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Introduction Nonvalvular atrial fibrillation (NVAF) is associated with a substantial economic burden, particularly in patients with comorbid conditions. This study compared healthcare resource utilization (HRU) and costs of rivaroxaban and warfarin in patients with NVAF, obesity, and diabetes. Methods A de-identified healthcare claims database was used to identify adult patients newly initiating rivaroxaban or warfarin and having at least one medical claim with a diagnosis of AF, obesity determined by validated algorithm, and at least one claim with a diagnosis of diabetes or for antidiabetic medication from December 2011 to March 2020. Propensity score matching was used to balance the treatment cohorts on the basis of demographics and baseline characteristics. All-cause and NVAF-related HRU rates and costs were compared between treatments using rate ratios, and mean cost differences were calculated on a per patient per year (PPPY) basis. Results A total of 9999 matched pairs of patients with NVAF, obesity, and diabetes were identified in the rivaroxaban and warfarin cohorts. Rate ratios of all-cause HRU were significantly reduced with rivaroxaban versus warfarin in all healthcare settings evaluated, except emergency room visits. The greatest impact was on physician office visits followed by hospital outpatient and inpatient visits. NVAF-related HRU was significantly lower for rivaroxaban versus warfarin in all care settings. Consistent with these findings, the length of hospital stay was significantly reduced by approximately 4 days among all patients for both all-cause and NVAF-related hospitalizations in the rivaroxaban cohort compared with the warfarin cohort. Rivaroxaban was associated with reductions in all-cause total healthcare costs by more than $5000 PPPY and NVAF-related medical costs by approximately $1100 PPPY. Conclusion In comparison with warfarin, rivaroxaban reduced HRU and costs, particularly hospital inpatient and outpatient visits and physician office visits, in patients with NVAF and comorbidities of obesity and diabetes. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01161-4., Plain Language Summary People who are overweight or obese are at risk of developing atrial fibrillation (AF) along with other medical conditions, such as diabetes. Standard therapy with oral anticoagulants or blood thinners is recommended to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF (NVAF). In this study, we evaluated healthcare insurance claims for people with NVAF, obesity, and diabetes who started therapy with warfarin or rivaroxaban from 2011 to 2020 to compare the use and cost of healthcare services, such as hospitalizations and doctor visits, using diagnosis and procedure codes. The study included nearly 20,000 patients with similar characteristics. Patients who started treatment with rivaroxaban used fewer healthcare services for any cause and for those related to NVAF than those who started treatment with warfarin. The difference in use of services was largest for hospital outpatient and inpatient visits and doctor office visits; emergency room visits were only different for those related to NVAF. Length of hospital stay was also shorter for patients receiving rivaroxaban versus those receiving warfarin. These differences in healthcare service use translated into lower costs associated with rivaroxaban versus warfarin. The findings of this study suggest that treatment with rivaroxaban reduces the use of healthcare services compared with warfarin. This difference may be related, in part, to the reduced risks of stroke and systemic embolism observed in other real-world studies with rivaroxaban compared to warfarin. In addition, rivaroxaban does not require routine blood testing, which is required with warfarin treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01161-4.

Introduction Multiple myeloma (MM) is a malignancy of plasma cells; most MM patients will eventually relapse or become refractory to treatment. Treating MM patients remains a challenge since patients eventually progress through several lines of therapy (LOTs), requiring the use of multiple MM drug classes. We examined healthcare resource utilization (HCRU) and the costs incurred by MM patients following triple class exposure (TCE; defined as exposure to a proteosome inhibitor, an immunomodulatory agent, and an anti-CD-38 antibody). Methods Adult MM patients were selected from the MarketScan® commercial and Medicare supplemental databases (January 2009–February 2021). From this cohort, patients who had TCE and ≥ 1 subsequent LOT that occurred after January 1, 2017 were included in the study population. The initiation date for the first post-TCE LOT was defined as the index date. All-cause and MM-related HCRU and the associated costs were examined post-index date. Results A total of 85 MM patients with TCE who initiated ≥ 1 subsequent LOT post-TCE and had ≥ 1 year of follow-up post-index date were included in the study population; mean age on index date was 58.8 years, and 60.0% were male. The time from first-observed MM diagnosis until index date averaged 47.5 months. During an average follow-up of 20.9 months post-index date, 64.7% of patients (N = 55) initiated a second LOT and 35.2% (N = 30) received at least 3 LOTs. During follow-up, mean total all-cause healthcare cost per patient was $722,992 (equivalent to $34,578 per patient per month [PPPM]). Approximately 90.7% ($655,524 per patient) of the total all-cause healthcare costs were MM related, 66.0% of which were MM drug/infusion costs. Conclusion In this real-world US study, MM patients with TCE incurred high healthcare costs, with the majority being MM related and primarily attributed to MM drug and infusion costs. Supplementary Information The online version contains supplementary material available at 10.1007/s40487-021-00175-z.

