Assessing the relationship between multimorbidity, NCD configurations, frailty phenotypes, and mortality risk in older adults.

BACKGROUND: Older adults are increasingly susceptible to prolonged illness, multiple chronic diseases, and disabilities, which can lead to the coexistence of multimorbidity and frailty. Multimorbidity may result in various noncommunicable disease (NCD) patterns or configurations that could be associated with frailty and death. Mortality risk may vary depending on the presence of specific chronic diseases configurations or frailty. METHODS: The aim was to examine the impact of NCD configurations on mortality risk among older adults with distinct frailty phenotypes. The population was analyzed from the Costa Rican Longevity and Healthy Aging Study Cohort (CRELES). A total of 2,662 adults aged 60 or older were included and followed for 5 years. Exploratory factor analysis and various clustering techniques were utilized to identify NCD configurations. The frequency of NCD accumulation was also assessed for a multimorbidity definition. Frailty phenotypes were set according to Fried et al. criteria. Kaplan‒Meier survival analyses, mortality rates, and Cox proportional hazards models were estimated. RESULTS: Four different types of patterns were identified: 'Neuro-psychiatric', 'Metabolic', 'Cardiovascular', and 'Mixt' configurations. These configurations showed a higher mortality risk than the mere accumulation of NCDs [Cardiovascular HR:1.65 (1.07-2.57); 'Mixt' HR:1.49 (1.00-2.22); ≥3 NCDs HR:1.31 (1.09-1.58)]. Frailty exhibited a high and constant mortality risk, irrespective of the presence of any NCD configuration or multimorbidity definition. However, HRs decreased and lost statistical significance when phenotypes were considered in the Cox models [frailty + 'Cardiovascular' HR:1.56 (1.00-2.42); frailty + 'Mixt':1.42 (0.95-2.11); and frailty + ≥ 3 NCDs HR:1.23 (1.02-1.49)]. CONCLUSIONS: Frailty accompanying multimorbidity emerges as a more crucial indicator of mortality risk than multimorbidity alone. Therefore, studying NCD configurations is worthwhile as they may offer improved risk profiles for mortality as alternatives to straightforward counts.

Improving morbidity and mortality in hip fragility fractures.

PURPOSE OF REVIEW: Hip fragility fractures (HFF) carry high morbidity and mortality for patients and will increase in frequency and in proportion to the average patient age. Provision of effective, timely care for these patients can decrease their morbidity and mortality and reduce the large burden they place on the healthcare system. RECENT FINDINGS: There are associative relationships between prefracture frailty, postoperative delirium and increased morbidity and mortality. The use of a multidisciplinary approach to HFF care has shown improved outcomes in care with focus on modifiable factors including admission to specialty care floor, use of peripheral nerve blocks preoperatively and Anesthesia and Physical Therapy involvement in the care team. Peripheral nerve blocks including pericapsular nerve group (PENG) blocks have shown benefit in lowering morbidity and mortality. SUMMARY: HFF are associated with >40% chance of continued pain and inability to return to prefracture functional status at 1 year as well as >30% mortality at 2 years. In this opinion piece, we will discuss how a multidisciplinary approach that includes Anesthesia as well as utilization of peripheral nerve blocks can help to lessen postoperative issues and improve recovery.

Impact of combinations of subscale declines in higher-level functional capacity on 8-year all-cause mortality among community-dwelling older Japanese adults.

BACKGROUND: The frequency of combined declines in domains of multi-faceted frailty and their impact on adverse health outcomes have not been adequately investigated. We aimed to examine the association between combined subscale declines in higher-level functional capacity and 8-year all-cause mortality among community-dwelling older Japanese individuals and the impact of multi-faceted frailty on mortality. MATERIALS AND METHODS: We administered a questionnaire to 7015 community-dwelling older adults aged 65-85 years. The higher-level functional capacity of the 3381 respondents was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Subscale decline was defined as (1) none, (2) only social role (SR), (3) only intellectual activity (IA), (4) SR and IA, (5) only instrumental activities of daily living (IADL), (6) IADL and SR, (7) IADL and IA, and (8) all. Associations between combined subscale declines and mortality were examined using adjusted Cox proportional hazards models. Follow-up was conducted from October 1, 2012, to death or November 1, 2020. RESULTS: The mortality rate was 16.7/1000 person-years. Moreover, 44% of respondents had declined SR, and half of them had multiple declines. Compared with no decline, SR (adjusted hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.14-1.93), SR and IA (HR: 1.59, 95% CI: 1.16-2.17), IADL and SR (HR: 1.97, 95% CI: 1.31-2.99), and all-domain (HR: 2.72, 95% CI: 1.98-3.74) declines were significantly associated with higher mortality risks. CONCLUSIONS: Overlapping SR and IADL declines increased mortality risk, suggesting the importance of measuring social frailty and overlapping physical and social frailty.

High Fragmented Physical Activity as an Early Risk Indicator of Frailty and Mortality in Adults Aged 50 Years and Over.

