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Item Association between Cognitive Function and Physical Function, Frailty, and Quality of Life in Older Breast Cancer Survivors(MDPI, 2024-07-31) Von Ah, Diane; Rio, Carielle Joy; Carter, Allie; Perkins, Susan M.; Stevens, Erin; Rosko, Ashley; Davenport, Ashley; Kalady, Mathew; Noonan, Anne M.; Crouch, Adele; Storey, Susan; Overcash, Janine; Han, Claire J.; Yang, Yesol; Li, Haiying; Saligan, Leorey N.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Older cancer survivors in general are at greater risk for cancer-related cognitive impairment (CRCI), yet few studies have explored its association with health outcomes. This study examined the association between subjective and objective measures of cognitive function and physical function, frailty, and quality of life (QoL) among older breast cancer survivors. Materials and methods: Older breast cancer survivors who reported cognitive concerns completed surveys on patient-reported cognitive function, physical function, frailty, and QoL as well as objective tests of visuospatial working memory and sustained attention. Data were analyzed using descriptive statistics and separate linear regression models. Results: A total of 219 female breast cancer survivors completed the study. Perceived cognitive abilities were associated with better physical function, frailty, and QoL (p ≤ 0.001) while cognitive concerns were negatively related with these metrics (p ≤ 0.001). Poorer visuospatial working memory and sustained attention were linked to increased frailty (p ≤ 0.001-0.01), whereas poorer sustained attention was associated with poorer physical function (p < 0.01). Conclusions: Older breast cancer survivors with perceived cognitive impairment and poorer cognitive performance reported poorer physical functioning, increased frailty, and poorer QoL. These findings underscore the importance of assessing cognitive concerns and their associated outcomes in older breast cancer survivors.Item Association of Tryptophan and NAD+ Metabolites with Brain and Skeletal Muscle Function in Critical Care Patients and Survivors(2024-07) Yates, Brandon Alston; Coggan, Andrew; Khan, Babar; Kroenke, Kurt; Liu, Ziyue; Newman, JohnBackground: Patients who survive Intensive Care Unit (ICU) acquired delirium will likely experience new or worsened physical, mental, and/or cognitive impairments (termed Post-Intensive Care Syndrome (PICS)). Although advances in critical care treatments have reduced mortality rates among older adult ICU survivors, roughly 67% suffer PICS. The most vulnerable to long-term physical and cognitive impairments are older adults or those who exhibit accelerated aging because of pre-existing physical frailty or cognitive frailty. Yet, identification of at-risk patients during admittance is likely difficult because of the 1) homogeneity in the clinical presentation of patients with pre-existing age-related physical frailty and critical illness compared to those suffering from only critical illness and 2) many patients arrive severely debilitated making administration of physical function or other volitional assessments difficult. Therefore, it is essential that new biomarkers to guide early diagnosis, prognosis, and disease monitoring are identified. To this point, tryptophan derivatives, particularly kynurenines and nicotinamide family (e.g., NAD+), have been shown to mediate the relationship between chronic inflammation and physical impairment or signal accelerated aging, respectively. However, it remains unknown if similar associations exist in ICU patients and the prognostic utility of elevated neurotoxic tryptophan metabolites relative to neuroprotective tryptophan metabolites to predict adverse health outcomes while in the ICU. Methods: A secondary analysis of pooled data from three randomized control trials was used to investigate the following aims. To address Aims 1 and 2, blood samples from patients with ICU acquired delirium were analyzed for kynurenine and salvage pathway metabolites. To address Aim 3, blood samples from patients who survived an ICU stay, experienced ICU delirium, and completed both objective and subjective physical function assessments within in month of ICU discharge and before the COVID-19 pandemic. Results: Delirium duration was significantly (p< 0.05) associated with elevated circulating kynurenine