tbuckley/cabot-search huggingface dataset:
Factors associated with clinical trial participation for patients with prostate cancer.
Authors: Brian Shinder, Sinae Kim, Hiren V. Patel, Arnav Srivastava, Tina M. Mayer, Biren Saraiya, Eric A. Singer
Journal: Journal of Clinical Oncology (2020)

96 Background: Clinical trials are critical for the development of new treatment paradigms for Prostate Cancer (PCa). The primary aim of this study was to characterize the factors associated with clinical trial participation for patients with PCa. The secondary objective was to examine survival outcomes in the clinical trial and control cohorts. Methods: The National Cancer Database (NCDB) was queried for patients with PCa who were coded as having enrolled in a clinical trial. Trial patients were matched in a 1:8 ratio to controls based on clinical stage. Sociodemographic variables were compared between the two groups and univariate and multivariate logistic regression models evaluated factors associated with clinical trial participation. Kaplan-Meier product limit estimate was used to compare overall survival (OS) between the groups. Results: From 2004-2015, 495 patients enrolled in clinical trials were included for analysis. The mean age of trial patients was 63.2 compared to 66.4 in the matched cohort (p &lt; 0.0001). More patients in the trial group had a Charlson-Deyo comorbidity score of 0 (89.3% vs. 82.1%, p = 0.0002). On multivariate analysis, patients who traveled between 50-250 miles (OR 1.59; 95%CI 1.15-2.19, p = 0.005) or came from a zip code where greater than 93% of the population has a high school degree (OR 4.97; 95%CI 2.89-8.54, p &lt; 0.0001) were more likely to participate in a clinical trial. There was no association between race and insurance status on clinical trial participation. Median OS was not significantly different among clinical trial participants than the control cohort (120.9 months vs. not reached, p = 0.928). Conclusions: In this contemporary analysis of PCa patients from a national hospital registry database, we found that certain patient sociodemographic factors remain associated with clinical trial participation, though clinical trial participants do not seem to experience a difference in OS. Further work, both qualitative and quantitative, is necessary to identify clinical and non-clinical barriers to research participation in order to improve the validity of PCa trials.
Misclassification of Hospital Performance Under the Hospital Readmissions Reduction Program
Authors: Changyu Shen, Rishi K. Wadhera, Robert W. Yeh
Journal: JAMA Cardiology (2020)

The Centers for Medicare and Medicaid Services (CMS) use point estimates of 30-day risk-standardized readmission rates (RSRRs) to compare hospitals under the Hospital Readmissions Reduction Program (HRRP). An important characteristic of this measure is that it is a point estimate with a margin of error, which may affect the CMS's ability to accurately evaluate and distinguish hospital performance in the program.To determine the number and percentage of hospitals with a penalty status misclassified under the HRRP.This cross-sectional study used the bayesian deconvolution method to estimate the rate of penalty status misclassification for hospitals participating in the HRRP in fiscal year 2019, using data from the CMS Hospital Compare website that were collected between July 1, 2014, and June 30, 2017. Beneficiaries of Medicare fee-for-service coverage who were 65 years or older and hospitalized with acute myocardial infarction, heart failure, or pneumonia in hospitals with 25 or more discharges per condition were included in the data set. Data analysis occurred from November 2019 to July 2020.None.The rate of penalty status misclassification for acute myocardial infarction, heart failure, or pneumonia under the HRRP.The study included 1633, 2626, and 2705 hospitals for acute myocardial infarction, heart failure, and pneumonia, respectively, that participated in the HRRP in fiscal year 2019. The percentages of hospitals that should have been penalized, but were not, were 20.9% (95% CI, 16.0%-25.8%) for acute myocardial infarction, 13.5% (95% CI, 9.8%-17.2%) for heart failure, and 13.2% (95% CI, 10.3%-16.1%) for pneumonia. In contrast, the percentages of hospitals that were incorrectly penalized by the HRRP were 10.1% (95% CI, 5.8%-14.4%) for acute myocardial infarction, 10.9% (95% CI, 7.2%-14.6%) for heart failure, and 12.3% (95% CI, 9.9%-14.6%) for pneumonia.The margin of error associated with the 30-day RSRRs resulted in the misclassification of condition-specific penalty status for up to 31% of hospitals. These findings suggest that the hospital-level 30-day RSRR measure may not reliably distinguish hospital performance in the HRRP. This has important implications for CMS value-based programs that use risk-standardized outcomes to evaluate and compare hospital performance.
Machine learning to predict tamoxifen adherence among U.S. commercially insured breast cancer patients.
Authors: Tyler J. O'Neill, Vishakha Sharma, Athanasios Siadimas, Amir Babaeian, Gayathri Yerrapragada
Journal: Journal of Clinical Oncology (2020)

