Frailty Indices Research Articles

EIGHT-YEAR CHANGES IN DEFICIT ACCUMULATION FRAILTY: RELATION TO GLYCEMIC CONTROL AND DIABETES MEDICATION USE

Abstract Type 2 diabetes mellitus (T2DM) has been linked to accelerated biological aging and the accumulation of health deficits. It is unknown whether glycemic control can slow the progression of aging, as expressed by deficit accumulation frailty indices (FIs). We examined the cross-sectional and longitudinal associations that glycemic control, diabetes medication use, and weight change (predictors) had with a FI calculated as the percent of 36 deficits in behavioral, functional, and clinical characteristics (outcome). We drew data from 4177 participants across 8 years of follow-up in the Look AHEAD clinical trial of a multidomain intensive lifestyle intervention in individuals aged 45-76 years with T2DM and overweight or obesity. At baseline, the means(SD) FI(as a percent) for participants grouped as HbA1c< 7%, 7-7.9%, and >8% were: 19.93(6.45), 20.82(6.89), and 21.53(7.27), p< 0.001. Compared with HbA1c>8%, HbA1c< 7% at baseline was associated with 23% less mean 8-year FI progression: 2.42(7.35) vs 3.14(8.02), p< 0.001). Maintaining average HbA1c< 7% vs >8% during follow-up was associated with 47% less 8-year FI progression: 2.05(7.35) vs 3.14(8.02), p< 0.001. With adjustment for HbA1c, sustained weight loss >5% compared with weight gain >5% was associated with an 81% reduction in 8-year FI progression: 1.18(7.25) vs 3.89(8.09), p< 0.001. Use of metformin across >50% of annual visits was associated with a 30% reduction in 8-year progression of FI as compared with less use or no use: 2.25(7.27) vs 3.22(7.90), p=0.002. We conclude that better control of HbA1c, and sustained weight loss (>5%) and metformin use, may slow the accelerated aging associated with T2DM.

Outcomes of Cardiac Transplantation in Western Australia - A Contemporary Single Centre Experience.

Cardiac transplantation remains the gold standard therapy for select patients with end-stage heart failure and outcomes have improved significantly over the past few decades. We report the 5-year contemporary experience of cardiac transplantation in Western Australia, one of the most remote transplant centres worldwide. Patients undergoing isolated cardiac transplant at Fiona Stanley Hospital (FSH) from February 2015 until April 2021 were included. Donor details were collected using donor electronic records (Donate Life, Australia). Recipient data was collated from electronic medical records at FSH and the Australia and New Zealand Society of Cardiothoracic Surgery database. The primary outcome measure was all-cause mortality. Secondary outcome measures included postoperative intensive care and total hospital length of stay and rates of acute kidney injury, rejection, serious infections, and cardiac allograft vasculopathy. Frailty indices were also assessed. A total of 60 patients were included (mean age 53±14 yrs, 66.7% male). The commonest indication for transplant was a non-ischaemic cardiomyopathy (46.7%). Mean donor age was 35±12 years and median donor ischaemia time was 171 minutes (IQR=138-240). After median follow up of 3.7 years, there were no mortalities. Postoperative renal failure occurred in 21 (35.0%) patients, pneumonia in four (6.7%), deep sternal wound infection in three (5.1%), acute rejection in 17 (28.3%) and cardiac allograft vasculopathy (CAV) in 23 (38.3%). With recipient and donor criteria comparable to national and international standards, compounded by the challenges of geographic isolation, we report the first published data on contemporary outcomes post isolated cardiac transplantation in Western Australia.

The longevity‐promoting intervention 17α‐Estradiol protects against aging phenotypes in APOE4 mice

AbstractBackgroundThe two primary risk factors for late onset Alzheimer’s Disease (AD) are aging and APOE4 genotype. While the causal relationship between aging and AD is not well defined, shared phenotypes, such as decreased metabolic function and increased inflammation, are strong leads. APOE genotype may be linked to AD phenotype through the regulation of aging processes. The NIA Interventions Testing Program found that 17α‐estradiol (17αE2) treatment can increase male mouse lifespan. Since 17αE2 has been shown to act upon systemic and neural pathways that have also been associated with AD pathology, we propose that 17αE2 may constitute a pleiotropic intervention strategy. Further, because APOE4 is associated with impaired healthspan and lifespan, 17αE2 may preferentially improve outcomes in the context of APOE4 genotype.MethodTo examine the effects at the earliest phases of AD development, we used 10‐month‐old APOE3 or APOE4 targeted replacement male mice maintained for 20 weeks on normal chow in the absence or presence of 14.4 ppm 17αE2. Mice were evaluated on various metabolic, behavioral, and molecular measures.ResultOur initial results indicate genotype differences in the impact of 17αE2 across multiple outcomes. APOE4 mice were impaired across metabolic measures including body weight, plasma leptin, and hepatic steatosis, and 17αE2 treatment significantly attenuated these metabolic phenotypes. APOE4 mice exhibited an aged phenotype compared to APOE3, notably with higher frailty indices; however, 17αE2 treatment reduced the frailty index more strongly in APOE4 mice compared to APOE3. Interestingly, transcriptomic analysis of isolated microglia from both APOE3 and APOE4 17αE2 treated mice displays a downregulation of genes relating to inflammation and upregulation of those in metabolic pathways.ConclusionThese data confirm and extend prior findings that APOE4 is linked to progeroid effects both peripherally and neurally, outcomes associated with AD risk. Importantly, although 17αE2 significantly improved a range of measure across genotypes, it showed the strongest effects in the APOE4 genotype.This research was funded by the Cure Alzheimer’s Fund.