and lower NAD+. Delirium severity was significantly associated with elevated circulating lower NAD+ but not kynurenine. Post-ICU physical function performance was significantly associated with elevated circulating kynurenine but not NAD+. Conclusion: Elevated concentration of frailty biomarkers are associated with delirium severity and duration in the ICU and post-ICU physical function.Item Body Weight Influences Musculoskeletal Adaptation to Long-Term Voluntary Wheel Running During Aging(Oxford University Press, 2022-12-20) Kitase, Yukiko; Julian, Vallejo; Xie, Yixia; Dallas, Mark; Dallas, Sarah; Johnson, Mark; Wacker, Michael; Bonewald, Lynda; Anatomy, Cell Biology and Physiology, School of MedicineFrailty is a key hallmark of aging and exercise has been shown to delay aging effects. This study was initiated based on the hypothesis that voluntary wheel running (VWR) starting at 12 mo until 18 or 22 mo of age would benefit the female murine musculoskeletal system. Based on the final body weight, the mice were separated into high (HBW) and low body weight (LBW) subgroups. Beneficial effects of VWR were observed on soleus muscle mass and contractile force at both ages, although HBW led to greater increases at 22 mo. VWR increased fiber cross-sectional area by 20%, leading to more type I and fewer IIA fibers in soleus. HBW mice were resistant to age-related decline in Extensor digitorum longus (EDL) mass and contractile force. EDL in 18 mo HBW also showed 15% higher contractile force following VWR while muscle from 18 & 22 mo LBW responded to VWR with greater osteocyte protective factor secretion. Skeletal adaptation to VWR was also dependent on body weight, with HBW showing higher femoral cortical thickness and area under sedentary conditions. VWR maintained osteocyte dendrite number in HBW. VWR increased periosteal and endosteal circumferences in HBW, suggesting compensation for loss of material strength. Consistent with this, VWR maintained higher bone mechanical properties in 18mo LBW. In summary, VWR alters musculoskeletal parameters depending on body weight with HBW contributing to more muscle mass and strength to prevent sarcopenia while bone retains better mechanical properties in LBW but HBW contributes structural modification to prevent osteopenia.Item Correlates of Frailty in Older Female Cancer Survivors(Elsevier, 2024) Rio, Carielle Joy; Saligan, Leorey N.; Li, Xiaobai; Crouch, Adele; Von Ah, Diane; School of NursingIntroduction: Cancer survivors are at risk of frailty because of cancer and its treatment. Understanding the factors that increase the risk of frailty is an important aspect of cancer care for the development of interventions to prevent or manage frailty, thus improving cancer survival and overall quality of life of cancer survivors. This study aimed to identify demographic, clinical, and psychosocial correlates of frailty in older, female cancer survivors. Materials and Methods: This is a sub-study focusing on the exploratory aim of a larger cross-sectional study (NURS-IIR-IUSCC-0748). A total of 213 female cancer survivors aged 59–87 years old were included from the parent study in the current analysis. Frailty, the primary outcome, was measured using the Tilburg Frailty Indicator scale. The independent variables were age, relationship status, clinical stage of cancer, treatment type, comorbidity, depression, affect, optimism, stress, and social support. Stepwise linear regression modeling identified the independent variables that were significantly associated with frailty. Results: The final regression model revealed that high patient-reported stress and depression, comorbidity, not being married or living with a partner, and low positive affect were significantly associated with worsening frailty in this population. Discussion: Understanding the context of frailty is important for the design of interventions that target factors known to be associated with frailty in older cancer survivors. Further validation with a larger and a more diverse sample from a broad spectrum of sociodemographic and clinical population would fully account for the multiple independent variables influencing frailty in cancer survivors.Item Critical Care Recovery Center: a model of agile implementation in intensive care unit (ICU) survivors(Cambridge University Press, 