Unseen Burden of Injury: Post-Hospitalization Mortality in Geriatric Trauma Patients

Background/Objectives Older adults are at risk for adverse outcomes after trauma, but little is known about post-acute survival as state and national trauma registries collect only inpatient or 30-day outcomes. This study investigates long-term, out-of-hospital mortality in geriatric trauma patients. Methods Level I Trauma Center registry data were matched to the US Social Security Death Index (SSDI) to determine long-term and out-of-hospital outcomes of older patients. Blunt trauma patients aged ≥65 were identified from 2009 to 2015 in an American College of Surgeons Level 1 Trauma Center registry, n = 6289 patients with an age range 65-105 years, mean age 78.5 ± 8.4 years. Dates of death were queried using social security numbers and unique patient identifiers. Demographics, injury, treatments, and outcomes were compared using descriptive and univariate statistics. Results Of 6289 geriatric trauma patients, 505 (8.0%) died as an inpatient following trauma. Fall was the most common mechanism of injury (n = 4757, 76%) with mortality rate of 46.5% at long-term follow-up; motor vehicle crash (MVC) (n = 1212, 19%) had long-term mortality of 27.6%. Overall, 24.1% of patients died within 1 year of trauma. Only 8 of 488 patients who died between 1 and 6 months post-trauma were inpatient. Mortality rate varied by discharge location: 25.1% home, 36.4% acute rehabilitation, and 51.5% skilled nursing facility, P < .0001. Conclusion Inpatient and 30-day mortality rates in national outcome registries fail to fully capture the burden of trauma on older patients. Though 92% of geriatric trauma patients survived to discharge, almost one-quarter had died by 1 year following their injuries.

Mortality after large artery occlusion acute ischemic stroke

Despite randomized trials showing a functional outcome benefit in favor of endovascular therapy (EVT), large artery occlusion acute ischemic stroke is associated with high mortality. We performed a retrospective analysis from a prospectively collected code stroke registry and included patients presenting between November 2016 and April 2019 with internal carotid artery and/or proximal middle cerebral artery occlusions. Ninety-day mortality status from registry follow-up was corroborated with the Social Security Death Index. A multivariable logistic regression model was fitted to determine demographic and clinical characteristics associated with 90-day mortality. Among 764 patients, mortality rate was 26%. Increasing age (per 10 years, OR 1.48, 95% CI 1.25–1.76; p < 0.0001), higher presenting NIHSS (per 1 point, OR 1.05, 95% CI 1.01–1.09, p = 0.01), and higher discharge modified Rankin Score (per 1 point, OR 4.27, 95% CI 3.25–5.59, p < 0.0001) were independently associated with higher odds of mortality. Good revascularization therapy, compared to no EVT, was independently associated with a survival benefit (OR 0.61, 95% CI 0.35–1.00, p = 0.048). We identified factors independently associated with mortality in a highly lethal form of stroke which can be used in clinical decision-making, prognostication, and in planning future studies.

Benchmark Method for Cost Computations Across Health Care Systems: Cost of Care per Patient per Day in Breast Cancer Care

PURPOSE: To estimate the value of cancer care and to compare value among episodes of care, a transparent, reproducible, and standardized cost computation methodology is needed. Charges, claims, and reimbursements are related to cost but are nontransparent and proprietary. We developed a method to measure the cost of the following phases of care: (1) initial treatment with curative intent, (2) surveillance and survivorship care, and (3) relapse and end-of-life care. METHODS: We combined clinical data from our electronic health record, the state cancer registry, and the Social Security Death Index. We analyzed the care of patients with breast cancer and mapped Common Procedural Terminology (CPT) codes to the corresponding cost conversion factor and date in the CMS Medicare fee schedule. To account for varying duration of episodes of care, we computed a cost of care per day (CCPD) for each patient. RESULTS: Median CCPD for initial treatment was $29.45 in US dollars (USD), the CCPD for surveillance and survivorship care was $2.45 USD, and the CCPD for relapse care was $13.80 USD. Among the three breast cancer types (hormone receptor-positive or human epidermal growth factor receptor 2 [HER2]-negative, HER2-positive, and triple-negative), there was no difference in CCPD. Relapsed patients in the most expensive surveillance CCPD group had significantly shorter survival. CONCLUSION: We developed a method to identify high-value oncology care—cost of care per patient per day (CCPD)—in episodes of initial, survivorship, and relapse care. The methodology can help identify positive deviants (who have developed best practices) delivering high-value care. Merging our data with claims data from third-party payers can increase the accuracy and validity of the CCPD.