Association Between the Modified Frailty Index and Outcomes Following Lobectomy

Elective thoracic surgery is safe in well-selected elderly patients. The association of frailty with postoperative morbidity in elective-lobectomy patients is understudied. We examined frailty as defined by abbreviated modified frailty index (mFI-5), mFI-11 in the thoracic surgery population, and the correlation between frailty and postoperative complications. We studied outcomes of patients in two cohorts, 2010-2012 and 2013-2019, from the National Surgical Quality Improvement Program (NSQIP) database and used multivariable logistic regression models to predict all postoperative morbidity, mortality, and major morbidity. The mFI-5 could be calculated for all subjects (both 2010-2012, and 2013-2019); the mFI-11 could only be calculated for the 2010-2012 cohort. Patient frailty was defined as mFI≥3 (with either index). We used odds ratios (ORs) to examine associations of preoperative characteristics with postoperative complications and C-statistics to assess overall predictive power. Complications were less prevalent in the 2013-2019 cohort (17.9% versus 19.5%, P=0.008). Open lobectomies were more common in the 2010-2012 cohort (53.9% versus 34.6%) and were strongly associated with postoperative morbidity and mortality (ORs >1.5) in both cohorts. Each frailty measure was associated with morbidity and mortality (ORs >1.4) after adjusting for other significant preoperative factors. Models on the 2010-2012 cohort had nearly identical C-statistics using the mFI-11 versus mFI-5 frailty indices (0.6142 versus 0.6139; P>0.8). Frailty, as captured in the mFI-5, is a significant associated factor of postoperative morbidity and mortality following elective lobectomies. As a modifiable risk factor, frailty should be considered in surgical decision-making and when counseling patients regarding perioperative risks.

Systematic review: the role of frailty in advanced chronic liver disease.

Frailty is a known predictor of outcome and mortality in patients undergoing liver transplantation. However, most patients remain unsuitable transplant candidates. It is not yet known if the assessment of frailty in non-transplant candidates can aid prognostication. To collate and interrogate the various frailty tools presently used to predict mortality in the non-transplant cirrhosis setting. A comprehensive review of MEDLINE and EMBASE databases for articles published from inception to March 2022 was undertaken, excluding those where patients underwent transplantation or had hepatocellular carcinoma. We identified 12 observational cohort studies, featuring 9 frailty indices. These were from various global healthcare settings and of fair or good quality. Most were objective tools utilising clinician-based assessments. All frailty scores predicted prognosis, with variability in the method of application, and utilisation in long- or short-term mortality. Three studies directly compared different indices in the same population. There was some evidence that simple tools could perform as well, if not better, than more complex, time-consuming scores. Various frailty tools can reproducibly evaluate mortality in patients with cirrhosis who are ineligible for transplant. However, further prospective head-to-head comparative studies are needed. In addition to determining model utility, studies should focus on important relative considerations which may limit widespread implementation including, ease of use and limited resources, given the global disparity of liver care provision. These tools may positively identify specific patient cohorts at risk of impending deterioration, thereby stratifying those patients likely to benefit from early integration with palliative care.

Evaluating Concordance between International Myeloma Working Group (IMWG) and Simplified Frailty Index (SFI) Among Older Adults with Multiple Myeloma (MM)