Objective. To explore the anthropometric indicators suitable for screening for nonalcoholic fatty liver disease (NAFLD) in the elderly population. Methods. This cross-sectional study screened subjects over 65 years, who had undergone a physical examination in 2019. Their height, weight, waist circumference, and fasting blood glucose and triglyceride levels were measured. Body mass index (BMI), waist circumstance (WC), waist-to-height ratio (WHtR), relative fat mass (RFM), ponderal index (PI), conicity index (CI), lipid accumulation product (LAP), and body shape index (ABSI) were calculated. Statistical analyses were performed using the Chi-square test, logistic regression, and receiver operating characteristic (ROC) curve. Subjects. Of a total of 4985 subjects, 1173 diagnosed with NAFLD and 3812 without NAFLD were included. Results. The NAFLD group had increased BMI, WC, WHtR, RFM, PI, CI, and LAP. ABSI was only significantly different in males between the groups. Logistic regression analysis showed that RFM was an effective prognostic factor for males with NAFLD, and LAP, BMI, and WC were effective prognostic factors for females. ROC curve analysis showed that LAP played a significant role in the prediction of NAFLD. Conclusion. LAP is closely related to the occurrence of NAFLD and could be an efficient screening and treatment tool for NAFLD in the elderly people. Lay Summary. We conducted a screening and study of nonalcoholic fatty liver disease in the elderly population by determining the association between obesity indexes and nonalcoholic fatty liver disease. We found that LAP is practical, easy-to-measure tool for screening and studying NAFLD in the high-risk community elderly population, making it a valuable indicator in research.

Objective: To describe chemotherapy treatments, associated health care use and costs, and survival for women diagnosed with cervical cancer in the United States.Methods: This was a retrospective co...

Expedited reporting of unexpected serious adverse reactions that occur during clinical trials conducted under an IND is a critical component of the clinical trial process designed to protect patients by identifying potential safety issues with new agents. However, in recent years, the US FDA has presented extensive data about the problem of uninformative IND safety reporting. Despite published guidance documents aimed at clarifying requirements for submission of IND safety reports for individual events, there continues to be significant over-reporting of these events by many sponsors. This leads to excessive burden for the sponsors, the investigators who conduct clinical trials, and the FDA reviewers, who must evaluate each individual report submitted by the sponsor. This trend has the potential to endanger patients by obscuring true safety signals. To address this problem, LUNGevity Foundation empaneled a multi-sector working group of its Scientific and Clinical Research Roundtable (SCRT) charged with identifying ways to reduce unnecessary distribution of serious adverse events (SAEs) reports. This paper outlines the working group's activities, including a brief list of serious adverse events "anticipated" to occur within the lung cancer population that are either related to the underlying disease or condition being studied, concomitant or background therapy, or events associated with a demographic parameter such as age. These "anticipated" events, while required to be reported by investigators to sponsors, in general, should not then be individually reported by sponsors to FDA and to individual investigators in an IND safety report because these events require aggregate analysis across the development program to determine if they occur more frequently in treated versus untreated patients. This paper also includes discussion of how the use of background threshold values, generated from real-world data, could serve as one potential tool to guide sponsors in making causality assessments. If sponsors and other key stakeholders within the clinical research ecosystem embrace this type of approach and refrain from reporting "anticipated" events as single IND safety reports to the FDA staff and to each participating investigator, it could significantly reduce the amount of unnecessary reporting and serve as a model for other disease areas.

Most cases of small cell lung cancer (SCLC) are diagnosed at an advanced stage. The objective of this study was to investigate patient characteristics, survival, chemotherapy treatments, and health care use after a diagnosis of advanced SCLC in subjects enrolled in a health system network. This was a retrospective cohort study of patients aged ≥ 18 years who either were diagnosed with stage III/IV SCLC or who progressed to advanced SCLC during the study period (2005–2015). Patients identified from the Indiana State Cancer Registry and the Indiana Network for Patient Care were followed from their advanced diagnosis index date until the earliest date of the last visit, death, or the end of the study period. Patient characteristics, survival, chemotherapy regimens, associated health care visits, and durations of treatment were reported. Time-to-event analyses were performed using the Kaplan-Meier method. A total of 498 patients with advanced SCLC were identified, of whom 429 were newly diagnosed with advanced disease and 69 progressed to advanced disease during the study period. Median survival from the index diagnosis date was 13.2 months. First-line (1L) chemotherapy was received by 464 (93.2%) patients, most commonly carboplatin/etoposide, received by 213 (45.9%) patients, followed by cisplatin/etoposide (20.7%). Ninety-five (20.5%) patients progressed to second-line (2L) chemotherapy, where topotecan monotherapy (20.0%) was the most common regimen, followed by carboplatin/etoposide (14.7%). Median survival was 10.1 months from 1L initiation and 7.7 months from 2L initiation. Patients in a regional health system network diagnosed with advanced SCLC were treated with chemotherapy regimens similar to those in earlier reports based on SEER-Medicare data. Survival of patients with advanced SCLC was poor, illustrating the lack of progress over several decades in the treatment of this lethal disease and highlighting the need for improved treatments.