2020-12) Wang, Sophia; Hanneman, Philip; Xu, Chenjia; Gao, Sujuan; Allen, Duane; Golovyan, Dmitry; Kheir, You Na; Fowler, Nicole; Austrom, Mary; Khan, Sikandar; Boustani, Malaz; Khan, Babar; Psychiatry, School of MedicineBackground: As many as 70% of intensive care unit (ICU) survivors suffer from long-term physical, cognitive, and psychological impairments known as post-intensive care syndrome (PICS). We describe how the first ICU survivor clinic in the United States, the Critical Care Recovery Center (CCRC), was designed to address PICS using the principles of Agile Implementation (AI). Methods: The CCRC was designed using an eight-step process known as the AI Science Playbook. Patients who required mechanical ventilation or were delirious ≥48 hours during their ICU stay were enrolled in the CCRC. One hundred twenty subjects who completed baseline HABC-M CG assessments and had demographics collected were included in the analysis to identify baseline characteristics that correlated with higher HABC-M CG scores. A subset of patients and caregivers also participated in focus group interviews to describe their perceptions of PICS. Results: Quantitative analyses showed that the cognitive impairment was a major concern of caregivers. Focus group data also confirmed that caregivers of ICU survivors (n = 8) were more likely to perceive cognitive and mental health symptoms than ICU survivors (n = 10). Caregivers also described a need for ongoing psychoeducation about PICS, particularly cognitive and mental health symptoms, and for ongoing support from other caregivers with similar experiences. Conclusions: Our study demonstrated how the AI Science Playbook was used to build the first ICU survivor clinic in the United States. Caregivers of ICU survivors continue to struggle with PICS, particularly cognitive impairment, months to years after discharge. Future studies will need to examine whether the CCRC model of care can be adapted to other complex patient populations seen by health-care professionals.Item Deficit Accumulation Frailty Trajectories of Older Breast Cancer Survivors and Non-Cancer Controls: The Thinking and Living With Cancer Study(Oxford University Press, 2021) Mandelblatt, Jeanne S.; Zhou, Xingtao; Small, Brent J.; Ahn, Jaeil; Zhai, Wanting; Ahles, Tim; Extermann, Martine; Graham, Deena; Jacobsen, Paul B.; Jim, Heather; McDonald, Brenna C.; Patel, Sunita J.; Root, James C.; Saykin, Andrew J.; Cohen, Harvey Jay; Carroll, Judith E.; Radiology and Imaging Sciences, School of MedicineBackground: We evaluated deficit accumulation and how deficits affected cognition and physical activity among breast cancer survivors and non-cancer controls. Methods: Newly diagnosed nonmetastatic survivors (n = 353) and matched non-cancer controls (n = 355) ages 60-98 years without neurological impairments were assessed presystemic therapy (or at enrollment for controls) from August 2010 to December 2016 and followed for 36 months. Scores on a 42-item index were analyzed in growth-mixture models to determine deficit accumulation trajectories separately and combined for survivors and controls. Multilevel models tested associations between trajectory and cognition (FACT-Cog and neuropsychological tests) and physical activity (IPAQ-SF) for survivors and controls. Results: Deficit accumulation scores were in the robust range, but survivors had higher scores (95% confidence intervals [CI]) than controls at 36 months (0.18, 95% CI = 0.16 to 0.19, vs 0.16, 95% CI = 0.14 to 0.17; P = .001), and averages included diverse deficit trajectories. Survivors who were robust but became frailer (8.8%) had similar baseline characteristics to those remaining robust (76.2%) but experienced a 9.6-point decline self-reported cognition (decline of 9.6 vs 3.2 points; P = .04) and a 769 MET minutes per week decline in physical activity (P < .001). Survivors who started and remained prefrail (15.0%) had self-reported and objective cognitive problems. At baseline, frail controls (9.5%) differed from robust controls (83.7%) on deficits and self-reported cognition (P < .001). Within combined trajectories, frail survivors had more sleep disturbances than frail controls (48.6% [SD = 17.4%] vs 25.0% [SD = 8.2%]; P = .05). Conclusions: Most survivors and controls remained robust, and there were similar proportions on a frail trajectory. However, there were differences in deficit patterns between survivors and controls. Survivor