bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &gt; 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

AbstractObesity 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.
CRISPR/Cas9-mediated genome editing in nonhuman primates
Authors: Kang Yu , Chu Chu , Wang Fang , Niu Yuyu 
Published: October 2019

ABSTRACT
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.
Fully automated and comprehensive MRI-based left-ventricular contractility analysis in post-chemotherapy breast cancer patients
Authors: Kar Julia , Cohen Michael V. , McQuiston Samuel A. , Figarola Maria S. , Malozzi Christopher M. 
Published: October 2019

Objective:
This study investigated the occurrence of cardiotoxicity-related left-ventricular (LV) contractile dysfunction in breast cancer patients following treatment with antineoplastic chemotherapy agents.

Methods:
A validated and automated MRI-based LV contractility analysis tool consisting of quantization-based boundary detection, unwrapping of image phases and the meshfree Radial Point Interpolation Method was used toward measuring LV chamber quantifications (LVCQ), three-dimensional strains and torsions in patients and healthy subjects. Data were acquired with the Displacement Encoding with Stimulated Echoes (DENSE) sequence on 21 female patients and 21 age-matched healthy females. Estimates of patient LVCQs from DENSE acquisitions were validated in comparison to similar steady-state free precession measurements and their strain results validated via Bland–Altman interobserver agreements. The occurrence of LV abnormalities was investigated via significant differences in contractility measurements (LVCQs, strains and torsions) between patients and healthy subjects.

Results:
Repeated measures analysis showed similarities between LVCQ measurements from DENSE and steady-state free precession, including cardiac output (4.7 ± 0.4 L, 4.6 ± 0.4 L, p = 0.8), and LV ejection fractions (59±6%, 58±5%, p = 0.2). Differences found between patients and healthy subjects included enlarged basal diameter (5.0 ± 0.5 cm vs 4.4 ± 0.5 cm, p &lt; 0.01), apical torsion (6.0 ± 1.1° vs 9.7 ± 1.4°, p &lt; 0.001) and global longitudinal strain (−0.15 ± 0.02 vs. -0.21 ± 0.04, p &lt; 0.001), but not LV ejection fraction (59±6% vs. 63±6%, p = 0.1).

Conclusion:
The results from the statistical analysis reveal the possibility of LV abnormalities in the post-chemotherapy patients via enlarged basal diameter and reduced longitudinal strain and torsion, in comparison to healthy subjects.

Advances in knowledge:
This study shows that subclinical LV abnormalities in post-chemotherapy breast cancer patients can be detected with an automated technique for the comprehensive analysis of contractile parameters.