276 Background: Adherence to tamoxifen among women diagnosed with hormone receptor positive metastatic breast cancer (mBC) can improve survival and minimize recurrence. Screening for non-adherence at treatment initiation may support personalized care, improve health outcomes, and minimize cost of care. This study aimed to use real world data (RWD) and machine learning (ML) methods to classify tamoxifen non-adherence. Methods: A cohort of women diagnosed with incident mBC from 2012 to 2018 were identified from Truven MarketScan Commercial Claims and Encounters and Medicare supplemental administrative claims databases. Patients with &lt; 80% proportion of days coverage (PDC) in the year following treatment initiation were classified non-adherent. Training and internal validation cohorts were randomly generated (4:1 ratio). Clinical procedures, comorbidity, treatment and healthcare encounter features in the year prior to treatment initiation were used to train logistic regression, boosted logistic regression, random forest, and feed forward neural network models and internally validated based on area under receiver operating characteristic (AUROC) curve. The most predictive ML approach was evaluated to assess feature importance. Results: A total of 3,022 patients were included with 39.9% classified as non-adherent. All ML models had moderate predictive accuracy. Logistic regression (AUROC 0.64) was easily interpreted with sensitivity 94% (95% confidence interval [CI]: 0.89, 0.92) and specificity 0.31 (95% CI: 0.29, 0.33). The model accurately classified adherence (negative predictive value 88.7%) but was non-discriminate for non-adherence (positive predictive value 47.7%). Variable importance identified top predictive factors, including patient features (≥55 years old) and pre-treatment procedures (lymphatic nuclear medicine, radiation oncology, arterial surgery). Conclusions: ML using baseline administrative data predicts tamoxifen adherence. Baseline claims may not be sufficient to predict treatment non-adherence. Further validation with enriched longitudinal data may improve model performance for incorporation of predictions into clinical decision support.
Nocturnal peripheral vasoconstriction predicts the frequency of severe acute pain episodes in children with sickle cell disease
Authors: Patjanaporn Chalacheva, Yunhua Ji, Carol L. Rosen, Michael R. DeBaun, Michael C. K. Khoo, Thomas D. Coates
Journal: American Journal of Hematology (2020)

The basic model of SCD physiology states that vaso-occlusion occurs when hemoglobin S-containing red blood cells (RBC) undergo sickling before they escape the capillary into a larger vessel. We have shown that mental stress, pain and cold, and events reported by patients to trigger SCD vaso-occlusive crisis (VOC), cause rapid and significant decrease in blood flow, reducing the likelihood that RBC could transit the microvasculature before sickling occurs. However, the critical link between decrease in microvascular blood flow and the incidence of future sickle VOC has never been established experimentally in humans. Using data from centrally adjudicated, overnight polysomnograms (PSG), previously collected in a prospective multi-center cohort sleep study, we analyzed the beat-to-beat amplitudes of vasoconstriction reported by the fingertip photoplethysmogram in 212 children and adolescents with SCD and developed an algorithm that detects vasoconstriction events and quantifies the magnitude (Mvasoc ), duration, and frequency of vasoconstriction that reflect the individual's inherent peripheral vasoreactivity. The propensity to vasoconstrict, quantified by median Mvasoc , predicted the incidence rate of post-PSG severe acute vaso-occlusive pain events (P = .006) after accounting for age and hemoglobin. Indices of sleep-disordered breathing contributed to median Mvasoc but did not predict future pain rate. Median Mvasoc was not associated with vaso-occlusive pain events that occurred prior to each PSG. These results show that SCD individuals with high inherent propensity to vasoconstrict have more frequent severe acute pain events. Our empirical findings are consistent with the fundamental SCD hypothesis that decreased microvascular flow promotes microvascular occlusion.
Care redesign of pelvic radiotherapy using Design Thinking: An enhanced quality improvement initiative.
Authors: Cho Hao Francis Ho, Jeremy Chee Seong Tey, Kiat Huat Ooi, Teng Hwee Tan, Yiat Horng Leong, David Chia
Journal: Journal of Clinical Oncology (2020)

