bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualizing treatment patterns and survival in metastatic breast cancer.
Authors: Gilbert Aidan , Williams Courtney , Kandhare Pravinkumar , Nakhmani Arie , Meersman Stephen C. , Garrett-Mayer Elizabeth , Kaltenbaugh Melinda , Azuero Andres , Ingram Stacey A. , Burkard Mark E. , Bhatia Smita , Kenzik Kelly , Rocque Gabrielle Betty
Published: October 2019

316

Background: Optimal treatment sequencing (i.e., the order in which drugs are given) for metastatic breast cancer (MBC) is unknown. We aimed to develop an approach to visualize treatment patterns and survival in MBC. Methods: This retrospective study utilized ASCO’s CancerLinQ Discovery® database generated from electronic health records. Subjects included 3,312 women aged ≥18 years who were diagnosed with and received treatment for MBC after 1980. Hormone receptor (HR) status was determined by concordant diagnosis and treatment records. Human epidermal growth factor (HER2) status was determined by delivery of HER2-targeted therapy. Ordered and administered treatments were included. We created spatiotemporal plots of treatment patterns for HR+/HER2-, HER2+, and triple negative (TN) MBC. Individuals were represented on the Y-axis, and time on the X-axis with development of MBC aligned at time 0. Treatment classes were identified by colors: hormone therapies in shades of red, chemotherapies in shades of blue, HER2-targeted therapies in shades of green, and novel therapies in shades of orange. Concurrent treatments were represented by split bars. An overlaid Kaplan-Meier curve allowed for observations about the relationship between survival and treatment. Results: We developed a novel visualization approach to simultaneously display heterogeneous, longitudinal treatments and survival. Median survival after first documentation of MBC was 3.1 (IQR 1.4-7.2), 1.3 (IQR 0.6-2.8), and 2.6 (IQR 1.0-5.2) years for HR+/HER2-, TN, and HER2+ MBC, respectively. Patients with longer survival often had long duration of initial therapy, suggesting a more indolent or responsive disease. Substantial heterogeneity in treatment sequencing was observed for HR+HER2- and TN cohorts. In the HER2+ cohort, HER2-targeted therapy was commonly administered for the duration of treatment with more homogeneous sequencing. Conclusions: This novel visualization approach allows for observing the relationship between treatment patterns and survival, which is challenging to demonstrate with traditional quantitative methods. This approach can generate hypotheses regarding impact of treatment patterns on survival.
Utilizing visualization to qualitatively evaluate electronic health record-derived database limitations.
Authors: Gilbert Aidan , Kandhare Pravinkumar , Nakhmani Arie , Meersman Stephen C. , Garrett-Mayer Elizabeth , Kaltenbaugh Melinda , Burkard Mark E. , Williams Courtney , Azuero Andres , Bhatia Smita , Kenzik Kelly , Rocque Gabrielle Betty
Published: October 2019

317

Background: Electronic health record (EHR) databases are a promising platform for clinical research using real-world data. However, information on potential limitations of these data sources is lacking. We sought to understand how data visualization might be used to identify data inconsistencies and the applicability of previously validated claims-based algorithms used to identify patients with metastatic breast cancer (MBC). Methods: This retrospective study utilized ASCO’s CancerLinQ Discovery database derived from EHR data. Subjects included women ≥18 years treated for MBC diagnosed ≥1980. Subjects with MBC were identified using two billing codes for metastasis on separate dates following primary breast cancer diagnosis. Treatment course sequences were visualized. Patients were represented by a horizontal bar on the Y-axis. Treatments were displayed using colored bars (blue: chemotherapy, red: endocrine therapy, green: HER2 targeted, orange: novel therapy) with time of treatment on the X-axis. Visualizations were qualitatively evaluated, and treatment patterns inconsistent with clinical practice were identified. Results: We identified 4,760 women treated for MBC using billing codes for primary breast cancer diagnosis and distant metastasis. Most patients (96%) had a primary breast cancer diagnosed in 2000 later. Treatment patterns inconsistent with clinical practice identified using the visualization technique included: 1% of patients received adjuvant chemotherapy continuously for ≥1.5 years, suggesting missed coding for metastatic disease; 5% of patients did not receive any treatment in the year following metastasis, suggesting the billing code may have been used in workup and not for confirmed metastatic disease. Among patients with MBC, 50% identified as HR+ across all records had not received hormone therapy, while 39% identified as HR- across all records received hormone therapy. Conclusions: Because previously validated algorithms may not translate well to EHR databases, quality auditing should always be performed. The proposed data visualization can be used for improving algorithms, qualitatively identifying errors, and avoiding biased or inaccurate results.
An NLP tool to identify molecular diagnostic testing in veterans with stage IV NSCLC.
Authors: Lynch Julie Ann , Kelley Michael J. , Lee Kyung Min , Hung Anna , Li Yanhong , Hintze Bradley J , Pendergraft Trudy , Pavilack Melissa , Efimova Olga , DuVall Scott L , Reed Shelby D.
Published: October 2019