Introduction: Despite significant advances in therapeutics, older adults with MM are at increased risk of treatment related toxicity and mortality. Frailty is an aging-associated state of cumulative decline in many physiological systems, resulting in diminished resistance to stressors, including cancer therapy. In 2015, the International Myeloma Working Group (IMWG) developed a geriatric assessment (GA) based frailty index (IMWG-FI) using age, comorbidities, and physical function (instrumental activities of daily living, IADL; activities of daily living, ADL) to predict risk of toxicity and mortality among older adults with MM (Palumbo, et al., Blood 2015). However, GA is not routinely incorporated in clinical practice and a simplified frailty index (SFI; Facon et al Leukemia 2020) has been proposed as an alternative to using ECOG performance status (ECOG PS) as a proxy for physical function (IADL/ADL). However, the concordance between IMWG-FI and SFI remains relatively unknown, as well as their predictive ability in clinical practice, particularly among patients with relapsed, refractory multiple myeloma (RR-MM). Our goal was to describe the prevalence of frailty using IMWG-FI and SFI as well as evaluate their concordance among patients with newly-diagnosed (ND) and RR-MM. Methods: The Cancer and Aging Resilience Evaluation in Hematologic Malignancies (CARE-Heme) Registry is an ongoing prospective registry enrolling adults ≥50 years of age with a diagnosis of a hematologic malignancy undergoing treatment at a single institution. For this analysis, we included patients ≥50yo with ND- or RR-MM initiating a new treatment regimen (ranging from first to sixth line of treatment). All of the patients included in this study underwent a comprehensive GA prior to beginning a new line of therapy or stem cell transplant. We abstracted physician reported ECOG PS and comorbidities by reviewing medical records. We calculated IMWG frailty score as well as SFI using published methods. Each patient was categorized into frail/non-frail using the IMWG frailty score (fit, intermediate-fit, frail; collapsing fit/intermediate fit into the non-frail category) and the simplified frailty score (non-frail, frail) using published cutoffs. We measured the agreement between the total frailty scores using Spearman Correlation Coefficient and the frail/non-frail categorization using the Kappa statistic. Relevant treatment outcomes including progression-free survival, overall survival, and grade 2-5 toxicities (both hematologic and non-hematologic) were recorded until disease progression, death, or 6 cycles of treatment were completed. Results: A total of 146 adults with MM (49 ND-MM, 51 pre-transplant, and 46 RR-MM) starting a new line of therapy or ASCT between 8/2020 to 1/2022 were included in this study. The median age was 62 (IQR 57-70) with 53% males and 36% blacks. Most patients had IgG isotype (64%) with International Staging System (ISS) stage III disease (38%) whereas 30% patients had high risk cytogenetics. The distribution by IWMG Frailty category was as follows: 43% fit, 32% intermediate-fit, and 25% frail. Using SFI, 32% of patients were characterized as frail and 68% were characterized as non-frail (Figure 1). Although, the frailty scores were well correlated with each other (Spearman rho 0.67, p value <.001), the agreement between SFI and IMWG-FI in terms of frailty categorization was moderate (Kappa statistic 0.50); 79% of patients were classified in the same frailty group, however about 21% of patients were characterized in different frailty categories using the two scales (Table 1). SFI over-estimated frailty in about 14% of patients. There was very little agreement between a patient-reported vs physician rated ECOG-PS (Kappa statistic 0.13). The discordance between the two FI worsened if a patient reported version of ECOG PS (Kappa statistic 0.30) was used. Conclusions: Among older adults with MM, the prevalence of frailty ranged 25% by IMWG-FI to 32% by SFI. There was only a modest agreement between SFI and IMWG FI, which was worse when using patient reported version of ECOG PS. Studies comparing outcomes across the two frailty indices should take into account the potential for misclassification bias. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Association between lower Hounsfield units and proximal junctional kyphosis and failure at the upper thoracic spine.

The aim of this study was to analyze risk factors and avoidance techniques for proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) in the upper thoracic spine with an emphasis on bone mineral density (BMD) as estimated by Hounsfield units (HU). A retrospective chart review identified patients at least 50 years of age who underwent instrumented fusion extending from the pelvis to an upper instrumented vertebra (UIV) between T1 and T6 and had a preoperative CT, pre- and postoperative radiographs, and a minimum follow-up of 12 months. HU were measured in the UIV, the vertebral body cephalad to the UIV (UIV+1), and the L3 and L4 vertebral bodies. Numerous perioperative variables were collected, including basic demographics, smoking and steroid use, preoperative osteoporosis treatment, multiple frailty indices, use of a proximal junctional tether, UIV soft landing, preoperative dual-energy x-ray absorptiometry, spinopelvic parameters, UIV screw tip distance to the superior endplate, UIV pedicle screw/pedicle diameter ratio, lumbar lordosis distribution, and postoperative spinopelvic parameters compared with age-adjusted normal values. Eighty-one patients were included in the study (21 men and 60 women) with a mean (SD) age of 66 years (6.9 years), BMI of 29 (5.5), and follow-up of 38 months (25 months). Spinal fusion constructs at the time of surgery extended from the pelvis to a UIV of T1 (5%), T2 (15%), T3 (25%), T4 (33%), T5 (21%), and T6 (1%). Twenty-seven patients (33%) developed PJK and/or PJF; 21 (26%) had PJK and 15 (19%) had PJF. Variables associated with PJK/PJF with p < 0.05 were included in the multivariable analysis, including HU at the UIV/UIV+1, HU at L3/L4, DXA femoral neck T-score, UIV screw tip distance to the superior endplate, UIV pedicle screw/pedicle diameter ratio, and postoperative lumbar lordosis distribution. Multivariable analysis (area under the curve = 0.77) demonstrated HU at the UIV/UIV+1 to be the only independent predictor of PJK and PJF with an OR of 0.96 (p = 0.005). Patients with < 147 HU (n = 27), 147-195 HU (n = 27), and > 195 HU (n = 27) at the UIV/UIV+1 had PJK/PJF rates of 59%, 33%, and 7%, respectively. In patients with upper thoracic-to-pelvis spinal reconstruction, lower HU at the UIV and UIV+1 were independently associated with PJK and PJF, with an optimal cutoff of 159 HU that maximizes sensitivity and specificity.

A Prospective Study Correlating Preoperative Modified Frailty Index With One-Year Mortality in the Elderly With Hip Fractures.