INTRODUCTION: This study aimed to explore the associations of activity fragmentation with frailty status and all-cause mortality in a representative US sample of people 50 years and over. METHODS: This prospective study used data from the 2003-2006 waves of the National Health and Nutrition Examination Survey (NHANES). Participants 50 years or over were included in the study (n = 2,586). Frailty status was assessed using a valid modification of the Fried criteria. Linked data from the National Death Index registry were used to ascertain mortality. Physical activity fragmentation was measured by accelerometry. To calculate activity fragmentation, an active-to-sedentary transition probability was calculated as the number of physical activity bouts divided by the total sum of minutes spent in physical activity. Age, gender, ethnicity, education, mobility issues, drinking status, smoking status, BMI, and self-reported chronic diseases were reported in the NHANES study. RESULTS: An increment of 1 SD in activity fragmentation was associated with an increased likelihood of frailty (odds ratio [95% confidence interval] = 1.36 [1.13-1.664]). Compared with participants in the high activity fragmentation/low physical activity category, participants in the low activity fragmentation/low physical activity and low activity fragmentation/high physical activity categories were associated with a lower likelihood of frailty. We found a nonlinear association between activity fragmentation and all-cause mortality. Compared with participants in the high activity fragmentation/low physical activity category, participants in the low activity fragmentation/low physical activity, low activity fragmentation/high physical activity, and high activity fragmentation/high physical activity categories were associated with a lower mortality risk. Participants with a low fragmented activity pattern may also overcome some of the detrimental effects associated with sedentary behavior. CONCLUSIONS: Our results suggest that a high fragmented physical activity pattern is associated with frailty and risk of mortality in adults and older adults. This association was independent of total volume of physical activity and time spent sedentary.

Population-Based Estimates of 1-Year Mortality After Major Surgery Among Community-Living Older US Adults.

Importance: Despite their importance to guiding public health decision-making and policies and to establishing programs aimed at improving surgical care, contemporary nationally representative mortality data for geriatric surgery are lacking. Objective: To calculate population-based estimates of mortality after major surgery in community-living older US adults and to determine how these estimates differ according to key demographic, surgical, and geriatric characteristics. Design, Setting, and Participants: Prospective longitudinal cohort study with 1 year of follow-up in the continental US from 2011 to 2018. Participants included 5590 community-living fee-for-service Medicare beneficiaries, aged 65 years or older, from the National Health and Aging Trends Study (NHATS). Data analysis was conducted from February 22, 2021, to March 16, 2022. Main Outcomes and Measures: Major surgeries and mortality over 1 year were identified through linkages with data from the Centers for Medicare & Medicaid Services. Data on frailty and dementia were obtained from the annual NHATS assessments. Results: From 2011 to 2017, of the 1193 major surgeries (from 992 community-living participants), the mean (SD) age was 79.2 (7.1) years; 665 were women (55.7%), and 30 were Hispanic (2.5%), 198 non-Hispanic Black (16.6%), and 915 non-Hispanic White (76.7%). Over the 1-year follow-up period, there were 206 deaths representing 872 096 survey-weighted deaths and 13.4% (95% CI, 10.9%-15.9%) mortality. Mortality rates were 7.4% (95% CI, 4.9%-9.9%) for elective surgeries and 22.3% (95% CI, 17.4%-27.1%) for nonelective surgeries. For geriatric subgroups, 1-year mortality was 6.0% (95% CI, 2.6%-9.4%) for persons who were nonfrail, 27.8% (95% CI, 21.2%-34.3%) for those who were frail, 11.6% (95% CI, 8.8%-14.4%) for persons without dementia, and 32.7% (95% CI, 24.3%-41.0%) for those with probable dementia. The age- and sex-adjusted hazard ratios for 1-year mortality were 4.41 (95% CI, 2.53-7.69) for frailty with a reduction in restricted mean survival time of 48.8 days and 2.18 (95% CI, 1.40-3.40) for probable dementia with a reduction in restricted mean survival time of 44.9 days. Conclusions and Relevance: In this study, the population-based estimate of 1-year mortality after major surgery among community-living older adults in the US was 13.4% but was 3-fold higher for nonelective than elective procedures. Mortality was considerably elevated among older persons who were frail or who had probable dementia, highlighting the potential prognostic value of geriatric conditions after major surgery.