318

Background: ASCO Quality Oncology Practice Initiative (QOPI) encourages hospitals to determine if patients (pts) with stage IV NSCLC adenocarcinoma have activating EGFR mutations. Guidelines recommend tumor testing to identify ALK, BRAF, EGFR, ROS1 and other gene alterations before treatment. Studies have shown EGFR testing underutilization. We developed and tested a tool to identify EGFR tests in Veterans Affairs (VA) electronic health record (EHR). We examined whether Veterans with newly diagnosed NSCLC-IV underwent EGFR testing. We measured EGFR testing trends and analyzed differences by patient, VA Medical Center (VAMC) and region. Methods: VA EHR data identified Veterans with NSCLC-IV diagnosed 2013-2017, who survived 45+ days and had 2+ visits with a VA oncologist within 120 days of diagnosis. All NSCLC histologies were included. Demographics and VAMC were obtained from VA Corporate Data Warehouse. EGFR testing results performed outside VA were from commercial laboratory data. We deployed a natural language processing (NLP) tool to identify EGFR tests in VA EHR clinical notes. Testing rates and characteristics associated with testing were examined by descriptive analysis. Results: Of 3484 pts, 623 (18%) had evidence of EGFR testing. There was a 244% rise in testing. 54 (9%) pts diagnosed in 2013 were tested vs 186 (25%) diagnosed in 2017 ( χ2 82.3, p-value 0.00). No statistically significant differences by sex, race, or urban/rural address existed. Testing decreased as pts aged ( χ2 27, p-value 0.00). 35% of pts age ≤49 and 12% of pts age ≥80 were tested. Testing varied widely by VAMC and region (VAMC χ2 795.6, p-value 0.00; region χ2 90.3, p-value 0.00). 28% of pts in the Pacific were tested vs 10% of pts in the Southeast. The main contributor to regional variation was VAMC differences. VAMCs that conducted EGFR testing within their own laboratories (64% and 53%), or were co-located with the national precision oncology program (NPOP, 59%) tested the most pts. NPOP was temporally associated with increased testing nationally. 9% of pts diagnosed in 2017 were tested using NPOP. Conclusions: EGFR testing underutilization in the VA persists. QOPI and the NLP tool for this initiative will help system-wide quality improvement initiatives.
Enhancing community capacity to deliver value-based cancer care at the end-of-life.
Authors: Patel Manali I. , Ramirez David , Agajanian Richy , Agajanian Hilda H. , Coker Tumaini
Published: October 2019

4

Background: To improve value-based cancer care, we designed an intervention using lay health workers (LHWs) who we trained to assess patient's symptoms. LHWs referred patients to palliative care and/or behavioral health in response to positive assessments. We implemented the intervention in collaboration with a community oncology group and a Medicare Advantage payer for patients with all stages of cancer. At ASCO 2019 we demonstrated the associated reductions in patient-reported symptoms, acute care use, and total costs of care. This study evaluates the effect of the intervention on end-of-life cancer care, specifically healthcare use in the last month of life and total costs of care from diagnosis until death. Methods: We enrolled all newly diagnosed health plan beneficiaries with solid and hematologic malignancies from 11/2016 through 9/2018 and compared outcomes to all patients diagnosed with cancer in the year prior to the intervention (control arm). For all patients who died within 12-months follow-up, we compared risk of death using Cox Models and generalized linear regression to compare healthcare use in the last month of life, and total costs of care from diagnosis until death. All models were adjusted for age, stage, comorbidities, diagnosis, and length of follow-up. Results: 180 patients in the intervention and 156 in the control died during the study. In both groups, the mean age was 80 years; 49% were non-Hispanic White, 40% Hispanic, 5% Asian/Pacific Islander, and 4% black. There were no differences in survival (HR 0.96, p = 0.6). Intervention patients as compared to the control had lower mean inpatient admissions (0.3 +/- 0.04 versus 0.5 +/- 0.07, p = 0.02) and emergency department visits per thousand members per year (0.11 +/- 0.02 versus 0.49 +/- 0.06, p < 0.001) in the last month of life, greater proportion of patients with hospice use (69% versus 48%, p < 0.001), lower proportion of patients with acute care facility deaths (37.5% versus 62.5%, p = 0.02) and lower median total healthcare costs from diagnosis until death ($24,902 versus $33,145, p = 0.02). Conclusions: An LHW intervention significantly improved the value of end-of-life cancer care and may be a solution to improve burdensome and costly care for patients.
Trends in the use of novel hormonal agents at the end of life in metastatic castration-resistant prostate cancer.
Authors: Hu Jason , Aprikian Armen G. , Vanhuyse Marie , Dragomir Alice
Published: October 2019