Healthcare resource utilization (HCRU), costs, and mortality in relation to select immune-related adverse events (irAEs) and line of therapy (LOT) in patients (pts) with advanced or metastatic urothelial cancer (UC) treated with immune checkpoint inhibitor (ICI) monotherapy.

427 Background: Data on HCRU and costs in US UC patients treated with ICIs is in its infancy, as there is little information by LOT or focused on irAEs due to ICI use. In addition, the relationship between irAEs and mortality is controversial, with some studies suggesting lower risk of mortality in pts with irAEs, whereas others have found no association between irAEs and mortality. We assessed the associations of 1) irAEs and 2) LOT with HCRU, costs, and mortality in UC pts treated with ICI monotherapy. Methods: This retrospective cohort study used administrative claims data linked with mortality data from the National Death Index and Social Security Death Index to identify US commercial and Medicare Advantage plan members with UC treated with ICI monotherapy between 1 Sep 2014 and 30 Apr 2019. The LOT number of ICI therapy was captured. Twenty-one irAEs were chosen a priori based on ASCO and NCCN guidelines and clinical input. Based on ICD codes from claims, newly occurring irAEs were captured from ICI initiation to the earliest of 6 months after initial ICI LOT ended, start of new treatment, death, disenrollment, or 30 Apr 2019; HCRU and costs were assessed during same time. Using Cox regression with ICI LOT and time-varying irAEs as the exposures, we computed adjusted hazard ratios (HRs). Lin’s regression analysis was used to calculate adjusted 6-month all-cause costs by irAE. Results: Among UC pts treated with ICI monotherapy (N=417; mean age 74 ± 10 years; 72% male; 17% received prior systemic steroids; 32% initiated ICI as LOT 1, 43% as LOT 2), 22% (n=90) had an irAE. Pts who received ICIs as 2L therapy were 1.5 (95% CI: 1.1-2.0) and 1.7 (95% CI: 1.2-2.4) times more likely to have an all-cause ER visit and inpatient stay, respectively, than those who received 1L. There was no difference in mortality risk between 2L and 1L subgroups (HR, 1.2 [95% CI: 0.9-1.6]). Pts with irAEs had a 60% higher risk of an all-cause ER visit (95% CI: 1.0-2.5) and more than double the risk of an all-cause inpatient stay (HR, 2.6 [95% CI: 1.7-4.0]) than pts without irAEs. Pts who experienced an irAE had higher mean all-cause healthcare costs over 6 months vs those without irAEs ($98,415 vs $75,300; p<0.001). Mortality rates were similar between UC pts with and without irAEs (HR, 1.2 [95% CI: 0.9-1.6]). Conclusions: Pts with irAEs had higher all-cause HCRU and costs than pts without, and pts who received ICIs as 2L therapy had higher HCRU and costs than those who received 1L. This real-world study did not find that irAEs were associated with mortality in UC pts treated with ICI monotherapy. To inform optimum use of ICIs and management of irAEs, future work should include longer follow-up and grade of severity and number of irAEs.

