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Background The relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence. Patients and Methods Using data from a previously reported phase III trial, we assessed patients’ recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs. extended CINV as a secondary analysis. Complete response (CR) and CINV duration were primary and secondary endpoints, respectively. CR was considered prophylaxis success; lack of CR was considered treatment failure (TF). Results Among 402 female patients, 99 (24.6%) had TF in C1 (TF1). The remaining 303 patients (CR1) had ≥93% CR rates in each subsequent cycle, while the 99 patients with TF1 had TF rates of 49.8% for cycles 2-4 (P < .001). The 51 patients with extended TF (≥3 days) in C1 had recurrent TF in 73/105 later cycles (69.5%, P < .001), while the 48 patients with short TF (1-2 days) in C1 had recurrent TF in 33/108 later cycles (30.6%). The relative risk of recurrence after C1 extended TF was 2.28 (CI 1.67-3.11; P < .001) compared to short TF. Conclusions Prophylaxis success in C1 led to >90% repeat success across cycles of AC-based chemotherapy. For patients with breakthrough CINV, extended duration strongly predicted recurrent CINV. The duration of CINV should be closely monitored, and augmenting antiemetic prophylaxis considered for future cycles when extended CINV occurs.

Background OS, the “gold standard” endpoint in oncology studies, is challenging to measure in earlier stages of BC because of considerably long survival. Further, during extended patient follow-up, treatment effect on OS can become impacted by multiple factors such as non-malignant causes of death, treatment cross-over, and post-progression treatments, making it difficult to isolate the true treatment effect. As an alternative, surrogate endpoints (SE) such as DFS, EFS, and pCR can be used to ascertain meaningful benefit in true endpoint (TE). While studies have previously explored the association of such SEs with OS in different BC populations, there is a dearth in literature of studies reporting on correlation in the NAdj/Adj settings in the HR+/HER2- BC population. The aim of this study is to conduct a correlation analysis between various SE-TE pairs (DFS/EFS vs OS, pCR vs OS and pCR vs DFS/EFS) in this population, from data reported in studies identified from a systematic literature review (SLR). For each pair of endpoints, both absolute and relative treatment effects were evaluated. Methods An SLR was conducted in NAdj/Adj setting for HR+/HER2- BC to identify studies that reported any two of pCR, DFS/EFS and OS. The search was carried out using MEDLINE, Embase, Cochrane Library databases (2000 onward), four BC-related conference proceedings (2018-2020) and clinical trial registries. Relative treatment effect sizes were quantified in terms of HRs for DFS/EFS and OS, and odds ratios (ORs) for pCR. Absolute treatment effects were analyzed in terms of survival probability of EFS/DFS and OS at landmark time points and pCR rates. A weighted least squares regression analysis was carried out to determine the strength of association between the various TE-SE pairs. The regression analysis was carried out on log scale for relative treatment effects and on linear scale for absolute treatment effects. Pearson correlation coefficient (r) was used to quantify the strength of association; coefficient of determination (R2) was also reported to evaluate goodness-of-fit. Sensitivity analyses were performed by considering linear scale (for relative outcomes only), using inverse of variance as weights, and by removing outliers. Results A total of 135 publications were identified in the SLR. Regression analysis showed that there is a statistically significant positive association (r= 0.91; 95%CI, 0.83-0.96, p Correlation analysis for HR(DFS/EFS) vs. HR(OS) and OR(pCR) vs. HR(DFS/EFS)Model# studies# observationsPearson coefficient, r (95% CI)p-valueCoefficient of determination, R2 (95% CI)Slope (95% CI)P-valueHRDFS/EFS vs. HROS24320.91 (0.83-0.96) Citation Format: Anagha Gogate, Inkyu Kim, Sandip Ranjan, Amit Kumar, Eros Papademetriou, Hitesh Bhandari, Ravi Potluri. Correlation between pathologic complete response (pCR), event-free survival (EFS)/disease-free survival (DFS) and overall survival (OS) in neoadjuvant and/or adjuvant (NAdj/Adj) hormone receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) breast cancer (BC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-09.

Pulmonary arterial hypertension (PAH), a rare vasculopathy progressively leading to right heart failure and death, is associated with considerable economic burden. Oral prostacyclin pathway agents (PPAs) like selexipag and treprostinil address an underlying PAH pathway, yet are often under-utilized. Data on head-to-head cost comparison of various PPAs is lacking. In this retrospective study using a large health claims database, we compared the per-patient-per-year (PPPY) costs and healthcare resource utilization (HRU) among PAH patients taking either oral selexipag, inhaled treprostinil or oral treprostinil in the United States between July 2015 and March 2020. Patients with ≥1 prescription for one of the drugs of interest, ≥1 in-patient pulmonary hypertension (PH) diagnosis, or ≥ 2 outpatient PH diagnoses were included in this study. Baseline differences between the three groups were adjusted using an inverse probability of treatment weighting approach. 411 patients were selected for the final study cohorts. All-cause hospitalization costs were highest for oral treprostinil ($39,983) compared to oral selexipag ($20,635) and inhaled treprostinil ($16,548; p = .037). Total PAH-related medical costs were 40% lower for patients on oral selexipag compared to patients on oral and inhaled treprostinil ($24,351 vs. $40,398 and $40,339, respectively; p = .006). PAH-related outpatient visits were lowest for patients on oral selexipag (14 PPPY visits) compared to oral treprostinil (16 PPPY visits) and inhaled treprostinil (22 PPPY visits; p = .001). Compared to oral and inhaled treprostinil, oral selexipag may incur lower medical costs and reduce PAH related outpatient visits for patients with PAH.