246 Background: Cone Beam Computed Tomography(CBCT) is the cornerstone of image guided radiotherapy(IGRT) which is an integral part of pelvic cancers like prostate cancer. Each pelvic radiotherapy (RT) session is preceded by a planned CBCT to ensure target localisation and organ at risk avoidance. When these criteria are not met, an unplanned CBCT is performed until the CBCT is satisfactory. Possible reasons for an unsatisfactory CBCT include an under filled bladder, distended rectum or prostate gland movement. Repeated unplanned CBCT results in unnecessary excess radiation for patients. We aimed to reduce the incidence of unplanned CBCT from a baseline of 21% to 9% over 5 months. Methods: We conducted the project using both conventional quality improvement methodology and the design thinking methodology. In the diagnostic phase up to March 2017, the baseline incidence of CBCT in patients receiving pelvic RT was 21%. We hypothesized that there were reversible factors leading to a higher incidence of unplanned CBCT and sought to identify and rectify these reversible factors to reduce the incidence of unplanned CBCT. Using human centred design, we designed a new process of performing a bladder ultrasound prior to CBCT to ensure a full bladder prior to RT using the steps empathy, define, ideation, prototype, testing, sharing. Results: A total of 97 patients that underwent pelvic radiotherapy were included in this study, 40 patients were pre intervention and 61 patients received the bladder ultrasound intervention implemented from April 2017 onwards. After intervention, incidence of unplanned decreased from 21% to 5.8%. A 2 sample t test was used to compare the unplanned CBCT pre and post intervention. We found the mean pre and post intervention difference in pooled mean incidence of unplanned CBCT to be significantly different by 13.3%. The reduction in unplanned CBCT translated to saving each patient on average equivalent to 3000 chest x rays worth of unnecessary radiation. Conclusions: Design Thinking is a feasible strategy in quality improvement. We report the first design thinking project in radiation oncology quality improvement. An automated ultrasound bladder is a feasible strategy to screen for bladder filling prior to each CBCT to reduce reliance on CBCT and also patient exposure to radiation in IGRT of pelvic cancers.
Click CAR-T cell engineering for robustly boosting cell immunotherapy in blood and subcutaneous xenograft tumor
Authors: Hong Pan, Wenjun Li, Ze Chen, Yingmei Luo, Wei He, Mengmeng Wang, Xiaofan Tang, Huamei He, Lanlan Liu, Mingbin Zheng, Xin Jiang, Ting Yin, Ruijing Liang, Yifan Ma, Lintao Cai
Journal: Bioactive Materials (2020)