Capacidad predictiva de mortalidad del índice Frágil-VIG (IF-VIG) en pacientes ancianos con fractura de fémur / Predictive capacity for mortality of the Frail-VIG index (IF-VIG) in old patients with hip fracture

Introducción: La fragilidad y la fractura de fémur están relacionadas y comportan un mayor riesgo de deterioro funcional y de mortalidad. El objetivo de este estudio es analizar si el Frágil-VIG [IF-VIG] (índice de fragilidad validado en población geriátrica) mantiene su capacidad predictiva de mortalidad en pacientes ancianos con fractura de fémur.Métodos: Estudio observacional, de cohortes, longitudinal y ambispectivo en pacientes ingresados en una unidad de geriatría de agudos con fractura de fémur. Se dividieron los pacientes según el grado de fragilidad en tres grupos según el IF-VIG: no fragilidad/fragilidad inicial (≤0,35), fragilidad intermedia (0,36-0,50) y fragilidad avanzada (>0,50). El tiempo de seguimiento fue de 24meses. Se compararon los tres grupos mediante curvas de supervivencia y se analizaron las curvas ROC para valorar la capacidad pronóstica del IF-VIG.Resultados: Se incluyeron 103 pacientes, de los que el 73,8% eran mujeres, con edad media de 87años. No hubo diferencias entre grupos en relación con el tipo de fractura, el tipo de cirugía, el tiempo de espera hasta la cirugía y la indicación de descarga. La mortalidad intrahospitalaria global fue del 7,76% y significativamente superior en el grupo con fragilidad avanzada (23,3%). También encontramos diferencias significativas en mortalidad a los 24meses de seguimiento según el IF-VIG. El área bajo la curva ROC a los 3, 6, 12 y 24meses fue de 0,90 (0,83-0,97), de 0,90 (0,82-0,97), de 0,91 (0,86-0,97) y de 0,88 (0,81-0,94), respectivamente.Conclusión: El IF-VIG parece tener una buena capacidad predictiva de mortalidad en pacientes ancianos con fractura de fémur. (AU)

Introduction: Frailty and hip fracture are closely related and are associated with high risk of functional decline and mortality. The objective of this study is to analyze whether the Frail-VIG index [IF-VIG] (fragility index validated in the geriatric population) maintains its predictive capacity for mortality in old patients with hip fracture.Methods: Observational, cohort, longitudinal and ambispective study on patients admitted to an acute geriatric unit with a hip fracture. Patients were classified according to their degree of frailty into three groups by the IF-VIG: no frailty/initial frailty (≤0.35), moderate frailty (0.36-0.50) and advanced frailty (>0.50). The follow-up period was 24months. The three groups were compared using survival curves and ROC curves were analyzed to assess the prognostic capacity of IF-VIG.Results: A total of 103 patients were included; 73.8% were women, with a mean age of 87years. There were no differences between groups in relation to the type of fracture, the kind of surgery, the waiting time until surgery and the mobilization time. Overall, in-hospital mortality was 7.76%, significantly higher in the advanced frailty group (23.3%). We also found significant differences in mortality at 24months of follow-up according to the IF-VIG. The under the ROC curve area at 3, 6, 12 and 24months was 0.90 (0.83-0.97), 0.90 (0.82-0.97), 0.91 (0.86-0.97) and 0.88 (0.81-0.94), respectively.Conclusion: The IF-VIG appears to be a good tool in predicting mortality in old patients with hip fracture. (AU)

Frailty in Older Patients Undergoing Hemodialysis and Its Association with All-Cause Mortality: A Prospective Cohort Study.

Purpose: The study aimed to determine the prevalence and risk factors of frailty among a Chinese cohort of hemodialysis patients and to assess the degree to which frailty was associated with all-cause mortality. Participants and Methods: We enrolled a group of older adults (≥60 years old) in a prospective cohort study of cognitive impairment in Chinese patients undergoing hemodialysis (registered in Clinical Trials.gov, ID: NCT03251573). We assessed the prevalence of frailty using Fried's definition in the Cardiovascular Health Study, then we evaluated the associated risk factors of frailty using multivariate logistic regression analysis. Finally, we assessed the association of frailty and all-cause mortality with multivariable Cox proportional hazard regression analyses. Results: The prevalence of frailty in these 204 enrolled hemodialysis patients was 72.1%. Patients with frailty were more inclined to have composite abnormal components that included poor physical functioning, exhaustion, low physical activity, and undernutrition. Multivariable logistic regression analysis suggested that increased age, female gender, history of diabetes, longer dialysis vintage, lower Kt/V, lower serum level of albumin concentrations, and increased serum iPTH concentrations were independently associated with frailty. Cox regression analysis indicated that frailty as a dichotomous construct was strongly associated with an increased risk of mortality (HR 6.092, 95% CI 1.886-19.677, P = 0.003) in unadjusted analyses. After adjusting (Model I = no adjusted; II = adjusted for age, gender; III = adjusted for age, gender, history of diabetes; IV = adjusted for all covariates associated at the p ≤ 0.10 level with death in unadjusted analyses, including age, history of diabetes, MoCA<26, single-pool Kt/V, and the levels of albumin and iPTH), the association was slightly affected but observed consistent as before. Conclusion: Frailty is extremely common and is associated with serious clinical outcomes among older hemodialysis patients. Based on those clinical features of frailty, future studies should focus on exploring effective interventions aimed to prevent or attenuate frailty in the older hemodialysis population.