Background The choice of chemotherapy for women diagnosed with metastatic breast cancer (BC) has been evolving as new agents and clinical trial results become available. Current NCCN guidelines recommend sequential single chemotherapeutic agents and combination therapy including platinum-based regimens for patients with high risk disease. Platinum-based chemotherapies are recommended for triple-negative breast cancer (TNBC) and, in particular, for a more defined population of TNBC with a BRCA mutation that may have particular sensitivity to platinum agents due to the impaired ability to repair DNA damage inherent in these patients.1 Here, we aim to leverage real world data to ascertain the use of platinum-based treatments in BRCA-mutation positive (BRCA+) metastatic BC patients, characterized by their hormonal receptor status. Methods Optum’s electronic health records (EHR) database was used to identify a cohort of women with 1) confirmed BC ICD-9/ICD-10 diagnosis between 2008 and 2018, 2) at least 12 months of history in the EHR, 3) at least one distant metastasis diagnosis (per ICD-9/ICD-10, or from physician notes), and 4) no previous diagnosis of other primary cancers in previous 12 months. BRCA-mutation status, ER, PR and HER2 test results were used to create relevant biomarker subgroups. Distinct lines of therapy (LOT) in the post-metastatic period were established using business rules, and the extent of use of platinum-based treatments, overall and of specific platinum regimens, were analyzed in various LOTs. Results Among 33,878 metastatic BC patients receiving a systemic chemotherapy, 8.7% were treated with a platinum-based regimen, while among the subgroup who were BRCA+, the proportion receiving platinum-based regimens was higher at 12.3%. In LOT2 and LOT3, the proportion receiving platinum regimens was 3.9% and 2.5% for the overall cohort, compared with 5.2% and 3.0% for the BRCA+ cohort. Within the BRCA+ cohort, the use of platinum-based regimens in TNBC patients was substantially higher than in other patients, accounting for 21.6%, 15.3% and 14.2% of patients in LOT1, LOT2 and LOT3 respectively, compared with 8.7%, 3.1% and 1.7% in ER+/PR+ patients (Table 1). The choice of specific platinum-containing combination regimens differed by biomarker cohorts; the combination of carboplatin and paclitaxel was most common in TNBC patients, while a quadruplet regimen was most used in the ER+/PR+ cohort. Conclusions Real-world evidence on use of platinum-based regimens in metastatic BC patients revealed differences across BRCA and hormonal status phenotypes. Women with TNBC had higher use of platinum agents than other subgroups across all lines of treatment. The observation that the use of platinum-based chemotherapy, including combination regimens, was highest in TNBC across lines of treatment highlights the persistent unmet need around alternative therapies for women affected with TNBC and BRCA+ disease. Table 1. Use of platinum-based regimens in women with metastatic BC in LOTs 1-3All metastatic BCBRCA+All BRCA+ER+/PR+TNBCN (treated with LOT1)33,8785,6494,228782Age at LOT1 start (in years): Median (IQR)63 (53-73)54 (46-64)54 (46-64)54 (45-62)Total proportion (%) of platinum-based regimens in LOT18.7%12.3%8.7%21.6%REGIMENCarboplatin+paclitaxel1.8%2.8%1.4%8.3%Carboplatin+docetaxel+pertuzumab+trastuzumab1.7%2.8%2.6%0.4%Carboplatin+docetaxel+trastuzumab1.2%1.9%1.8%0.3%Carboplatin+gemcitabine0.9%1.4%0.7%5.5%Carboplatin0.7%0.8%0.5%1.9%Carboplatin+docetaxel0.3%0.4%0.2%1.3%Cisplatin0.3%0.4%0.2%1.0%Other platinum-based regimens1.9%2.0%1.4%2.9%N (treated with LOT2)21,1484,1973,317495Total proportion (%) of platinum-based regimens in LOT23.9%5.2%3.1%15.3%N (treated with LOT3)13,9372,9592,523226Total proportion (%) of platinum-based regimens in LOT32.5%3.0%1.7%14.2%Footnotes1 Isakoff, SJ. Triple-Negative Breast Cancer: Role of Specific Chemotherapy Agents. Cancer J 2010;16: 53-61 Citation Format: Wendy Sebby, Alexander Liede, Debasish Mazumder, Anirban Ghosh, Eros Papademetriou, Ravi Potluri, Bruce Bach, Jerzy Tyczynski. Real-world evidence of platinum-based chemotherapy for the treatment of BRCA-positive metastatic breast cancer in a cohort of 33,878 women in the United States [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-41.

Purpose Chemotherapy-induced nausea and vomiting (CINV) contributes to avoidable acute care, a metric now tracked in Medicare's oncology outcome measure. CINV is preventable, yet guidelines are often not followed. We sought to quantify acute care involving CINV and other avoidable toxicities after highly emetogenic chemotherapy (HEC) to identify excess risk and assess clinician adherence to antiemesis guidelines for HEC. Materials and Methods We retrospectively evaluated U.S. electronic health records (2012-2018) using Medicare's OP-35 outcome measure to identify avoidable acute care involving any of 10 toxicities, including CINV, after HEC regimens relative to non-HEC. Antiemetic guideline adherence was defined as use ofneurokinin-1 (NKl) receptor antagonists Q5 (RAs) plus 5-hydroxytryptamine type 3 RA+ dexamethasone at HEC initiation. Results Among 17,609 patients receiving HEC, acute care rates associated with HEC chemotherapy included 32% cisplatin, 31% carboplatin, and 21% anthracycline/cyclosphospharnide (AC), with 76% meeting the criteria as avoidable events. Oxaliplatin rates were 29%. Avoidable acute care occurred 1.83 times (95% confidence interval, 1.76-1.91, p < .0001) as often after HEC versus non-HEC excluding oxaliplatin; CINV-related acute care occurred 2.29 times as often. Nonadherence to antiemesis guidelines occurred in 34% and 24% of cisplatin and AC courses, respectively, because of omission of a NKl RA. Conclusions Patients treated with HEC regimens experienced high avoidable acute care use, 1.8 times the risk seen for other chemotherapy. Nonadherence to guideline-directed antiemetic prophylaxis highlights the need to ensure adherence to antiemetic guidelines, including the use of NKl RA in HEC. Implications for Practice After survival, perhaps the most important goal in oncology is limiting avoidable acute care, a goal now used by Medicare to impact cancer reimbursement. This study found that patients treated with highly emetogenic chemotherapy (HEC) regimens had high rates of avoidable acute care use, 1.8 times the risk seen for other chemotherapy. A substantial proportion of the avoidable acute care involved chemotherapy-induced nausea and vomiting. Results showed that incomplete adherence to national antiemetic guidelines for HEC regimens primarily driven by omission of upfront neurokinin-1 receptor antagonist use, suggesting that improved adherence can meaningfully resolve this gap in quality and cost of care.

Background: Anthracycline and cyclophosphamide (AC) is a highly emetogenic chemotherapy (HEC) regimen. Combination netupitant/palonosetron (NEPA) + dexamethasone (DEX) is guideline-recommended for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in HEC and moderately emetogenic chemotherapy. CMS’ OP-35 measure deems 30-day post-chemotherapy acute care as avoidable if involving nausea and emesis (NV) or any of 8 other toxicities. Results will be publicly reported and impact Medicare reimbursement. CMS (2017) found that 10% of >58,000 patients with avoidable acute care after chemotherapy involved NV. Because NEPA is new, insufficient real world data exist to assess its CINV resource use. CINV-related acute-care after NEPA prophylaxis in AC has been reported in a prospective clinical trial. Our aim was to compare these rates to those seen after prophylaxis with other antiemetics for AC outside of a clinical trial. Methods: Pre-specified endpoints in a prospective trial of oral or IV NEPA + DEX in AC included acute-care use (emergency [ED] visits or inpatient admissions [IP]) involving CINV, defined as emesis or rescue drug use ≤5 days after AC, and concomitant ED/IP in the same period. We also evaluated CINV-related acute care after non-NEPA prophylaxis for AC in breast cancer from 10/2012-8/2018 in IBM Explorys electronic health records. We age-matched patients 3:1 to the NEPA trial. We further adjusted the event rate to address under-reporting of a) CINV rates (vs. 49.2% for aprepitant in AC in a clinical trial [Warr 2005]) and b) acute-care use, projected at 17-50% at sites external to the dataset. To compare the resulting adjusted event rate to the NEPA study, we conducted 10,000 Monte Carlo simulations, using random probabilities from 5.2-8.7% for Explorys patients, and from 0-2% for NEPA patients to address potential reporting variability, despite the trial including daily patient diaries. Analysis of data was limited to the first two cycles, the median duration in the NEPA trial. Results: In the NEPA trial, 402 patients received ≥1 cycle; 391 completed two cycles. Nine patients had IP admissions; none involved CINV. Five patients had 6 total ED visits; one met criteria for involving CINV; the resulting rate of acute care rate involving CINV was 0.25 per 100 patients. For other antiemetics, 2598 patients received AC (excluding NEPA prophylaxis). Among 1206 age-matched to the NEPA trial, 15 patients had acute-care events in the first 2 cycles, (1.24 per 100 patients), an odds ratio of 1:5.1 (CI 0.7-38.5) in favor of NEPA. After adjusting via the simulation, the odds ratio was 1:8.3 (CI: 2.43-24.21) in favor of NEPA. Conclusions: Comparing CINV-related acute care seen in a large prospective trial relative to real-world evidence in patients with breast cancer treated with AC, Citation Format: Lee Schwartzberg, Kathryn J Ruddy, Rudolph M Navari, Thomas W LeBlanc, Rebecca Clark-Snow, Rita Wickham, Gary Binder, William L. Bailey, Ravi Potluri, Luke M Schmerold, Eros Papademetriou, Eric J Roeland. Avoidable acute care involving chemotherapy-induced nausea and vomiting (CINV) among patients with breast cancer receiving anthracycline + cyclophosphamide (AC) with NEPA prophylaxis relative to other antiemetics: An external control arm analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-07.

