Baseline Frailty Research Articles

Plasma proteomic signature of risk and prognosis of frailty in the UK Biobank.

The availability of proteomics data in large, population-based cohort studies offers an unprecedented opportunity to understand the onset and progression of aging-related diseases and syndromes. We examined the proteomic signature of the onset of frailty and the progression to death among the prefrail and frail. A total of 2920 proteins were assayed using Olink among 43,895 participants (aged 39-70years) in the UK Biobank. Using multinomial logistic models, we identified 102 and 90 proteins cross-sectionally associated with baseline prefrailty and frailty (Bonferroni-corrected p-value < 0.05), respectively. Additionally, cox regression identified 87 and 48 proteins associated with death among initially prefrail (n = 16,661) and frail (n = 1647) individuals, respectively. Eight overlapping proteins were cross-sectionally associated with prefrailty and frailty at baseline and prospectively associated with death among prefrail and frail individuals. CD300E, GDF15, and PLAUR were the most significant proteins among these eight proteins. LASSO regression selected 73 and 23 proteins predicting death in prefrail and frail participants, respectively. Protein-based prediction models based on LASSO regression and the light gradient boosting machine classifier demonstrated satisfactory discrimination, calibration, and reclassification among the prefrail and frail. GDF15, WFDC2, and NEFL were the most important proteins predicting death among prefrail and frail individuals. Proteins associated with the onset and progression of prefrailty and frailty were enriched in pathways involving protein metabolism, cellular signaling in disease, apoptosis, and inflammation. Our research could uncover novel therapeutic targets for addressing the onset and progression of frailty, potentially informing the design of patient-centered treatment strategies and management plans.

Impact of Enhanced Recovery After Surgery (ERAS) Protocols on Outcomes Up to Two Years After Adult Structural Spine Disorder Surgery

Study Design. Retrospective cohort study of prospectively enrolled database Objective. We analyze the recovery pattern of Adult Structural Spine Disorder (ASD) patients who underwent corrective surgery with Enhanced Recovery After Surgery protocol (ERAS+), including physical and psychological prehabilitation components, compared to non-ERAS protocol (ERAS-) up to 2-years after surgery. Summary of Background Data. Spine surgery for ASD is often highly invasive, which can contribute to prolonged recovery. The trajectory of recovery may be accelerated by the application of enhanced recovery principles. Methods. Inclusion criteria were operative patients with ASD&gt;18yrs with complete baseline, 90 days perioperative, and 2-year postoperative data. We assessed differences in baseline demographics, surgical details, baseline Health-Related Quality of Life (HRQL), and surgical outcomes between ERAS+ and ERAS- patients. Outcomes included adverse events, reoperations, and radiographic parameters such as sacral slope (SS), pelvic tilt (PT), pelvic incidence-lumbar lordosis (PI-LL) mismatch, sagittal vertical axis (SVA), lumbar lordosis (LL), T2–T12 kyphosis, and maximum Cobb angle. Additionally, HRQL measures included the PCS, ODI, NDI, EQ-5D, SRS-22r total and domain scores, NRS-Back, and NRS-Leg. We used multivariable logistic regression and ANCOVA to adjust for confounding. Results. 471 patients with ASD met inclusion criteria, with 59 designated ERAS+. Those individuals ERAS+ were older (64.1±13.0 vs. 58.0±16.0;P=0.005), had a higher CCI, (2.4±1.8 vs. 1.4±1.6;P&lt;0.001), and exhibited a higher modified ASD frailty index (8.2±5.4 vs. 6.3±4.9;P=0.019). Adjusted analysis demonstrated the ERAS+ cohort demonstrated lower likelihood of overall reoperations (OR:0.3; 95%CI:0.13-0.89), and a lower likelihood of overall adverse events (OR:0.4;CI95%:0.19-0.93). ERAS+ was more likely to achieve the MCID in the SRS-22r Total scores at 6 months(OR:3.1;CI95%:1.2-8.4), self-image domain at 6 months (OR:9.0;CI95%:1.6-50.0), in the pain domain at 6 months (OR:3.5;CI95%:1.01-11.9) and 1 year postoperatively (OR:2.6;CI95%:1.03-6.7), and in the SF-36’s physical component summary scores (PCS) at 1 year (OR:2.1;CI95%:1.05-4.2). No other statistically significant differences in HRQL were observed at the remaining time points (P&gt;0.05). Conclusion. Our work is the first to evaluate HRQL metrics and complication over two-years following ASD correction with ERAS. Despite presenting with more severe baseline frailty and higher comorbidity profiles, patients with ASD who underwent corrective surgery with an ERAS protocol experienced fewer short-term adverse events, and improved HRQL. We believe ERAS following ASD surgery leads to faster functional recovery, reduced postoperative deconditioning, and improved quality of life.

