Use of Ultrasound in the Evaluation of Cryptorchidism: A Single-Institution Analysis.

INTRODUCTION: The American Urological Association guidelines recommend against the performance of ultrasound and other imaging modalities in the evaluation of patients with cryptorchidism before expert consultation. We aimed to examine our institutional experience with cryptorchidism and measure adherence to currently available guidelines. METHODS: An institutional review board-approved retrospective review of ultrasound utilization in the evaluation of patients with cryptorchidism was performed from June 1, 2016, to June 30, 2019, at a single tertiary level pediatric hospital. RESULTS: We identified 1796 patients evaluated in surgical clinics for cryptorchidism. Surgical intervention was performed in 75.2% (n = 1351) of the entire cohort. Ultrasound was performed in 42% (n = 754), most of which were ordered by referring physicians (91% n = 686). Of those who received an ultrasound, surgical intervention was performed in 78% (n = 588). Those 166 patients (22%) who did not undergo surgical intervention were referred with ultrasounds suggesting inguinal testes; however, all had normal physical examinations or mildly retractile testes at the time of consultation and were discharged from the outpatient clinic. There were 597 patients referred without an ultrasound, 81% (n = 483) were confirmed to have cryptorchidism at the time of specialist physical examination and underwent definitive surgical intervention, the remainder (19%, n = 114) were discharged from the outpatient clinics. CONCLUSIONS: Ultrasound evaluation of cryptorchidism continues despite high-quality evidence-based guidelines that recommend otherwise, as they should have little to no bearing on the surgeon's decision to operate or the type of operation. Instead, physical examination findings should guide surgical planning.

Comparative performance of distinct frailty measures among patients undergoing percutaneous left atrial appendage closure.

AIMS: Frailty is associated with increased morbidity and mortality in patients undergoing left atrial appendage closure (LAAC). This study aimed to compare the performance of two claims-based frailty measures in predicting adverse outcomes following LAAC. METHODS: We identified patients 66 years and older who underwent LAAC between October 1, 2016, and December 31, 2019, in Medicare fee-for-service claims. Frailty was assessed using the previously validated Hospital Frailty Risk Score (HFRS) and Kim Claims-based Frailty Index (CFI). Patients were identified as frail based on HFRS ≥5 and CFI ≥0.25. RESULTS: Of the 21,787 patients who underwent LAAC, frailty was identified in 45.6% by HFRS and 15.4% by CFI. There was modest agreement between the two frailty measures (kappa 0.25, Pearson's correlation 0.62). After adjusting for age, sex, and comorbidities, frailty was associated with higher risk of 30-day mortality, 1-year mortality, 30-day readmission, long hospital stay, and reduced days at home (p < .01 for all) regardless of the frailty measure used. The addition of frailty to standard comorbidities significantly improved model performance to predict 1-year mortality, long hospital stay, and reduced days at home (Delong p-value < .001). CONCLUSION: Despite significant variation in frailty detection and modest agreement between the two frailty measures, frailty status remained highly predictive of mortality, readmissions, long hospital stay, and reduced days at home among patients undergoing LAAC. Measuring frailty in clinical practice, regardless of the method used, may provide prognostic information useful for patients being considered for LAAC, and may inform shared decision-making in this population.

Relative risks of adverse events among older adults receiving opioids versus NSAIDs after hospital discharge: A nationwide cohort study.