Background Hip fractures occur frequently in the elderly population over the age of 60 years following low-energy domestic falls. The postoperative mortality after hip fracture surgery depends on numerous factors like comorbidities, pre-fall ambulatory status, nutritional status, cognition, and overall physical health. In this context, the physiological age and reserve playa vital role in mortality after hip fracture surgeries. This physiological reserve is measured in terms of "frailty."There are many frailty indices that assess the physiological reserves of an elderly patient. The modified frailty index (MFI) is one of the validated indexes predicting postoperative complications and mortality. So we concluded there is a need to assess the patients with MFI preoperatively, based on which mortality and postoperative complications could be predicted in our patients. Materials and methods We included 100 patients aged more than 60 years with intertrochanteric and neck of the femur fractures, who were managed surgically. We followed the patients for one year and observed the immediate and late complications and mortality at the end of one year. To reduce bias, patients with pathological fractures, revision surgeries, contralateral fractures, high-energy trauma, younger than 60 years of age, and previous proximal femur fracture surgery on the side of injury were excluded from the study. Results The primary objective was to study the correlation between the MFI with one-year mortality. We observe that the MFI score had a significant effect on mortality at one year (p-value = 0.0316). With a unit increase in the MFI score, the odds of death increase by a factor of 1.52. Conclusion There is a strong correlation between MFI with one-year mortality and postoperative complications after hip fracture surgeries in the elderly. This MFI can be used as a preoperative predictive model to predict the mortality and postoperative complications after hip fractures in the elderly. It will also help patients and their caretakers in decision-making and elucidating surgery choices.

Can Frailty Indices Predict Surgical Risk in Open Reduction and Fixation of Facial Fractures?

PURPOSE: Facial fractures, often resulting from high impact trauma, necessitate surgical fixation with postoperative complications occurring in 3-30% of patients.1 Thus, risk prediction of unfavorable postoperative complications is essential for preoperative planning and postoperative management. Existing literature has linked smoking, alcohol use, age, BMI, and comorbidities to increased risk of adverse postoperative outcomes following facial fracture repair.1 More recently, frailty indices, including the Modified Five-Item Frailty Index (mFI-5) and the Modified Charlson Comorbidity Index (mCCI), have emerged as potentially more accurate predictors of surgical risk and 30-day postsurgical complications than their historical counterparts.2,3 The authors aimed to evaluate whether the mFI-5 and mCCI are stronger predictors of 30-day postoperative complications after open facial fracture reduction, versus historic risk proxies. METHODS: A retrospective review of the National Surgical Quality Improvement Program (NSQIP) database was performed of patients undergoing open facial fracture reduction from 2013-2019. Age, smoking, BMI, comorbidities, and American Society of Anesthesiologists (ASA) class were extracted, and mFI-5 and mCCI scores were calculated using this data. Univariate logistic regressions were performed (p<0.05). RESULTS: A total of 2,667 patients were analyzed, of which 2,131 (80%) were male. Most patients were nonfrail across both indices, with 86% (n=2,292) having an mFI-5 of 0, and 75% (n=1,994) having a mCCI of 0. Both mCCl score ≥2 (OR=2.19, p<0.001) and mFI-5 =1 (OR=1.96, p<0.001) were strong independent predictors of overall 30-day complication rate and complication severity. However, ASA class ≥3 was the strongest predictor (OR=3.60, p<0.001). Age was statically significant, but a low-impact, predictor of complications and complication severity (OR= 1.02, p<0.001). The only significant predictors of surgical site infections (SSI) were smoking (OR=1.56, p=0.042) and ASA class ≥3 (OR=2.37, p=0.013). An mFI-5 of 1 was also found to be a significant predictor of hospital readmission rates (7% vs 3% p<0.001). BMI was not associated with any increased risk. CONCLUSION: The mCCI and mFI-5 are significant independent predicators of total complications and complication severity following facial fracture repair. ASA class ≥3 was the strongest predictor of postoperative complications, likely attributable to concurrent multi-organ system trauma and its global impact on risk in facial fracture injury. An mFI-5 ≥1 was additionally predictive of increased readmission rates. Smoking increased risk of surgical site infections specifically but not overall complications. Newer frailty indices (mFI-5 and mCCI) predicted adverse postsurgical events more strongly than several historic risk proxies, offering potential utility as risk predictors during surgical planning. Further research should continue to clarify their predictive value. REFERENCES: 1. Perez D, Ellis E, 3rd. Complications of Mandibular Fracture Repair and Secondary Reconstruction. Semin Plast Surg. 2020;34(4):225-231. 2. Austin SR, Wong YN, Uzzo RG, Beck JR, Egleston BL. Why Summary Comorbidity Measures Such As the Charlson Comorbidity Index and Elixhauser Score Work. Med Care. 2015;53(9):e65-72. 3. Lee CC, Hunter WP, Hajibandeh JT, Peacock ZS. Does the Modified Frailty Index (mFI-5) Predict Adverse Outcomes in Maxillofacial Fracture Repair? J Oral Maxillofac Surg. 2021.

Comparison of Frailty Indices and the Charlson Comorbidity Index in Traumatic Brain Injury.