40

Background: The approval of novel hormonal agents (NHAs), abiraterone and enzalutamide, have increased the therapeutic arsenal available in metastatic castration-resistant prostate cancer (mCRPC). However, the use of chemotherapy and other antineoplastics at the end of life has been suggested as an indicator of poor quality of care. In this study, we report the use of NHAs at the end of life in men with mCRPC in the province of Quebec, Canada. Methods: Using Quebec public healthcare administrative databases, we identified patients with prostate cancer who used an NHA (abiraterone or enzalutamide) after androgen deprivation therapy and who died between 2012 and 2016. The primary outcome was the use of an NHA in the 30 days before death. Use of an NHA in the 60 and 90 days before dying, and initiation (first prescription) of an NHA in the 30 days before death were evaluated as secondary outcomes. Multivariable analysis of the primary outcome was performed with logistic regression with results reported as odds ratios (OR) with 95% confidence intervals (95%CI). Results: The cohort consists of 1316 patients who used an NHA over the course of their disease and died at a median age of 78 years old, with 292 (22.2%), 464 (35.3%), and 575 (43.7%) having used an NHA in the 30, 60 and 90 days of life, respectively. Use of NHA 30 days before dying decreased over the study period, from 44.8% in 2012 to 17.0% in 2016 (Cochran-Armitage test p-value < 0.001). On multivariable analyses, later years of death remained associated with lower odds of NHA use 30 days before death (OR 0.74, 95%CI 0.66 to 0.81, p < 0.001). Fifty-eight (4.4%) patients initiated a NHA 30 days before dying. Conclusions: Rates of NHA use 30 days before dying were high initially but decreased over the study period. Further assessment of NHA use at the end of life is warranted to examine if the trend will be maintained given the recent approval of additional oral NHAs for prostate cancer.
Primary care providers propensity to order non-recommended surveillance testing after curative breast cancer treatment.
Authors: Wallner Lauren P. , Abrahamse Paul , Radhakrishnan Archana , Hamilton Ann S. , Ward Kevin C. , Hawley Sarah T. , Katz Steven J.
Published: October 2019

52

Background: Team-based cancer care models promote primary care providers taking on a larger role in survivorship care. However, little is known about PCP attitudes toward and propensity to order non-recommended surveillance testing. Methods: A stratified random sample of PCPs identified by early-stage breast cancer patients diagnosed in 2013-15 who participated in iCanCare Study (Georgia and Los Angeles SEER registries) were surveyed about their experiences caring for cancer patients (N = 519, 58% response rate). PCPs were asked in a clinical vignette whether they would order non-recommended bone scans, other imaging (i.e. PET) or tumor marker testing (i.e. CA-125) in an asymptomatic, early-stage breast cancer survivor. A composite score was created by averaging their responses to the individual items, and categorized by tertiles into low, selective and high propensity to order non-recommended testing. PCP confidence in their knowledge about appropriate testing was also measured (5 pt. Likert-type scale; not all all-very confident) and compared with propensity to order. Multivariable, weighted, multinomial logistic regression was used to then evaluate PCP-reported factors associated with high and selective propensity to order non-recommended testing (vs. low). Results: In this sample, 32% of PCPs had a low propensity, 40% selective, and 28% a high propensity to order non-recommended surveillance tests. Of the 80% of PCPs who reported they were confident in their knowledge about appropriate testing, 27% had a high propensity to order. PCPs practicing in staff-model HMOs were less likely to have a high or selective propensity to order (vs. low) when compared to PCPs in private practice. (high aOR: 0.4, 95%CI: 0.2-0.7; selective aOR: 0.3, 95%CI: 0.2-0.6). Conclusions: Over a quarter of PCPs had a high propensity to order non-recommended surveillance testing for early-stage breast cancer patients, yet the majority reported they were confident in their knowledge about appropriate surveillance testing. Efforts to increase PCP knowledge about the specifics of breast cancer surveillance may be warranted to reduce the overuse of non-recommended testing during survivorship.
Improving lung cancer screening in the HIV population.
Authors: Galeas Jose Nahun , Grossberg Robert M. , Serrano Maria , Shmukler Anna , Sakalian Susan , Mehta Vikas , Halmos Balazs , Packer Stuart H.
Published: October 2019

69

Background: Lung cancer screening for high risk populations has a major impact in reducing mortality.In our population, HIV patients are younger (mean age 68.0 vs 56.8, p= 0.014) and have a higher percentage of advanced disease at diagnosis (49% vs 68%, p< 0.001),when compared to non-HIV lung cancer patients.Due to this increased risk and aggressiveness, we embarked on a quality improvement initiative to increase screening in our HIV smoking population. Methods: Data was collected retrospectively from 10/18 to 1/19 in the HIV clinic. A multidisciplinary team was created involving thoracic oncologists, radiologists and HIV physicians to discuss methods to improve screening. We identified areas to be improved and utilized performance improvement tools such as a Pareto chart and PICK chart. Data was then collected prospectively. Results: In the initial 4 month period,among HIV positive patients 55–77 years old with significant smoking history, 13% (total n=54) of patients had a chest CT done for lung cancer screening and only 3.7% were referred for lung cancer screening during that specific period. Main barriers were lack of proper identification of screening candidates, discrepancies in smoking history within the EMR and lack of a consistent system for referral. An algorithm was created in the referral workflow, in which providers would need only to identify patients in the age group of 55-77 years old with any history of smoking and refer to a lung cancer screening program. The screening program would contact the patient and screen as per CMS guidelines. 17 Patients were referred from the HIV clinic from 4/8/19 to 5/2/19. Of these patients, 29% had a lung cancer screening CT scan done or scheduled, 18% of patients did not qualify for screening,and the remaining 53% of referrals are pending to be screened by telephone call. Further data on subsequent PDSAs and results of screening scans will be presented at the meeting. Conclusions: Modifying the screening algorithm for lung cancer in our HIV clinic by adding support from a dedicated screening program increased screening rates by 25% in the first month of intervention. Subsequent interventions include: patient education to reduce the stigma of lung cancer and EMR alerts when a patient meets criteria for screening.
ASCO Quality Training Program: Five-year review.
Authors: Keng Michael Kenneth , Cunningham Gene , Gilmore Terry , Gilligan Timothy D. , Quinn Doris , Kaufman Laura , Bingham John , Guerrier Vedner , Chiang Anne C. , Mohamed Ashraf Mahmoud , Hagemann Jordan
Published: October 2019