Aims To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes. Methods Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. Results A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74–0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78–1.09). Conclusions In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Background Despite the availability of pharmacologic and nonpharmacologic treatment options, depression continues to be one of the leading causes of disability worldwide. This study evaluated whether depression symptom severity, as measured by PHQ-9 score, of patients diagnosed with MDD is associated with short-term risk of a hospital encounter (ER visit or inpatient stay). Methods Adults with ≥1 PHQ-9 assessment in an outpatient setting (index date) and ≥ 1 MDD diagnosis within 6 months prior were included from the de-identified Optum Electronic Health Record database (April 2016–June 2019). Patients were categorized by depression symptom severity based on PHQ-9 scores obtained by natural language processing. Crude rates, adjusted absolute risks, and adjusted relative risks of all-cause and MDD-related hospital encounters within 30 days following assessment of depression severity were determined. Results The study population consisted of 280,145 patients with MDD and ≥ 1 PHQ-9 assessment in an outpatient setting. Based on PHQ-9 scores, 26.9% of patients were categorized as having none/minimal depression symptom severity, 16.4% as mild, 24.7% as moderate, 19.6% as moderately severe, and 12.5% as severe. Among patients with none/minimal, mild, moderate, moderately severe, and severe depression, the adjusted absolute short-term risks of an initial all-cause hospital encounter were 4.1, 4.4, 4.8, 5.6, and 6.5%, respectively; MDD-related hospital encounter adjusted absolute risks were 0.8, 1.0, 1.3, 1.6, and 2.1%, respectively. Compared to patients with none/minimal depression symptom severity, the adjusted relative risks of an all-cause hospital encounter were 1.60 (95% CI 1.50–1.70) for those with severe, 1.36 (1.29–1.44) for those with moderately severe, 1.18 (1.12–1.25) for those with moderate, and 1.07 (1.00–1.13) for those with mild depression symptom severity. Conclusions These study findings indicate that depression symptom severity is a key driver of short-term risk of hospital encounters, emphasizing the need for timely interventions that can ameliorate depression symptom severity.

Aim: We evaluated the relationship between clinical and genomic characteristics and tumor mutational burden (TMB) in small cell lung cancer. Materials & methods: In a retrospective analysis of small cell lung cancer patients aged ≥18, we assessed treatment patterns and survival in relation to TMB; the association of clinical and genomic characteristics with TMB was determined by multivariate regression. High TMB (TMB-H) was defined as ≥10 mutations/megabase. Results: Among 186 patients, treatment patterns and overall survival were similar for TMB-H and non-TMB-H patients. TMB was determined for 179 patients, 41.9% of whom were TMB-H. Short variants of LRP1B, FAT3, MLL3, MED12 and NOTCH3 were significantly associated with TMB-H (p ≤ 0.01). Conclusion: Neither treatment patterns nor survival differed by TMB status.