Heart Failure, Atrioventricular Block, and Ventricular Tachycardia in Sarcoidosis

Background Sarcoidosis is a granulomatous disease usually affecting the lungs, although cardiac morbidity may be common. The risk of these outcomes and the characteristics that predict them remain largely unknown. This study investigates the epidemiology of heart failure, atrioventricular block, and ventricular tachycardia among patients with and without sarcoidosis. Methods and Results We identified California residents aged ≥21 years using the Office of Statewide Health Planning and Development ambulatory surgery, emergency, or inpatient databases from 2005 to 2015. The risk of sarcoidosis on incident heart failure, atrioventricular block, and ventricular tachycardia were each determined. Linkage to the Social Security Death Index was used to ascertain overall mortality. Among 22 527 964 California residents, 19 762 patients with sarcoidosis (0.09%) were identified. Sarcoidosis was the strongest predictor of heart failure (hazard ratio [HR], 11.2; 95% CI, 10.7–11.7), atrioventricular block (HR, 117.7; 95% CI, 103.3–134.0), and ventricular tachycardia (HR, 26.1; 95% CI, 24.2–28.1) identified among all risk factors. The presence of any cardiac involvement best predicted each outcome. Approximately 22% (95% CI, 18%–26%) of the relationship between sarcoidosis and increased mortality was explained by the presence of at least 1 of these cardiovascular outcomes. Conclusions The magnitude of risk associated with sarcoidosis as a predictor of heart failure, atrioventricular block, and ventricular tachycardia, exceeds all established risk factors. Surveillance for and anticipation of these outcomes among patients with sarcoidosis is indicated, and consideration of a sarcoidosis diagnosis may be prudent among patients with heart failure, atrioventricular block, or ventricular tachycardia.

The Obesity Paradox in Emergency General Surgery Patients

Operative management of emergency general surgery (EGS) diagnoses involves a range of procedures which can carry high morbidity and mortality. Little is known about the impact of obesity on patient outcomes. The aim of this study was to examine the association between body mass index (BMI) >30 kg/m2 and mortality for EGS patients. We hypothesized that obese patients would have increased mortality rates. A regional integrated health system EGS registry derived from The American Association for the Surgery of Trauma EGS ICD-9 codes was analyzed from January 2013 to October 2015. Patients were stratified into BMI categories based on WHO classifications. The primary outcome was 30-day mortality. Longer-term mortality with linkage to the Social Security Death Index was also examined. Univariate and multivariable analyses were performed. A total of 60 604 encounters were identified and 7183 (11.9%) underwent operative intervention. Patient characteristics include 53% women, mean age 58.2 ± 18.7 years, 64.2% >BMI 30 kg/m2, 30.2% with chronic obstructive pulmonary disease, 19% with congestive heart failure, and 31.1% with diabetes. The most common procedure was laparoscopic cholecystectomy (36.4%). Overall, 90-day mortality was 10.9%. In multivariable analysis, all classes of obesity were protective against mortality compared to normal BMI. Underweight patients had increased risk of inpatient (OR = 1.9, CI = 1.7-2.3), 30-day (OR = 1.9, CI = 1.7-2.1), 90-day (OR = 1.8, CI 1.6-2.0), 1-year (OR = 1.8, CI = 1.7-2.0), and 3-year mortality (OR = 1.7, CI = 1.6-1.9). When stratified by BMI, underweight EGS patients have the highest odds of death. Paradoxically, obesity appears protective against death, even when controlling for potentially confounding factors. Increased rates of nonoperative management in the obese population may impact these findings.

Abstract 16182: Prognostic Value of Peak Oxygen Uptake Trajectories for Mortality Risk in Patients With Heart Failure