Enhancing vascular surgery outcomes through geriatric co-management: a study on the impact of the POPS team.

Peripheral arterial disease (PAD) involves atherosclerotic stenosis and occlusion of lower leg arteries, leading to significant disability, high cardiovascular and cerebrovascular morbidity and mortality. Critical limb ischemia (CLI) is the most severe form of PAD. With the UK's aging population set to increase, the prevalence of PAD and the burden on vascular teams are expected to rise. This study evaluates the impact of regular input from the Proactive Care of Older People Undergoing Surgery (POPS) team on vascular surgery outcomes. This prospective cohort study examined the impact of Care of the Elderly (CoE) input on predefined parameters, focussing primarily on the length of stay (LoS) over 12 months. Data included baseline demographics, comorbidities, frailty scores (assessed using the Rockwood frailty score), LoS and referrals to medical specialties. A retrospective pilot study of 50 consecutive patients indicated a need for CoE input, showing higher local LoS compared with the national average. Patients in both pilot and project groups were matched for comorbidities, frailty scores and interventions. Despite higher mean age and a greater proportion of patients aged 75+ years in the project group, the study aimed to reduce LoS. Post-quality improvement project implementation, LoS beyond fit-for-discharge decreased from 11.7 days to 9 days in 6 months and to 6 days after 12 months. Referrals to medical specialties decreased from 77% to 40%, and new diagnoses on discharge increased from 28% to 37%. CoE team input in vascular surgery patient care significantly improved outcomes, reducing LoS and medical specialty referrals, demonstrating cost-effectiveness and suggesting a feasible multidisciplinary approach for other regions.

Clinical Impact of Baseline Frailty Status and Residual Mitral Regurgitation After Transcatheter Edge-to-Edge Repair: Insights From the OCEAN-Mitral Registry.

The Clinical Frailty Scale (CFS) is a useful frailty marker for predicting clinical outcomes in patients undergoing invasive therapy. However, the clinical impact of CFS after transcatheter edge-to-edge repair in patients with mitral regurgitation (MR) remains unclear. This study aimed to elucidate the association between the baseline frail status defined by the CFS and clinical outcomes with or without postprocedural MR ≥2+ (post-MR ≥2+) after transcatheter edge-to-edge repair. Based on a Japanese multicenter registry (OCEAN [Optimized Catheter Valvular Intervention]-Mitral), data from 2078 patients with MR who underwent transcatheter edge-to-edge repair were analyzed. The patients were classified into 5 groups: CFS 1 to 3, 4, 5, 6, and ≥7. The procedural and clinical outcomes and post-MR ≥2+ were compared among the groups. All-cause mortality for up to 2 years was explored using Cox proportional hazards regression analysis. Although the rates of acute procedural success and post-MR ≥2+ were similar, all-cause mortality at 2 years was significantly increased across the 5 CFS categories (15.5%, 23.8%, 27.7%, 34.6%, and 48.8%, respectively, P<0.001). The incremental CFS categories and post-MR ≥2+ were independent predictive risk factors of all-cause mortality (all P<0.05). Among the patients with 5 CFS categories, the incidence of all-cause mortality was higher in those with post-MR ≥2+ than in those without (all P<0.05). Although prognosis was poor in patients with higher CFS grade after transcatheter edge-to-edge repair, minimizing modifiable factors of residual MR is warranted to improve the clinical outcomes. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000027188; Unique identifier: UMIN000023653.