Background: In order to improve care and reduce costs of cancer treatment, attention has focused on reducing inpatient (IP) and emergency room (ED) utilization. The US Centers for Medicare and Medicaid Services (CMS) recently implemented an oncology outcome measure (OP-35) to assess the quality of care and determine outpatient hospital payment. It assesses 30-day post-chemotherapy rates of IP or ED events deemed “potentially avoidable” by CMS due to association with any of 10 CMS-defined toxicities: anemia, dehydration, diarrhea, fever, nausea, emesis, neutropenia, pain, pneumonia, or sepsis. Although CMS found that 20% of chemotherapy treatment resulted in such events, event rates with highly emetogenic chemotherapy (HEC) are understudied, particularly for breast cancer (bCA) patients treated with anthracycline + cyclophosphamide (AC), carboplatin, or cisplatin. Methods: In a large electronic health record database focused on US integrated delivery networks, HEC courses of therapy were identified from 4Q 2012 to 3Q 2017. IP/ED events within 30 days of chemotherapy administration were considered related to the OP-35 measure if they included a diagnosis code of any of the ten OP-35 toxicities, per CMS' definitions. HEC chemotherapy use, IP/ED events, bCA diagnosis, and toxicities were identified by ICD-9, ICD-10, and procedural codes. Subgroups were evaluated for 3 common HECs: AC, carboplatin (>14 days apart, as a proxy for AUC ≥4), and cisplatin. Results: 4128 courses of HEC in bCA were identified. Of these, 2304 involved AC (median 4 cycles), 1721 involved carboplatin (median 6 cycles), and 103 involved cisplatin (median 4 cycles), with median ages of 55, 59, and 64, respectively. 30-day IP/ED events were seen in 25% of these HEC bCA courses (22%, 30% and 23% for AC, carboplatin, and cisplatin, respectively). The 10 CMS-defined toxicities were associated with an IP/ED event for 73%, 72%, and 76% of events for these AC, carboplatin, and cisplatin courses respectively, confirming that these are principal contributors to 30-day IP/ED use for patients receiving HEC in bCA. The top five that were most commonly associated with IP/ED for bCA for patients receiving AC, carboplatin, or cisplatin were pain 53%/49%/63%, anemia 51%/51%/38%, fever 48%/31%/38%, neutropenia 46%/27%/31%, and nausea/emesis 30%/40%/25%; patients may have had ≥1 toxicity associated with each IP/ED event. The IP/ED rate may be understated because some events, particularly ED, may occur out of the network the EHR data covers. Conclusion: One quarter of patients receiving AC, carboplatin, or cisplatin for bCA visit the ED or are hospitalized within 30 days of at least one of their chemotherapy administrations. Most events involved ≥1 of 10 toxicities deemed avoidable causes of hospitalization by CMS and now tracked as an oncology outcome measure. Relative to patients receiving AC, acute care rates for patients receiving carboplatin were lower for fever and neutropenia and higher for nausea/emesis, perhaps because the study period largely precedes the 2017 addition of carboplatin AUC ≥4 to national guidelines as HEC requiring triplet antiemetic prophylaxis. Toxicity prevention and symptom monitoring are crucial to reduce acute care needs. Citation Format: Ruddy KJ, Roeland EJ, LeBlanc TW, Binder G, Sebastiani S, Potluri R, Schmerold LM, Papademetriou E, Navari RM. Avoidable acute care use associated with nausea and emesis among patients receiving AC, carboplatin, or cisplatin for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-05.

e13056 Background: Real-world evidence on the risk of seizures in subgroups of women with advanced breast cancer (BC) across treatment-related or clinical subtypes is limited. A large electronic health record (EHR) dataset was used in this study to measure incidence and risk factors for seizures among women diagnosed with BRCA-associated metastatic BC (mBC). Methods: We used the Optum EHR database, which includes natural language processing (NLP) abstracted details from physicians’ notes, to identify a cohort of females with mBC (based on secondary malignancy ICD-9/-10 codes or NLP) diagnosed between 2008-2018 with 12 months of pre-index history, evidence of BRCA mutation positive (BRCA+) status, and no history of prior cancers. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR-, HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC). Incidence of seizures was measured using diagnosis codes and NLP, and incidence rates were calculated as the number of women with a seizure over the period from metastasis to first seizure or the end of follow up. Incidence rates were also measured across the following risk factors: PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsant use before BC diagnosis, while controlling for age at metastasis, number of prior lines, and metastasis location. Results: Of the 7,941 BRCA+ patients identified, 27.8% had ≥1 seizure during mean follow-up of 2.35 years, with an incidence rate of 11.83 (95% CI: 11.35-12.33) per 100 person-years. The HER2-/HR+ and TNBC subgroups had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). Kaplan-Meier analysis of time to seizure showed that HR- phenotype was associated with a longer time to first seizure. Patients with diagnosed brain metastases or a history of seizures had higher seizure incidence rates compared to patients without the respective risk factors (42.55 [95% CI: 28.59-63.30] vs 5.26 [4.20-6.59] and 34.76 [23.24-52.01] vs 6.35 [5.11-7.88]). Incidence trended higher with PARP inhibitor use, but patient numbers were low. Conclusions: Using both diagnosis codes and NLP, this study shows that seizures occur frequently in women with BRCA+ mBC, even those without diagnosed brain metastases. The seizure incidence rates by phenotype underscore their relevance when assessing seizure risk. These findings may have implications for clinical practice and for assessing benefit-risk ratios of novel agents.[Table: see text]

Background: A specific sequence for psoriasis (PsO) therapy has not been defined.Objectives: This retrospective, observational cohort study characterized pathways of PsO treatment over 3 ye...

Objectives To create and validate a model to predict depression symptom severity among patients with treatment‐resistant depression (TRD) using commonly recorded variables within medical claims databases. Methods Adults with TRD (here defined as > 2 antidepressant treatments in an episode, suggestive of nonresponse) and ≥ 1 Patient Health Questionnaire (PHQ)‐9 record on or after the index TRD date were identified (2013–2018) in Decision Resource Group's Real World Data Repository, which links an electronic health record database to a medical claims database. A total of 116 clinical/demographic variables were utilized as predictors of the study outcome of depression symptom severity, which was measured by PHQ‐9 total score category (score: 0–9 = none to mild, 10–14 = moderate, 15–27 = moderately severe to severe). A random forest approach was applied to develop and validate the predictive model. Results Among 5,356 PHQ‐9 scores in the study population, the mean (standard deviation) PHQ‐9 score was 10.1 (7.2). The model yielded an accuracy of 62.7%. For each predicted depression symptom severity category, the mean observed scores (8.0, 12.2, and 16.2) fell within the appropriate range. Conclusions While there is room for improvement in its accuracy, the use of a machine learning tool that predicts depression symptom severity of patients with TRD can potentially have wide population‐level applications. Healthcare systems and payers can build upon this groundwork and use the variables identified and the predictive modeling approach to create an algorithm specific to their population., In this study, we created and validated a machine learning model using commonly recorded variables within a medical claims database to predict depression symptom severity of patients with TRD based on Patient Health Questionnaire (PHQ)‐9 scores available within an electronic health record (EHR) database. The model was found to predict depression symptom severity category from the three possible severity category choices with an overall accuracy of 62.7%. Of the 116 clinical and demographic variables evaluated in our study, six were found to be the most important predictors. To our knowledge, this is the first study which attempts to predict depression symptom severity of patients with TRD using clinical and demographic characteristics in a medical claims database.