298 Background: Guidelines recommend mutation testing prior to initiating first-line therapy (L1) for patients with advanced non-small cell lung cancer (aNSCLC), including testing for epidermal growth factor receptor (EGFR) mutations. Guidelines also recommend further testing after patients progress on targeted therapy to identify possible resistance mutations and inform selection of subsequent treatment. The present study characterized real-world (RW) EGFR testing patterns in aNSCLC patients. Methods: This retrospective observational cohort study evaluated an aNSCLC cohort (stage IIIB or higher) from the Flatiron Health database. Eligible patients were newly diagnosed, ≥18 years old, and received at least one line of therapy (LOT) during 2015-2020. Patients were followed to last activity, death, or end of the study period, whichever came first. Results: The final study cohort included a total of 22,726 patients. Of these, 17,165 (75.5%) had ≥1 EGFR test and 2,611 (15.2% of the tested study population) tested positive for EGFR mutations at any time during the study. The proportion of aNSCLC patients receiving EGFR testing prior to L1 initiation increased from 45.2% in 2015 to 56.6% in 2020. Among 11,791 patients who had an EGFR test prior to initiation of L1, 1,944 (16.5%) had positive results. Of these, the cumulative proportion of patients receiving a second EGFR test prior to L2, L3, and L4 (contingent on receiving the following LOT) was 36.3% (322 out of 888), 55.4% (241 out of 435), and 67.0% (146 out of 218), respectively. From 2015-2020, the median time from sample collection to EGFR test results decreased from 26 to 16 days for next generation sequencing (NGS) tests and from 17.5 to 12 days for polymerase chain reaction (PCR) tests. During this same period, the proportion of NGS EGFR tests increased from 27.6% to 75.0%. In addition, use of plasma samples for EGFR tests increased substantially (6.3% to 36.5%). Conclusions: The proportion of aNSCLC patients tested for EGFR mutations has increased over time (2015-2020). Median time to available EGFR test result has decreased for both NGS and PCR tests. NGS testing has become increasingly more common as has use of plasma samples. However, opportunities for improvement exist, including further increasing the proportion of patients tested prior to initiation of L1 therapy, as well as testing prior to the selection of subsequent therapy when indicated. As more targeted therapies emerge and resistance mutations to current therapies are further characterized, continued refinement of RW testing practices is required to optimize patient care.

Temozolomide (TMZ) is used to treat adult patients with glioblastoma multiforme (GBM). Cases of hepatotoxicity have been reported among patients using TMZ. The objective of the study was to assess the relation, if any, between exposure to TMZ and serious acute liver injury (SALI). We used the HealthCore Integrated Research Database to perform a case-control study nested within a retrospective cohort of adult patients aged 18-100 years with at least two diagnoses of brain cancer anytime between 2006 and 2014. Patients without continuous eligibility or with a SALI diagnosis within 6 months prior to the date of incident brain cancer diagnosis were excluded. Medical records were sought for potential SALI cases and reviewed by two hepatologists. Five controls were selected for each case using incidence density sampling, matched on age and calendar year of index date. The analysis included 61 confirmed SALI cases and 305 selected controls. Exposure to TMZ was classified according to dispensing date and days supply of medication dispensed. We estimated odds ratios using conditional logistic regression models. The odds ratio for any exposure to TMZ was 0.91 (95% CI 0.44-1.91), for recent exposure to TMZ was 0.62 (95% CI 0.21-1.85). There was no increased risk of SALI with increasing duration of exposure to TMZ. When patients with unconfirmed SALI were included in the analysis, results were similar (OR 1.04; 95% CI 0.70-1.54). In conclusion, this study did not find an association between TMZ and SALI risk among patients with brain cancer.

BACKGROUND NF1-related PN can cause substantial morbidity, with no currently approved drug treatment available for PN treatment. Although surgery is the standard of care, complete resection of PN is often difficult due to encasement of vital structures and invasive and extensive PN growth. With limited real-world data among children with NF1-related PN, the study objectives were to describe the demographic, clinical characteristics, and treatment of these children. METHODS A cross-sectional analysis of existing CTF web-based, patient-entered, registry data collected between 2012–2018 was conducted. To be included in analysis, patients had to complete at least one registry survey, and be ≤ 19 years of age at the time of first survey completion, with patient- or parent/ guardian reported diagnosis of NF1 and at least 1 PN. Descriptive statistical analysis was conducted on data collected from the first survey for each patient, to describe patient characteristics and treatment patterns. Results were stratified by region (US, ex-US). RESULTS The sample included 943 pediatric patients (n=750 US, n=193 ex-US). The majority (85.9%) were less than 5 years of age at NF1 diagnosis (US: 87.6%; ex-US: 79.3%). Approximately half were male, and half reported more than 1 PN. The most common PN site include head (15.1%) and neck (12.6%). More than half of patients received no treatment (53.1%) for their PN. The most common treatments reported for PN were surgery (27.0%) and chemotherapy or drug therapy (10.0%). These results were generally consistent across regions. A malignant peripheral nerve sheath tumor (MPNST) and optic glioma (OG) were diagnosed in 21 (2.2%) and 308 (32.7%) patients, respectively; a large proportion of OG patients remained untreated (57.5%). Too few ex-US patients were available for detailed regional analysis. CONCLUSIONS This study demonstrated that a large proportion of children diagnosed with NF1-related PN remain untreated, highlighting a substantial unmet need.