Frailty, age, and treatment effect of surgical coronary revascularization in ischemic cardiomyopathy: a post hoc analysis of the STICHES trial.

Frailty is common among older patients with heart failure (HF). The efficacy of coronary artery bypass grafting (CABG) on the risk of mortality amongfrailpatients with ischemic cardiomyopathy and HF is uncertain, and whether frailty burden modifies the treatment benefits of CABG among these patients is unknown. We performed a post hoc analysis of the STICHES trial, a randomized trial of CABG with medical therapy vs medical therapy alone among participants with ischemic cardiomyopathy with ejection fraction ≤ 35%. Baseline frailty was assessed through a Rockwood Frailty Index (FI), and based on FI cut-offs from prior HF studies, participants with FI ≥ 0.311 were classified as more frail, and those with FI < 0.311 were classified as less frail. A multivariable Cox proportional hazard model with multiplicative interaction terms was constructed to evaluate whether frailty status modified the treatment effect of CABG on mortalityin the overall trial cohort and among those < 60 vs ≥ 60 years of age. Of 1187 participants (12.4% female, 2.6% Black, median FI = 0.33 [IQR 0.27-0.39]), 678 were characterized as more frail. Frailty burden did not modify the efficacy of CABG on the risk of all-cause death in the overall cohort (Pint CABG × frailty = 0.2). In age stratified analysis,Baseline frailty status did not modify the treatment effect of CABG on the risk of all-cause mortality among younger (< 60years, Pint CABG × frailty = 0.2) as well as older participants (≥60years, Pint CABG × frailty = 0.6). In this post hoc analysis of the STICHES trial, baseline frailty status did not modify the efficacy of CABG in the overall cohort as well asamong younger or older participants. Frailty alone should not be used as a criterion to determine the utilization of CABG among patients with ischemic cardiomyopathy.

Quadriceps Muscle Layer Thickness and its association with frailty in critically ill patients: A prospective observational study

BackgroundFrailty is a well-recognized clinical entity known to influence the outcomes of critically ill patients. Muscle ultrasound, particularly Quadriceps Muscle Layer Thickness (QMLT), assesses muscle mass, which is a key component determining frailty. However, no studies have assessed the association between frailty and QMLT. This study aimed to determine the association between the QMLT and frailty in critically ill elderly patients. MethodIn this prospective, observational, single-center study conducted in an ICU in India, patients aged >65 years were enrolled. Baseline frailty was assessed using the Clinical Frailty Scale (CFS). Quadriceps muscle thickness was measured via axial cross-section ultrasound at admission. Patients were categorized as non-frail (CFS 1–4) and frail (CFS ≥5), and their characteristics were compared. Multivariate regression analysis was used to identify factors associated with frailty. Results120 patients were included. The median APACHE II and SOFA scores were 19 [IQR 14.25–23] and 4.5 [IQR 3–6], respectively. The median age was 75 years [IQR 70–82]; 62.5 % were male. The most common comorbidities were diabetes mellitus (60 %) and hypertension (59 %). 65 % were mechanically ventilated. 65 % of patients were frail. Frail patients had higher mortality (37.17 % vs. 16.66 %, p = 0.022). QMLT was lesser in frail than non-frail (1.77 cm vs 2.21 cm, p < 0.001). QMLT decreased with an increase in CFS (p < 0.001). Frail and non-frail patients were further divided into four groups based on the median QMLT (1.96 cm). Frail patients with QMLT below the median had a higher 28-day mortality than non-frail and frail patients with QMLT above the median (48.97 % vs. 16.12 % vs. 18.18 % vs. 17.24 %, p = 0.003). Frailty was independently associated with increasing age (OR, 1.14; 95 % CI: 1.055–1.231, p = 0.001), higher APACHE II score (OR, 1.078; 95 % CI: 1.009–1.151, p = 0.025), and lower QMLT (OR, 0.205; 95 % CI: 0.083–0.509, p = 0.001). ConclusionsWe found an independent association between Quadriceps Muscle Layer Thickness (QMLT) and frailty. QMLT decreased progressively with CFS scores. Frail patients with lower QMLT had increased 28-day mortality. These findings highlight the role of incorporating QMLT measurements along with CFS in frailty evaluations to improve decision-making in critically ill elderly patients.