Aims: The primary objective was to examine direct costs and health resource utilization (HRU) among commercially insured young adults with schizophrenia in Colorado. Materials and methods: The Colorado All-Payer Claims Database, covering approximately 76% of the insured Colorado population was used. Members aged 18���34, with and without schizophrenia (SCZ), having commercial insurance were included. All-cause, mental health related (MH) and non-MH related per patient per month (PPPM) costs and per 100 patients per month (PHPPM) HRU were compared between a SCZ cohort and a propensity score matched non-SCZ cohort before and after index date up to 48 months. Results: 501 patients with SCZ and 2,510 matched individuals without SCZ were included. HRU and costs were higher for SCZ patients both pre- and post-index date. Pre-index, there were 32.3 (24.0 MH; 8.4 non-MH) PHPPM more office visits; 2.1 (2.7 MH) PHPPM more admissions; 104.8 (67.02 MH; 37.7 non-MH) PHPPM more prescriptions in the SCZ cohort (all p Limitations: This study was based on data from a single state, thus may not be generalizable to other states. Conclusions: Healthcare costs and HRU for young adults diagnosed with schizophrenia are significantly more burdensome to commercial payers than matched patients without schizophrenia, both before and after an official schizophrenia diagnosis.

INTRODUCTION : Managing patients with acute myeloid leukemia (AML) requires extensive healthcare resource utilization and costs; hospitalization is the largest component of medical costs for AML. In the phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA [CC-486]) was associated with significant improvements in overall survival and relapse-free survival (RFS) vs. placebo (Wei, 2020). Prolonged RFS with Oral-AZA may translate into substantial economic benefits, with lower hospitalization-related costs due to reduced rates of hospitalization and days in hospital (Oliva, ASH 2020). Real-world economic benefits of prolonged remission remain insufficiently studied. OBJECTIVE: This study aimed to examine the economic burden of hospitalizations among patients with newly diagnosed AML in remission from a retrospective analysis of real-world data from a US claims database. METHODS: Using a retrospective cohort design, adult patients were selected from the IBM MarketScan TM Commercial and Medicare Supplemental Databases, with ≥2 outpatient claims or 1 inpatient claim with a primary International Classification of Disease 9th/10th Revision (ICD-9/ICD-10) code for AML between July 1, 2012, and September 30, 2019. Patients were required to have 1) at least 6 months of continuous enrollment, with pharmacy benefits, prior to diagnosis, 2) received systemic induction therapy as first-line (1L) therapy for AML on or after the index diagnosis date, and 3) attained remission from 1L systemic therapy. Patients were followed from remission after systemic induction therapy, with or without consolidation, until the end of the follow-up period. Eligible patients were organized into cohorts based on their duration of remission (DOR): Cohort A included patients with < median DOR and Cohort B had patients with ≥ median DOR. Hospitalization incidence and duration during the follow-up period were calculated using a per-patient per-year (PPPY) metric. Hospitalization-related costs were compared using a generalized linear model (GLM) with gamma distribution and log-link function. Generalized estimating equations (GEE) clustered on the patient were used to compare incidence and duration of hospitalizations. All costs were adjusted for inflation and reported in 2019 US dollars (USD). RESULTS: In all, 693 patients met all selection criteria and were assessed for DOR. The median DOR for all patients was 167 days; cohorts A and B included 346 and 347 patients, respectively, with median times from remission to end of follow-up of 106.5 and 460 days. Baseline characteristics were comparable between cohorts; mean [SD] age was 55.1 [14.4] years, 49.4% of patients were male, and mean [SD] Charlson comorbidity index [CCI] was 0.8 [1.2]. The PPPY number of hospitalizations was higher in Cohort A than in Cohort B (4.56 vs 2.09, respectively), as was the PPPY total length of hospital stay (51.1 vs 19.7 days). The PPPY hospitalization-related costs were $345,728 in Cohort A and $125,018 in Cohort B; the cumulative hospitalization cost per patient was $148,430 higher in Cohort A at 12 months and $177,500 higher at 18 months (Figure). Multivariate GEE and GLM models with adjustment for patient characteristic covariates (eg, age, sex, CCI) identified prolonged remission was significantly associated with reduced number, duration, and cost of hospitalization (P < 0.001, all comparisons). CONCLUSIONS: In a real-world setting, prolonged AML remission was associated with significantly lower rates and durations of hospitalization, which were estimated to result in substantial cumulative cost savings. These data underscore the importance of active maintenance therapies that delay relapse for patients with AML. While the costs of long-term therapy face increasing scrutiny, these costs should be weighed relative to the potential economic benefit of prolonged remission and reduced burden of healthcare resource utilization. Figure 1 Figure 1. Disclosures Chen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Papademetriou: SmartAnalyst Inc.: Current Employment. Potluri: Bristol Myers Squibb: Consultancy.

Context: Healthcare resource utilization and costs of managing AML patients are substantial, with hospitalization being the main cost driver of AML care. In the Phase 3 QUAZAR AML-001 maintenance trial, lower rates and durations of hospitalization with oral azacitidine vs placebo corresponded with substantial reductions in hospitalization-related costs in patients with AML in remission. Objective: Examine the impact of remission duration on the economic burden of hospitalizations among AML patients in a real-world setting. Methods: Adult patients with an AML diagnosis (ICD-9-CM/ICD-10-CM) who achieved remission after first-line induction chemotherapy were identified from an administrative claims health database (Optum® Clinformatics® Data Mart). Additional inclusion/exclusion criteria were applied to match the QUAZAR AML-001 trial population. Eligible patients were organized into cohorts based on their duration of remission (DOR): cohort A Results: Overall, median DOR was 125 days; cohorts A and B included 220 and 231 patients, respectively, with median times from remission to end of follow-up of 89 and 378 days. Baseline characteristics were comparable between cohorts (mean [SD] age 62.8 [14.7] years, Charlson comorbidity index [CCI] 1.7 [1.6]) except for sex (male: 59.5% vs 47.6%). The number of hospitalizations (4.71 vs 2.68 per patient per year [PPPY]) and total length of stays (43.88 vs 23.59 days PPPY) were higher in cohort A vs B, respectively; estimated hospitalization-related costs (2019 USD) were $242,511 vs $132,554 PPPY, respectively. Cumulative mean hospitalization cost per patient was $61,371 higher in Cohort A at 12 months and $108,593 higher at 24 months. When adjusted for confounding baseline variables (e.g., age, sex, CCI), the number, length, and cost of hospitalization were each significantly greater in cohort A than in cohort B (P Conclusions: In a real-world setting, prolonged remission was associated with significantly lower rates and durations of hospitalization in patients with AML in remission following induction chemotherapy, which were estimated to result in substantial cumulative cost savings.