BACKGROUND: Although analgesics are initiated on hospital discharge in millions of adults each year, studies quantifying the risks of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) among older adults during this transition are limited. We sought to determine the incidence and risk of post-discharge adverse events among older adults with an opioid claim in the week after hospital discharge, compared to those with NSAID claims only. METHODS AND FINDINGS: We performed a retrospective cohort study using a national sample of Medicare beneficiaries age 65 and older, hospitalized in United States hospitals in 2016. We excluded beneficiaries admitted from or discharged to a facility. We derived a propensity score that included over 100 factors potentially related to the choice of analgesic, including demographics, diagnoses, surgeries, and medication coadministrations. Using 3:1 propensity matching, beneficiaries with an opioid claim in the week after hospital discharge (with or without NSAID claims) were matched to beneficiaries with an NSAID claim only. Primary outcomes included death, healthcare utilization (emergency department [ED] visits and rehospitalization), and a composite of known adverse effects of opioids or NSAIDs (fall/fracture, delirium, nausea/vomiting, complications of slowed colonic motility, acute renal failure, and gastritis/duodenitis) within 30 days of discharge. After propensity matching, there were 13,385 beneficiaries in the opioid cohort and 4,677 in the NSAID cohort (mean age: 74 years, 57% female). Beneficiaries receiving opioids had a higher incidence of death (1.8% versus 1.1%; relative risk [RR] 1.7 [1.3 to 2.3], p < 0.001, number needed to harm [NNH] 125), healthcare utilization (19.0% versus 17.4%; RR 1.1 [1.02 to 1.2], p = 0.02, NNH 59), and any potential adverse effect (25.2% versus 21.3%; RR 1.2 [1.1 to 1.3], p < 0.001, NNH 26), compared to those with an NSAID claim only. Specifically, they had higher relative risk of fall/fracture (4.5% versus 3.4%; RR 1.3 [1.1 to 1.6], p = 0.002), nausea/vomiting (9.2% versus 7.3%; RR 1.3 [1.1 to 1.4], p < 0.001), and slowed colonic motility (8.0% versus 6.2%; RR 1.3 [1.1 to 1.4], p < 0.001). Risks of delirium, acute renal failure, and gastritis/duodenitis did not differ between groups. The main limitation of our study is the observational nature of the data and possibility of residual confounding. CONCLUSIONS: Older adults filling an opioid prescription in the week after hospital discharge were at higher risk for mortality and other post-discharge adverse outcomes compared to those filling an NSAID prescription only.

Frailty in Critical Care Medicine: A Review.

Traditional approaches to clinical risk assessment utilize age as a marker of increased vulnerability to stress. Relatively recent advancements in the study of aging have led to the concept of the frailty syndrome, which represents a multidimensional state of depleted physiologic and psychosocial reserve and clinical vulnerability that is related to but variably present with advancing age. The frailty syndrome is now a well-established clinical entity that serves as both a guide for clinical intervention and a predictor of poor outcomes in the primary and acute care settings. The biological aspects of the syndrome broadly represent a network of interrelated perturbations involving the age-related accumulation of molecular, cellular, and tissue damage that leads to multisystem dysregulation, functional decline, and disproportionately poor response to physiologic stress. Given the complexity of the underlying biologic processes, several well-validated approaches to define frailty clinically have been developed, each with distinct and reasonable considerations. Stemming from this background, the past several years have seen a number of observational studies conducted in intensive care units that have established that the determination of frailty is both feasible and prognostically useful in the critical care setting. Specifically, frailty as determined by several different frailty measurement tools appears associated with mortality, increased health care utilization, and disability, and has the potential to improve risk stratification of intensive care patients. While substantial variability in the implementation of frailty measurement likely limits the generalizability of specific findings, the overall prognostic trends may offer some assistance in guiding management decisions with patients and their families. Although no trials have assessed interventions to improve the outcomes of critically ill older people living with frailty, the particular vulnerability of this population offers a promising target for intervention in the future.

Malnutrition and Mortality in Frail and Non-Frail Older Adults Undergoing Aortic Valve Replacement.