The impact of frailty on chemotherapy intolerance in patients with cervical cancer : A longitudinal study

ObjectivesTo explore the potential effects of frailty on chemotherapy intolerance in patients with cervical cancer. MethodsA longitudinal study of patients with cervical cancer undergoing postoperative Adjuvant Chemotherapy(ACT)was conducted at a hospital in Northwest China from July 2020 to December 2021. Baseline frailty was assessed using the Tilburg Frailty Indicator. Chemotherapy intolerance was obtained from electronic medical records during the intervals between each postoperative chemotherapy session. We used Generalized Estimating Equations (GEE) to determine the predictors and cox regression analysis to analyze the impact of frailty on chemotherapy intolerance. ResultsA total of 259 patients with postoperative cervical cancer with a mean age of 52.5 years (SD=10.3) participated in this study. The incidence of chemotherapy intolerance in the frail group at T1, T2, T3 and T4 was 51.6%, 38.9%, 55.6% and 73.7%, respectively. The patients with frailty were more likely to have chemotherapy intolerance (OR=1.495, 95% CI: 1.074-2.080, P<0.05), prolonged hospitalizations (OR=1.577, 95% CI: 1.086-2.291, P<0.05) and unplanned readmissions (OR=2.304, 95% CI: 1.387-3.829, P<0.05) compared to the patients without frailty. Cox regression analysis showed that frailty increased the risk of chemotherapy intolerance by 1.681-fold (HR = 1.681, 95%CI 1.041∼2.713; P<0.05) and unplanned readmissions by 2.812-fold (HR = 2.812, 95%CI 1.521∼5.200; P<0.05). ConclusionsFrailty can lead to an increased risk of chemotherapy intolerance in patients with cervical cancer undergoing postoperative ACT, and patients with frailty are more likely to experience prolonged hospitalizations and unplanned readmissions.

UroARC: A Novel Surgical Risk Calculator for Older Adults Undergoing Suprapubic Tube Placement

ObjectivesTo develop a surgical risk calculator for older adults undergoing suprapubic tube (SPT) placement that specifically factors in frailty, a key predictor of surgical risk in this vulnerable and heterogenous population. MethodsMedicare MedPAR, Outpatient, and Carrier files for beneficiaries undergoing SPT placement between 2014-2016 were examined. The Claims-Based Frailty Index (CFI), a validated measure of frailty, was used to calculate baseline frailty for each beneficiary. Stepwise regression models were used for each variable within the CFI and Charlson Comorbidity Index to determine the variables most highly predictive of postoperative complications. The most highly predictive variables were then combined into parsimonious categories. To ensure the prognostic accuracy for each outcome, calibration curves and tests of model fit, including C-statistics, Brier scores, and Spiegelhalter p-values were calculated. ResultsA total of 26,999 beneficiaries were included. Among these, 39.1% were pre-frail, 36.8% were mildly frail, and 12.3% were moderately-to-severely frail. Thirteen prognostic variable categories were deemed highly predictive of postoperative complications of interest. All models demonstrated low Brier scores, indicating high model accuracy, and high C-statistic and Spiegelhalter p-values, consistent with excellent model discrimination and calibration, respectively. Excellent model fit was seen on calibration curves for each outcome. ConclusionsUroARC is a novel surgical tool for older adults undergoing SPT placement that specifically factors in frailty. This risk calculator has high accuracy, calibration, and discrimination, and serves as a valuable resource to patients and clinicians for those undergoing consideration for SPT placement.

Association between frailty and subsequent disability trajectories among older adults: a growth curve longitudinal analysis from the Survey of Health, Ageing and Retirement in Europe (2004-19).