deficit accumulation trajectory was associated with patient-reported outcomes. Additional research is needed to understand how breast cancer and its treatments affect deficit accumulation.Item Depression and anxiety symptoms are related to pain and frailty but not cognition or delirium in older surgical patients(Wiley, 2021-06) Wang, Sophia; Cardieri, Brielle; Lin, Hung Mo; Liu, Xiaoyu; Sano, Mary; Deiner, Stacie G.; Psychiatry, School of MedicineObjective: In community dwelling older adults, depression and anxiety symptoms can be associated with early cognitive decline. Symptoms of depression and anxiety are common in older adults prior to surgery. However, their significance is unknown. Our objective was to determine whether preoperative depression and anxiety symptoms are associated with postoperative cognitive decline (POCD) and in-hospital delirium, in older surgical patients. Methods: We conducted a secondary data analysis of postoperative cognitive dysfunction in a cohort study of patients 65 and older undergoing elective noncardiac surgery. We used the Hospital Anxiety and Depression Scale (HADS) to screen for depression and anxiety symptoms at a home visit prior to surgery and 3 months after surgery. Patients with a history of psychiatric (major depressive disorder, bipolar disorder, and schizophrenia) or neurologic disorder (Parkinson's disease and stroke) were excluded from the parent study. Results: Out of the 167 patients, 9.6% (n = 16) reported significant depressive symptoms and 21.6% (n = 36) reported significant anxiety symptoms on preoperative screening. There was no association between preoperative or new-onset postoperative depression and anxiety symptoms and the incidence of delirium or POCD three months after surgery. Patients with preoperative depressive symptoms had higher preoperative pain (scores 69 vs. 35.7, p = .002) and frailty (56 vs. 14.6, p <.001). Conclusion: In our cohort, we did not detect an association between preoperative depression and anxiety symptoms and neurocognitive disorders. Preoperative depression and anxiety symptoms were related to physical pain and frailty. Taken together, these suggest that in patients without a formal psychiatric diagnosis, preoperative depression and anxiety symptoms are related to physical state rather than a harbinger of early cognitive decline. Future studies are needed to understand the nature of the relationship between depression and anxiety symptoms and physical state in surgical patients.Item Differences in preoperative frailty assessment of surgical candidates by sex, age, and race(Elsevier, 2024-05-11) Nicaise, Edouard H.; Palmateer, Gregory; Schmeusser, Benjamin N.; Futral, Cameron; Liu, Yuan; Goyal, Subir; Nabavizadeh, Reza; Kooby, David A.; Maithel, Shishir K.; Sweeney, John F.; Sarmiento, Juan M.; Ogan, Kenneth; Master, Viraj A.; Urology, School of MedicineIntroduction: Surgical decision-making often relies on a surgeon's subjective assessment of a patient's frailty status to undergo surgery. Certain patient demographics can influence subjective judgment when compared to validated objective assessments. In this study, we explore the relationship between subjective and objective frailty assessments according to patient age, sex, and race. Methods: Patients were prospectively enrolled in urology, general surgery, and surgical oncology clinics. Using a visual analog scale (0-100), operating surgeons independently rated the patient's frailty status. Objective frailty was classified using the Fried Frailty Criteria ranging from 0 to 5. Multivariable proportional odds models were conducted to examine the potential association of factors with objective frailty, according to surgeon frailty rating. Subgroup analysis according to patient sex, race, and age was also performed. Results: Seven male surgeons assessed 203 patients preoperatively with a median age of 65. A majority of patients were male (61 %), white (67 %), and 60 % and 40 % underwent urologic and general surgery/surgical oncology procedures respectively. Increased subjective surgeon rating (OR 1.69; p < 0.001) was significantly associated with the presence of objective frailty. On subgroup analysis, a higher magnitude of such association was observed more in females (OR 1.86; p = 0.0007), non-white (OR 1.84; p = 0.0019), and older (>60, OR 1.75; p = 0.0001) patients, compared to male (OR 1.45; p = 0.0243), non-white (OR 1.48; p = 0.0109) and patients under 60 (OR 1.47; p = 0.0823). Conclusion: The surgeon's subjective assessment of frailty demonstrated tendencies to rate older, female, and non-white patients as frail; however, differences in patient sex, age, and race were not statistically significant.Item Early Origins of Frailty: Do Later-Life Social Relationships Alter Trajectories of Decline?