Background: Clinician adherence to antiemetic guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC) remains poorly characterized. The primary aim of this study was to evaluate individual clinician adherence to HEC antiemetic guidelines. Patients and Methods: A retrospective analysis of patients receiving HEC was conducted using the IBM Watson Explorys Electronic Health Record Database (2012–2018). HEC antiemetic guideline adherence was defined as prescription of triple prophylaxis (neurokinin-1 receptor antagonist [NK1 RA], serotonin type-3 receptor antagonist, dexamethasone) at initiation of cisplatin or anthracycline + cyclophosphamide (AC). Clinicians who prescribed ≥5 HEC courses were included and individual guideline adherence was assessed, noting the number of prescribing clinicians with >90% adherence. Results: A total of 217 clinicians were identified who prescribed 2,543 cisplatin and 1,490 AC courses. Patients (N=4,033) were primarily women (63.3%) and chemotherapy-naïve (92%) with a mean age of 58.6 years. Breast (36%) and thoracic (19%) cancers were the most common tumor types. Guideline adherence rates of >90% were achieved by 35% and 58% of clinicians using cisplatin or AC, respectively. Omission of an NK1 RA was the most common practice of nonadherence. Variation in prophylaxis guideline adherence was considerable for cisplatin (mean, 71%; SD, 29%; coefficient of variation [CV], 0.40) and AC (mean, 84%; SD, 26%; CV, 0.31). Conclusions: Findings showed substantial gaps in clinician adherence to HEC CINV guidelines, including a high variability across clinicians. Clinicians should review their individual clinical practices and ensure adherence to evidence-based CINV guidelines to optimize patient care.

e13046 Background: BRCA1/2 mutations account for 5-10% of breast cancer (BC) patients. BRCA1 mutations are associated with aggressive tumors, often triple negative (TNBC) (HER2, estrogen-receptor [ER], progesterone-receptor [PR] negative) and are mainly treated with combination chemotherapy or platinum agents. This study aimed to compare real world treatment patterns in breast cancer patients who were BRCA-mutation positive (BRCA+) and those who were BRCA-mutation negative (BRCA-), focusing on hormone-receptor positive (HR+) and TNBC subgroups. Methods: Optum’s Humedica electronic health records (EHR) database was used to identify a cohort of women with 1) confirmed BC ICD-9/ICD-10 diagnosis between 2008 and 2018, 2) at least 12 months of history in EHR, 3) at least one distant metastasis diagnosis (per ICD-9/ICD-10 or physician notes), and 4) no previous diagnosis of other primary cancers in previous 12 months. HR and HER2 test results were used to create relevant subgroups. Distinct lines of therapy (LOT) in the post-metastatic period were established using business rules. Treatment patterns and duration of treatment were analyzed. Results: Among 65,934 metastatic BC patients identified, 7941 were BRCA+, of whom 5366 (68%) were HR+ and 1323 (17%) had TNBC phenotype, while 4027 were BRCA-, of whom 2859 (71%) were HR+ and 561 (14%) had TNBC phenotype. Seventy-one percent of BRCA+ women underwent drug treatment, compared to 65% of BRCA- women. Drug treatments included hormonal treatment (+/-other agents), targeted therapy, and chemotherapy only, and varied across the different cohorts (Table). Mean (median) duration of treatment in LOT1 in the BRCA+ and BRCA- cohorts was 117 (73) and 117 (72) days, respectively. Conclusions: Real-world evidence on treatment patterns in BC patients revealed substantial differences across important biomarker and hormonal status BC phenotypes. As a preponderance of women with TNBC are still being treated exclusively with chemotherapy, these data highlight how the need for development of effective treatment options for TNBC remains high. [Table: see text]

e20088 Background: Pleural (Pl) and pericardial (Pc) effusions are often encountered clinical problems in patients with lung cancer, contributing to a poor quality of life. Population-based data on predictors for Pl and Pc effusions in small cell lung cancer (SCLC) are scarce, particularly, in later lines. Methods: We estimated the predictors for treatment-emergent Pl and Pc effusions in SCLC patients treated with third-line of therapy (LOT) using Optum’s electronic health records (EHR) de-identified database. Of 8,291 patients with newly diagnosed SCLC between 01/01/2008 and 09/30/2016, 428 patients received 3rd LOT. Pc/Pl effusions were identified by a combination of ICD-9/ICD-10 codes, procedures, or natural language processing (NLP) SDS term and sentiment. Each patient contributed to follow-up time from start of 3rd LOT to the day prior to start of next LOT or earlier of (loss to follow-up date or 365 days from end of 3rd LOT) if there was no subsequent LOT, or first occurrence for those with an outcome event. Stepwise Cox regression with sle = 0.25 and sls = 0.10 was applied for variable selection. Results: At start of 3rd LOT, median age was 65, 46% were male, 97% had extensive disease (excluding n = 53 with missing staging). Cardiac history, pulmonary history, renal impairment (eGFR < 60 mL/min/1.73m2), prior Pl and Pc effusion, albumin levels below 3.5 g/dl, sodium levels below < 136 mmol/l, treatment regimens (others except platin-containing vs. topotecan mono) was each associated with increased risk of Pl effusions. Cardiac history, prior Pl and Pc effusion, and region (South vs. Midwest/West) was each associated with increased risk of Pc effusions. When the stepwise Cox regression was applied, cardiac history, prior Pl effusion, and treatment regimens were selected as significant predictors of Pl effusions (p < 0.05). Prior Pc effusion and cardiac history were selected as significant predictors of Pc effusion (p < 0.05). Conclusions: Awareness of the determinants associated with development of Pl and Pc effusions in SCLC patients treated in third-line therapy may aid in earlier recognition of patients at risk and lower the risk of developing Pl/Pc effusions in this group of patients.

e23108 Background: ASCO antiemetic guidelines recommend upfront triple prophylaxis (NK1 receptor antagonist (RA) + 5HT3 RA + dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). Physicians exhibit high variation in HEC guideline adherence, principally involving inclusion of NK1 RA. Whether adherence is associated with selection of the specific 5HT3 RA agent remains inadequately studied. Methods: In the IBM Explorys electronic health record database, we used procedure and diagnosis codes to identify HEC courses and related nausea/vomiting (NV) from 2012 to 2018. We defined HEC guideline adherence as triple prophylaxis at chemotherapy initiation. We assigned HEC courses for ≥ 7 day cycles of cisplatin or anthracycline + cyclophosphamide (AC), or carboplatin (≥ 14 day cycles as a proxy for AUC ≥ 4) to prescribing oncologists based on encounter frequency. We categorized 5HT3 RA use of each physician treating ≥ 5 HEC courses based on their most commonly used 5HT3 and performed descriptive statistics. Results: Of 12,262 HEC courses, 57% involved physicians having greater use of ondansetron (OND) (mean OND to palonosetron (PALO) ratio of 3.9:1). These courses had lower guideline adherence (due to NK1 RA omission) and higher rates of NV for combined HEC, AC, and carboplatin. NV rates for cisplatin did not vary by 5HT3 agent used. Courses involving physicians with greater PALO use (mean OND:PALO ratio of 0.2:1) had superior adherence and NV rates, despite involving a slightly higher risk population (younger and/or female). Conclusions: According to HEC antiemetic guidelines, NK1 RA use should occur independent of 5HT3 RA agent selection. However, we observed less NK1 RA use where OND was preferred, which may have caused the observed higher rates of NV with OND. Further evaluation should assess whether pharmacy cost minimization is a driver of both OND preference and NK1 omission in HEC. [Table: see text]

e16012 Background: 75–85% of bladder cancer patients present with non-muscle invasive disease (NMIBC). While transurethral resection of bladder tumors (TURBT) is the initial standard treatment for visible lesions, there is variation in the utilization of adjuvant intravesical treatments in the real world. This study aims to assess current treatment patterns in privately insured NMIBC patients. Methods: Bladder cancer patients were identified from Truven MarketScan Commercial and Medicare Supplemental databases using ICD-9/ICD-10 codes. In the absence of tumor staging information, patients were considered to have NMIBC based on diagnosis of CIS or an algorithm centered on the use of TURBT, intravesical treatments and absence of immediate progression to muscle invasive disease. Patients were included in the final cohort if they had one year of continuous insurance coverage prior to index diagnosis, and were without any bladder cancer treatment during this period. Results: 18,683 patients met the eligibility criteria and had a median follow-up of 23 months; the mean age was 68.6 years and 75% were male. The median time from diagnosis to TURBT was 8 days. 54% of the cohort had an intravesical treatment (35% specifically with Bacillus Calmette–Guérin (BCG), with median time from TURBT of 69 days). 77% of BCG-treated patients received 5 or more administrations during induction. However, only 22% of patients received maintenance BCG after induction. 16% of the total cohort developed a recurrence or progression during the available follow-up; five percent underwent a cystectomy, while seven percent were diagnosed with metastatic disease. Only 4% of patients with 5 or more BCG administrations during induction met the definition for being BCG-unresponsive; this is influenced by the low adherence to BCG maintenance protocol. Conclusions: Only a third of NMIBC patients are given intravesical BCG treatment. Adherence to BCG maintenance protocols is suboptimal. Rates of cystectomy/ exenteration are low, suggesting patients’ preference of bladder preservation and the unmet need for new bladder-sparing alternatives.

