92]) exercise group participants completed an average of ≥2 exercise sessions/week. Eight (28% [95% CI 13-47]) participants were lost to follow-up. Retained participants (n=21, 100% [95% CI 84-100]) completed all outcome measures. There were 32 adverse events in the exercise group and 22 in the UC group. Within the exercise group, there were 2 hospitalisations (considered unrelated to exercise) and 12 adverse reactions: musculoskeletal pain (9), fall (1), nocturnal leg cramps (1) and postural dizziness (1). The odds ratio for improvement in frailty status with exercise was 5.50 (95% CI 0.46-65.16) and odds ratio for deterioration in frailty status was 0.63 (95% CI 0.05-8.20). The adjusted mean group difference in walking speed, grip strength and SPPB between exercise and UC groups were: 0.01 metres/second (95% CI -0.07-0.10), 3.6 kg (95% CI -0.6-7.9) and 0.5 (95% CI -0.9-1.8), respectively. The adjusted mean group difference in POS-S RENAL, FESI, SF-12 Physical Component Summary and SF-12 Mental Component Summary scores were: -1.4 (95% CI -6.6-3.7), 3.4 (95% CI -3.5-10.3), -3.9 (95% CI -9.3-1.5) and 0.2 (95% CI -6.2-6.6), respectively. Conclusion Eligibility, adherence and outcome measure progression criteria thresholds were exceeded; however, recruitment and loss to follow-up progression criteria thresholds were not achieved. Analysis of a nested qualitative study will explore perceived barriers to participation and retention. The EX-FRAIL CKD trial demonstrates that it is possible to progress to a definitive RCT with adaptations that address the barriers described. It has also provided preliminary evidence that frailty status and physical function may be improved with a home-based exercise programme in patients living with frailty and CKD.

Healthy lifestyle behaviors and transitions in frailty status among independent community-dwelling older adults: The Yabu cohort study

Frailty is a dynamic condition that can worsen or improve. Although previous studies have identified demographic and intrinsic factors associated with transitions in frailty status, less evidence is available regarding associations with daily activities. This longitudinal study examined associations of behavioral factors with incident frailty, adverse events (e.g. residence in a nursing home, hospitalization, and death), and frailty improvement among older adults. The analysis included data from 3,769 independent older adults aged 65 years or more (mean age, 76.3 ± 7.2years; proportion of frail participants, 30.1%) from the Yabu cohort study (baseline, 2012; follow-up, 2017). The Kaigo-Yobo Checklist, a standardized questionnaire, was used to assess frailty status (non-frail or frail) and seven behavioral factors: farming, shopping, exercise, eating habit, intellectual activity, social participation, and smoking. At the 5-year follow-up survey, the proportions of participants transitioning from non-frail to frail, from non-frail to incident adverse events, from frail to non-frail, and from frail to incident adverse events were 16.8%, 13.9%, 15.2%, and 50.1%, respectively. In the analysis of non-frail participants, farming, exercise, intellectual activity, and social participation were associated with lower odds of becoming frail and experiencing adverse events. In the analysis for frail participants, farming, intellectual activity, and social participation were significantly associated with improvement in frailty status, and farming, shopping, and social participation were associated with lower odds of incident adverse events. These findings suggest that farming, healthy daily activities, and social participation help improve and prevent frailty/adverse events.

Longitudinal Trajectory of Frailty in Blood or Marrow Transplant (BMT) Survivors - a BMT Survivor Study (BMTSS)