Comorbidity scales for outcome prediction in traumatic brain injury (TBI) include the 5-component modified Frailty Index (mFI-5), the 11-component modified Frailty Index (mFI-11), and the Charlson Comorbidity Index (CCI). To compare the accuracy in predicting clinical outcomes in TBI of mFI-5, mFI-11, and CCI. The National Trauma Data Bank (NTDB) of the American College of Surgeons (ACS) was utilized to study patients with isolated TBI for the years of 2017 and 2018. After controlling for age and injury severity, individual multivariable logistic regressions were conducted with each of the 3 scales (mFI-5, mFI-11, and CCI) against predefined outcomes, including any complication, home discharge, facility discharge, and mortality. All 3 scales demonstrated adequate internal consistency throughout their individual components (0.63 for mFI-5, 0.60 for CCI, and 0.56 for mFI-11). Almost all studied complications were significantly more likely in frail patients. mFI-5 and mFI-11 had similar areas under the curve (AUC) for all outcomes, while CCI had lower AUCs (0.62-0.61-0.53 for any complication, 0.72-0.72-0.52 for home discharge, 0.78-0.78-0.53 for facility discharge, and 0.71-0.70-0.52 for mortality, respectively). mFI-5 and mFI-11 demonstrated similar accuracy in predicting any complication, home discharge, facility discharge, and mortality in TBI patients across the NTDB. In addition, CCI's performance was poor for the aforementioned metrics. Since mFI-5 is simpler, yet as accurate as the 2 other scales, it may be the most practical both for clinical practice and for future studies with the NTDB.

Electronic Frailty Index: A risk stratification tool for survival and health care outcomes in veterans with colorectal cancer.

375 Background: Frailty reflects decreased physiologic reserve and subsequent increased vulnerability to stress. Frailty has been associated with poor health outcomes in patients with cancer, however traditional frailty indices are time consuming and not widely implemented in clinical oncology practice. An electronic frailty index (EFI) derived from electronic medical records (EMR) is an objective and standardized approach to frailty that can be automated. Little is known about the association between EFI and survival and healthcare utilization outcomes in patients with colorectal cancer (CRC). Methods: We used VA administrative files from 2016 – 2020 and the VA Central Cancer Registry to identify a cohort of patients diagnosed with CRC. EFI was calculated based on the Veterans Affairs-FI (VA-FI), a validated 31-item cumulative deficit FI, to define three groups: robust (≤0.1), prefrail (0.1-0.2), and frail (&gt; 0.2). We conducted Cox proportional hazard analyses to evaluate survival. We performed logistic regression to examine prolonged length of stay (LOS) ≥ median (11 days) during all-cause hospitalization and emergency department (ED) visits within one year after diagnosis. All models were adjusted for age, gender, race, Charlson comorbidity index, and stage. Confidence intervals (CI) were calculated as 95%. Results: Of 6,043 CRC patients (age: 69.7 ± 10.6 years), 45.6% were robust, 34.5% were prefrail, and 19.9% were frail. The cohort included 22.9% rectal cancer and 77.1% colon cancer cases, distributed across stages I (29.2%), II (25.0%), III (25.2%), and IV (20.6%). Increased risk of death was found in prefrail (adjusted hazard ratio [aHR] 1.21; CI 1.10-1.32) and frail (aHR 1.90; CI 1.71-2.11) patients when compared to robust patients. Increased odds of one-year ED visits were identified in prefrail (adjusted odds ratio [aOR] 1.18; CI 1.06 – 1.35) and frail (aOR, 1.66, CI 1.43-1.94) patients. Frailty status was associated with increased odds of one-year hospitalization of prolonged LOS among prefrail (aOR 1.38; CI 1.11-1.70) and frail patients (aOR 1.79; 95% CI 1.39-2.30). Conclusions: EFI was significantly associated with survival and healthcare utilization among patients with CRC, independent of stage. Frail patients had nearly 80% increased likelihood of prolonged hospitalization. EFI has the potential to be an automated and objective decision support tool at the point of care for risk assessment prior to CRC treatment-related stressors, such as surgery or chemotherapy. Future work is needed to develop a cancer specific EFI with dynamic variables that can be followed prospectively, as well as evaluating barriers to implementation within the EMR to guide treatment decisions and improve the quality of cancer care.

Transcatheter Tricuspid Valve Repair in Prohibitive Risk Patients: Impact on Quality of Life and Major Organ Systems