BACKGROUND: Older adults undergoing aortic valve replacement (AVR) are at risk for malnutrition. The association between preprocedural nutritional status and midterm mortality has yet to be determined. METHODS: The FRAILTY-AVR (Frailty in Aortic Valve Replacement) prospective multicenter cohort study was conducted between 2012 and 2017 in 14 centers in 3 countries. Patients ≥70 years of age who underwent transcatheter or surgical AVR were eligible. The Mini Nutritional Assessment-Short Form was assessed by trained observers preprocedure, with scores ≤7 of 14 considered malnourished and 8 to 11 of 14 considered at risk for malnutrition. The Short Performance Physical Battery was simultaneously assessed to measure physical frailty, with scores ≤5 of 12 considered severely frail and 6 to 8 of 12 considered mildly frail. The primary outcome was 1-year all-cause mortality, and the secondary outcome was 30-day composite mortality or major morbidity. Multivariable regression models were used to adjust for potential confounders. RESULTS: There were 1158 patients (727 transcatheter AVR and 431 surgical AVR), with 41.5% females, a mean age of 81.3 years, a mean body mass index of 27.5 kg/m2, and a mean Society of Thoracic Surgeons-Predicted Risk of Mortality of 5.1%. Overall, 8.7% of patients were classified as malnourished and 32.8% were at risk for malnutrition. Mini Nutritional Assessment-Short Form scores were modestly correlated with Short Performance Physical Battery scores (Spearman R=0.31, P<0.001). There were 126 deaths in the transcatheter AVR group (19.1 per 100 patient-years) and 30 deaths in the surgical AVR group (7.5 per 100 patient-years). Malnourished patients had a nearly 3-fold higher crude risk of 1-year mortality compared with those with normal nutritional status (28% versus 10%, P<0.001). After adjustment for frailty, Society of Thoracic Surgeons-Predicted Risk of Mortality, and procedure type, preprocedural nutritional status was a significant predictor of 1-year mortality (odds ratio, 1.08 per Mini Nutritional Assessment-Short Form point; 95% CI, 1.01-1.16) and of the 30-day composite safety end point (odds ratio, 1.06 per Mini Nutritional Assessment-Short Form point; 95% CI, 1.001-1.12). CONCLUSIONS: Preprocedural nutritional status is associated with mortality in older adults undergoing AVR. Clinical trials are needed to determine whether pre- and postprocedural nutritional interventions can improve clinical outcomes in these vulnerable patients.

Development, Construct Validity, and Predictive Validity of a Continuous Frailty Scale: Results From 2 Large US Cohorts.

Frailty is an age-related clinical syndrome of decreased resilience to stressors. Among numerous assessments of frailty, the frailty phenotype (FP) scale proposed by Fried et al. has been the most widely used. We aimed to develop a continuous frailty scale that could overcome limitations facing the categorical FP scale and to evaluate its construct validity, predictive validity, and measurement properties. Data were from the Cardiovascular Health Study (n = 4,243) and Health and Retirement Study (n = 7,600), both conducted in the United States. Frailty was conceptualized as a continuous construct, assessed by 5 measures used in the FP scale: gait speed, grip strength, exhaustion, physical activity, and weight loss. We used confirmatory factor analysis to investigate the relationship between the 5 indicators and the latent frailty construct. We examined the association of the continuous frailty scale with mortality and disability. The unidimensional model fit the data satisfactorily; similar factor structure was observed across 2 cohorts. Gait speed and weight loss were the strongest and weakest indicators, respectively; grip strength, exhaustion, and physical activity had similar strength in measuring frailty. In each cohort, the continuous frailty scale was strongly associated with mortality and disability and continued to be associated with outcomes among robust and prefrail persons classified by the FP scale.

Mobility Device Use and Frailty Progression in Community-Dwelling Older Adults With Mobility Limitations.

Objective: Examine the association between mobility device use and changes in a frailty index (FI) over one year in community-dwelling older adults with mobility limitations. Methods: Analyses utilized 2015-2016 data from the National Health and Aging Trends Study community-dwelling older adults (n = 3934). We calculated a validated 40-item deficit accumulation frailty index (FI) in 2015 and 2016 and compared one year change in FI in older adults with/without canes or walkers using multivariable logistic regression. Analyses were repeated with stratification by baseline frailty. Results: Device use was not associated with worsening frailty in the overall cohort, but was associated with worsening frailty in non-frail individuals when stratified by baseline frailty. Discussion: Device use does not worsen frailty in individuals who are frail at baseline. Device users who were not frail at baseline experienced worsening frailty suggesting additional contributing factors to their frailty aside from mobility limitations.