Introduction: Frailty is a state of increased vulnerability resulting in a decline in reserve and function across multiple physiologic systems such that the ability to cope with every day or acute stressors is compromised. We previously reported that BMT recipients with frailty were at a 2.8-fold higher risk of subsequent mortality (JAMA Oncol. 2016;2:1277-86) when compared with non-frail survivors. However, longitudinal trends in frailty several years after BMT are not known, and could possibly help in identifying the vulnerable sub-populations at highest risk of subsequent adverse events. We used BMTSS to report transitions in the frailty state over time. Methods: We included 484 patients who were i) transplanted for a hematologic malignancy between 1974 and 1998 at 2 sites and had survived ≥2y post-BMT; ii) were ≥18y of age at study participation; and iii) were alive both at completion of the baseline survey (t1: median of 7.3 y after BMT) and at follow-up survey (t2: median of 20.6y after BMT); median interval between t1 and t2 was 13.2y. Frailty phenotype used the previous definition (JAMA Oncol. 2016;2:1277-86), and included the presence of ≥3 of the following indices: 1) clinically underweight (body mass index [BMI] &amp;lt;18.5); (2) exhaustion; (3) low energy expenditure; (4) slowness; and (5) weakness. Patients reporting the presence of 1-2 of the 5 indices were classified as pre-frail. We created the following categories of change in frailty status over time; A) Worsening of frailty status/ stable frail status : pre-frailty [t1] → frailty [t2]; no-frailty [t1] → pre-frailty/frailty [t2]; and frailty [t1] → frailty [t2]; B) Improvement of frailty status: frailty [t1] → pre-frailty [t2]; pre-frailty [t1] → no frailty [t2]; C) Stable non-frail/pre-frail status: non-frail [t1]→ non-frail [t2]; pre-frail [t1] → pre-frail [t2]. We used logistic regression to evaluate predictors of A) worsening of frailty status/stable frail status, and B) frailty at t2, controlling for age at questionnaire, sex, diagnosis, smoking status, socio-economic, and BMT related variables (conditioning, donor type, presence of cGvHD), grade 3-4 chronic health conditions, and pre-BMT treatments therapeutic exposures. Results: Median age (range) at t1 was 42.9y (18.5-67.4) and at t2 was 56.5y (31.0-80.0); 49.4% were females; 85.4% non-Hispanic whites; 15% had &amp;lt;high school education, and 50% had annual household income of &amp;lt;$60,000. Primary diagnoses included acute leukemia (31%), lymphoma (31%), and chronic myelogenous leukemia (25%); 57% had received an allogeneic BMT; 77% received TBI; 40.3% had cGvHD. Prevalence of frailty was 4.8% at t1 and 9.6% at t2, and that of pre-frailty was 13.9% at t1 and 16.1% at t2 (Figure). Worsening of frailty status was seen in 18.8% of the patients, improvement in 9.7%; 68.7% of the patients remained non-frail or pre-frail. Predictors of worsening of frailty status: Pre-BMT exposure to vincristine (OR=5.1, 95%CI: 2.3-11.4) and female sex (OR=1.5, 95%CI, 0.9-2.6, p=0.08) were associated with worsening. Predictors of frailty at t2: Pre-BMT exposure to vincristine (OR=4.6, 95%CI, 1.7-12.5, p=0.003), history of cGvHD at t1 (OR=2.3, 95%CI, 1.0-5.2, p=0.04) and grades 3-4 chronic health conditions at t1 (OR=2.1, 95%CI, 1.0-4.5, p=0.04) were associated with frailty at t2. Age was not a significant predictor in either analysis. Conclusions: In a cohort of patients followed longitudinally for a median of 20.6y from BMT, with measurement of frailty status 13.2y apart, we observed that the frailty status worsened for ~20% of the patients. Pre-transplant exposure to vincristine was associated with worsening of frailty status. Patients with cGvHD or morbidity at t1, as well as pre-BMT vincristine exposure placed BMT survivors at high risk for subsequent frailty, identifying sub-populations that could benefit from targeted interventions. Disclosures Weisdorf: Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy.

SUN-PO154: Improvement in Frailty Status After Pulmonary Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease

The aim of this study, is to assess changes in prevalence and frailty score during pulmonary rehabilitation (PR) in patients with COPD.