Purpose Few studies have examined patients with prediabetes in usual, “real-world” clinical practice settings. Among patients with impaired fasting glucose (IFG), we aimed to describe the rates of progression to diabetes and to examine the long-term reduction in diabetes risk associated with regression to normoglycemia at 1 year. Methods The UK-based study included 120 055 non-diabetic patients in Clinical Practice Research Datalink from 2001 to 2012 aged 25+ years and with ≥1 fasting plasma glucose (FPG) test between ≥6.1 and

Context Understanding clinical characteristics and treatment selection for elderly patients is essential in the era of novel agents. informCLL ( NCT02582879 , September 2015 initiation) is an ongoing, US-based, prospective, real-world observational registry of patients with CLL. Objective To characterize overall demographics of previously untreated elderly CLL patients and compare clinical factors and treatment choice of those aged 65-74 years (Group 1) versus ≥75 years (Group 2). Design/Patients An interim analysis (November 2018 data cut) of previously untreated patients from the informCLL registry who were aged ≥65 years and received single-agent ibrutinib, chemoimmunotherapy, or immunotherapy at enrollment. Association between age groups and treatment choice was assessed by multinomial logistic regression after adjusting for comprehensive demographic and clinical factors. Results Analysis included 449 elderly patients (Group 1: 238; Group 2: 211); median age was 74 years. Most patients were male (64.1%), white (92.4%), treated in community settings (94.9%), and Medicare/Medicaid-insured (88.4%). Median time from initial diagnosis to first treatment was 2.0 years. The majority had an Eastern Cooperative Oncology Group (ECOG) score ≤ 1 (87.1%) and Charlson Comorbidity Index (CCI) score ≤ 1 (62.0%). The most common comorbidities were hypertension (69.3%), other cardiovascular disorders (29.2%), non-CLL malignancies (26.3%), and connective tissue diseases (24.5%). Documented cytogenetic/molecular testing rates were low: TP53, 6.01%; IGHV, 5.35%; CLL FISH, 17.8%; any of the three, 18.7%. 202 (45.0%) patients received ibrutinib, 170 (37.9%) received chemoimmunotherapy, and 77 (17.1%) received immunotherapy. Group 2 (vs Group 1) had poorer performance status (ECOG scores ≥2, 12.9% vs 5.7%, p=0.01), more comorbidities (CCI scores ≥2, 45.5% vs 31.1%, p Conclusions Previously untreated real-world CLL patients aged ≥75 years (vs 65-74 years) had poorer performance status, more comorbidities, lower cytogenetic/molecular testing rates, and a higher likelihood of receiving ibrutinib versus chemoimmunotherapy as initial treatment.

e18069 Background: Historically, recurrence in ovarian cancer (OC) following first-line (1L) chemotherapy (CT) occurs in up to 80% of patients within 2 years. The Clinical Classification Software (CCS) systematically classifies thousands of ICD-9 codes into a smaller number of clinically meaningful categories. We sought to use CCS and other routinely collected variables to differentiate the clinical and demographic profiles of patients with good prognosis (GP) versus poor prognosis (PP) in the United States (US). Methods: This was a retrospective cohort study of newly diagnosed (FIGO stage II - IV), treatment-naïve patients, ≥ 66 years, who received 4-10 cycles of platinum-based 1L CT between Jan 2009 - Dec 2015 using the SEER-Medicare database, a nationally representative cancer registry. Patient were assumed to have progressed to a subsequent line of therapy following a gap between consecutive CT cycles ≥ 63 days. Patients were classified as GP if alive ≥4 years with no further treatment following 1L CT; PP was defined as receipt of ≥2L CT within 12 months of initial 1L CT. Demographic and prognostic characteristics were assessed during a 6-month baseline period prior to initiation of 1L CT. We assessed clinically meaningful differences in baseline characteristics with absolute standardized differences (ASD) using a threshold of 0.1 (indicating negligible difference between two cohorts). Results: There were a total of 2,262 patients (mean age: 74.6 ±6.2 years) including 251 GP (11%) and 209 PP (9%) patients (table below). PP patients were significantly more likely to be older than 70 years, and present at stage IV, liver disease and ascites, and anemia at diagnosis. PP patients were also less likely to have primary debulking surgery. Conclusions: Approximately one tenth of OC patients received no further treatment 4 years after the initial treatment with contemporary standard of care. GP may be differentiated from PP on the basis of commonly used clinical characteristics such as stage and also specific comorbidities such as liver disease and ascites. [Table: see text]