Identifying Dementia Severity Among People Living With Dementia Using Administrative Claims Data.

OBJECTIVES: There is currently no reliable tool for classifying dementia severity level based on administrative claims data. We aimed to develop a claims-based model to identify patients with severe dementia among a cohort of patients with dementia. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We identified people living with dementia (PLWD) in US Medicare claims data linked with the Minimum Data Set (MDS) and Outcome and Assessment Information Set (OASIS). METHODS: Severe dementia was defined based on cognitive and functional status data available in the MDS and OASIS. The dataset was randomly divided into training (70%) and validation (30%) sets, and a logistic regression model was developed to predict severe dementia using baseline (assessed in the prior year) features selected by generalized linear mixed models (GLMMs) with least absolute shrinkage and selection operator (LASSO) regression. We assessed model performance by area under the receiver operating characteristic curve (AUROC), area under precision-recall curve (AUPRC), and precision and recall at various cutoff points, including Youden Index. We compared the model performance with and without using Synthetic Minority Oversampling Technique (SMOTE) to reduce the imbalance of the dataset. RESULTS: Our study cohort included 254,410 PLWD with 17,907 (7.0%) classified as having severe dementia. The AUROC of our primary model, without SMOTE, was 0.81 in the training and 0.80 in the validation set. In the validation set at the optimized Youden Index, the model had a sensitivity of 0.77 and specificity of 0.70. Using a SMOTE-balanced validation set, the model had an AUROC of 0.83, AUPRC of 0.80, sensitivity of 0.79, specificity of 0.74, positive predictive value of 0.75, and negative predictive value of 0.78 when at the optimized Youden Index. CONCLUSIONS AND IMPLICATIONS: Our claims-based algorithm to identify patients living with severe dementia can be useful for claims-based pharmacoepidemiologic and health services research.

Fall risk and cardiovascular outcomes of first-line antihypertensive medications in nursing home residents.

BACKGROUND: Little evidence exists about the comparative effects of first-line antihypertensive medications (i.e., renin-angiotensin-aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short-term cardiovascular events between different first-line antihypertensive medication classes in adults receiving care in nursing homes (NH). METHODS: This was a retrospective cohort of Medicare fee-for-service beneficiaries receiving care in NHs. Patients newly dispensed first-line antihypertensive medications were identified using Part D claims (2015-2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall-related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6-month follow-up. Inverse-probability-of-treatment-weighted (IPTW) cause-specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides. RESULTS: Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non-white race. During a mean follow-up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention-to-treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66-1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88-1.66). The rates of MACE were similar between those taking anti-hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as-treated analyses. Subgroup analyses were generally consistent. CONCLUSIONS: Older adults with limited life expectancy experience similar rates of injurious falls and short-term cardiovascular events after initiating any of the first-line antihypertensive medications.

Osteosarcopenia and Mortality in Older Adults Undergoing Transcatheter Aortic Valve Replacement.