Clinical Significance of Frailty on Treatment Outcome in Nongeriatric Patients With Head and Neck Cancer and Esophageal Cancer Undergoing Curative-Intent Concurrent Chemoradiotherapy.

BACKGROUND: Whether the prevalence of frailty and its clinical significance are relevant to treatment outcomes in younger (aged < 65 years) cancer patients remains uncertain. This study aimed to evaluate the impact of frailty on treatment outcomes in younger cancer patients with head and neck and esophageal malignancy. MATERIAL AND METHODS: This multicenter prospective study recruited 502 patients with locally advanced head and neck and esophageal cancer during 2016-2017 in Taiwan, aged 20-64 years who received curative-intent concurrent chemoradiotherapy (CCRT) as first-line antitumor treatment. Baseline frailty assessment using geriatric assessment (GA) was performed for each patient within 7 days before CCRT initiation. RESULTS: Frailty was observed in 169 (33.7%) of 502 middle-aged patients. Frail patients had significantly higher incidences of chemotherapy incompletion (16.6% versus 3.3%, P < .001) and radiotherapy incompletion (16.6% versus 3.6%, P < .001) than fit patients. During CCRT, frail patients had a significantly higher percentage of hospitalizations (42.0% versus 24.6%, P < .001) and a trend toward a higher percentage of emergency room visits (37.9% versus 30.0%, P = .08) than fit patients. Frail patients more likely had a significantly higher incidence of grade ≥ 3 adverse events than fit patients during CCRT. The 1-year survival rate was 68.7% and 85.2% (hazard ratio 2.56, 95% confidence interval 1.80-3.63, P < .001) for frail and fit patients, respectively. CONCLUSIONS: This study demonstrated the significance of pretreatment frailty on treatment tolerance, treatment-related toxicity, and survival outcome in younger patients with head and neck and esophageal cancer undergoing CCRT. While GA is commonly targeted toward the older population, frailty assessment by GA may also be utilized in younger patients for decision-making guidance and prognosis prediction.

Systolic Blood Pressure and Mortality in Community-Dwelling Older Adults: Frailty as an Effect Modifier.

Current evidence is insufficient to support different hypertension treatment targets in older adults. We evaluated whether frailty modifies the association between systolic blood pressure (SBP) and 8-year all-cause mortality in community-dwelling older adults. Longitudinal data from the ActiFE Ulm study (Activity and Function in the Elderly in Ulm; Germany) was collected. The association between SBP and mortality was analyzed using Cox proportional hazards models adjusted for age, sex, education, smoking, alcohol consumption, sleep disturbance, diastolic blood pressure, and antihypertensive medications, evaluating the presence of effect modification by frailty according to a frailty index based on the accumulation of deficits. Among 1170 participants (median age 73.9 years, 41.6% women), the prevalence of history of hypertension was 53.8% (median SBP, 144.0 mm Hg [interquartile range, 135.0-149.5], median diastolic blood pressure 78.0 mm Hg [interquartile range, 71.0-86.5]). The median follow-up time was 8.1 years, detecting 268 deaths. We identified 251 (21.5%, 114 deaths) frail participants (frailty index ≥0.2). Effect modification by frailty was detected. Among non-frail a J-shaped association was found with hazard ratio, 4.01 (95% CI, 1.13-14.28) for SBP<110 mm Hg, hazard ratio, 0.92 (95% CI, 0.53-1.59) for SBP 140-150 mm Hg, and hazard ratio, 1.98 (95% CI, 0.75-5.27) for SBP≥160 mm Hg. For frail older adults, a tendency toward lower risk among those with SBP≥130 mm Hg was observed. Our results suggest the presence of effect modification by frailty indicating a possible protective effect for elevated SBP in frail older adults with respect to all-cause mortality even after adjusting for diastolic blood pressure and antihypertensive treatment.

The impact of age on quality of life and frailty outcomes after parathyroidectomy in patients with primary hyperparathyroidism.

OBJECTIVE: Parathyroidectomy (PTx) improves quality of life (QoL) in patients with primary hyperparathyroidism (PHPT). Whether this effect is modified according to the patients' age is unknown. The aim of this study was to evaluate the impact of age on the effect of PTx on QoL and frailty in patients with PHPT, six months post-PTx. METHODS: This was a prospective cohort study, including patients with PHPT, admitted from January 2016 to December 2019, divided into two categories: younger (≤ 65 years old) and older (> 65 years old). QoL was assessed with the Pasieka questionnaire (PAS-Q) two days pre- and six months post-operatively. Frailty was also assessed at the same time intervals, with the Frailty Index (FI). RESULTS: One hundred and thirty-four patients (younger group: 96 patients, mean age 50.4 ± 9.8 years; older group: 38 patients, mean age 72.1 ± 4.9 years) were included. PTx resulted in a significant reduction in PAS-Q score in both groups. Notably, a greater reduction in "mood swings", "irritability", "itchy skin" and "feeling thirsty" PAS-Q domains was observed in the younger group. In contrast, a greater decrease in "bone pain", "tiredness", "weakness", "joint pain", "getting off chair" and "headaches" items was observed in the older group. Moreover, PTx led to a decrease in FI only in this group. CONCLUSIONS: PTx leads to an improvement in QoL both in older (> 65 years) and younger (≤ 65 years) patients with PHPT, attributed to a differential effect on PAS-Q items. Frailty improves only in the older group.

