Impact of COVID-19 Pandemic Exacerbation of Depressive Symptoms for Social Frailty from the ORANGE Registry

Background: Recent longitudinal studies have reported proportion of frailty transition in older individuals during the COVID-19 pandemic. Our study aimed at clarifying the impact of social frailty in community-dwelling older adults during the COVID-19 pandemic and at identifying factors that can predict transition to social frailty. Methods: We performed this study from 2019 (before declaration of the state of emergency over the rising number of COVID-19 cases) to 2020 (after declaration of the emergency). We applied Makizako’s social frail index to our study subjects at the baseline and classified into robust, social prefrailty, and social frailty groups. Multiple logistic regression analysis was performed using robust, social prefrailty, or social frailty status as dependent variable. Results: Analysis by the Kruskal–Wallis test revealed significant differences in the score on the GDS-15 among the robust, social prefrailty, and social frailty groups (p < 0.05). Furthermore, multiple regression analysis identified a significant association between the social frailty status and the score on GDS-15 (odds ratio, 1.57; 95% confidence interval (95% CI), 1.15–2.13; p = 0.001). Conclusion: The increase in the rate of transition of elderly individuals to the social frailty group could have been related to the implementation of the stay-at-home order as part of the countermeasures for COVID-19. Furthermore, the increased prevalence of depressive symptoms associated with the stay-at-home order could also have influenced the increase in the prevalence of social frailty during the COVID-19 pandemic.

To What Extent Does Frailty Influence the Risk of Developing Urolithiasis?

Urolithiasis has become more prevalent in recent years, given the rapid rise of the global geriatric population. Although factors such as ethnicity, dietary and fluid intake, co-morbidity status and age have been associated with increased incidence of urolithiasis, the links between frailty status and risks of developing urolithiasis are not yet known. In this commentary, we will explore the scale and significance of this relationship based on emerging evidence. We will review the plausible factors on how a more severe frailty status may be significantly associated with greater risks of developing urolithiasis. We will also discuss the strategies that may help to lower the incidence of urolithiasis in older and frail individuals. We hope our article will bring greater awareness on this issue and motivate further research initiatives evaluating the relationship between frailty and urolithiasis, as well as holistic prevention strategies to lower the risks of developing urolithiasis within this vulnerable population.

Self-Management Behaviours and Change in Frailty Status among Community-Dwelling Older Adults: A National Longitudinal Population-based Cohort Study

Background: Frailty in older adults is a common geriatric syndrome that can be reversed, thus coping strategies for the aging population are essential. Self-management behaviours may represent cost-effective strategies to reverse 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 of self-management behaviours with changes in frailty status over a four-year follow-up period (2007 to 2011).Methods: This data was retrieved from the Taiwan Longitudinal Study of Aging (TLSA), which is a prospective cohort study of 1,283 community-dwelling older adults aged 65 years and older without cognitive impairment. Frailty was assessed based on Fried's frailty phenotype, in which ≥ three criteria indicate frail. Self-management behaviours (maintaining body weight, quitting smoking, drinking less, exercising, diet control, and maintaining a regular lifestyle) were assessed using a questionnaire. Multivariate logistic regression analyses were used to investigate the associations between self-management behaviours and changes in frailty status.Results: The prevalence of frailty was 8.7% at baseline and 8.1% after four years of follow-up, with 196 (15.3%) deaths. Overall, 74.6% of participants remained in the same state (non-frail or frail), 23.5% worsened (non-frail to frail, including missing data, and frail to death), and only 1.95% improved (frail to non-frail). Being aged ≥ 75-years-old, chronic diseases, and an absence of self-management behaviours were associated with higher risks of frailty at baseline and after follow-up. Exercise was significantly associated with a reversal of frailty in community-dwelling older adults (RR, 3.11; 95% CI, 1.95, 4.95) after adjusting for personal and disease covariates, regardless of whether death was coded as frail or not.Conclusions: Self-management behaviours beneficially reverse frailty status; maintaining regular exercise was especially associated with a reversal of frailty in community-dwelling older adults, even among individuals over 75-years-old and with chronic diseases. Older adults should be encouraged to perform adequate physical exercise to prevent the progression of frailty and ameliorate frailty status.