7

Background: ASCO introduced a Quality Training Program (QTP) in 2013 with an aim: train oncology professionals to design, implement and lead successful quality improvement (QI) activities and assume leadership positions to champion culture change in their practices. Methods: The QTP is a formal 6-month program taught by QI faculty and mentored by QI coaches over five days of in-person learning across three sessions, and hands-on learning at the participants’ practices. Sessions include seminars, case examples, and small group exercises. Participants attend in multi-disciplinary teams and focus on a problem they wish to solve in their practice. Scheduled conference calls with QI coaches were held between sessions. Participants complete pre and post QTP surveys (10 point Likert scale; 1 - no knowledge/competence to 10 - complete knowledge/competence) and provide direct written feedback. Results: Since its inception, QTP has had 15 courses (10 domestic and 5 international) with 120 teams and 544 total participants. QTP is led by an 8-member steering group with 16 faculty and coaches. All post-survey items had an increase in knowledge and competence. Each item’s score was calculated as the mean difference between ‘before’ and ‘after’ score. Participants stated increase of 46% to 84%: overall mean increase for knowledge 38% and competence 37%. The greatest increase were: methodology and practical tools to make changes in practice (writing an aim statement, implementing rapid improvement, process analysis tools, and flowcharting the process). Most common suggestion for improvement was allowing more time for the project. Participants are encouraged to write articles and present work in poster and plenary sessions. QTP have led to 7 manuscripts and 21 abstract presentations to national meetings. Six QTP alumni currently are now QI coaches and faculty. Conclusions: The QTP is a successful QI course for oncology professionals who need to measure performance, investigate quality and safety issues, and implement change. It is the only oncology-focused QI training, as all faculty and coaches are providers and QI specialists with oncology experience, making this a unique opportunity. The success will provide further momentum to offer QTP domestically and around the world.
Impact of a student pharmacist-directed pilot intervention on influenza vaccination documentation and administration rates in older adults receiving parenteral anticancer therapy.
Authors: Kim E. Bridget , Zangardi Mark , Rostamnjad Leila , Nipp Ryan David , Bartholomay Mimi , White Laura , Blouin Gayle C.
Published: October 2019

71

Background: Annual influenza vaccination is recommended for individuals 6 months and older. Older adults are at high-risk of developing influenza and complications associated with the virus. However, < 50% of patients with cancer receive the influenza vaccine annually. In previous work at our institution, a quality improvement project identified that only 40% of adult patients initiating parenteral anticancer therapy between September and December 2017 were documented to have received the influenza vaccine. Therefore, a multidisciplinary student pharmacist-directed pilot intervention was developed to improve influenza vaccine documentation and administration rates, and we sought to investigate the impact of this intervention. Methods: All adult patients (≥65 years old) scheduled for parenteral anticancer therapy during November 2018 were screened for influenza vaccination documentation. Patients were identified by reviewing infusion center schedule. Under supervision of board-certified oncology pharmacists, two student pharmacists evaluated influenza vaccination documentation in the institution/network electronic medical record (EMR) and outside records. Patients with unknown vaccination history were identified for interview by pharmacy students. The student pharmacists collaborated with oncology nurses and clinicians to order and administer influenza vaccine to patients who agreed to vaccination. Influenza vaccination status was updated in the EMR following record reviews/interviews. Results: Student pharmacists screened 617 patient EMRs and interviewed 124 patients to verify vaccination status. Furthermore, 33 patients received influenza vaccination as a direct result of student pharmacist intervention. Overall, rate of influenza vaccination status documentation was 60.5%. Conclusions: Compared with historic data, we found promising results for a student pharmacist-directed pilot intervention, which demonstrated the potential to improve influenza vaccination status documentation and administration among older adults receiving parenteral anticancer therapy.
Out-of-pocket costs and financial toxicity experienced by patients in early-phase clinical trials.
Authors: Huey Ryan , George Goldy , Phillips Penny , White Revenda , Fu Siqing , Janku Filip , Karp Daniel D. , Naing Aung , Piha-Paul Sarina Anne , Subbiah Vivek , Tsimberidou Apostolia Maria , Pant Shubham , Yap Timothy A , Rodon Ahnert Jordi , Meric-Bernstam Funda , Shih Ya-Chen T. , Hong David S.
Published: October 2019