Identification of Sarcopenia in Elderly Trauma Patients: The Value of Clinical Competency and Experience.

INTRODUCTION: There is currently no standard definition of sarcopenia, which has often been associated with frailty. A commonly cited surrogate measure of sarcopenia is psoas muscle size. The purpose of this prospective study is to assess medical providers' capabilities to identify frail elderly trauma patients and consequent impact on outcomes after intensive care unit admission. METHODS: Trauma intensive care unit patients over the age of 50 were enrolled. A preadmission functional status questionnaire was completed on admission. Attendings, residents, and nurses, blinded to their patient's sarcopenic status, completed surveys regarding 6-month prognosis. Chart review included cross-sectional psoas area measurements on computerized tomography scan. Finally, patients received phone calls 3 and 6 months after admission to determine overall health and functional status. RESULTS: Seventy-six participants had an average age of 70 years and a corrected psoas area of 383 ± 101 mm2/m2. Injury Severity Score distribution (17.2 ± 8.9) was similar for both groups. Patients also had similar preinjury activities of daily living. Both groups had similar hospital courses. While sarcopenic patients were less likely to be predicted to survive to 6 months (60% vs. 76%, P = 0.017), their actual 6-month mortality was similar (22% vs. 21%, P = 0.915). CONCLUSION: Despite similar objective measures of preadmission health and trauma injury severity, medical providers were able to recognize frail patients and predicted they would have worse outcomes. Interestingly, sarcopenic patients had similar outcomes to the control group. Additional studies are needed to further delineate factors influencing provider insight into functional reserves of elderly trauma patients.

Outcome Analysis Using the Modified Frailty Index-5 in Patients With Complex Aortoiliac Disease.

OBJECTIVES: Vascular surgery patients commonly have several comorbidities that cumulatively lead to a frailty status. The cumulative comorbidities disproportionately increase the risk of adverse events and are also associated with worsened long-term prognosis. In recent years, several tools have been elaborated with the objective of quantifying a patient's frailty. One of them is the modified frailty index-5 (mFI-5), a simplified and easy to use index. There is scarce data regarding its value as a prognostic factor in aortoiliac occlusive disease. The aim of this work is to validate mFI-5 as a potential postoperative prognostic indicator in this population. METHODS: From January 2013 to January 2020, 109 patients who underwent elective revascularizations, either endovascular or open surgery, having Trans-Atlantic Inter-Society Consensus II type D aortoiliac lesions in a tertiary and a regional hospital were selected from a prospective vascular registry. Demographic data was collected including diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease, arterial hypertension requiring medication and functional status. The 30-d and subsequent long-term surveillance outcomes were also collected including major adverse cardiovascular events (MACE), major adverse limb events (MALE) and all-cause mortality were assessed in the 30-d post-procedure and in the subsequent long-term surveillance period. The mFI-5 was applied to this population to evaluate the prognostic impact of this frailty marker on mortality and morbidity. RESULTS: In the long-term follow-up, mFI-5 was significantly associated with MACE (hazard ratio [HR] 2.469; 95% confidence interval [CI]: 1.267-4.811; P = .008) and all-cause mortality (HR 2.585; 95% CI: 1.270-5.260; P = .009). However, there was no significant association with 30-day outcomes. Along with the presence of chronic kidney disease, mFI-5 was the prognostic factor better able of predicting MACE. No prognostic value was found regarding short-term outcomes. CONCLUSION: The mFI-5 index may have a role in predicting long term outcomes, namely MACE and all-cause mortality, in the subset of patients with extensive aortoiliac occlusive disease. Its ease of use can foster its application in risk stratification and contribute for the decision-making process.

A single center's 15-year experience with palliative limb care for chronic limb threatening ischemia in frail patients.