BackgroundPercutaneous repair for severe tricuspid regurgitation (TR) is emerging as a viable option, but patient selection is challenging and predetermined by comorbidities. This study evaluated mid-term outcomes of transcatheter tricuspid valve repair (TTVR) in very sick inoperable patients and explored the concept of risk-based therapeutic futility. MethodsTTVR patients treated in our centre were prospectively assigned to prohibitive-risk (PR) and high-risk (HR) subgroups, based on Society of Thoracic Surgeons (STS) Score, frailty indices, and major organ system compromise. Efficacy and safety outcomes were compared at baseline, 30 days, and 6 months. ResultsThirty-three patients (mean age 81.9 ± 5.1 years) completed follow-up from May 2021 to March 2022: 18 PR (mean STS Score 15.5 ± 7%) and 15 HR (mean STS Score 6.4 ± 1.7%). The primary efficacy end point of at least 1 grade of TR reduction by 30 days was recorded in 93.9% of all patients, with no device-related adverse events. Improvement in initial New York Heart Association functional class III/IV occurred in 74% of PR and 93% of HR patients. Six-minute walk test increased by 81 ± 43.6 metres (P < 0.001) and 85.8 ± 47.9 metres (P < 0.001), respectively. Renal function tests improved by 15% (P = 0.048) and 7% (P = 0.050), while liver enzymes decreased by 18% (P = 0.020) and 28% (P = 0.052). Right ventricular systolic function increased in both subgroups by at least 24% (P < 0.001). Six-month mortality was 12.1%, with 6 hospitalisations for acute heart failure. ConclusionsTR reduction significantly affected quality of life, functional capacity, cardiac remodelling, and multiorgan involvement similarly in PR and HR patients. TTVR is feasible in very sick symptomatic patients, regardless of predicted risk.

Maximizing Opportunities: Primary Hyperparathyroidism in the Older Adult

Primary hyperparathyroidism creates a multisystem and life-limiting disease burden requiring early recognition to mitigate potential complications. A single parathyroid adenoma is responsible for 80% to 85% of primary hyperparathyroidism, causing subjective cognitive impairment, neuropsychiatric symptoms, osteoporosis-associated bone/joint pain, renal damage, functionality, and poor quality of life. The benefits of treatment include clinically significant fracture risk reduction, improvement in left ventricular hypertrophy, and frailty indices. The criteria for parathyroidectomy to resolve primary hyperparathyroidism are less clear for those over age 85. Evidence-based screening tools are available for advanced practice nurses to quantify the associated risk of complications and poor outcomes.

P102. Chronological comparison of existing frailty indices to predict complications throughout the postoperative course following adult spinal deformity surgery

<h3>BACKGROUND CONTEXT</h3> The comparison of various frailty indices and their ability to predict complications after ASD surgery has not been investigated. <h3>PURPOSE</h3> Assess whether certain frailty indices have predictability of complication rates following ASD surgery. <h3>STUDY DESIGN/SETTING</h3> Retrospective. <h3>PATIENT SAMPLE</h3> A total of 689 ASD patients. <h3>OUTCOME MEASURES</h3> Complication rates, clinical outcomes, cost-utility. <h3>METHODS</h3> Operative ASD patients with baseline (BL) and 2-year (2Y) data were included. Four frailty indices were used for comparison: Passias et al modified ASD frailty index (mFI), Miller et al ASD frailty index (FI-ASD), the ACS-NSQIP 5-Factor frailty index (ACS-FI5), and the FRAIL Scale (PMID:29792992). Patients were stratified into not frail (NF), frail (F) and severely frail (SF). Associations of the indices with EBL, op time, complications, hospital-acquired conditions (HAC: UTI, DVT/PE, SSI), reoperations, SICU stay, and LOS were compared using one-way ANOVA, logistic and linear regression analyses. <h3>RESULTS</h3> There were 421 ASD patients included (Age: 60.4, BMI: 28.0, CCI: 1.9). Total cohort complication rates: 71% any comp, 27% major (68% were surgical, 32% medical), 35% minor, 25% intraoperative, 18% mechanical, 22% underwent reoperation. Upon presentation, severely frail patients were much more likely to present with a severe ODI (OR: 16, [7.2-29.8]). All four indices significantly correlated with intraop details and comps. During hospital stay, all four indices correlated to SICU time and total LOS. Only FRAIL Scale correlated with SICU admission rate (OR: 1.2, [1.03-8.8]), while no index was predictive of comps prior to discharge (all p>.05). ASD-FI had the strongest correlation with periop comps, including HACs (OR: 1.2, [1.1-6.3]), any (OR: 1.2, [1.02-7.3]) and major comps (OR: 1.5, [1.1-4.7]). When assessing 2Y comps, logistic regression analysis demonstrated correlation between ASD-FI, mFI, and FRAIL Scale indices and any comps, major comps and reoperation. However, mFI was the only correlate for all 2Y comps (any, major, minor, mech, reop), along with highest OR for predicting mechanical comps (OR: 1.6, [1.3-1.9]). Clinically, ASD-FI SF group had the greatest improvement (ODI,SRS-Total), while mFI SF had lowest rates of improvement. Given their higher complication rates, this translated to higher cost per QALY by 2 years for SF pts when stratified by mFI (p<.001). <h3>CONCLUSIONS</h3> Frailty imposes a significant burden on adult spinal deformity patients from the moment of presentation through cost-utility at two years. Assessing frailty by different measures demonstrated meaningful differences in complications and outcomes. These findings highlight the impact of frailty stratification during surgical planning to effectively assess the risk of patients undergoing corrective surgery. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

A machine-vision-based frailty index for mice.