Importance: Osteosarcopenia is an emerging geriatric syndrome characterized by age-related deterioration in muscle and bone. Despite the established relevance of frailty and sarcopenia among older adults undergoing transcatheter aortic valve replacement (TAVR), osteosarcopenia has yet to be investigated in this setting. Objective: To determine the association between osteosarcopenia and adverse outcomes following TAVR. Design, Setting, and Participants: This is a post hoc analysis of the Frailty in Aortic Valve Replacement (FRAILTY-AVR) prospective multicenter cohort study and McGill extension that enrolled patients aged 70 years or older undergoing TAVR from 2012 through 2022. FRAILTY-AVR was conducted at 14 centers in Canada, the United States, and France between 2012 and 2016, and patients at the McGill University-affiliated center in Montreal, Québec, Canada, were enrolled on an ongoing basis up to 2022. Exposure: Osteosarcopenia as measured on computed tomography (CT) scans prior to TAVR. Main Outcomes and Measures: Clinically indicated CT scans acquired prior to TAVR were analyzed to quantify psoas muscle area (PMA) and vertebral bone density (VBD). Osteosarcopenia was defined as a combination of low PMA and low VBD according to published cutoffs. The primary outcome was 1-year all-cause mortality. Secondary outcomes were 30-day mortality, hospital length of stay, disposition, and worsening disability. Multivariable logistic regression was used to adjust for potential confounders. Results: Of the 605 patients (271 [45%] female) in this study, 437 (72%) were octogenarian; the mean (SD) age was 82.6 (6.2) years. Mean (SD) PMA was 22.1 (4.5) cm2 in men and 15.4 (3.5) cm2 in women. Mean (SD) VBD was 104.8 (35.5) Hounsfield units (HU) in men and 98.8 (34.1) HU in women. Ninety-one patients (15%) met the criteria for osteosarcopenia and had higher rates of frailty, fractures, and malnutrition at baseline. One-year mortality was highest in patients with osteosarcopenia (29 patients [32%]) followed by those with low PMA alone (18 patients [14%]), low VBD alone (16 patients [11%]), and normal bone and muscle status (21 patients [9%]) (P < .001). Osteosarcopenia, but not low VBD or PMA alone, was independently associated with 1-year mortality (odds ratio [OR], 3.18; 95% CI, 1.54-6.57) and 1-year worsening disability (OR, 2.11; 95% CI, 1.19-3.74). The association persisted in sensitivity analyses adjusting for the Essential Frailty Toolset, Clinical Frailty Scale, and geriatric conditions such as malnutrition and disability. Conclusions and Relevance: The findings suggest that osteosarcopenia detected using clinical CT scans could be used to identify frail patients with a 3-fold increase in 1-year mortality following TAVR. This opportunistic method for osteosarcopenia assessment could be used to improve risk prediction, support decision-making, and trigger rehabilitation interventions in older adults.

Dietary fat types and 4-year cognitive change in community-dwelling older women.

OBJECTIVE: A study was undertaken to relate dietary fat types to cognitive change in healthy community-based elders. METHODS: Among 6,183 older participants in the Women's Health Study, we related intake of major fatty acids (saturated [SFA], monounsaturated [MUFA], total polyunsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years after dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory, and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariate-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake. RESULTS: Higher SFA intake was associated with worse global cognitive (p for linear trend = 0.008) and verbal memory (p for linear trend = 0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest versus lowest SFA quintiles; the multivariate-adjusted odds ratio (OR) with 95% confidence interval (CI) was 1.64 (1.04-2.58) for global cognition and 1.65 (1.04-2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive (p for linear trend < 0.001) and verbal memory (p for linear trend = 0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31-0.88]) and verbal memory (0.56 [0.34-0.94]). Total fat, PUFA, and trans-fat intakes were not associated with cognitive trajectory. INTERPRETATION: Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, whereas higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging.

Frailty and Time at Home After Post-Acute Care in Skilled Nursing Facilities.

OBJECTIVES: To examine the association of a claims-based frailty index with time at home, defined as the number of days alive and spent out of hospital or skilled nursing facility (SNF). DESIGN: Cohort Study. SETTING AND PARTICIPANTS: A 5% Medicare random sample of fee-for-service beneficiaries, who had continuous part A and B enrollment in the prior 6 months, that were discharged from a short SNF admission in 2014‒2016. METHODS: Frailty was measured with a validated claims-based frailty index (CFI) (range: 0‒1, higher scores indicating worse frailty) and categorized into nonfrail (CFI <0.25), mild frailty (CFI 0.25‒0.34), and moderate-to-severe frailty (CFI ≥0.35). We measured home time in the 6 months following SNF discharge (range: 0‒182 days with higher values representing more days at home and thus a better outcome). We used logistic regression to assess the association between frailty and short home time, defined as <173 days, adjusting for age, sex, race, region, a comorbidity index, clinical SNF admission characteristics in the Minimum Data Set, and SNF characteristics. RESULTS: In our sample of 144,708 beneficiaries (mean age, 80.8 years, 64.9% female, 85.9% white) who were discharged to community after SNF stay, the mean CFI was 0.26 (standard deviation, 0.07). The mean home time was 165.6 (38.1) days in nonfrail, 154.4 (47.4) days in mild frailty, 145.0 (52.0) days in moderate-to-severe frailty group. After full model adjustments, moderate to severe frailty was associated with a 1.71 (95% CI 1.65‒1.78) higher odds of having short time at home in the 6 months following SNF discharge. CONCLUSION AND IMPLICATIONS: Higher CFI is associated with short time at home in Medicare beneficiaries who are discharged to the community after post-acute SNF stay. Our results support the utility of CFI in identifying SNF patients who need additional resources and interventions to prevent health decline and poor quality of life.