OBJECTIVE: Our institution's multidisciplinary Prevention of Amputation in Veterans Everywhere (PAVE) program allocates veterans with critical limb threatening ischemia (CLTI) to immediate revascularization, conservative care, primary amputation, or palliative limb care according to previously reported criteria. These four groups align with the approaches outlined by the global guidelines for the management of CLTI. In the present study, we have delineated the natural history of the palliative limb care group of patients and quantified the procedural risks and outcomes. METHODS: Veterans prospectively enrolled into the palliative limb cohort of our PAVE program from January 2005 to January 2020 were analyzed. The primary outcome was mortality. The secondary outcomes included overall and limb-related readmissions, limb loss, and wound healing. The clinical frailty scale (CFS) score was calculated, and the 5-year expected mortality was estimated using the Veterans Affairs Quality Enhancement Research Initiative tool. Regression analysis was performed to establish associations among the following variables: mortality, wound, ischemia, and foot infection (WIfI) score, CFS score, overall admissions, and limb-related admissions. RESULTS: The PAVE program enrolled 1158 limbs during 15 years. Of the 1158 limbs, 157 (13.5%) in 145 patients were allocated to the palliative limb care group. The overall mortality of the group was 88.2% (median interval, 3.5 months; range, 0-91 months). Of the 128 patients who had died, 64 (50%) had died within 3 months of enrollment. The predicted 5-year mortality for the group was 66%. The average CFS score for the group was 6.2, denoting persons moderately to severely frail. Using the CFS score, 106 patients were considered frail and 39 were considered not frail. No differences were found in mortality between the frail and nonfrail patients. However, a statistically significant difference was found in early (<3 months) mortality (56.2% vs 37.5%; P = .032). The 30-day limb-related readmission rate was 4.7%. Eventual major amputation was necessary for 18 limbs (11.5%). Wound healing occurred in 30 patients (20.6%). Regression analysis demonstrated no association between the CFS score and mortality (r = 0.55; P = .159) or between the WIfI score and mortality (r = 0.0165; P = .98). However, a significant association was found between the WIfI score and limb-related admissions (r = 0.97; P < .001). CONCLUSIONS: Frail patients with CLTI had high early mortality and a low risk of limb-related complications. They also had a low incidence of deferred primary amputation or limb-related readmissions. In our cohort, the vast majority of patients had died within a few months of enrollment without requiring an amputation. A comprehensive approach to the treatment of CLTI patients should include a palliative limb care option because a significant proportion of these patients will have limited survival and can potentially avoid unnecessary surgery and major amputation.

Predicting 1 year mortality after traumatic injury using the Clinical Frailty Scale.

BACKGROUND: Frailty is known to affect how people admitted with traumatic injuries recover during their inpatient stay and shortly after discharge. However, few studies have examined the effect of frailty on long-term mortality when adjusted for significant factors including age. We aimed to determine the effect of frailty on 1-year morality in older adults admitted with traumatic injuries. METHODS: We undertook an observational study at the Severn Major Trauma Network's major trauma centre based in South West England. Patients ≥65 years old admitted between November 2018 and September 2019 with traumatic injuries were included. Isolated hip fractures and inpatient injuries were excluded. A geriatrician assessed all patients for frailty using the Clinical Frailty Scale. Follow-up occurred at 1 year. A multivariable Cox proportional baseline hazards model assessed the effect of frailty on time-to-mortality. The adjusted model included age, sex, multimorbidity, surgery, most injured site, injury severity, postinjury complications, and geriatrician review. RESULTS: Five hundred and eighty-five patients were included. Median age was 81 years old (IQR 74-88), and median injury severity score was 13 (IQR 9-25). At 1 year 147 (25.1%) patients had died. Living with frailty was associated with mortality. The risk of dying increased with frailty severity. Compared to CFS 1-3: CFS 4 aHR = 1.73 (95% CI 0.89-3.36, p = 0.11); CFS 5 aHR = 3.82 (95% CI 2.11-6.93, p < 0.001); CFS 6 aHR = 4·05 (95% CI 2.21-7.45, p < 0.001); CFS 7-8 aHR = 6.57 (95% CI 3.43-12.59, p < 0.001). CONCLUSION: This study is the first to demonstrate a consistent effect of frailty, at all levels of severity and independent of age, on older peoples' survival 1 year after traumatic injury. These data support performing an admission frailty assessment to aid long-term management decisions and provide opportunity to modify frailty to improve outcomes.

Life expectancy estimates based on comorbidities and frailty to inform preventive care.

BACKGROUND: Long-term prognostication is important to inform preventive care in older adults. Existing prediction indices incorporate age and comorbidities. Frailty is another important factor in prognostication. In this project, we aimed at developing life expectancy estimates that incorporate both comorbidities and frailty. METHODS: In this retrospective cohort study, we used data from a 5% sample of Medicare beneficiaries with and without history of cancer from Surveillance, Epidemiology, and End Results (SEER) cancer registry areas. We included adults aged 66-95 years who were continuously enrolled in fee-for-service Medicare for ≥1 year from 1998 to 2014. Participants were followed for survival until 12/31/2015, death, or disenrollment. Comorbidity (none, low/medium, high) and frailty categories (low, high) were defined using established methods for claims. We estimated 5- and 10-year survival probabilities and median life expectancies by age, sex, comorbidities, and frailty. RESULTS: The study included 479,646 individuals (4,128,316 person-years), of whom most were women (58.7%). Frailty scores varied widely among participants in the same comorbidity category. In Cox models, both comorbidities and frailty were independent predictors of mortality. Individuals with high comorbidities (HR, 3.24; 95% CI, 3.20-3.28) and low/medium comorbidities (HR, 1.36; 95% CI, 1.34-1.39) had higher risks of death than those with no comorbidities. Compared to low frailty, high frailty was associated with higher risk of death (HR, 1.55; 95% CI, 1.52-1.58). Frailty affected life expectancy estimates in ways relevant to preventive care (i.e., distinguishing <10-year versus >10-year life expectancy) in multiple subgroups. CONCLUSION: Incorporating both comorbidities and frailty may be important in estimating long-term life expectancies of older adults. Our life expectancy tables can aid clinicians' prognostication and inform simulation models and population health management.