8

Background: Clinical trials are an important therapeutic option for cancer patients. Although financial burden in cancer treatment is well-described, the financial burden associated with clinical trials is not well understood, especially for patients with lower socioeconomic status. Methods: We conducted a survey regarding economic burden and financial toxicity among cancer patients on Phase I clinical trials for at least 1 month. Financial Toxicity Score (FTS) was assessed using the validated COmprehensive Score for Financial Toxicity (COST) survey (scale 0-44, lower scores indicating worse financial toxicity). Patients also reported monthly out of pocket (OOP) medical and non-medical expenses. Results: Of 147 consecutive patients approached, 105 agreed to participate; median age = 60y; 62% female; 49% had annual income < $60K; 50% lived < 300 miles from the clinic; 34% required air travel; 41% had Medicare, 50% had employer sponsored insurance. Median FTS = 20, with interquartile range of 12.5. Median monthly OOP costs for non-medical expenses was $985, and for medical expenses was $475. Median total monthly OOP costs was $1695. Compared to patients in the highest quartile of FTS, a significantly lower % of patients in the lowest (worst) quartile of FTS had incomes > $60K (27% v. 77%, P < 0.001), and a significantly higher % were unemployed or not working outside the home (54% v. 12%, P = 0.001), and incurred higher than expected medical (39% vs. 12%, P = 0.025) and non-medical (64% vs. 15%, P = 0.003) expenses. Compared with patients for whom medical costs were not much higher than expected, a significantly higher % of patients with medical costs much higher than expected were non-White (77% v. 46%, P = 0.004) and unemployed/not working outside the home (46% v. 19%, P = 0.009). Conclusions: Among cancer patients participating on clinical trials, economic burden is high and financial toxicity is disproportionally higher in patients with lower income. OOP costs can be substantial and are often unexpected for patients.
Hospice and medical oncology collaboration in a statewide collaborative.
Authors: Bedard Louise , Procailo Kelly Marie , Beusterien Sam , Kolizeras Kleanthe , Straight Cindy , Griggs Jennifer J.
Published: October 2019

83

Background: Hospice enrollment (QOPI measure 42) has consistently been lower in practices in the Michigan Oncology Quality Consortium (MOQC), a collaborative of nearly all medical oncology practices. MOQC enrollment has been 47% during CY2014-18 compared to national QOPI, which ranged from 53 to 59% during the same time period. We describe our approach to improve hospice use in the care of oncology patients. Methods: MOQC providers suggested that hospices across the state be involved in facilitating patient-centered approaches to increase enrollment of patients to hospice care. Beginning in Spring 2018, hospices in each of the six MOQC regions were invited to participate in standing regional meetings as well as teleconferences (one per region). Root cause analyses identified barriers universal and specific to that region. Each region was asked to choose at least one hospice-oncology project. Results: Thirty hospices are participating, including the five largest hospices in the state and hospices associated with the largest healthcare systems. Barriers to hospice include lack of hospice services in rural areas, in complete understanding among oncologists about what hospice can provide, resistance from patients and families due to misperceptions, communication issues with oncologists, between practices and hospices, and/or with patients once referred to hospices, lack of appreciation by hospice providers regarding the long standing relationship between patients and oncologists, and variation in use of palliative treatment such as radiation therapy. A total of 13 projects have been selected by the hospices and oncology practices to be developed by the regions. Once harmonized by the Coordinating Center, the projects will be shared across the state. The Coordinating Center is addressing lack of access to hospice in remote rural areas. Conclusions: Our partnership between oncology practices and hospices across a statewide collaborative has been a mutually beneficial relationship that promises to address some of the key systemic barriers to hospice enrollment. Feedback has indicated that communication between oncology and hospice providers is becoming more seamless and that referrals to hospice have increased.
Intensity of end-of-life (EOL) cancer care in Western Washington (WA) versus Alberta (AB), Canada (CA).
Authors: Khaki Ali Raza , Xu Yuan , Fedorenko Catherine R. , Grivas Petros , Ramsey Scott David , Cheung Winson Y. , Shankaran Veena
Published: October 2019

89

Background: Aggressive care at the EOL may lead to unnecessary suffering and healthcare costs for patients (pts) with cancer. Despite similar populations and state-of-the-art cancer delivery systems, we hypothesize that EOL care may be more intense in the United States (US) multi-payer system vs the CA single-payer system. Using cancer registry and claims data, we compared EOL cancer care between WA and AB. Methods: Adult pts with AJCC stage II-IV solid tumors who died between 2014 and 2016 were identified from regional population-based cancer registries in WA and AB. Data sources were 1) WA State Cancer Registry (WSCR) and Western WA Cancer Surveillance System (CSS) linked to enrollment files and claims from four regional insurers and 2) CA National Ambulatory Care Reporting System (NACRS), Discharge Abstracts Database (DAD), and CT records from AB Health Services. Proportions of pts receiving chemotherapy (CT), ICU admission, or > 1 ED visit in the last 30 days of life (DOL) in WA and AB were determined and compared using two sample z-test with two-tailed hypothesis (α = 0.05). Results: 11,177 AB and 7,906 WA pts met study inclusion criteria. Median age was 71 (IQR 61-79) and 75 (IQR 68-82) for AB and WA, respectively. The most common cancer types represented include lung (31% AB; 35% WA), colorectal (17% AB; 9% WA), breast (10% AB; 6% WA) and prostate (11% AB; 4% WA). A similar proportion of pts in WA and AB experienced multiple ED visits in the last 30 DOL (12.4% WA vs 12.1% AB). CT use in the last 14 and 30 DOL was greater in WA vs AB (6.3% and 13.4% vs 2.7% and 6.6%, respectively) and ICU admissions in the last 30 DOL were substantially greater in WA vs AB (19.9% vs 3.9%). Conclusions: CT use and ICU admissions in the last 30 DOL were more common in WA than AB. The lower rate of ICU admissions in AB may be due to a provincial effort to prioritize goals of care discussions . Future studies to characterize and compare drivers of inappropriately aggressive EOL care may help improve cancer care for patients (pts) in the US and AB.