Comparison of Claims-Based Frailty Indices in U.S. Veterans 65 and Older for Prediction of Long-Term Institutionalization and Mortality.

BACKGROUND: Frailty is increasingly recognized as a useful measure of vulnerability in older adults. Multiple claims-based frailty indices (CFIs) can readily identify individuals with frailty, but whether 1 CFI improves prediction over another is unknown. We sought to assess the ability of 5 distinct CFIs to predict long-term institutionalization (LTI) and mortality in older Veterans. METHODS: Retrospective study conducted in U.S. Veterans ≥65 years without prior LTI or hospice use in 2014. Five CFIs were compared: Kim, Orkaby (Veteran Affairs Frailty Index [VAFI]), Segal, Figueroa, and the JEN-FI, grounded in different theories of frailty: Rockwood cumulative deficit (Kim and VAFI), Fried physical phenotype (Segal), or expert opinion (Figueroa and JFI). The prevalence of frailty according to each CFI was compared. CFI performance for the coprimary outcomes of any LTI or mortality from 2015 to 2017 was examined. Because Segal and Kim include age, sex, or prior utilization, these variables were added to regression models to compare all 5 CFIs. Logistic regression was used to calculate model discrimination and calibration for both outcomes. RESULTS: A total of 3 million Veterans were included (mean age 75, 98% male participants, 80% White, and 9% Black). Frailty was identified for between 6.8% and 25.7% of the cohort with 2.6% identified as frail by all 5 CFIs. There was no meaningful difference between CFIs in the area under the receiver operating characteristic curve for LTI (0.78-0.80) or mortality (0.77-0.79). CONCLUSIONS: Based on different frailty constructs, and identifying different subsets of the population, all 5 CFIs similarly predicted LTI or death, suggesting each could be used for prediction or analytics.

Preoperative frailty and adverse outcomes following coronary artery bypass grafting surgery in US veterans.

BACKGROUND: Contemporary guidelines emphasize the value of incorporating frailty into clinical decision-making regarding revascularization strategies for coronary artery disease. Yet, there are limited data describing the association between frailty and longer-term mortality among coronary artery bypass grafting (CABG) patients. METHODS: We conducted a retrospective cohort study (2016-2020, 40 VA medical centers) of US veterans nationwide that underwent coronary artery bypass grafting (CABG). Frailty was quantified by the Veterans Administration Frailty Index (VA-FI), which applies the cumulative deficit method to render a proportion of 30 pertinent diagnosis codes. Patients were classified as non-frail (VA-FI ≤ 0.1), pre-frail (0.1 < VA-FI ≤ 0.2), or frail (VA-FI > 0.2). We used Cox proportional hazards models to ascertain the association of frailty with all-cause mortality. Our primary study outcome was 5-year all-cause mortality; the co-primary outcome was days alive and out of the hospital within the first postoperative year. RESULTS: There were 13,554 CABG patients (median 69 years, 79% White, 1.5% women). The mean pre-operative VA-FI was 0.21 (SD: 0.11); 31% were pre-frail (VA-FI: 0.17) and 47% were frail (VA-FI: 0.31). Frail patients were older and had higher co-morbidity burdens than pre-frail and non-frail patients. Compared with non-frail patients (13.0% [11.4, 14.7]), there was a significant association between frail and pre-frail patients and increased cumulative 5-year all-cause mortality (frail: 24.8% [23.3, 26.1]; HR: 1.75 [95% CI 1.54, 2.00]; pre-frail 16.8% [95% CI 15.3, 18.4]; HR 1.2 [1.08,1.34]). Compared with non-frail patients (mean 362[SD 12]), pre-frail (mean 361 [SD 14]; p < 0.01) and frail patients (mean 358[SD 18]; p < 0.01) spent fewer days alive and out of the hospital in the first postoperative year. CONCLUSIONS: Pre-frailty and frailty were prevalent among US veterans undergoing CABG and associated with worse mid-term outcomes. Given the high prevalence of frailty with attendant adverse outcomes, there may be an opportunity to improve outcomes by identifying and mitigating frailty before surgery.