The adoptive transfer of chimeric antigen receptor-T (CAR-T) cells has shown remarkable clinical responses in hematologic malignancies. However, unsatisfactory curative results and side effects for tumor treatment are still unsolved problems. Herein we develop a click CAR-T cell engineering strategy via cell glycometabolic labeling for robustly boosting their antitumor effects and safety in vivo. Briefly, paired chemical groups (N
Inflammasomes in cancer: Effect of epigenetic and autophagic modulations
Authors: Soumya Ranjan Mishra, Kewal Kumar Mahapatra, Bishnu Prasad Behera, Chandra Sekhar Bhol, Prakash Priyadarshi Praharaj, Debasna Pritimanjari Panigrahi, Srimanta Patra, Amruta Singh, Shankargouda Patil, Rohan Dhiman, Samir Kumar Patra, Sujit Kumar Bhutia
Journal: Seminars in Cancer Biology (2020)
Sex Differences in the Inflammatory Response: Pharmacological Opportunities for Therapeutics for Coronary Artery Disease
Authors: Asad Shabbir, Krishnaraj Sinhji Rathod, Rayomand Syrus Khambata, Amrita Ahluwalia
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Coordinated molecular responses are key to effective initiation and resolution of both acute and chronic inflammation. Vascular inflammation plays an important role in initiating and perpetuating atherosclerotic disease, specifically at the site of plaque and subsequent fibrous cap rupture. Both men and women succumb to this disease process, and although management strategies have focused on revascularization and pharmacological therapies in the acute situation to reverse vessel closure and prevent thrombogenesis, data now suggest that regulation of host inflammation may improve both morbidity and mortality, thus supporting the notion that prevention is better than cure. There is a clear sex difference in the incidence of vascular disease, and data confirm biological differences in inflammatory initiation and resolution between men and women. This article reviews contemporary opinions describing the sex difference in the initiation and resolution of inflammatory responses, with a view to explore potential targets for pharmacological intervention.
Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis
Authors: Dana Lukin, David Faleck, Ronghui Xu, Yiran Zhang, Aaron Weiss, Satimai Aniwan, Siri Kadire, Gloria Tran, Mahmoud Rahal, Adam Winters, Shreya Chablaney, Jenna L. Koliani-Pace, Joseph Meserve, James P. Campbell, Gursimran Kochhar, Matthew Bohm, Sashidhar Varma, Monika Fischer, Brigid Boland, Siddharth Singh, Robert Hirten, Ryan Ungaro, Karen Lasch, Eugenia Shmidt, Vipul Jairath, David Hudesman, Shannon Chang, Arun Swaminath, Bo Shen, Sunanda Kane, Edward V. Loftus, Bruce E. Sands, Jean-Frederic Colombel, Corey A. Siegel, William J. Sandborn, Parambir S. Dulai
Journal: Clinical Gastroenterology and Hepatology (2020)

We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice.A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately.A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754).Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.
Segmentation of cellular patterns in confocal images of melanocytic lesions in vivo via a multiscale encoder-decoder network (MED-Net)
Authors: Kivanc Kose, Alican Bozkurt, Christi Alessi-Fox, Melissa Gill, Caterina Longo, Giovanni Pellacani, Jennifer G. Dy, Dana H. Brooks, Milind Rajadhyaksha
Journal: Medical Image Analysis (2020)
Nanoparticle-delivered miriplatin ultrasmall dots suppress triple negative breast cancer lung metastasis by targeting circulating tumor cells
Authors: Yunfei Li, Dali Qian, Hsuan-Pei Lin, Jie Xie, Ping Yang, Drew Maddy, Yajuan Xiao, Xuefei Huang, Zhishan Wang, Chengfeng Yang
Journal: Journal of Controlled Release (2020)
Tag you’re it! Development of a clinical decision support tool to identify NCCN regimens without a costly pathways program.
Authors: Aarti Sonia Bhardwaj, Edward Gu, Damaris Peralta Hernandez, Michael McLean, Haley Hines Theroux, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2020)