(Sage, 2024) Williams-Farrelly, Monica M.; Ferraro, Kenneth F.; Medicine, School of MedicineObjectives: Social relationships are widely regarded as salubrious, but do they mediate the influence of childhood experiences on frailty in later life? Drawing from cumulative inequality theory, we assess the influence of childhood experiences and adult relationships on frailty trajectories. Methods: We analyzed data from the Health and Retirement Study to examine the influence of six domains of childhood experiences and social relationships on frailty trajectories over 8 years. Mediation analyses were completed with structural equation models. Results: Risky adolescent behavior, chronic disease, and impairments during childhood are associated directly with higher risk of initial frailty, but not over time. More social roles and higher social support mediate the relationship between childhood experiences and frailty, and the effect of more social roles continues over time. Discussion: This study provides compelling evidence that supportive social relationships mediate the risk and severity of frailty in later life associated with noxious childhood experiences.Item Hospital frailty risk score is superior to legacy comorbidity indices for risk adjustment of in-hospital cirrhosis cases(Elsevier, 2023-11-03) Desai, Archita P.; Parvataneni, Swetha; Knapp, Shannon M.; Nephew, Lauren D.; Chalasani, Naga; Ghabril, Marwan S.; Orman, Eric S.; Medicine, School of MedicineBackground & aims: The hospital frailty risk score (HFRS) identifies older patients at risk of poor outcomes and may have value in cirrhosis. We compared the Charlson (CCI), Elixhauser (ECI), and cirrhosis (CirCom) comorbidity indices with the HFRS in predicting outcomes for cirrhosis hospitalisations. Methods: Using the National Inpatient Sample (quarter 4 of 2015-2019), we analysed cirrhosis hospitalisations. For each index, we described the prevalence of comorbid conditions and inpatient mortality. We compared the ability of CCI, ECI, CirCom, and HFRS to predict inpatient mortality. Raw and adjusted models predicting inpatient mortality were compared using the area under the receiver operating characteristic curve and the Akaike information criterion. Results: The cohort's (N = 626,553) median age was 61 years (IQR 52-68 years), 60% were male, cirrhosis was caused by alcohol in 43%, and 38% had ascites. The median comorbidity scores are as follows: ECI 4 (IQR 3-6), CCI 5 (IQR 4-8), and HFRS 5.6 (IQR 3.0-8.6). The most common CirCom score was 0 + 0 (44%). Across the range of values of each index, we observed different mortality ranges: CCI 1.9-13.1%, ECI 3.2-8.7%, CirCom 4.9-13.8%, and HFRS 1.0-15.2%. An adjusted model with HFRS had the highest area under the receiver operating characteristic curve in predicting mortality (HFRS 0.782 vs. ECI 0.689, CCI 0.695, and CirCom 0.692). We observed substantial variation in mortality with HFRS within each level of CCI, ECI, and CirCom. For example, for ECI 4, mortality increased from 0.6 to 16.4%, as HFRS increased from 0 to 15. Conclusions: Comorbidity indices predict inpatient cirrhosis mortality, but HFRS performs better than CCI, ECI, and CirCom. HFRS is an ideal tool for measuring comorbidity burden and disease severity risk adjustment in cirrhosis-related administrative database studies. Impact and implications: We compared commonly used comorbidity indices to a more recently described risk score (hospital frailty risk score [HFRS]) in patients with cirrhosis using a national sample of hospital records. Comorbid conditions are common in hospitalised patients with cirrhosis. There is significant variability in mortality across the range of each index. HFRS outperforms the Charlson comorbidity index, Elixhauser comorbidity index, and CirCom (cirrhosis-specific comorbidity scoring system) in predicting inpatient mortality. HFRS is a valuable index for risk adjustment in inpatient administrative database studies.