More intensive therapy as more effective treatment for frail patients with multiple myeloma [corrected].

Although randomized controlled trial data suggest that the more intensive triplet bortezomib-lenalidomide-dexamethasone (VRd) is superior to the less intensive doublet lenalidomide-dexamethasone (Rd) in patients newly diagnosed with multiple myeloma (MM), guidelines have historically recommended Rd over VRd for patients who are frail and may not tolerate a triplet. We identified 2573 patients (median age, 69.7 years) newly diagnosed with MM who were initiated on VRd (990) or Rd (1583) in the national US Veterans Affairs health care System from 2004 to 2020. We measured frailty using the Veterans Affairs Frailty Index. To reduce imbalance in confounding, we matched patients for MM stage and 1:1 based on a propensity score. Patients who were moderate-severely frail had a higher prevalence of stage III MM and myeloma-related frailty deficits than patients who were not frail. VRd vs Rd was associated with lower mortality (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70-0.94) in the overall matched population. Patients who were moderate-severely frail demonstrated the strongest association (HR 0.74; 95% CI, 0.56-0.97), whereas the association weakened in those who were mildly frail (HR, 0.80; 95% CI, 0.61-1.05) and nonfrail (HR, 0.86; 95% CI, 0.67-1.10). VRd vs Rd was associated with a modestly higher incidence of hospitalizations in the overall population, but this association weakened in patients who were moderate-severely frail. Our findings confirm the benefit of VRd over Rd in US veterans and further suggest that this benefit is strongest in patients with the highest levels of frailty, arguing that more intensive treatment of myeloma may be more effective treatment of frailty itself.

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

INTRODUCTION: The 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 METHODS: Using 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. RESULTS: Lung 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. DISCUSSION: The 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.

Alteration of the ß-catenin pathway in spiradenoma.

BACKGROUND: Although skin carcinogenesis has been widely investigated, only limited information is available for epidermal tumors, while even less is known about other skin structures. Alterations in the ß-catenin pathway have been reported in several epidermal tumors, while little is known about in adnexal tumors. This study was performed to assess alterations in the ß-catenin pathway associated with adnexal tumors, and to investigate the mechanisms underlying these alterations. METHODS: ß-Catenin expression in 48 adnexal tumors (trichoepithelioma, trichofolliculoma, pilomatricoma, syringoma, eccrine poroma, spiradenoma, sebaceous hyperplasia and nevus sebaceus) was assessed using immunohistochemistry. The tumors showing intense nuclear reactivity for ß-catenin were further evaluated by immunohistochemistry for ß-catenin degradation complex such as adenomatosis polyposis coli (APC), Axin and glycogen synthase kinase 3ß (GSK-3ß). RESULTS: Intense nuclear immunoreactivity for ß-catenin was observed in pilomatricoma and spiradenoma. Among 12 eccrine spiradenomas, APC was downregulated in 2 (16.7%) cases, and Axin and GSK-3ß were downregulated in 11 (91.7%) and 10 (83.3%) cases, respectively. CONCLUSIONS: This is the first reported analysis of the role of alterations in the ß-catenin pathway in spiradenoma. We suggest that downregulation of Axin and GSK-3ß in the ß-catenin pathway may be an important signaling alteration in the development of spiradenoma.