Purpose This study sought to better understand real-world treatment patterns, overall and non–small-cell lung cancer (NSCLC)-specific survival, adverse event (AE) occurrence, and economic impact of first-line cancer therapies in Medicare patients. Patients and Methods This retrospective cohort study identified patients ≥ 65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database who received a first-time advanced (stage IV) NSCLC diagnosis from 2007 to 2011, and who received first-line platinum-based chemotherapy from 2007 through mid-2013. First-line regimens, healthcare resource use, occurrence of AEs, and associated costs (2013 US dollars) were analyzed. Median survival was determined using the Kaplan-Meier method. Results Surprisingly, only 46% of patients (n = 13,472) with stage IIIB/IV NSCLC received systemic therapy, and 5931 received platinum-based therapy. The mean age was 73 years, with 3354 (57%) males; 1489 (25%) had squamous and 4442 (75%) nonsquamous histology. The most common regimens were carboplatin doublets (70%), including carboplatin/paclitaxel (38%), carboplatin/pemetrexed (12%), carboplatin/gemcitabine (11%), and carboplatin/docetaxel (7%). The median overall survival from first-line therapy initiation was 7.2 months (95% confidence interval, 7.0-7.5 months). Dyspnea and anemia were the most common AEs of interest, whereas atypical pneumonia was associated with the greatest AE-related costs (mean, $5044). The mean total per-patient-per-month cost was $11,909, with AE-related costs comprising 9% of total costs. The highest costs and survival were observed for patients treated with carboplatin/pemetrexed and bevacizumab/carboplatin/paclitaxel. Conclusions These real-world data illustrate the most common first-line regimens by histology, overall survival, AEs, and some of the high AE-related costs of therapy for advanced NSCLC, and provides extremely useful information for clinicians.

Systemic chemotherapy has long been the standard of care for advanced bladder cancer, but its cost implications are poorly understood. The objective of this analysis was to estimate survival and health care costs for patients with stage IV bladder cancer who did or did not receive chemotherapy.This was a retrospective cohort study of patients identified in the Surveillance, Epidemiology, and End Results-Medicare database with a new primary diagnosis of stage IV bladder cancer between January 2007 and December 2011. Survival and health care visits and costs following the date of diagnosis were determined for treated and untreated patients. Costs were expressed in 2016 US dollars.A total of 1215 patients were diagnosed with stage IV bladder cancer, of whom 411 (33.8%) were treated with chemotherapy and 804 (66.2%) were untreated. Median overall survival was 10 months longer for treated than for untreated patients: 13.2 (95% confidence interval, 12.3-14.1) months versus 3.2 (95% confidence interval, 3.0-3.5) months. Treated patients had fewer per-patient-per-month (PPPM) health care visits than untreated patients (7.5 vs. 10.2, P .01) and lower total PPPM health care costs ($10,707 vs. $18,935). Overall mean total lifetime costs were greater for treated than for untreated patients ($139,893 vs. $66,829, P .05), which was driven by an approximate 4-fold increase in life expectancy for the treated patients.Approximately two thirds of patients diagnosed with stage IV bladder cancer were not treated with systemic chemotherapy. Increasing the percentage of treated patients in this population could potentially extend overall survival while simultaneously lowering PPPM costs.

e18226 Background: Limited chemotherapy data is available for elderly cervical cancer patients (pts). This study aimed to investigate real-world use of systemic therapies, survival, and costs among elderly pts in U.S. Methods: Pts who aged 65+ years and initially diagnosed with cervical cancer between 2007 and 2013 were identified using the SEER-Medicare data. Regimens were classified into 3 mutually-exclusive categories, i.e. cisplatin (Cis), carboplatin (Car), and Other based therapies. Chemotherapy within 90 days of surgery or radiation therapy were not considered as first line (1L) systemic therapy. All costs were converted to 2016 US dollars. Results: A total of 1 651 eligible pts were identified with 430 (26%) being stage IV at diagnosis. Among pts received systemic therapies, the median overall survival (OS) was 14 m from 1L initiation and 10 m from 2L initiation. Among 225 pts who received 1L, 58% pts received Cis-based therapy, and 17% pts received Car-based therapy. Car + paclitaxel was the most commonly used regimen (44%). Among 73 pts who received 2L, 34% and 15% pts received Cis- and Car-based therapy, respectively. Pts with 2L therapy received a variety of regimens with the top 3 being Car + paclitaxel (19%), gemcitabine (11%), and topotecan (9.6%). Median duration of treatment (DOT) was 4-6 m across line of therapies (LOTs), yet median time to next treatment (TTNT) ranged 10-32 m for 1L, and 9-11 m for 2L. The average per person per month (PPPM) costs were 7.1k for 1L and 8.8k for 2L with primary drivers of spending being outpatient and emergency room visits. Conclusions: Elderly pts with advanced cervical cancer requiring chemotherapy had poor prognosis and had no standard of care for 2L therapy. Per-patient economic burden is substantial for both 1L and 2L therapy, exceeding 7k dollars per month. [Table: see text]