Introduction: Peak oxygen uptake (VO 2peak ), as determined by cardiopulmonary exercise testing (CPET), is informative of cardiovascular fitness and heart failure (HF) disease progression. Due to their clinical meaningfulness, many patients with HF undergo multiple CPETs throughout their lifetimes. However, a gap in knowledge exists regarding the prognostic value of longitudinal changes in VO 2peak for mortality risk. The aim of this study was to investigate whether VO 2peak trajectories are predictive of mortality among patients with HF. Methods: Patients with HF who completed two CPETs (separated by at least 3 months, mean = 25.3 months) at Washington University School of Medicine between May 1993 and February 2020 were included in the study. Vital statuses and mortality dates were collected from May 2019 to May 2020 via electronic health records and the Social Security Death Index. Kaplan-Meier and Cox proportional hazards regression analyses were used to evaluate associations between changes in VO 2peak and mortality. Results: The sample included 162 patients with a mean age of 48.5 years (SD 10.5) at baseline. VO 2peak averaged 18.1 (SD 4.9) ml·kg -1 ·min -1 in 121 men and 15.1 (SD 4.1) ml·kg -1 ·min -1 in 41 women. During a median follow-up of 11.8 years (range 1-23 years), 70 patients died. A significant negative association between VO 2peak and mortality was observed (hazard ratio [HR] = 0.92; 95% Confidence Interval [CI] = 0.87 to 0.98; P = 0.011). Patients whose VO 2peak increased from their baseline to second CPET had higher survival rates compared to patients whose VO 2peak decreased. Moreover, the annual rate of change in VO 2peak was associated with mortality rates. A 9% lower mortality rate was observed for each unit increase in VO 2peak change (i.e., 1 ml·kg -1 ·min -1 ) for the entire follow-up period (HR = 0.91; 95% CI = 0.85 to 0.97) and at 10-year follow-up (HR = 0.91; 95% CI = 0.85 to 0.98), while a 12% lower mortality rate was observed at 5-year follow-up (HR = 0.88, 95% CI = 0.78 to 1.00) relative to baseline CPETs. Conclusion: Increases in VO 2peak were associated with increased survival rate among patients with HF. These findings highlight the importance of promoting exercise and cardiac rehabilitation for patients with HF.

187 Real-world treatment patterns and clinical predictors of overall survival among anti-PD-1 exposed advanced melanoma patients with documented evidence of disease progression

BackgroundImmuno-oncology (I-O) plays a major role in the treatment of advanced melanoma (aMel); however, resistance to therapy remains an important clinical problem. This study examined treatment patterns and overall survival (OS) for aMel patients who progressed on anti-programmed death ligand 1 (anti-PD-1) therapy in a real-world clinical setting.MethodsA retrospective database study of Flatiron electronic medical records (EMR) was conducted with 304 aMel patients who progressed on first or second line anti-PD1 (baseline) therapy with pembrolizumab or nivolumab and received subsequent (index) therapy with ≥3 months of potential follow-up. Patients who discontinued treatment for reasons other than progression (primarily toxicity) were excluded. The primary outcome was OS, defined using EMR data linked to external mortality sources (e.g. Social Security Death Index). OS analysis was stratified by several factors (e.g. age, ECOG, BRAF, LDH, type of index therapy, and best overall response [BOR] to baseline anti-PD-1 therapy). BOR defined as response, stable disease, or disease progression was based on clinician assessment following radiographic imaging. Descriptive and log-rank test statistics for OS were used.ResultsAmong patients receiving index therapy (n=304), 50% received I-O (n=91/151 combination therapy), 36% received BRAFi/MEKi (n=102/109 combination therapy) and 14% received other therapies (n=34/44 chemotherapy). Median (range) age was 67 (23–85) years, with 65% male, 62% ECOG≤1, 33% elevated LDH, and 51% with BRAF mutations. Most patients received baseline anti-PD1 monotherapy (77%) as first line therapy. Median OS (95%CI) was 7.2 (6.4, 8.8) months, with a significant OS association with ECOG≤1 (p<0.001), normal LDH (p<0.001), and BRAFi/MEKi (p=0.02), with higher median OS of 9 vs 5 months, 11 vs 6 months, and 11 vs 7 and 6 months, respectively, compared to patients with ECOG≥2, elevated LDH, and treated with I-O and other therapies. For a subgroup of index therapy patients with a BOR assessment to baseline anti-PD-1 therapy (n=237), there was a significant association (p<0.01) of OS with BOR to baseline therapy, with higher median OS for those with an initial response (12 months) or stable disease (14 months) compared to a BOR of disease progression (6 months). There was also a significant OS association with BOR to baseline anti-PD-1 therapy for the subgroups receiving I-O therapy (n=119/237, p<0.01) and other therapies (n=37/237, p=0.01).ConclusionsSuboptimal OS in patients who progress on anti-PD-1 therapy in a real-world clinical setting, with predictors of enhanced survival, highlights the need for further research to inform optimal treatment strategies.AcknowledgementsThe authors would like to acknowledge the contributions of Bo Zheng, Clemens Krepler, Diana Malandrucollo, and Shelby Marx of Merck & Co, Inc.