Background: Avoiding acute care services can improve cancer care and reduce cost. The US Centers for Medicare and Medicaid Services’ (CMS) new oncology outcome measure (OP-35) defines 30-day post-chemotherapy inpatient (IP) and/or emergency department (ED) events (IP/ED) as “potentially avoidable” if involving any of 10 toxicities, including nausea or vomiting (NV). Evidence demonstrates meaningful gaps in oncologists’ adherence to antiemetic prophylaxis guidelines for highly emetogenic chemotherapy (HEC), and that NV-related IP use costs >$10,000; yet the incidence of avoidable acute care events involving NV is not well studied. Methods: We assessed chemotherapy courses using IBM Explorys electronic health records (4Q 2012–1Q 2018). We identified rates of IP/ED ≤30 days post-chemotherapy, and OP-35 toxicities (NV, anemia, dehydration, diarrhea, fever, neutropenia, pain, pneumonia, or sepsis) by ICD-9, ICD-10, procedure codes, and CMS criteria. We evaluated cisplatin, anthracycline + cyclophosphamide (AC), carboplatin (>14 days apart, as a proxy for AUC ≥4), oxaliplatin (OX), and other non-HEC chemotherapy. We assessed guideline adherence, defined as triple prophylaxis (NK1 RA + 5HT3 RA +dexamethasone) rates at HEC initiation. Results: In 17,609 HEC and 56,624 non-HEC courses, we observed 30-day IP/ED utilization in 29% and 19% of courses, respectively (Table 1). For HEC, 76% of IP/ED use involved ≥1 of the 10 CMS toxicities, most often anemia (42%), pain (41%), dehydration (24%), and NV (24%). Rates of all-cause IP/ED, IP/ED with OP-35 toxicity, and NV-related IP/ED were consistent for HEC and OX. Gaps in triple prophylaxis were common in HEC. Conclusion: Roughly one-third of patients receiving HEC or OX experienced IP/ED events ≤30 days after chemotherapy. Three-quarters of IP/ED events involved ≥1 of 10 OP-35 toxicities linked by CMS to potentially avoidable acute care; of these, one-third involved NV. NV-associated acute care use is considerable, costly, and potentially avoidable with better adherence to antiemesis guidelines.

651 Background: Oxaliplatin (OX), used primarily in gastrointestinal cancers, is considered moderately emetogenic while multiple guidelines classify carboplatin and cisplatin as highly emetogenic chemotherapy (HEC). The new oncology outcome measure (OP-35) from the US Centers for Medicare and Medicaid Services (CMS) deems 30-day post-chemotherapy inpatient (IP) and emergency room (ED) events “potentially avoidable” if involving nausea or emesis (NV) or any of eight other toxicities. We lack data comparing avoidable IP/ED and NV events for OX relative to platinums classified as HEC. Methods: We assessed OX, cisplatin, and carboplatin courses of therapy from 4Q 2012 to 1Q 2018 using the IBM Watson Explorys database. We identified IP/ED and OP-35 toxicities (anemia, dehydration, diarrhea, fever, NV, neutropenia, pain, pneumonia, or sepsis) by diagnosis and procedure codes, and stratified results by sex and age < 70 (median age at diagnosis for colorectal cancer). An IP/ED event could involve ≥ 1 OP-35 toxicity. We also evaluated a FOLFIRINOX subgroup (receiving irinotecan ≤ 3 days after OX). Results: In sum, we identified 4,231 OX courses (382 FOLFIRINOX) (Table). OP-35 toxicities occurred in 75% of IP/ED events; of these, 34% OX and 42% FOLFIRINOX involved NV. Rates of IP/ED, IP/ED OP-35-defined toxicity, and NV after OX were consistent with cisplatin and carboplatin. Among patients receiving OX, women age < 70 (n = 1388) had higher NV rates vs. others (p < 0.001). Conclusions: Roughly one-third of patients receiving OX experienced IP/ED events ≤ 30 days post chemotherapy. Most involved ≥ 1 of 10 OP-35 toxicities, meeting CMS’ criteria as potentially avoidable acute care. OX IP/ED rates and NV rates were similar to other platinums and were worse among women age < 70, suggesting more aggressive antiemetic prophylaxis should be evaluated. [Table: see text]

74 Background: U.S. National Antiemetic Guidelines recommend upfront triple prophylaxis (NK1 receptor antagonist (RA) + 5HT3 RA + dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC), including carboplatin AUC ≥ 4 per 2017 guidelines. While existing data show gaps in guideline compliance, variation between individual physicians is less studied, and a realistic target compliance rate remains unknown. Methods: In a large electronic health record database (IBM Explorys), we identified HEC courses of therapy initiated from 2012 to 2017. Guideline compliance was defined as triple prophylaxis at chemotherapy initiation. Patient courses for ≥ 7 day cycles of cisplatin or anthracycline + cyclophosphamide (AC), or carboplatin (≥ 14 day cycles as a proxy for AUC ≥ 4) were ascribed to oncologists based on encounter frequency. We then ranked physicians treating ≥ 5 HEC courses and evaluated guideline compliance and individual physician variation. Results: In total, 10,074 HEC courses were identified and attributed to 451 unique physicians. Overall antiemetic guideline compliance with cisplatin and AC averaged 68% and 81% respectively. When ranked by compliance, the top 20% of physicians were 2.5 - 1.5 times as compliant as the bottom 20% (cisplatin 100% vs 40%; AC 100% vs 67%). For cisplatin, 32% of physicians had > 90% compliance; the remaining 68% were evenly distributed from 0 - 90%. For AC, 56% of physicians had > 90% compliance, and another 14% had 80 - 90%; the remaining 30% were evenly distributed. For carboplatin, 62% of physicians had ≤ 10% compliance, and another 17% had 11 - 20%; however, the majority of these data preceded guideline inclusion of carboplatin AUC ≥ 4 as HEC. Rates were independent of course volume per physician. Conclusions: Considerable physician-level variation exists in triple antiemetic prophylaxis guideline adherence for HEC. Hundreds of physicians had > 90% compliance with guidelines, suggesting 90% is a realistic target. However, the majority exhibited substantial gaps in NK1 RA use in HEC, placing patients unnecessarily at risk for CINV. Interventions are needed to bolster triple antiemetic prophylaxis in HEC, perhaps especially for carboplatin.