Heterogeneity in biological aging manifests itself in health status and mortality. Frailty indices (FIs) capture health status in humans and model organisms. To accelerate our understanding of biological aging and carry out scalable interventional studies, high-throughput approaches are necessary. Here we introduce a machine-learning-based visual FI for mice that operates on video data from an open-field assay. We use machine vision to extract morphometric, gait and other behavioral features that correlate with FI score and age. We use these features to train a regression model that accurately predicts the normalized FI score within 0.04 ± 0.002 (mean absolute error). Unnormalized, this error is 1.08 ± 0.05, which is comparable to one FI item being mis-scored by 1 point or two FI items mis-scored by 0.5 points. This visual FI provides increased reproducibility and scalability that will enable large-scale mechanistic and interventional studies of aging in mice.

Posterior Instrumented Spinal Surgery Outcomes in the Elderly: A Comparison of the 5-Item and 11-Item Modified Frailty Indices.

Retrospective Cohort. To validate the most concise risk stratification system to date, the 5-item modified frailty index (mFI-5), and compare its effectiveness with the established 11-item modified frailty index (mFI-11) in the elderly population undergoing posterior instrumented spine surgery. A single centre retrospective review of posterior instrumented spine surgeries in patients aged 65years and older was conducted. The primary outcome was rate of post-operative major complications (Clavien-Dindo Classification ≥ 4). Secondary outcome measures included rate of all complications, 6-month mortality and surgical site infection. Multi-variate analysis was performed and adjusted receiver operating characteristic curves were generated and compared by DeLong's test. The indices were correlated with Spearman's rho. 272 cases were identified. The risk of major complications was independently associated with both the mFI-5 (OR 1.89, 95% CI 1.01-3.55, P = .047) and mFI-11 (OR 3.73, 95% CI 1.90-7.30, P = .000). Both the mFI-5 and mFI-11 were statistically significant predictors of risk of all complications (P = .007 and P = .003), surgical site infection (P = .011 and P = .003) and 6-month mortality (P = .031 and P = .000). Adjusted ROC curves determined statistically similar c-statistics for major complications (.68 vs .68, P = .64), all complications (.66 vs .64, P = .10), surgical site infection (.75 vs .75, P = .76) and 6-month mortality (.83 vs .81, P = .21). The 2 indices correlated very well with a Spearman's rho of .944. The mFI-5 and mFI-11 are equally effective predictors of postoperative morbidity and mortality in this population. The brevity of the mFI-5 is advantageous in facilitating its daily clinical use.

Outcomes of Exercise Interventions in Patients With Advanced Liver Disease: A Systematic Review of Randomized Clinical Trials.

Frailty and sarcopenia are common complications of advanced liver disease. Owing to associated morbidity/mortality, there have been targeted efforts to prevent and/or improve both by enrolling these patients in focused exercise programs. This review systematically analyzes the data of randomized clinical trials (RCTs) on anthropometric, physical fitness, quality-of-life, and safety outcomes of exercise interventions in patients with advanced liver disease. Two authors independently searched trials on PubMed and EMBASE from inception up to November 18, 2021. A third independent arbitrator adjudicated all disagreements. We qualitatively summarized these outcomes as follows: (i) muscular fitness (maximal inspiratory/expiratory pressures, muscle size, muscle strength, and bioimpedance testing), (ii) cardiorespiratory fitness (cardiopulmonary exercise testing and 6-minute walk distance), (iii) quality of life, and (iv) others (safety or frailty indices). There were 11 RCTs (4 home-based interventions) with 358 participants. Interventions ranged from 8 to 14 weeks and included cycling, walking, resistance exercises, balance and coordination training, and respiratory exercises. All described outcomes compared preintervention with postintervention measurements. Nine studies showed statistically significant improvements in at least 1 physical fitness variable. Ten studies showed statistically significant improvements in at least 1 muscular fitness variable. Six studies showed statistically significant improvements in at least 1 quality-of-life variable. Attrition rates ranged from 5% to 36%, and adherence rates ranged very widely from 14% to 100%. Only 1 study reported frailty indices. Notably, no complications of portal hypertension were seen in intervention groups in the 9 studies that reported these data. A review of 11 RCTs with 358 participants with advanced liver disease demonstrates that exercise interventions can have favorable outcomes on muscular/cardiorespiratory fitness and quality of life. Although attrition and adherence varied, these interventions seem to be safe in patients with cirrhosis and are well tolerated.

Can Frailty Indices Predict Surgical Risk in Open Reduction and Fixation of Facial Fractures?