[Table: see text]
A practice transformation model to improve lung cancer care.
Authors: Escobar Daisy E. , Khushman Mohd , Young Pierce Jennifer , Tinnea Cathy , Cadden Austin , Wujcik Debra , Owenby Susie , Pai Sachin Gopalkrishn
Published: October 2019

92

Background: Lung cancer has the highest cause of cancer death, treatment of which is both complicated and expensive. Emerging actionable biomarkers and treatments provide both opportunity and treatment challenges. Adherence to evidence-based treatment and advanced care discussions add value to care. Oncology practices need to document the above to participate in value-based care reimbursement models. A Practice Transformation (PT) model was implemented to address quality and cost issues. Methods: After IRB approval, baseline data on lung cancer patients diagnosed during a 6-month period (Jul-Dec 2017) were collected through chart abstraction and treatment planning surveys. Rates of molecular testing ordered, results available at time of treatment decision-making, guideline concordant treatment decisions, and documentation of advanced care discussions were presented to the PT team. After education on recent clinical trial results and NCCN treatment guidelines, the PT team determined strategies for change. The PT team met after two 3-month periods of PT for education updates and progress reports. Data was compared on newly diagnosed patients during a 6-month period (Jul-Dec 2018), one year after the baseline period. Results: A total of forty-two patients were diagnosed in two 6-month periods, baseline and study period. Average age was 65 years, 57% male, 71% Caucasian, 95% ever smokers, 71% adenocarcinoma histology. Rate of ordering any molecular testing was (16/19) 84% in the baseline period vs (20/23) 86% in the study period. However, extended molecular testing increased from 16% (3/19) to 60% (12/20), p = .05 Fishers exact test. At treatment initiation, evidence-based treatment selections went from 47% to 52%. Documentation of advanced care discussions, 42% (8/19) to 56% (13/23), did not change significantly. Conclusions: A PT model that included education, and two cycles of implementation and feedback, resulted in increased molecular testing to inform evidence-based treatment selections. Increased awareness of the lack of documentation of advanced care discussions provides opportunity for continued improvement to effect quality care.
Cost-effectiveness of pembrolizumab as first-line treatment of locally advanced or metastatic urothelial carcinoma ineligible for cisplatin-based therapy in the United States.
Authors: Lai Yizhen , Zhong Yichen , Li Haojie , Patterson Karl , Hale Oliver , Meng Yang , Frenkl Tara L. , Godwin James Luke , Mamtani Ronac
Published: October 2019

93

Background: Pembrolizumab is indicated as first-line therapy for cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma (mUC) whose tumors express PD-L1 with a combined positive score (CPS) ≥ 10. This study aims to evaluate the cost‐effectiveness of pembrolizumab versus carboplatin plus gemcitabine in this setting from the US payer perspective. Methods: A partitioned-survival model was developed to measure the costs and effectiveness over a 20-year time horizon with an annual discount of 3%. Clinical outcomes of overall survival (OS) and progression-free survival, safety outcomes and time on treatment were modeled using data from the KEYNOTE-052 clinical trial for pembrolizumab and four clinical trials for carboplatin plus gemcitabine. Because clinical trials directly comparing these treatment strategies are not available, a simulation treatment comparison and a network meta-analysis were conducted to estimate comparative efficacy. Quality of life data extracted from EQ-5D questionnaires administered in KEYNOTE-052 were used to estimate utility, while cost data were estimated using US pricing lists and real-world data. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Pembrolizumab was also compared with gemcitabine monotherapy in the scenario analyses. Results: Pembrolizumab was associated with a survival gain of 2.47 years and 1.90 quality adjusted life years (QALY), an incremental cost of $155,238, and an incremental cost per QALY gained of $81,493 versus carboplatin plus gemcitabine. Results were most sensitive to the time horizon, discount rate, pembrolizumab dosing intensity and OS hazard ratio. Pembrolizumab had 87% or 100% probability of being cost-effective vs. chemotherapy at a $100,000 or $150,000 willingness-to-pay threshold, respectively. Conclusions: Pembrolizumab appears cost-effective versus carboplatin plus gemcitabine as first-line treatment of cisplatin-ineligible and PD-L1 positive mUC patients in the US. The comparison of pembrolizumab with gemcitabine monotherapy yields similar conclusions.
Treatment decision-making and financial toxicity in metastatic breast cancer.
Authors: Wan Clara , Williams Courtney , Ingram Stacey A. , Lawhon Valerie , Young Pierce Jennifer , Dekle Kendal , Lowman Janel , Jones Jonathan , Azuero Andres , Gilbert Aidan , Rocque Gabrielle Betty
Published: October 2019