Frailty is associated with adverse health outcomes in ageing populations, yet its long-term effect on the development of disability is not well defined. The study examines to what extent frailty affects disability trajectories over 15 years in older adults aged 50+. Using seven waves of data from the Survey of Health, Ageing and Retirement in Europe (SHARE), the study estimates the effect of baseline frailty on subsequent disability trajectories by multilevel growth curve models. The sample included 94360 individuals from 28 European countries. Baseline frailty was assessed at baseline, using the sex-specific SHARE-Frailty-Instrument (SHARE-FI), including weight loss, exhaustion, muscle weakness, slowness, and low physical activity. Disability outcomes were the sum score of limitations in activities of daily living (ADL) and Instrumental ADL (IADL). Analyses were stratified by sex. Over 15 years, baseline frailty score was positively associated with disability trajectories in men [βADL = 0.074, 95% confidence interval (CI) = 0.064; P = .083; βIADL = 0.094, 95% CI = 0.080; P = 0.107] and women (βADL = 0.097, 95% CI = 0.089; P = .105; βIADL = 0.108, 95% CI = 0.097; P = .118). Frail participants showed higher ADL and IADL disability levels, independent of baseline disability, compared with prefrail and robust participants across all age groups. Overall, participants displayed higher levels of IADL disability than ADL disability. Study findings indicate the importance of early frailty assessment using the SHARE-FI in individuals 50 and older as it provides valuable insight into future disability outcomes.

Cross‐Sectional and Prospective Associations between Parkinsonism and Parkinson's Disease with Frailty in Latin America

AbstractBackgroundLittle is known about the relationship between parkinsonism or Parkinson's disease (PD) and frailty in Latin America.ObjectiveThe study aimed to determine the cross‐sectional and prospective associations between parkinsonism and PD with frailty in a large multi‐country cohort in Latin America. Frailty was assessed using three different models to explore which definitions are more appropriate to screen for frailty in a PD population.Methods12,865 older adults (aged ≥65 years) from the 10/66 population‐based cohort study in six Latin American countries were analyzed. Logistic regression models assessed the cross‐sectional association between parkinsonism/PD with baseline frailty. Individual country analyses were combined via fixed‐effect meta‐analysis. In non‐frail participants who were followed up for 4 years, Cox proportional hazards regression models assessed the prospective association between parkinsonism/PD with incident frailty accounting for competing risk of mortality.ResultsAt baseline, the prevalence of parkinsonism and PD was 7% and 2%, respectively, and the prevalence of frailty varied across the three models with rates of 18% for frailty phenotype, 20% for frailty index and 30% for multidimensional frailty model. PD was associated with baseline and incident frailty after accounting for age, sex, and education: odds ratios and 95% confidence intervals (95% CI) for frailty were 2.49 (95% CIs 1.87–3.31), 2.42 (95% CIs 1.80–3.25), and 1.57 (95% CIs 1.16–2.21), and cause‐specific hazard ratios were 1.66 (95% CIs 1.07–2.56), 1.78 (95% CIs 1.05–3.03), and 1.58 (95% CIs 0.91–2.74). Similar results were found for parkinsonism.ConclusionParkinsonism and PD were cross‐sectionally and prospectively associated with frailty in Latin America. Routine screening for frailty in PD patients may aid earlier detection of those at greater risk of adverse outcomes.

The effects of age and frailty on the risks of end-stage renal disease, death, and severe infection in older adults with antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study