e20647 Background: Given a dearth of literature, this study aimed to investigate real-world use of systemic therapies, survival, and costs among elderly SCLC patients (pts) in U.S. Methods: Pts (65+ years old) with an initial diagnosis of SCLC during 2007-2013 were identified using the SEER-Medicare data. Overall survival (OS), duration of treatment (DOT) and time to next treatment (TTNT) were estimated based on the Kaplan-Meier method. Costs (2016 US dollars) were derived from Medicare claims. Results: A total of 11 812 pts were identified with 7 797 (66%) being stage IV at diagnosis. During an average of 10 months (m) follow-up post diagnosis, 6 509 (55%), 2 238 (19%) and 679 (6%) received first line (1L), 2L and 3L therapy, respectively. The median OS was 9 m from 1L start and 6 m from 2L or 3L start, suggesting existing treatment providing limited survival benefit. Majority pts (93%) received platinum-based therapy for 1L with Car + etoposide (Eto, 59%) being the most commonly used regimen, followed by Cis + Eto (18%) and Car monotherapy (8%). Car + Eto, Top and Pac were the top 3 regimens used in 2L and 3L. Median DOTs were 4-6 m, yet TTNT ranged from 7 to 18 m across lines of therapy. The average per person per month (PPPM) costs were $9.4k for 1L, $8.9k for 2L, and $8.8k for 3L. Conclusions: Advanced SCLC remains an aggressive malignancy with poor prognosis, lack of ideal therapy and high medical cost, which highlighted high unmet medical need of SCLC among elderly pts. [Table: see text]

Objective: To predict the effect of nesiritide on clinical outcomes based on the renal function change demonstrated in the Nesiritide Administered Peri-Anesthesia (NAPA) in patients undergoing cardiac surgery trial. Methods: We built a decision analytical model to replicate the NAPA trial with 1000 hypothetical patients in both nesiritide and placebo arms. The incident rates of dialysis, hospital death, and their composite were predicted based on the renal function data obtained from the NAPA trial. All analyses were further repeated for two subgroups stratified by the presence of preoperative renal dysfunction (RD). Results: The base-case analyses significantly favored nesiritide for the three clinical end points. In the total NAPA sample, the absolute risk reductions (ARRs) for dialysis, hospital death, and their composite across 100 simulated trials were 1.3%, 3.3%, and 4.1%, respectively. The improvement was more pronounced in the preoperative RD subgroup with the three ARRs of 4.1%, 7.1%, and 9.4%, respectively. The beneficial effect diminished in the normal preoperative renal function (NRF) subgroup with the three ARRs of 0.6%, 3.0%, and 3.4%, respectively. The best case analyses confirmed the robustness of the base-case results in the total NAPA sample and RD subgroup, but not in the NRF subgroup. Conclusion: If the demonstrated renal preservation can be extrapolated, nesiritide may reduce dialysis and hospital death in cardiac surgery patient with preoperative RD, but to a much lesser extent or not in patients with normal preoperative renal function.

e18235 Background: Large automated electronic medical record (EMR) databases have the potential to be valuable tools in studying the patterns and effectiveness of treatment. Therefore, the current study sought to develop novel tools to identify bladder cancer cases, their clinical stage, and the chemotherapy they receive in electronic medical records. Methods: EMR data were obtained from Indiana University Health hospitals from 2008 to 2015. We developed 2 novel algorithms using natural language processing on unstructured data to identify (a) bladder cancer cases and clinical stage, and (b) chemotherapy names and line of chemotherapy. Performance characteristics for each algorithm were assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Each algorithm’s performance for case ascertainment was measured against the gold standard of manual chart review. Results: A total of 2,559 unique bladder cancer patients were identified and stratified using the clinical staging algorithm, defined as metastatic, muscle invasive, or non-muscle invasive. We identified 657 metastatic cases, 567 muscle invasive cases, and 604 non-muscle invasive cases. Next, the treatment algorithm was applied to metastatic patients to identify the type of chemotherapy received and 1st or 2nd line of therapy. The sensitivity, specificity, PPV, and NPV for the clinical staging and treatment algorithm were calculated against the gold standard of manual chart review (Table). Conclusions: The performance of the staging algorithm demonstrates the strength of using innovative approaches. The poor performance of the treatment algorithm sets a framework from which to build upon in future work and suggests that structured approaches may still be the preferable approach. [Table: see text]