Development of a new clinical index to easily assess frailty of elderly patients with multiple myeloma in Asian population.

The number of elderly people is rapidly growing, and the proportion of elderly patients with multiple myeloma (MM) continues to increase. This study aimed to develop a frailty assessment tool based on clinical data and to estimate its feasibility in elderly patients with MM. This study analyzed data from 728 elderly transplant-ineligible patients with newly diagnosed MM who were treated between January 2010 and October 2019. Our clinical frailty index included age (< 75, and ≥ 75 years), Charlson comorbidity index (CCI; < 3 and ≥ 3), and Eastern Cooperative Oncology Group performance status score (ECOG score; 0, 1-2, and ≥ 3). Patients were classified as fit, intermediate, or frail if they had a score of 0, 1, or ≥ 2, respectively. The overall survival rates differed significantly according to frailty (fit vs. intermediate: hazard ratio [HR] = 2.41; 95% confidence interval [CI] = 1.43-4.06; P = 0.001; fit vs. frail: HR = 4.61; 95% CI = 2.74-7.77; P < 0.001 and intermediate vs. frail: HR = 1.91, 95% CI = 1.49-2.45, P < 0.001, respectively). The frail had significantly shorter EFS compared with the fit and intermediate group in our frailty index (fit vs. intermediate: HR = 1.34, 95% CI = 0.92-1.96, P = 0.132; fit vs. frail: HR = 2.06, 95% CI = 1.40-3.02, P < 0.001; and intermediate vs. frail: HR = 1.53, 95% CI = 1.22-1.92, P < 0.001, respectively). The new clinical frailty index, which is based on age, CCI, and ECOG PS, can easily assess frailty in elderly patients with MM and can be helpful in predicting survival outcomes in real world clinical setting.

Comparative validation of three DNA methylation algorithms of ageing and a frailty index in relation to mortality: results from the ESTHER cohort study.

BACKGROUND: Three DNA methylation (DNAm) based algorithms, DNAm PhenoAge acceleration (AgeAccelPheno), DNAm GrimAge acceleration (AgeAccelGrim), and mortality risk score (MRscore), based on methylation in 513, 1030, and 10 CpGs, respectively, were established to predict health outcomes and mortality. We aimed to compare and validate the predictive ability of these scores and frailty in relation to mortality in a population-based cohort from Germany. METHODS: DNA methylation in whole blood was measured by the Infinium Methylation EPIC BeadChip kit (EPIC, Illumina, San Diego, CA, USA) in two random subsets of the ESTHER cohort study (n = 741 and n = 1030). AgeAccelPheno, AgeAccelGrim, and a revised MRscore to adapt EPIC, the MRscore with 8 CpGs (MRscore-8CpGs), were calculated. Frailty was assessed by a frailty index (FI). FINDINGS: During 17 years of follow-up, 458 deaths were observed. All DNAm algorithms and FI were positively correlated with each other. AgeAccelPheno, AgeAccelGrim, MRscore, and FI showed independent associations with all-cause mortality [hazard ratio (95% CI) per SD increase = 1·32 (1·19-1·46), 1·47 (1·32-1·64), 1·73 (1·49-2·01), and 1·31 (1·20-1·43), respectively]. Harrell's C-statistic was 0·710 for a model predicting mortality by age, sex, and leukocyte composition and increased to 0·759 in a model including MRscore-8CpGs and FI. The predictive performance was further improved (Harrell's C-statistic = 0·766) when additionally including AgeAccelPheno and AgeAccelGrim into the model. INTERPRETATION: The combination of a DNA methylation score based on 8 CpGs only and an easy to ascertain frailty index may strongly enhance mortality prediction beyond age and sex. FUNDING: The ESTHER study was funded by grants from the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany), and the Saarland State Ministry of Health, Social Affairs, Women and the Family (Saarbrücken, Germany). The work of Xiangwei Li was supported by a grant from Fondazione Cariplo (Bando Ricerca Malattie invecchiamento, #2017-0653).

Intrinsic capacity and its associations with incident dependence and mortality in 10/66 Dementia Research Group studies in Latin America, India, and China: A population-based cohort study.