Frailty, a measure of biological age, might predict poor outcomes in older adults better than chronological age. We aimed to compare the effect of age and frailty on end-stage renal disease, death, and severe infection within 2 years of diagnosis in older adults with incident antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This retrospective cohort study included individuals aged 65 years or older from the Mass General Brigham ANCA-associated vasculitis cohort in the USA who were treated between Jan 1, 2002, and Dec 31, 2019. Individuals with a diagnosis of eosinophilic granulomatosis with polyangiitis were excluded from the analysis. Baseline frailty was measured with a claims-based frailty index using data collected in the year before the date of treatment initiation in individuals with at least one health-care encounter before baseline; individuals who did not have an encounter within the 12 months before baseline were classified as pre-frail. Incidence rates of end-stage renal disease or death and severe infections (ie, infections leading to hospital admission or death) at 2 years were estimated, and multivariable analyses were performed to compare the association of age and frailty with these outcomes. Cumulative incidence rates and an additive interaction analysis were used to assess the interaction of age and frailty groupings. Of the 234 individuals included, 136 (58%) were women, 98 (42%) were men, 198 (85%) were White, and 198 (85%) were positive for myeloperoxidase-specific ANCA. Frailty was present in 25 (22%) of 116 individuals aged 65-74 years and 44 (37%) of 118 aged 75 years or older. In the multivariable analysis, an age of 75 years or older was associated with an increased risk of end-stage renal disease or death (hazard ratio [HR] 4·50 [95% CI 1·83-11·09]), however, frailty was not (1·08 [0·50-2·36]). Both an age of 75 years or older (HR 2·52 [95% CI 1·26-5·04]) and frailty (8·46 [3·95-18·14]) were independent risk factors for severe infections. The effect of frailty on the incidence of end-stage renal disease or death was greater in individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 7·5 cases vs 2·0 cases per 100 person-years) than in those aged 75 years or older (13·5 cases vs 16·0 cases per 100 person-years). The effect of frailty on the incidence of serious infections varied by age, with large differences observed among both individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 38·9 cases vs 0·8 cases per 100 person-years) and individuals aged 75 years or older (61·9 cases vs 12·3 cases per 100 person-years). Despite the observed differences between the age groups, the additive interaction terms were not statistically significant for either frailty and end-stage renal disease or death (p for interaction=0·276) or frailty and serious infections (p for interaction=0·650). Adults with ANCA-associated vasculitis aged 75 years or older had a higher incidence of end-stage renal disease, death, and severe infections within 2 years of diagnosis than adults aged 65-74 years. Frailty, an approximation of biological age, was a risk factor for severe infection. Assessment beyond chronological age could better inform management decisions in older adults with ANCA-associated vasculitis. National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Association between polypharmacy and 2-year outcomes among Chinese older inpatients: a multi-center cohort study

BackgroundThe escalating global prevalence of polypharmacy presents a growing challenge to public health. In light of this issue, the primary objective of our study was to investigate the status of polypharmacy and its association with clinical outcomes in a large sample of hospitalized older patients aged 65 years and over.MethodsA two-year prospective cohort study was carried out at six tertiary-level hospitals in China. Polypharmacy was defined as the prescription of 5 or more different medications daily, including over-the-counter and non-prescription medications. Baseline polypharmacy, multimorbidity, and other variables were collected when at admission, and 2-year outcomes were recorded by telephone follow-up. We used multivariate logistic regression analysis to examine the associations between polypharmacy and 2-year outcomes.ResultsThe overall response rate was 87.2% and 8713 participants were included in the final analysis. The mean age was 72.40 years (SD = 5.72), and women accounted for 42.2%. The prevalence of polypharmacy among older Chinese inpatients is 23.6%. After adjusting for age, sex, education, marriage status, body mass index, baseline frailty, handgrip strength, cognitive impairment, and the Charlson comorbidity index, polypharmacy is significantly associated with frailty aggravation (OR 1.432, 95% CI 1.258–1.631) and mortality (OR 1.365, 95% CI 1.174–1.592), while inversely associated with readmission (OR 0.870, 95% CI 0.764–0.989). Polypharmacy was associated with a 35.6% increase in the risk of falls (1.356, 95%CI 1.064–1.716). This association weakened after adjustment for multimorbidity to 27.3% (OR 1.273, 95%CI 0.992–1.622).ConclusionsPolypharmacy was prevalent among older inpatients and was a risk factor for 2-year frailty aggravation and mortality. These results highlight the importance of optimizing medication use in older adults to minimize the risks associated with polypharmacy. Further research and implementing strategies are warranted to enhance the quality of care and safety for older individuals exposed to polypharmacy.Trial registrationChinese Clinical Trial Registry, ChiCTR1800017682, registered 09/08/2018.