The aim of the study is to examine the comparative effectiveness of unfractionated heparin 5000 units given subcutaneously two or three times daily and enoxaparin given 30 mg subcutaneously twice daily or 40 mg daily for the prevention of venous thromboembolism in burn patients. This is a retrospective cohort study conducted in adult burn patients admitted between January 1, 1998, and September 30, 2008, who received only one agent for prophylaxis against venous thromboembolism during their admission. The primary outcome was a symptomatic venous thromboembolism, defined as any lower extremity deep venous thrombosis or pulmonary embolism. A total of 1111 patients were included; 600 received heparin and 511 received enoxaparin. Five patients (0.45%) experienced a symptomatic venous thromboembolic event. All five events occurred in the heparin group (P = .07). Heparin patients were older, had a larger TBSA burned, and a longer length of stay. No incidences of heparin-induced thrombocytopenia were identified. In this retrospective study of burned patients, the authors report a low incidence of symptomatic venous thromboembolic events. All events occurred in patients receiving unfractionated heparin as prophylaxis; however, the number of risk factors for venous thromboembolism was also greater in this group. Future prospective studies are needed to determine definitive conclusions regarding appropriate chemical VTE prophylaxis and dosing regimens for burn patients.

Background Dysphagia after acute stroke is associated with poor prognosis, particularly if prolonged. Acupuncture has been widely used for this complication in China. However, its therapeutic effect is unclear. Objectives To determine the therapeutic effect of acupuncture for dysphagia after acute stroke compared with placebo, sham or no acupuncture intervention. Search strategy We searched the Cochrane Stroke Group Trials Register (last searched September 2007), the Chinese Stroke Trials Register and the Trials Register of the Cochrane Complementary Medicine Field (last searched January 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2007). In January 2007 we searched the following databases from the first available date; MEDLINE, EMBASE, CINAHL, AMED, CISCOM, BIOSIS Previews, ProQuest Digital Dissertations, Science Citation Index, ISI Proceedings, ACUBRIEFS, ACP Journal Club, Books@Ovid and Journals@Ovid, Chinese Biological Medicine Database, Chinese scientific periodical database of VIP INFORMATION, China periodical in China National Knowledge Infrastructure, Chinese Evidence-Based Medicine Database, Science China, Chinese Social Science Citation Index, and the Chinese Science and Technology Document Databases. We also searched databases of ongoing trials, conference proceedings, and grey literature, handsearched three Chinese journals and contacted authors and researchers. Selection criteria We included all truly randomised controlled trials that evaluated the effect of acupuncture, irrespective of type, in patients with dysphagia within 30 day after the onset of ischaemic or haemorrhagic stroke. All types of acupuncture interventions were eligible. The control intervention could be placebo acupuncture, sham acupuncture, or no acupuncture. The primary outcome was recovery of normal feeding. The secondary outcomes were case fatality, deterioration, late disability, length of hospital stay, quality of life, feeding tube removal, aspiration pneumonia and nutritional measures. Data collection and analysis Two review authors independently selected trials, assessed trial quality, and extracted data. Disagreements were resolved by a third review author. Main results Only one trial of 66 participants was included. In the acupuncture group, 12 out of 34 participants recovered to normal feeding (35.3%). In the control group, seven out of 32 participants recovered to normal feeding (21.9%). The relative risk of recovery was 1.61 with a 95% confidence interval of 0.73 to 3.58. No statistical significance was detected. Authors' conclusions There is not enough evidence to make any conclusion about the therapeutic effect of acupuncture for dysphagia after acute stroke. High quality and large scale randomised controlled trials are needed.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias. Patients with A-T also have high incidences of type 2 diabetes mellitus. The gene mutated in this disease, ATM (A-T, mutated), encodes a protein kinase. Previous studies have demonstrated that cytoplasmic ATM is an insulin-responsive protein and a major upstream activator of Akt following insulin treatment. To further investigate the function of ATM in insulin signal transduction, insulin resistance was induced in rats by feeding them a high-fat diet. Muscle tissue of rats with insulin resistance had both dramatically reduced ATM levels and substantially decreased Akt phosphorylation at Ser473 in comparison to that of regular chow-fed controls. The decreased ATM expression suggests that ATM is involved in the development of insulin resistance through down-regulation of Akt activity. The role of ATM in activation of Akt was further confirmed in mouse embryonic fibroblast (MEF) A29 (ATM+/+) and A38 (ATM-/-) cells. In addition, insulin-mediated Akt phosphorylation in mouse L6 muscle cells was greatly reduced by KU-55933, a specific inhibitor of ATM. A 2-deoxyglucose incorporation assay showed that this inhibitor also caused a significant reduction in insulin-mediated glucose uptake in L6 cells. An immunofluorescence experiment demonstrated that in L6 cells transfected with wild-type (WT) ATM, insulin caused a dramatic increase of the cell surface glucose transporter 4 (GLUT4), while in cells transfected with kinase-dead (KD) ATM, translocation of GLUT4 to the cell surface in response to insulin was markedly inhibited.