308 Background: Reducing variation in care can improve outcomes and decrease costs. Evidence based medicine drives cancer guidelines and adherence promotes quality cancer care. Value based programs are based on adherence to pathways. Most institutions adopt costly cloud based clinical pathways products but none are mature products that fully integrate with the EHR and they require additional data entry. We present our simple Clinical Decision Support (CDS) tool for identifying best practice treatment protocols driven by the cancer diagnosis in the EMR for our large, multi-site, mixed academic and community cancer system. Methods: Our chemotherapy council must approve all protocols that are published in the system’s Epic Beacon library using a rigorous scoring system based on level of evidence and FDA or NCCN approval. Then each protocol is “tagged” appropriately: “Tier 1A”: Preferred Regimens/NCCN Approved; “Tier 1B”: Preferred Regimens/Chemo Council Approved (but not NCCN Approved); Tier 2: Specific Disease Management Team approved regimens; and finally “Other” or research protocols. When the oncologist enters the treatment plan in EPIC, a list of protocols are suggested, ordered by level of evidence, based on the cancer diagnosis and with the easily visible level of evidence or “tag” to allow data driven decision making. Results: We implemented our CDS tool December 12, 2019. As of mid-June, 2020 a total of 1637 treatment plans have been implemented. Of those, 1323 (81%) are Tier 1A, 310 (2%) are Tier 1B and 4 (.2%) are Tier 2. Thus demonstrating 81% adherence to NCCN approved regimens across the system, regardless of the line of treatment. GI and breast cancers were responsible for the most plans with the highest adherence to Tier 1A plans, specifically 92% among the breast cancer group. Multiple Myeloma and Sarcoma were tied for the lowest adherence rate of 58%. This data can be further stratified by medical oncologist. Interestingly, Multiple Myeloma had the highest utilization of Tier 1B protocols perhaps reflecting the rapidly changing literature that is ahead of the guidelines. Conclusions: We demonstrated adherence to NCCN protocols 81% of the time over a 6 month period and over multiple cancer types. Protocol tagging and reporting utilizing the EMR alone could be used as a powerful model for value based care. We identified disease areas that will require further education regarding evidence based treatment and can consider interventions including real time feedback to clinicians and/or best practice advisories or quality based incentives.
Precision Prevention and Cancer Interception: The New Challenges of Liquid Biopsy
Authors: Maria Jose Serrano, Maria Carmen Garrido-Navas, Juan Jose Diaz Mochon, Massimo Cristofanilli, Ignacio Gil-Bazo, Patrick Pauwels, Umberto Malapelle, Alessandro Russo, Jose A. Lorente, Antonio J. Ruiz-Rodriguez, Luis G. Paz-Ares, Eduardo Vilar, Luis E. Raez, Andres F. Cardona, Christian Rolfo
Journal: Cancer Discovery (2020)

Despite major therapeutic progress, most advanced solid tumors are still incurable. Cancer interception is the active way to combat cancer onset, and development of this approach within high-risk populations seems a logical first step. Until now, strategies for the identification of high-risk subjects have been based on low-sensitivity and low-specificity assays. However, new liquid biopsy assays, "the Rosetta Stone of the new biomedicine era," with the ability to identify circulating biomarkers with unprecedented sensitivity, promise to revolutionize cancer management. This review focuses on novel liquid biopsy approaches and the applications to cancer interception. Cancer interception involves the identification of biomarkers associated with developing cancer, and includes genetic and epigenetic alterations, as well as circulating tumor cells and circulating epithelial cells in individuals at risk, and the implementation of therapeutic strategies to prevent the beginning of cancer and to stop its development. Large prospective studies are needed to confirm the potential role of liquid biopsy for early detection of precancer lesions and tumors.
68Ga–Prostate-Specific Membrane Antigen Focal Pulmonary Activity With No Corresponding CT Abnormality
Authors: Arun Sasikumar, Sam Thampan, Nivya Thomas, Retcy Paul
Journal: Clinical Nuclear Medicine (2020)

We describe a case of 68Ga-prostate-specific membrane antigen PET/CT scan with focal tracer concentration in the lung without any abnormalities in the CT part. 18F-FDG focal uptake in lungs without corresponding CT lesions is described. Two possible mechanisms proposed to explain this finding in FDG PET/CT scans are iatrogenic pulmonary microembolism and 18F-FDG-avid infection or inflammation that precedes structural findings. Logically, these proposed mechanisms seem to be applicable to 68Ga-prostate-specific membrane antigen as well. In our case, there were no features of any lung infection/inflammation, and the most plausible explanation would be iatrogenic microembolism.