Recent real-world data on comorbidities and concomitant medications in SCLC patients are scarce, particularly for later-lines of treatment. The purpose of this study was to describe comorbidities' pattern and concomitant medication use in SCLC patients who received third- and later-lines of therapy (LOT). We conducted an analysis of 8,291 patients with newly diagnosed SCLC between 01/01/2008 and 09/30/2016 using Optum's electronic health records (EHR) database. The database consists of de-identified EHR data from a network of health care provider organizations in the United States. Of the 8,291 SCLC patients followed longitudinally, 428 received 3rd LOT. 206 LOTs were 4th or later-lines. At start of 3rd LOT, median age was 65, 46% were male, 97% had extensive disease (excluding n=52 with missing staging). The most prevalent comorbidities by the Charlson Comorbidity Index (CCI) category in SCLC patients during 6 months before start of 3rd LOT were metastatic solid tumor, chronic pulmonary disease, cardiovascular disease, and diabetes (top 10 are listed in Table 1). The frequently prescribed concomitant medications in SCLC patients within 6 month after start of 3rd LOT include analgesics, systemic corticosteroids, drugs for gastrointestinal complaints, anxiolytics, respiratory agents, antihypertensives and other cardiovascular agents, antidiabetics, and anti-infectives (top 10 are listed in Table 1). The patterns of comorbidities and concomitant medications were similar between 3rd LOT and 4th+ LOTs (4th+ LOT data not shown). In conclusion, this analysis provides unique real-world comorbidity and concomitant medication data in SCLC with 3rd and later-lines of therapy. These patients are mostly prescribed with medications for pain and inflammation due to the ongoing disease. Comorbidity conditions that are common in older adults are also observed in SCLC patients receiving later-lines therapy. Table 1. Top 10 comorbidities by Charlson Comorbidity Index (CCI) and top 10 concomitant medicationsCCIPercentage (%), n=428Metastatic solid tumor76.4Chronic pulmonary disease47.4Diabetes21.5Mild liver disease21.3Peripheral vascular disease16.1Cerebrovascular disease11.2Renal disease7.7Congestive heart failure6.8Myocardial infarction5.1Diabetes with chronic complications4.0Drug ClassNarcotic analgesics79.4Glucocorticoids72.2Intravenous supplies69.95-hydroxytryptamine-3 antagonists (antiemetic agent)69.6Heparins or glycosaminoglycans58.2Anxiolytics57.5Antidopaminergics (antiemetic agents)53.0Antihistamines (sedating)45.6Acetaminophen and proton pump inhibitors44.4Intravenous nutritional therapy; electrolyte; trace element; metal; vitamin; alone or combinations39.7 Citation Format: Rui Jiang, Scott H. Gulbranson, Philip Komarnitsky, Fabio A. Lievano, Martina M. Koch, Eros Papademetriou, Jerzy E. Tyczynski. Comorbidities and concomitant medication use in small cell lung cancer patients treated with third and later-lines of therapy: An analysis of electronic health records data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1213.

Objective To compare the frequency of anxiety disorders in older and younger persons with major depressive disorder with psychotic features. Design Cross-sectional. Setting University medical centers. Participants Two hundred fifty-nine persons (N = 117 aged 18–59 years and N=142 aged ≥60 years) with major depressive disorder with psychotic features who were enrolled in the Study of the Pharmacotherapy of Psychotic Depression (STOP-PD). Measurements Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) defined anxiety disorders were determined by Structured Clinical Interview for DSM-IV interview at baseline assessment. Younger and older participants were compared on the frequencies of any current anxiety disorder and any lifetime anxiety disorder, as well as the frequencies of individual anxiety disorders. Results Older persons had significantly lower frequencies of any current anxiety disorder and any lifetime anxiety disorder, even after controlling for relevant demographic and clinical variables. With respect to specific anxiety disorders, older persons had significantly lower frequencies of current and lifetime panic disorder, current and lifetime social anxiety disorder, and current and lifetime posttraumatic stress disorder. Conclusion The findings of this study are consistent with those of community-based epidemiologic surveys that anxiety disorders are less prevalent in older than younger adults. Because of the rigorous assessment used in STOP-PD, our findings suggest that the age-related decline in the prevalence of anxiety disorders is not simply due to a failure to detect cases in older people, as has been previously suggested.

not available. Disclosures: Study sponssored by LEO Pharma. Copyright 2018 SKIN

Objective To identify study-level and treatment group-level characteristics that are associated with attrition in antidepressant trials for the depressed elderly. Methods This meta-analysis used 68 published antidepressant randomized trials for the elderly depressed. Study-level and treatment group-level variables were extracted. The former consisted of: use of placebo arm, number of arms, unbalanced treatment allocation, year conducted, study duration, study location, number of centers, and patient pool. The latter consisted of: assigned treatments, baseline mean Hamilton Depression Rating Scale (HDRS), baseline mean age, gender ratio, attrition size, and sample size. Univariate logistic regressions with attrition as the dependent variable were applied, followed by application of a forward stepwise selection method for identification of independent attrition correlates. Results The 68 studies had a total of 153 treatment groups and 8,385 subjects. Among them, 2,287 subjects were terminated early, resulting in an overall 27.3% attrition rate. The stepwise results showed that higher attrition was significantly associated with active antidepressant groups as opposed to placebo groups, higher baseline HDRS, smaller sample size, unbalanced allocation of treatments, longer duration, and studies conducted in USA. Conclusions The attrition in geriatric antidepressant trials can be affected by study and group-level design characteristics that include severity of depression symptoms and active treatments among others. Copyright © 2009 John Wiley & Sons, Ltd.

Among patients with major depression with psychotic features, little is known about the extent to which those with and without somatic delusions differ.The first 183 participants in the STOP-PD study were divided into two groups based on the presence or absence of somatic delusions and were compared on multiple demographic and clinical characteristics.In the multivariate analysis, those with somatic delusions reported more somatic symptoms, rated their health as worse, and were less likely to have persecutory delusions.Based on the methods we used, we could not detect meaningful differences between subjects with and without somatic delusions. This suggests that the presence of irrational somatic ideation does not define a distinct clinical subgroup among patients with psychotic depression. This finding needs to be replicated.

Studies using estrogen receptor alpha (ERalpha) knock-out mice indicate that ERalpha masculinizes male behavior. Recent studies of ERalpha and male prosocial behavior have shown an inverse relationship between ERalpha expression in regions of the brain that regulate social behavior, including the medial amygdala (MeA), and the expression of male prosocial behavior. These studies have lead to the hypothesis that low levels of ERalpha are necessary to "permit" the expression of high levels of male prosocial behavior. To test this, viral vectors were used to enhance ERalpha in male prairie voles (Microtus ochrogaster), which display high levels of prosocial behavior and low levels of MeA ERalpha. Adult male prairie voles were transfected with ERalpha in the MeA (MeA-ERalpha) or the caudate-putamen (ERalpha control) or luciferase (MeA-site-specific control), and 3 weeks later tested for spontaneous alloparental behavior and partner preference. Enhancing ERalpha in the MeA altered/reduced male prosocial behavior. Only one-third of MeA-ERalpha males, compared with all control males, were alloparental. MeA-ERalpha males also displayed a significant preference for a novel female. This is a critical finding because the manipulations of neuropeptides, oxytocin and vasopressin, can inhibit the formation of a partner preference, but do not lead to the formation of a preference for a novel female. The results support the hypothesis that low levels of ERalpha are necessary for high levels of male prosocial behavior, and provide the first direct evidence that site-specific ERalpha expression plays a critical role in the expression of male prosocial behavior.