Association of Body Mass Index With Coronary Artery Calcium and Subsequent Cardiovascular Mortality

Background: Obesity is associated with higher risk for coronary artery calcium (CAC), but the relationship between body mass index (BMI) and mortality is complex and frequently paradoxical. Methods: We analyzed BMI, CAC, and subsequent mortality using data from the CAC Consortium, a multi-centered cohort of individuals free of established cardiovascular disease (CVD) who underwent CAC testing. Mortality was assessed through linkage to the Social Security Death Index and cause of death from the National Death Index. Multivariable logistic regression was used to determine odds ratios for the association of clinically relevant BMI categories and prevalent CAC. Cox proportional hazards regression modeling was used to determine hazard ratios for coronary heart disease, CVD, and all-cause mortality according to categories of BMI and CAC. Results: Our sample included 36 509 individuals, mean age 54.1 (10.3) years, 34.4% female, median BMI 26.6 (interquartile range, 24.1–30.1), 46.6% had zero CAC, and 10.5% had CAC ≥400. Compared with individuals with normal BMI, the multivariable adjusted odds of CAC >0 were increased in those overweight (odds ratio, 1.13 [95% CI, 1.1–1.2]) and obese (odds ratio, 1.5 [95% CI, 1.4–1.6]). Over a median follow-up of 11.4 years, there were 1550 deaths (4.3%). Compared with normal BMI, obese individuals had a higher risk of coronary heart disease, CVD, and all-cause mortality while overweight individuals, despite a higher odds of CAC, showed no significant increase in mortality. In a sex-stratified analysis, the increase in coronary heart disease, CVD, and all-cause mortality in obese individuals appeared largely limited to men, and there was a lower risk of all-cause mortality in overweight women (hazard ratio, 0.79 [95% CI, 0.63–0.98]). Conclusions: In a large sample undergoing CAC scoring, obesity was associated with a higher risk of CAC and subsequent coronary heart disease, CVD, and all-cause mortality. However, overweight individuals did not have a higher risk of mortality despite a higher risk for CAC.

Sipuleucel-T (sip-T) and oral androgen axis inhibitors in black men being treated for metastatic castration-resistance prostate cancer (mCRPC): Observations from the Medicare Fee for Service (FFS) population.

e17589 Background: Black men historically have been underrepresented in clinical trials, contributing to poor understanding of potential race-based differences in prostate cancer care and biology. This retrospective, real world analysis examines survival outcomes in black men who received sip-T or oral agents like abiraterone or enzalutamide for mCRPC. Methods: Using Medicare Fee for Service Identifiable Research data, we identified racially black men with a qualifying prostate cancer diagnosis (ICD-9 185, ICD-10 C-61) and an initial drug claim for treatment (abiraterone acetate, cabazitaxel, docetaxel, enzalutamide, radium-223, or sip-T) in 2014 or 2015. Continuous Part A, B, and D eligibility and no HMO enrollment were required for 24 months or until death per Social Security Death Index. We compared outcomes in black patients who received sip-T at any time vs those who received an oral agent in any line and no sip-T. Survival was estimated using the Kaplan-Meier method (unadjusted) and hazard ratios using Cox proportional hazards regression. Results: Of 14,456 patients identified in 2014 and 2015, 1603 were racially black. Among eligible men, 140 received sip-T and 1266 received an oral agent. At 24 months, 76% of men who received sip-T were still alive compared with 49% of those who received the oral agents (Table). Median OS was not estimable in men who received sip-T but was 23.1 months (95% CI: 21.6, NE) in those who received oral agents (Table). In a univariate model, use of sip-T resulted in a 63% reduction in risk of death compared to never receiving sip-T (HR, 0.37 [95% CI, 0.26, 0.52], P < 0.0001). Conclusions: In this real world analysis of black mCRPC patients, sip-T at any point was associated with longer OS over those receiving the oral agents without ever receiving sip-T. Development of a multivariate model is planned. [Table: see text]