Association Between Neutrophil–Lymphocyte Ratio and Frailty: The Chinese Longitudinal Healthy Longevity Survey

Background: Inflammation has been reported to play an important role in frailty syndrome. The neutrophil–lymphocyte ratio (NLR) has recently emerged as an informative marker for systematic inflammation. However, few studies have examined the association between NLR and frailty. This study aims to examine the association between NLR and frailty in community-dwelling older adults.Methods: Community-dwelling older adults aged ≥ 65 years in the 2011 (n = 2,354) and 2014 (n = 2,458) waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included. Frailty status was determined using the 38-item frailty index (FI) and categorized into “robust” (FI ≤ 0.1), “pre-frail” (0.1 &lt; FI ≤ 0.21), or “frail” (FI &gt; 0.21). NLR was calculated using a derived formula: NLR = (white blood cell–lymphocyte)/lymphocyte.Results: A total of 3,267 participants were finally included. In cross-sectional analyses, participants with higher NLR levels had increased likelihood of frailty [the 3rd quartile: adjusted odds ratio (OR) = 1.29; 95% confidence interval (CI): 1.02–1.63; the 4th quartile: OR = 1.59; 95% CI: 1.23–2.02) compared with those in the 1st quartile group. During the 3-year follow-up, 164 of the 1,206 participants, robust or pre-frail at baseline, developed frailty, and 197 of the 562 participants, robust at baseline, developed pre-frailty or frailty. Among the robust and pre-frail participants in 2011, after multivariate adjustment, those in the 4th quartile group had a higher frailty incidence than those in the 1st quartile group (OR = 2.06; 95% CI: 1.18–3.59). Among the robust participants in 2011, those in the 4th quartile group also had a higher pre-frailty or frailty incidence than those in the 1st quartile group (OR = 1.95; 95% CI: 1.07–3.55).Conclusion: Among community-dwelling older adults, higher NLR levels were found to be associated with increased odds of prevalent and incident frailty.

Determinants of trajectories of fatigability and mobility among older medical patients during and after hospitalization; an explorative study

Background Fatigability is an important marker of functional decline in community dwelling older people, yet its relationship with functional decline after hospitalization is unclear. The objectives of this study were to identify trajectories of fatigability and mobility over time and to examine the association between demographic and clinical characteristics and these trajectories in medical patients aged 70 years and older admitted to a Dutch tertiary care teaching hospital. Methods In this prospective cohort study with baseline (in-hospital), discharge, three-, and six-months post discharge follow-up measurements, fatigability was assessed by the physical subscale of the Pittsburgh Fatigability Scale (PFS). Mobility was assessed by the De Morton Mobility Index (DEMMI). Group-based trajectory modeling was used to identify joint trajectories of fatigability and mobility. Covariates included demographic (age, sex, living situation, education) and clinical characteristics (functional status, frailty status, depression, comorbidity, length of hospital stay). Results Among 44 patients, three distinct fatigability trajectories and two mobility trajectories were identified over the course from hospital admission up to six months after discharge. Subsequently, three joint trajectories were identified, including low fatigability and high mobility (11%), improving fatigability and high mobility (52%), and high fatigability and low mobility (36%). Controlling for baseline functional status, patients with a lower comorbidity score (OR: 0.27, 95%CI 0.10; 0.74) and higher frailty status (OR: 1.36, 95%CI: 1.07; 1.74) were more likely to be a member of the high fatigability and low mobility trajectories. Conclusions From hospital admission up to six months after discharge, three distinct trajectories of fatigability and mobility were identified among older medical patients. Our results should be interpreted with caution due to the small sample size, but may inspire other researchers to determine the value of fatigability assessment in identifying older medical patients at risk for developing mobility problems.

Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA

In the phase 3 MAIA study of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd). We present a subgroup analysis of MAIA by frailty status. Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. Of the randomized patients (D-Rd, n = 368; Rd, n = 369), 396 patients were non-frail (D-Rd, 196 [53.3%]; Rd, 200 [54.2%]) and 341 patients were frail (172 [46.7%]; 169 [45.8%]). After a 36.4-month median follow-up, non-frail patients had longer PFS than frail patients, but the PFS benefit of D-Rd versus Rd was maintained across subgroups: non-frail (median, not reached [NR] vs 41.7 months; hazard ratio [HR], 0.48; P < 0.0001) and frail (NR vs 30.4 months; HR, 0.62; P = 0.003). Improved rates of complete response or better and minimal residual disease (10–5) negativity were observed for D-Rd across subgroups. The most common grade 3/4 treatment-emergent adverse event in non-frail and frail patients was neutropenia (non-frail, 45.4% [D-Rd] and 37.2% [Rd]; frail, 57.7% and 33.1%). These findings support the clinical benefit of D-Rd in transplant-ineligible NDMM patients enrolled in MAIA, regardless of frailty status.

The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty

Background: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 (“mild”) or 6 (“moderate”), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.

A Mobile App With Multimodality Prehabilitation Programs for Patients Awaiting Elective Surgery: Development and Usability Study

Background Complying with a prehabilitation program is difficult for patients who will undergo surgery, owing to transportation challenges and a limited intervention time window. Mobile health (mHealth) using smartphone apps has the potential to remove barriers and improve the effectiveness of prehabilitation. Objective This study aimed to develop a mobile app as a tool for facilitating a multidisciplinary prehabilitation protocol involving blood flow restriction training and sport nutrition supplementation. Methods The app was developed using “Appy Pie,” a noncoding app development platform. The development process included three stages: (1) determination of principles and requirements of the app through prehabilitation research team meetings; (2) app prototype design using the Appy Pie platform; and (3) app evaluation by clinicians and exercise and fitness specialists, technical professionals from Appy Pie, and non–team-member users. Results We developed a prototype of the app with the core focus on a multidisciplinary prehabilitation program with accessory features to improve engagement and adherence to the mHealth intervention as well as research-focused features to evaluate the effects of the program on frailty status, health-related quality of life, and anxiety level among patients awaiting elective surgery. Evaluations by research members and random users (n=8) were consistently positive. Conclusions This mobile app has great potential for improving and evaluating the effectiveness of the multidisciplinary prehabilitation intervention in the format of mHealth in future.

Effects of Resistance Training Intervention along with Leucine-Enriched Whey Protein Supplementation on Sarcopenia and Frailty in Post-Hospitalized Older Adults: Preliminary Findings of a Randomized Controlled Trial

Resistance training and protein supplementation are expected to exert the greatest effect in counteracting muscle-wasting conditions. Myokines might play a key role, but this remains to be elucidated. The aim of this study (NCT03815201) was to examine the effects of a resistance training program with post-exercise leucine-enriched protein supplementation on sarcopenia and frailty status and on the plasma myokine concentrations of post-hospitalized older adults. A total of 41 participants were included in this 12-week resistance training intervention and randomized either to the placebo group or the protein group. Sarcopenia, frailty, body composition and blood-based myokines were measured at baseline and after 12 weeks. Both groups improved in terms of physical performance (p < 0.005) and frailty (p < 0.07) following the resistance training intervention, but without any difference between groups. Myokine concentrations did not change after the intervention in either group. Changes in myostatin concentrations were associated with greater improvements in appendicular skeletal muscle mass at the end of the intervention (p < 0.05). In conclusion, the implementation of resistance training programs after hospitalization in older adults should be prioritized to combat sarcopenia and frailty immediately. The results regarding myostatin should be taken as preliminary findings.