97

Background: Shared decision-making (SDM), a process where patients partner with their physician to incorporate personal preferences into treatment decisions, is a tenet of high-value healthcare. It is unknown if high-value care associated with SDM manifests in the form of decreased out-of-pocket costs. Therefore, this study analyzes the relationship between patient preference for SDM and financial toxicity in metastatic breast cancer (MBC). Methods: This cross-sectional study utilized surveys of women age ≥ 18 with MBC who received care at two academic hospitals in Alabama between 2017 and 2019. SDM preference and financial toxicity were measured using the Control Preferences Scale and the Comprehensive Score for Financial Toxicity (COST) tool (11-item scale from 0-44, with lower scores indicating worse FT), respectively. Patient demographic and clinical data were abstracted from the electronic medical record. Effect sizes were calculated using Cohen’s d or Cramer’s V. Differences in financial toxicity by SDM preference were estimated using mixed models clustered by site and treating medical oncologist. Results: In 79 women with MBC, 41% preferred SDM, 33% preferred provider-driven decision making, and 22% preferred patient-driven decision making. Patients preferring SDM were more often college educated (48% vs. 40%; V = .15), higher income (52% vs. 44%; V = .09), and privately insured (47% vs. 41%; V = .11). Overall median COST score was 23 (interquartile range 16-30), which varied modestly by SDM preference. After adjusting for patient demographic and clinical characteristics, similar financial toxicity levels were found in patients who preferred SDM (COST 22, 95% confidence interval [CI] 19-25), patient-driven decision making (COST 22, 95% CI 18-26), and provider-driven decision making (COST 24, 95% CI 20-27). Conclusions: Similar levels of financial toxicity were found in patients with differing decision–making preferences regarding their MBC treatment, which may be secondary to lack of discussions about cost. Further research is needed to determine if and how financial toxicity is being identified or included within decision-making.
The Effect of Overweight and Obesity on Liver Biochemical Markers in Children and Adolescents
Authors: Johansen Magnus J , Gade Julie , Stender Stefan , Frithioff-Bøjsøe Christine , Lund Morten A V , Chabanova Elizaveta , Thomsen Henrik S , Pedersen Oluf , Fonvig Cilius E , Hansen Torben , Holm Jens-Christian
Published: October 2019

Background

Elevated plasma concentrations of liver enzymes are routinely used as markers of liver injury in adults and children. Currently, the age- and sex-specific effects of adiposity on pediatric liver enzyme concentrations are unclear.

Methods

We included participants from 2 cohorts of Danish children and adolescents: 1858 from a population-based cohort and 2155 with overweight or obesity, aged from 6 to 18 years. Age- and sex-specific percentile curves were calculated for fasting plasma concentrations of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP) in both cohorts. Hepatic fat content was assessed by proton magnetic resonance spectroscopy in 458 participants.

Results

Concentrations of ALT, AST, LDH, and ALP decreased with age in both girls and boys, while GGT and bilirubin were comparable across age groups in girls and increased slightly with age in boys. Children and adolescents with overweight or obesity exhibited higher concentrations of ALT in all age groups. Concentrations of ALT, and to a lesser degree GGT, increased with age in boys with overweight or obesity. Optimal ALT cut-points for diagnosing hepatic steatosis (liver fat content > 5%) was 24.5 U/L for girls (sensitivity: 55.6%, specificity: 84.0%), and 34.5 U/L for boys (sensitivity: 83.7%, specificity: 68.2%).

Conclusions

Pediatric normal values of liver enzymes vary with both age and sex. Overweight and obesity is associated with elevated biochemical markers of liver damage. These findings emphasize the need for prevention and treatment of overweight and obesity in children and adolescents. (J Clin Endocrinol Metab XX: 0-0, 2019)
Sexual Dimorphism in Obesity-Associated Endothelial ENaC Activity and Stiffening in Mice
Authors: Padilla Jaume , Woodford Makenzie L , Lastra-Gonzalez Guido , Martinez-Diaz Vanesa , Fujie Shumpei , Yang Yan , Lising Alexandre M C , Ramirez-Perez Francisco I , Aroor Annayya R , Morales-Quinones Mariana , Ghiarone Thaysa , Whaley-Connell Adam , Martinez-Lemus Luis A , Hill Michael A , Manrique-Acevedo Camila
Published: October 2019

Obesity and insulin resistance stiffen the vasculature, with females appearing to be more adversely affected. As augmented arterial stiffness is an independent predictor of cardiovascular disease (CVD), the increased predisposition of women with obesity and insulin resistance to arterial stiffening may explain their heightened risk for CVD. However, the cellular mechanisms by which females are more vulnerable to arterial stiffening associated with obesity and insulin resistance remain largely unknown. In this study, we provide evidence that female mice are more susceptible to Western diet–induced endothelial cell stiffening compared with age-matched males. Mechanistically, we show that the increased stiffening of the vascular intima in Western diet–fed female mice is accompanied by enhanced epithelial sodium channel (ENaC) activity in endothelial cells (EnNaC). Our data further indicate that: (i) estrogen signaling through estrogen receptor α (ERα) increases EnNaC activity to a larger extent in females compared with males, (ii) estrogen-induced activation of EnNaC is mediated by the serum/glucocorticoid inducible kinase 1 (SGK-1), and (iii) estrogen signaling stiffens endothelial cells when nitric oxide is lacking and this stiffening effect can be reduced with amiloride, an ENaC inhibitor. In aggregate, we demonstrate a sexual dimorphism in obesity-associated endothelial stiffening, whereby females are more vulnerable than males. In females, endothelial stiffening with obesity may be attributed to estrogen signaling through the ERα–SGK-1–EnNaC axis, thus establishing a putative therapeutic target for female obesity-related vascular stiffening.
Survey of Recent Work in the History of Econometrics
Authors: Boumans Marcel
Published: October 2019