Factors associated with changes of the frailty status after age 70: Findings in the MAPT study

PurposeFrailty has become a major issue in the prevention of functional decline and disability in aged populations. Using repeated measurements of frailty over 3 years, this work aimed to describe transitions between frailty states and associated factors. MethodsThis study used the data from the Multidomain Alzheimer Preventive Trial and included the 842 participants aged 70 and over who did not receive the multidomain intervention. Frailty was assessed using the phenotype proposed by Fried et al. at baseline and at 6, 12, 24, and 36 months. Factors influencing the transitions across frailty states were examined using multistate modeling. ResultsThe study population included 548 women and 294 men, mean age 75.4 ± 4.5 years. At baseline, 430 (53%) participants were nonfrail, 349 (43%) prefrail, and 28 (4%) frail. A total of 2271 pairs of consecutive measurements of frailty status were available over the 3 years of follow-up, with no change in frailty status in 1548 of them (68%), a worsening of frailty status in 426 of them (19%), and an improvement in frailty status in the remaining 297 (13%). Polypharmacy (i.e., ≥6 drugs) and probable depression were associated with incident prefrailty. Female gender was systematically associated with a lower probability of recovering from prefrailty and frailty. Older age, overweight, comorbidity, and abnormal C-reactive protein also reduced the probability of recovery from frailty or prefrailty. ConclusionsThis study sheds light on factors that should be further investigated in future research to help the prevention and management of frailty.

Is Neighborhood Green Space Associated With Less Frailty? Evidence From the Mr. and Ms. Os (Hong Kong) Study

ObjectivesTo examine whether neighborhood green space was related to frailty risk longitudinally and to examine the relative contributions of green space, physical activity, and individual health conditions to the frailty transitions. Design, setting, and participantsFour thousand community-dwelling Chinese adults aged ≥65 years participating in the Mr. and Ms. Os (Hong Kong) study in 2001-2003 were followed up for 2 years. MethodsThe percentage of green space within a 300-meter radial buffer around the participants’ place of residence was derived for each participant at baseline based on the normalized difference vegetation index. Frailty status was classified according to the Fried criteria at baseline and after 2 years. Ordinal logistic regression and path analysis were used to examine associations between green space and the frailty transitions, adjusting for demographics, socioeconomic status, lifestyle factors, health conditions, and baseline frailty status. ResultsAt baseline, 53.5% of the participants met the criterion for robust, 41.5% were classified as prefrailty, and 5.0% were frail. After 2 years, 3240 participants completed all the measurements. Among these, 18.6% of prefrail or frail participants improved, 66% remained in their frailty state, and 26.8% of robust or prefrail participants progressed in frailty status. In multivariable models, the frailty status of participants living in neighborhoods with more than 34.1% green space (the highest quartile) at baseline was more likely to improve at the 2-year follow-up than it was for those living in neighborhoods with 0 to 4.5% (the lowest quartile) [odds ratio (OR): 1.29, 95% confidence interval (CI): 1.04-1.60; P for trend: 0.022]. When men and women were analyzed separately, the association between green space and frailty remained significant in men (OR: 1.40, 95% CI: 1.03-1.90) but not in women. Path analysis showed that green space directly affects frailty transitions (β = 0.041, P < .05) and also exerts an effect through physical activity (β = 0.034, P < .05). Physical activity directly affects frailty (β = 0.134, P < .05), and also indirectly affects frailty through health conditions including number of diseases (β = −0.057, P < .05) and cognitive functions (β = 0.041, P < .05). The magnitude of the direct effect of green space on the 2-year frailty transitions is comparable to those of the indirect effect through physical activity. ConclusionOlder people living in neighborhoods with a higher percentage of green space were associated with improvement in frailty status, independent of a wide range of individual characteristics.

Patterns and Predictors of Frailty Transitions in Older Men: The Osteoporotic Fractures in Men Study.