BACKGROUND: The World Health Organization (WHO) has reframed health and healthcare for older people around achieving the goal of healthy ageing. The recent WHO Integrated Care for Older People (ICOPE) guidelines focus on maintaining intrinsic capacity, i.e., addressing declines in neuromusculoskeletal, vitality, sensory, cognitive, psychological, and continence domains, aiming to prevent or delay the onset of dependence. The target group with 1 or more declines in intrinsic capacity (DICs) is broad, and implementation may be challenging in less-resourced settings. We aimed to inform planning by assessing intrinsic capacity prevalence, by characterising the target group, and by validating the general approach-testing hypotheses that DIC was consistently associated with higher risks of incident dependence and death. METHODS AND FINDINGS: We conducted population-based cohort studies (baseline, 2003-2007) in urban sites in Cuba, Dominican Republic, Puerto Rico, and Venezuela, and rural and urban sites in Peru, Mexico, India, and China. Door-knocking identified eligible participants, aged 65 years and over and normally resident in each geographically defined catchment area. Sociodemographic, behaviour and lifestyle, health, and healthcare utilisation and cost questionnaires, and physical assessments were administered to all participants, with incident dependence and mortality ascertained 3 to 5 years later (2008-2010). In 12 sites in 8 countries, 17,031 participants were surveyed at baseline. Overall mean age was 74.2 years, range of means by site 71.3-76.3 years; 62.4% were female, range 53.4%-67.3%. At baseline, only 30% retained full capacity across all domains. The proportion retaining capacity fell sharply with increasing age, and declines affecting multiple domains were more common. Poverty, morbidity (particularly dementia, depression, and stroke), and disability were concentrated among those with DIC, although only 10% were frail, and a further 9% had needs for care. Hypertension and lifestyle risk factors for chronic disease, and healthcare utilisation and costs, were more evenly distributed in the population. In total, 15,901 participants were included in the mortality cohort (2,602 deaths/53,911 person-years of follow-up), and 12,939 participants in the dependence cohort (1,896 incident cases/38,320 person-years). One or more DICs strongly and independently predicted incident dependence (pooled adjusted subhazard ratio 1.91, 95% CI 1.69-2.17) and death (pooled adjusted hazard ratio 1.66, 95% CI 1.49-1.85). Relative risks were higher for those who were frail, but were also substantially elevated for the much larger sub-groups yet to become frail. Mortality was mainly concentrated in the frail and dependent sub-groups. The main limitations were potential for DIC exposure misclassification and attrition bias. CONCLUSIONS: In this study we observed a high prevalence of DICs, particularly in older age groups. Those affected had substantially increased risks of dependence and death. Most needs for care arose in those with DIC yet to become frail. Our findings provide some support for the strategy of optimising intrinsic capacity in pursuit of healthy ageing. Implementation at scale requires community-based screening and assessment, and a stepped-care intervention approach, with redefined roles for community healthcare workers and efforts to engage, train, and support them in these tasks. ICOPE might be usefully integrated into community programmes for detecting and case managing chronic diseases including hypertension and diabetes.

Epigenetic age is associated with baseline and 3-year change in frailty in the Canadian Longitudinal Study on Aging.

BACKGROUND: The trajectory of frailty in older adults is important to public health; therefore, markers that may help predict this and other important outcomes could be beneficial. Epigenetic clocks have been developed and are associated with various health-related outcomes and sociodemographic factors, but associations with frailty are poorly described. Further, it is uncertain whether newer generations of epigenetic clocks, trained on variables other than chronological age, would be more strongly associated with frailty than earlier developed clocks. Using data from the Canadian Longitudinal Study on Aging (CLSA), we tested the hypothesis that clocks trained on phenotypic markers of health or mortality (i.e., Dunedin PoAm, GrimAge, PhenoAge and Zhang in Nat Commun 8:14617, 2017) would best predict changes in a 76-item frailty index (FI) over a 3-year interval, as compared to clocks trained on chronological age (i.e., Hannum in Mol Cell 49:359-367, 2013, Horvath in Genome Biol 14:R115, 2013, Lin in Aging 8:394-401, 2016, and Yang Genome Biol 17:205, 2016). RESULTS: We show that in 1446 participants, phenotype/mortality-trained clocks outperformed age-trained clocks with regard to the association with baseline frailty (mean = 0.141, SD = 0.075), the greatest of which is GrimAge, where a 1-SD increase in ΔGrimAge (i.e., the difference from chronological age) was associated with a 0.020 increase in frailty (95% CI 0.016, 0.024), or ~ 27% relative to the SD in frailty. Only GrimAge and Hannum (Mol Cell 49:359-367, 2013) were significantly associated with change in frailty over time, where a 1-SD increase in ΔGrimAge and ΔHannum 2013 was associated with a 0.0030 (95% CI 0.0007, 0.0050) and 0.0028 (95% CI 0.0007, 0.0050) increase over 3 years, respectively, or ~ 7% relative to the SD in frailty change. CONCLUSION: Both prevalence and change in frailty are associated with increased epigenetic age. However, not all clocks are equally sensitive to these outcomes and depend on their underlying relationship with chronological age, healthspan and lifespan. Certain clocks were significantly associated with relatively short-term changes in frailty, thereby supporting their utility in initiatives and interventions to promote healthy aging.