This survey is a witness report of what is happening in the community of historians of econometrics. This survey is a follow-up of an earlier survey which investigated who was active in the history of econometrics. The conclusion of the earlier survey was that interest in the history of econometrics has arisen primarily from within econometrics itself and that its stories have been written mainly by econometricians. The conclusion of the current survey is that econometrics as a discipline remains of interest only to the econometricians but that the artifacts created by econometricians have caught the attention of historians of science.
The Practice of Slowness
Authors: Adeyemi Kemi
Published: October 2019

This essay understands slowness as an embodied method that black queer women mobilize to articulate their place within gentrifying neighborhoods oriented around speed and its by-product: white heteromasculinity. It follows the women as they participate in a queer dance party dedicated to slow jams, examining how they use slowness to theorize and take pleasure in the party as black queer women. As the party gets more popular, however, the music gets faster, the crowd gets whiter, and black queer women’s deployments of slowness shift as they see the party capitulating to a model of success in the neoliberal city that depends on black queer aesthetics even as it disavows black queer subjects. The essay subsequently situates black queer women’s conscious practices of slowness within a longer genealogy of black negotiations of the temporal, arguing that black and black queer management of space-time necessarily expands juridical-economic formulations of what David Harvey describes as the “right to the city.” In so doing, it argues for more acute attention to the racialized queer mechanics of temporal as well as affective and embodied capital as important terrains on which black queer subjects make themselves intelligible within neoliberal spaces that function through their removal.
Neko Case and the Molecular Turn
Authors: Hollingshead David
Published: October 2019

Few contemporary artists channel the utopian impulses of the nonhuman turn with more creative energy than Neko Case. In her work, the untraceable movements of poisonous gases, the uncanny desires of tornadoes, and the recalcitrant withdrawal of subatomic particles envision an array of transits, elusions, and exit strategies so often denied to the subjects whose bodies, trajectories, and affective lives are policed by the regulatory cultural and institutional forces endemic to heteronormative biocapitalism, particularly poor and marginalized women. Drawing on recent scholarship in feminist new materialism as well as its critics, this essay considers the implications of these imaginings. On the one hand, the modes of agency that Case’s songs invoke frequently entail a circumvention or suppression of specific political interests, making them susceptible to antifeminist and settler-colonialist appropriations; on the other hand, her work potentially offers a vision of the political that refuses to take human action as the inevitable starting point for its theories of power and domination, an increasingly urgent task in an age of ecological catastrophe, when the lives of earth’s most vulnerable gendered and racialized subjects are irreducibly enmeshed in precarious planetary networks of biodependencies that include the actions of microbes, tornadoes, and atoms alike. In Case’s most original compositions, a reductionist materialism attendant to the agency of the nonhuman complements rather than forecloses an older materialist tradition insistent on antagonism between conflicting interest groups as the motor engine of history and the social.
Polarized cellular mechanoresponse system for maintaining radial size in developing epithelial tubes
Authors: Hirashima Tsuyoshi , Adachi Taiji
Published: October 2019

Size control in biological tissues involves multicellular communication via mechanical forces during development. Although fundamental cellular behaviours in response to mechanical stimuli underlie size maintenance during morphogenetic processes, mechanisms underpinning cellular mechanoresponse system that maintains size along an axis of a polarized tissue remain elusive. Here, we show how the diameter of an epithelial tube is maintained during murine epididymal development by combining quantitative imaging, mechanical perturbation, and mathematical modelling. We found that epithelial cells counteract compressive forces caused by cell division exclusively along the circumferential axis of the tube to produce polarized contractile forces, eventually leading to an oriented cell rearrangement. Moreover, a mathematical model that includes the polarized mechanoresponsive regime explains how the diameter of proliferating tubes is maintained. Our findings pave the way for an improved understanding of the cellular response to mechanical forces that involves collective multicellular behaviours for organizing diverse tissue morphologies.
CRISPR/Cas9-mediated genome editing in nonhuman primates
Authors: Kang Yu , Chu Chu , Wang Fang , Niu Yuyu
Published: October 2019

Owing to their high similarity to humans, non-human primates (NHPs) provide an exceedingly suitable model for the study of human disease. In this Review, we summarize the history of transgenic NHP models and the progress of CRISPR/Cas9-mediated genome editing in NHPs, from the first proof-of-principle green fluorescent protein-expressing monkeys to sophisticated NHP models of human neurodegenerative disease that accurately phenocopy several complex disease features. We discuss not only the breakthroughs and advantages, but also the potential shortcomings of the application of the CRISPR/Cas9 system to NHPs that have emerged from the expanded understanding of this technology in recent years. Although off-target and mosaic mutations are the main concerns in CRISPR/Cas9-mediated NHP modeling, recent progress in genome editing techniques make it likely that these technical limitations will be overcome soon, bringing excellent prospects to human disease studies.