UK national observational cohort study investigating Tolerance of Anti-cancer Systemic Therapy in the Elderly: the TOASTIE study

ObjectiveThe Cancer and Aging Research Group (CARG) score was developed to predict severe chemotherapy-induced toxicity risk in older adults; validation study results have varied. The Tolerance of Anti-cancer Systemic Therapy...

Predictive role of depressive symptoms on frailty and its components in Chinese middle-aged and older adults: a longitudinal analysis

BackgroundTo investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults.MethodThe China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression.ResultsAt baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665–7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324–3.631) and the long term (OR = 1.926, 95%CI 1.021–3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250–3.166), slowness (OR = 1.395, 95%CI 1.044–1.865), and exhaustion (OR = 2.827, 95%CI 2.150–3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004–4.109) onset during the long-term.ConclusionAmong middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.

Sex differences in the impact of frailty on patients with heart failure: A retrospective cohort study.

Limited literature shows the existence of sex differences in the long-term prognosis of heart failure (HF) patients with frailty. In this study, whether sex differences exist in the impact of frailty on death from cardiovascular causes in patients with HF was investigated by conducting a retrospective cohort study. Data from the National Health and Nutrition Examination Survey (NHANES) study (2009-2018) were used to conduct a retrospective cohort study of 958 participants with HF. Patients were grouped based on sex and frailty index (FI). The relationship between death from cardiovascular causes and baseline frailty was assessed by Cox proportional hazard analysis and the Kaplan-Meier (K-M) plot. The study population had an age of 67.3±12.3. Among them, around 54.5% were male. A median follow-up of 3.6years was performed. After that, females who died from cardiovascular causes exhibited higher baseline FI values, while males did not show this trend (P<0.05; P=0.1253). Cox regression analysis demonstrated a significant association between FI and cardiovascular mortality in females (most frail: hazard ratio (HR)=3.65, 95% confidence interval (CI): 1.07~12.39, P<0.05; per 1-unit increase in FI: HR=1.78, 95% CI: 1.33~2.39, P<0.001). A dose-response association between FI and cardiovascular mortality was presented by restricted cubic splines. Frailty is related to an increased risk of cardiovascular mortality in HF patients, particularly female patients.

2203 Avoiding therapeutic nihilism in critically ill older adults: a single Centre approach to enhanced care in patients with frailty

Abstract Introduction Enhanced care units (ECU) are a novel concept, targeting the gap between ward-level and critical care. They care for patients requiring intensive medical or nursing care, who may not require, desire, or be suitable for, escalation above ward care (Society of Acute Medicine and Intensive Care Society, 2022). The ECU at Barnet Hospital opened in March 2022, and, because of the local population demographic, admits a high number of older patients living with frailty. We aimed to assess the performance of the ECU for this subset of patients. Methods A retrospective audit of electronic records of 75 randomly selected patients admitted to ECU between March and August 2023. Data were gathered on Clinical Frailty Score (CFS) at baseline, comorbidity, escalation status, APACHE II illness severity score, and outcome measures. Results The majority of patients in the sample, 52 of 75 (69.3%), were over 65 years of age with an average of 69.1 years. Baseline frailty score was high, with a modal CFS of 6. Of these patients, 32 (61.5%) had a DNACPR, and 17 (32.7%) had treatment ceiling at ECU level. Illness severity was similar across CFS groups, with a mean APACHE II score of 15.2 (representing a 25% mortality risk). Overall mortality in the over 65 s was 23.1% (12/52), without significant change when stratified by CFS. Mortality in the under 65 s was 8.7% (2/23). Conclusions Acutely unwell patients with frailty may benefit from ECU level care. In our centre, we found no significant increase in mortality linked to a higher frailty score. We suggest that this may represent good case selection by clinicians experienced in working with frailty: admitting patients with more reversibility and targeting therapies towards reversible causes. Limitations remain, especially in assessing illness severity, as the assessment tools are not targeted to this cohort.