The present study sought to evaluate whether the mFI-5 and modified Charlson Comorbidity Index (mCCI) are stronger predictors of 30-day postoperative complications after open reduction of facial fractures compared with historic risk proxies. A retrospective review of the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database was conducted to investigate patients who underwent open reduction facial fracture surgery between 2013 and 2018. Risk factors including age, smoking status, body mass index (BMI), comorbidities, and American Society of Anesthesiologists (ASA) class were extracted for each patient. The mFI-5 score and mCCI score were calculated based on this data. Univariate logistic regressions were performed (P<0.05). A total of 2667 cases were included. Of these, 2131 (80%) were male. The strongest predictors for overall 30-day complications and complication severity were ASA class ≥3 (Odds Ratio [OR]=3.34), comorbidities ≥2 (OR=2.78), mCCl score ≥2 (OR=2.19), and mFI-5 ≥1 (OR=1.96). Smoking status and BMI were not strong predictors of total complications or complication severity. Age was found to be a statically significant, but low-impact, predictor of complications, and severity (OR=1.02, P<0.001). The only significant predictors of surgical site infections (SSI) were smoking status (OR=1.56) and ASA class ≥3 (OR=2.40). mFI-5 ≥1 was a significant predictor of hospital readmission. BMI was not associated with any increased risk. The mCCI and mFI-5 are statistically significant predictors of total complications and complication severity in open reduction of facial fracture repair, and thus provide a tool to inform decision making and improve care. Smoking status may increase risk for SSIs following facial fracture repair.

Predicting frailty in older adults using vocal biomarkers: a cross-sectional study

BackgroundFrailty is a common issue in the aging population. Given that frailty syndrome is little discussed in the literature on the aging voice, the current study aims to examine the relationship between frailty and vocal biomarkers in older people.MethodsParticipants aged ≥ 60 years visiting geriatric outpatient clinics were recruited. They underwent frailty assessment (Cardiovascular Health Study [CHS] index; Study of Osteoporotic Fractures [SOF] index; and Fatigue, Resistance, Ambulation, Illness, and Loss of weight [FRAIL] index) and were asked to pronounce a sustained vowel /a/ for approximately 1 s. Four voice parameters were assessed: average number of zero crossings (A1), variations in local peaks and valleys (A2), variations in first and second formant frequencies (A3), and spectral energy ratio (A4).ResultsAmong 277 older adults, increased A1 was associated with a lower likelihood of frailty as defined by SOF (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.74–0.96). Participants with larger A2 values were more likely to be frail, as defined by FRAIL and CHS (FRAIL: OR 1.41, 95% CI 1.12–1.79; CHS: OR 1.38, 95% CI 1.10–1.75). Sex differences were observed across the three frailty indices. In male participants, an increase in A3 by 10 points increased the odds of frailty by almost 7% (SOF: OR 1.07, 95% CI 1.02–1.12), 6% (FRAIL: OR 1.06, 95% CI 1.02–1.11), or 6% (CHS: OR 1.06, 95% CI 1.01–1.11). In female participants, an increase in A4 by 0.1 conferred a significant 2.8-fold (SOF: OR 2.81, 95% CI 1.71–4.62), 2.3-fold (FRAIL: OR 2.31, 95% CI 1.45–3.68), or 2.8-fold (CHS: OR 2.82, 95% CI 1.76–4.51, CHS) increased odds of frailty.ConclusionsVocal biomarkers, especially spectral-domain voice parameters, might have potential for estimating frailty, as a non-invasive, instantaneous, objective, and cost-effective estimation tool, and demonstrating sex differences for individualised treatment of frailty.

Comparing the association between multiple chronic conditions, multimorbidity, frailty, and survival among older patients with cancer

IntroductionThe high prevalence of multiple chronic conditions (MCC), multimorbidity, and frailty may affect treatment and outcomes for older adults with cancer. The goal of this study was to use three conceptually distinct measures of morbidity to examine the association between these measures and mortality. Materials and MethodsUsing Medicare claims data linked with the 2012–2016 Ohio Cancer Incidence Surveillance System we identified older adults with incident primary cancer sites of breast, colorectal, lung, or prostate (n = 29,140). We used claims data to identify their Elixhauser comorbidities, Multimorbidity-Weighted Index (MWI), and Claims Frailty Index (CFI) as measures of MCC, multimorbidity, and frailty, respectively. We used Cox proportional hazard models to examine the association between these measures and survival time since diagnosis. ResultsLung cancer patients had the highest levels of MCC, multimorbidity, and frailty. There was a positive association between all three measures and a greater hazard of death after adjusting for age, sex (colorectal and lung only), and stage. Breast cancer patients with 5+ comorbidities had an adjusted hazard ratio (aHR) of 1.63 (95% confidence interval [CI]: 1.38, 1.93), and those with mild frailty had an aHR of 3.38 (95% CI; 2.12, 5.41). The C statistics for breast cancer were 0.79, 0.78, and 0.79 for the MCC, MWI, and CFI respectively. Similarly, lung cancer patients who were moderately or severely frail had an aHR of 1.82 (95% CI: 1.53, 2.18) while prostate cancer patients had an aHR of 3.39 (95% CI: 2.12, 5.41) and colorectal cancer patients had an aHR of 4.51 (95% CI: 3.23, 6.29). Model performance was nearly identical across the MCC, multimorbidity, and frailty models within cancer type. The models performed best for prostate and breast cancer, and notably worse for lung cancer. The frailty models showed the greatest separation in unadjusted survival curves. DiscussionThe MCC, multimorbidity, and frailty indices performed similarly well in predicting mortality among a large cohort of older cancer patients. However, there were notable differences by cancer type. This work highlights that although model performance is similar, frailty may serve as a clearer indicator in risk stratification of geriatric oncology patients than simple MCCs or multimorbidity.