This study examined the rate and predictors of major depression six months after outpatient mental health admission.Assessments were conducted at admission and three and six months later among 166 participants. Antidepressant treatment adequacy and depression outcomes were assessed at follow-ups.Predictors of major depression at six months included nonremission status at three months (odds ratio [OR]=3.56, p=.003), inadequacy of early pharmacotherapy (OR=2.73, p=.009), worse physical functioning measured by the 36-Item Short-Form Health Survey (OR=.975, p.001), and being unmarried (OR=2.54, p=.031).The findings support the effects of baseline physical disability, marital status, early treatment adequacy, and early remission on the course of major depression. The identification of individuals who do not receive intensive pharmacotherapy or who have not recovered by three months may provide opportunities for interventions to optimize six-month outcomes and to prevent the development of a persistent depression.

Weight gain has often been associated with olanzapine treatment, yet little is known about the influence of patient age or cumulative dose on olanzapine-associated weight gain. The first 118 participants in the National Institutes of Mental Health Study of the Pharmacotherapy of Psychotic Depression randomized clinical trial (Clinical Trials.gov Registration NCT00056472) completing at least 4 weeks of treatment with olanzapine were analyzed to determine the relationship between weight gain, age, and cumulative olanzapine dose. Younger (age 18-59 years) and older (age 60 + years) participants received open-label olanzapine and either sertraline or placebo for up to 12 weeks. Linear mixed effect regression modeling was used to determine the effects of age and cumulative olanzapine dose on weight gain, controlling for potential confounders. Age was observed to have a significant negative association with weight gain (P=0.01), even after controlling for differences in cumulative dose and baseline body mass index. Each 10-year increase in age was associated with a decrease in mean weight gain over 12 weeks of approximately 0.6 kg (95% confidence interval: 0.14-1.05 kg). Cumulative olanzapine dose was also significantly associated with weight gain (P< 0.0001). Approximately 60% of completers of the 12-week trial experienced clinically significant weight gain (≥ 7% of baseline weight).

Little is known about the health status of the 7.3 million Americans who enrolled in insurance plans through the Marketplaces established by the Affordable Care Act in 2014. Medication use may provide an early indicator of the health needs and access to care among Marketplace enrollees. We used data from January-September 2014 on more than one million Marketplace enrollees from Express Scripts, the largest pharmacy benefit management company in the United States. We compared the characteristics and medication use between early and late Marketplace enrollees and between all Marketplace enrollees and enrollees with employer-sponsored insurance. Among Marketplace enrollees, we found that those who enrolled earlier (October 2013-February 2014) were older and used more medication than later enrollees. Marketplace enrollees, as a whole, had lower average drug spending and were less likely to use most medication classes than the employer-sponsored comparison group. However, Marketplace enrollees were more likely to use medicines for hepatitis C and particularly for HIV.

The present study examined (1) rates of somatic complaints and (2) the association between stress and somatic complaints in low-income urban youth. Participants were 1030 low-income urban 6th–8th grade adolescents. Results indicate that, for both boys and girls, somatization was the most commonly reported internalizing symptom in this sample, and that heightened rates of urban stress predicted heightened rates of somatic complaints. In addition, a significantly higher percentage of youth in this sample reported clinically elevated levels of somatic complaints (17%) relative to that reported by normative samples (5%). The 2 most common somatic complaints were stomachaches and headaches, and females reported higher rates of somatic complaints than males. These findings suggest that somatic complaints are the most common expression of internalizing symptoms among low-income urban youth, and that exposure to heightened rates of stress places low-income urban adolescents at heightened risk for somatization. Implications of these findings and directions for future research are discussed.

Oxytocin (OT) has an organizational effect within the central nervous system and can have long-lasting effects on the expression of social behavior. OT has recently been implicated in modulating the release of serotonin through activation of receptors in the raphe nuclei. Here we test the hypothesis that OT can have an organizational effect on the serotonergic system. Male prairie voles received an intraperitoneal injection on postnatal day 1 with 3.0 or .3 µg OT, an OT antagonist, or a saline control. Brains were collected on day 21 and immunostained for serotonin. Serotonin axons were quantified in the anterior hypothalamus, cortical amygdala, medial amygdala, paraventricular nucleus of the hypothalamus, and ventromedial hypothalamus. Males treated with 3.0 µg OT displayed significantly higher serotonin axon length densities in the anterior hypothalamus, cortical amygdala, and the ventromedial hypothalamus than control males. These results support the hypothesis that OT has an organizational effect on the serotonin system during the neonatal period, and that these effects are site-specific.

Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features.To compare remission rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy; and to compare response by age.Twelve-week, double-blind, randomized, controlled trial.Clinical services of 4 academic sites. Patients Two hundred fifty-nine subjects with MD with psychotic features randomized by age (60 oror =60 years) (mean [standard deviation (SD)], 41.3 [10.8] years in 117 younger adults vs 71.7 [7.8] years in 142 geriatric participants). Intervention Target doses of 15 to 20 mg of olanzapine per day plus masked sertraline or placebo at 150 to 200 mg per day. Main Outcome Measure Remission rates of MD with psychotic features.Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47; P.001); 41.9% of subjects who underwent combination therapy were in remission at their last assessment compared with 23.9% of subjects treated with monotherapy (chi(2)(1) = 9.53, P = .002). Combination therapy was comparably superior in both younger (OR, 1.25; 95% CI, 1.05-1.50; P = .02) and older (OR, 1.34; 95% CI, 1.09-1.66; P = .01) adults. Overall, tolerability was comparable across age groups. Both age groups had significant increases in cholesterol and triglyceride concentrations, but statistically significant increases in glucose occurred only in younger adults. Younger adults gained significantly more weight than older subjects (mean [SD], 6.5 [6.6] kg vs 3.3 [4.9] kg, P = .001).Combination pharmacotherapy is efficacious for the treatment of MD with psychotic features. Future research must determine the benefits vs risks of continuing atypical antipsychotic medications beyond 12 weeks.clinicaltrials.gov Identifier: NCT00056472.

The independent association of age and other factors with suicidality in patients with major depression with psychotic features was examined. Of the 183 study participants, 21% had a suicide attempt during the current episode. Male gender, Hispanic background, past suicide attempt, higher depression scores, and higher cognitive scores were each independently associated with greater intensity of current suicidality. Older age was independently associated with a lower risk of a lifetime suicide attempt. These findings reinforce the evidence that patients with psychotic depression are at high risk for suicide and underscore the importance of examining correlates of suicidality specific to patients with psychotic depression.

Background Previous studies have demonstrated that neonatal manipulation of oxytocin (OT) has effects on the expression of estrogen receptor α (ERα) and the central production of oxytocin observed in juveniles (at weaning, 21 days of age). The goal of this study was to determine whether the effects of neonatal manipulation of OT last into adulthood, and if the effects differ from those observed during the early postnatal period. On the first day of life, prairie voles (Microtus ochrogaster) received one of three doses of OT (High, 3 μg; Med, 0.3 μg; Low, 0.03 μg), an OT antagonist, or isotonic saline. Another group was handled, but not injected. Then as adults, brains were collected, sectioned, and stained for ERα or OT using immunocytochemistry. Results In females, treatment with OT increased the expression of ERα immunoreactivity in the ventral lateral septum (0.03 μg) and the ventromedial nucleus of the hypothalamus and central amygdala (0.3 μg). In males, OT antagonist increased ERα expression in the bed nucleus of the stria terminalis. There was no apparent effect of OT on the number of cells producing OT in the paraventricular nucleus of the hypothalamus. Conclusion The current results suggest that neonatal manipulation of OT has long-term organizational effects on the expression of ERα in both males and females. The lack of effect on OT neurons in the paraventricular nucleus suggests that some developmental effects of OT previously observed in weanlings do not persist into adulthood. Developmental effects of OT on ERα patterns were sexually dimorphic, dose-dependent, and site-specific.