Revisiting unstable disability and the fluctuations of frailty: a measurement burst approach.

It has been hypothesised that frailty is the root cause of clinically observed but rarely systematically measured unstable disability among older adults. In this study, we measure the extent of short-term disability fluctuations and estimate their association with frailty using intensive longitudinal data. Repeated measurements of disability were collected under a measurement burst design in the FRequent health Assessment In Later life (FRAIL70+) study. A total of 426 community-dwelling older adults (70+) in Austria were interviewed about difficulties with basic, instrumental and mobility-related activities of daily living biweekly up to a total of 14 times in two measurement bursts (2891 and 2192 observations). Baseline frailty was assessed with both physical frailty (FP) and the frailty index (FI). Disability fluctuations were measured with the intra-individual interquartile range (iIQR) and estimated with a two-step generalised mixed regression procedure. Fewer participants were frail at baseline according to FP (11%) than FI (32%). Frail study participants reported not only more severe disability but also had more short-term disability fluctuations (iIQR = 1.0-1.5) compared with their robust counterparts (iIQR = 0). Regression models indicated that baseline frailty was associated with 2-3 times larger short-term disability fluctuations, which were also more prevalent among women, and increased with age and disability severity. Compared with those who were robust, frail older adults were characterised by not only more severe but also more unstable disability. Short-term disability fluctuations are closely tied to disability severity. Future studies should assess both stressors that may cause disability fluctuations among frail older adults as well as their potential consequences to inform frailty-centred care.

Progression of frailty and cardiovascular outcomes among Medicare beneficiaries.

Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain. To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee-for-Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims-based frailty index (CFI) over a 5-year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes. There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non-White race. In total, 60% had frailty progression and 40% frailty regression over median follow-up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31-1.31), all-cause mortality (HR 1.34, 95% CI 1.34-1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07-1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29-1.30), ischemic stroke (HR 1.14, 95% CI 1.14-1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001). In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression.

Retrospective, propensity score--matched study examining the relationship between frailty and Clostridioides difficile infection in a national cohort of US veterans

Frailty is often more predictive of disease and mortality compared with chronological age. This study determined the impact of frailty on Clostridioides difficile infection (CDI) risk and outcomes in a national veteran population. This was a retrospective cohort study of CDI and control veteran inpatients and outpatients from fiscal year 2003 to 2018. Baseline frailty was presented as the Veterans Affairs (VA) Frailty Index. Propensity score--matched analyses were conducted to compare CDI risk, CDI health outcomes, and 1-year new-onset frailty-associated conditions. A total of 11,451 CDI and 11,451 matched control patients were included. Baseline frailty conditions were more common among CDI patients, especially involuntary weight loss (6.0% vs3.4%, P<.001) and anemia (24.6% vs 18.7%, P<.001). VA Frailty Index was significantly higher for CDI patients (0.13 vs0.11, P=.019). Frail CDI patients were more likely to experience 30-day mortality (11.3% vs1.1%, P<.001) and 60-day CDI recurrence (20.4% vs16.3%, P<.001) compared with non-/prefrail CDI patients. At 1year, CDI patients were significantly more likely to be categorized as frail (19.6% vs17.0%, P<.001). This study demonstrated the potential association between frailty and CDI risk and health outcomes, as well as new-onset frailty diagnoses in patients who develop CDI.

Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases

Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by physical frailty and the frailty index, categorizing participants as non-frail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: hazard ratio [HR] 1.66, 95% CI 1.40-1.97; frailty index: HR 2.01, 95% CI 1.67-2.42) and frailty (physical frailty: HR 3.32, 95% CI 2.54-4.34; frailty index: HR 4.54, 95% CI 3.65-5.66) than in those with non-frailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as MRI-derived liver proton density fat fraction >5%, than the non-frail group (physical frailty: odds ratio 1.64, 95% CI 1.32-2.04; frailty index: odds ratio 1.48, 95% CI 1.30-1.68). Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. While frailty is common and associated with a poor prognosis in people with MASLD (metabolic dysfunction-associated steatotic liver disease) and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.