To describe the natural history of frailty transitions in a large cohort of community-dwelling older men and identify predictors associated with progression to or improvement from states of greater frailty. Prospective cohort study. Six U.S. sites. Community-dwelling men aged 65 and older (N = 5,086). Frailty was measured at baseline and an average of 4.6 years later. Frailty was defined as having three or more of the following components (low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed); prefrailty was defined as having one or two components. Separate multivariable logistic regression models were analyzed for progression and improvement in frailty status. Of the 5,086 men, 8% were frail, 46% were prefrail, and 46% were robust at baseline. Between baseline and follow-up, 35% progressed in frailty status or died, 56% had no change in frailty status, and 15% of prefrail or frail participants improved, although only 0.5% improved across two levels, from frail to robust. In multivariable models, factors associated with improvement in frailty status included greater leg power, being married, and good or excellent self-reported health, whereas presence of any instrumental activity of daily living (IADL) limitations, low albumin levels, high interleukin-6 levels, and presence of chronic obstructive pulmonary disease or diabetes mellitus were associated with lower likelihood of improvement in frailty status. Improvement in frailty status was possible in this cohort of community-dwelling older men, but improvement from frail to robust was rare. Several predictors were identified as possible targets for intervention, including prevention and management of comorbid medical conditions, prevention of IADL disability, physical exercise, and nutritional and social support.

Changes in Frailty Status and Risk of Depression: Results From the Progetto Veneto Anziani Longitudinal Study

To evaluate whether prefrailty was associated with the risk of developing depression and if longitudinal changes in frailty status corresponded to changes in incident depression during follow up. A population-based, prospective cohort study was conducted for 4.4 years in two separate geographic areas near the city of Padua in the Veneto Region of Northern Italy. In 891 nondepressed, nonfrail, community-dwelling Italian subjects aged ≥ 65 (46.6% men) belonging to the Progetto Veneto Anziani study, depression was defined according to the Geriatric Depression Scale and was confirmed by geriatricians skilled in psychogeriatric medicine. Prefrailty was defined by the presence of one or two criteria among the Fried criteria. The incidence rate of depression was 13.3% among subjects improving their frailty status at follow-up (N = 15), 15.0% in those who remained stable (N = 79), and 26.7% among worsening participants (N = 67) (p = 0.001). Prefrailty at baseline did not predict the onset of depression (HR: 0.82; 95% CI: 0.55-1.21; Wald χ2 = 0.73; df = 1; p = 0.43), but a deterioration during follow-up in at least one additional frailty criteria was associated with a significantly higher risk (HR: 1.95; 95% CI: 1.32-2.89; Wald χ2 = 5.78; df = 2; p = 0.01). Improvement in frailty status was not associated with the risk of incident depression (HR: 0.71; 95% CI: 0.35-1.42; Wald χ2 = 0.47; df = 2; p = 0.28). Our data did not offer evidence that prefrailty per se predisposes to the onset of depression, but worsening in frailty status is associated with an almost twofold increased risk of incident depression, irrespective from the initial level of impairment.

Effect of Telephone Exercise Counseling on Frailty in Older Veterans: Project LIFE

This study sought to determine if telephone exercise counseling attenuates frailty in older, male veterans through increased levels of physical activity. Eighty-one elderly, male veterans (age = 78.4 +/- 4.9 years) randomized to intervention (n = 39) or combined control groups (n = 42) completed baseline and 6-month follow-up measures of gait velocity, 6-min walk, chair stands, body mass index, and physical activity. Adapting the Fried frailty model, deficits in one or more of these outcomes indicated frailty. The intervention group had a 6-month decrease of 18% in the proportion of frail to not frail participants, whereas the control groups had no change in proportions (Fisher's p = .08). Frail participants had a mean 6-month decrease in physical activity levels of 124 kilocalories/week, whereas the not frail group increased by 619 kilocalories/week (p = .07). There was a clinically meaningful change in frailty status with intensive, telephone exercise counseling. Improvement in frailty status was likely due to improvement in functional limitations.