tbuckley/cabot-search huggingface dataset:
Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer
Authors: Vladimir Avkshtol, Karen J. Ruth, Eric A. Ross, Mark A. Hallman, Richard E. Greenberg, Robert A. Price, Brooke Leachman, Robert G. Uzzo, Charlie Ma, David Chen, Daniel M. Geynisman, Mark L. Sobczak, Eddie Zhang, Jessica K. Wong, Alan Pollack, Eric M. Horwitz
Journal: Journal of Clinical Oncology (2020)

The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure.Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment.Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use (P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%).H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.
Pharmacokinetic (PK) interactions between capecitabine (X), oxaliplatin (O) and bevacizumab (A) when used in combination for first-line treatment of metastatic colorectal cancer (MCRC)
Authors: B. Brennan, L. Siu, B. Dhesy-Thind, C. Cripps, A. Gandhi, M. Abt, K. Smith, K. Rittweger, S. Hussain, S. Choudhury
Journal: Journal of Clinical Oncology (2007)

2554 Background: X + O in combination (XELOX) has similar efficacy to FOLFOX-4 in untreated MCRC patients (pts) [1]. The addition of A to irinotecan/5-FU/LV improves progression-free survival (PFS) and overall survival [2], and the potential improvement of adding A to XELOX in MCRC is currently being investigated. Here we present the first PK evaluation of the effects of X on O, O on X, X+A on O, and O+A on X in a multicenter open-label study of pts with untreated MCRC. Methods: Pts received treatment for up to 16 cycles with blood samples for PK analysis taken during cycles 1–3. Treatment: cycle 1: X 1000 mg/m 2 orally on morning of d1, O 130 mg/m 2 i.v. infusion d2, X 1000 mg/m 2 bid orally d5–14, rest d15–21; cycle 2: O 130 mg/m 2 i.v. infusion d1 + X 1000 mg/m 2 bid orally d1–14, rest d15–21; cycle 3 (XOA): A 7.5 mg/kg i.v. infusion d1 + O 130 mg/m 2 i.v. infusion d1 + X 1000 mg/m 2 bid orally d1–14, q3w. Treatment with the XOA regimen continued for a further 13 cycles. Safety was evaluated throughout. Results: 36 pts were enrolled; 26 pts completed cycles 1–3 and were evaluable for PK analysis; all pts were evaluable for safety. Baseline characteristics were: M/F 42%/58%; median age 60 years (range 22–74). The primary parameter for PK analysis of X, AUC 0- 8 of 5’-DFUR, was slightly lower in cycle 2 d1 (XO) and cycle 3 d1 (XOA) vs. cycle 1 d1 (X) (10% and 13% lower, respectively, with CV 27–33%); a decrease in the C max of 5’-DFUR was also observed (26% and 36% lower, respectively, with CV 48–54%). However these differences were not considered clinically important. The primary parameter for PK analysis of O, AUC 0- 8 of free platinum, was very similar among cycle 2 d1 (XO), cycle 3 d1(XOA), and cycle 1 d2 (O), with geometric mean ratios very close to 1. Treatment with X, O and A in combination was generally well tolerated. Conclusions: No large differences in exposure of X or its metabolites, free platinum or total platinum occur when X, O and A are administered in combination. This provides further support for the development of the above dosing regimen in MCRC. References: 1. Cassidy J et al. J Clin Oncol 2004;22:2084–91. 2. Hurwitz H et al. N Eng J Med 2004;350:2335–42. No significant financial relationships to disclose.
Neutropenic complications in ovarian cancer patients receiving chemotherapy: Results of a prospective observational study
Authors: B. S. Myer, L. E. Cosler, J. Crawford, D. C. Dale, C. Selby, D. A. Wolff, M. S. Poniewierski, E. Culakova, G. H. Lyman
Journal: Journal of Clinical Oncology (2007)

19610 Background: A nationwide, prospective cohort study of patients receiving cancer chemotherapy was undertaken to better define treatment-associated toxicities and delivered dose intensity. Methods: Following informed consent, 3,670 patients initiating a new chemotherapy regimen with lymphoma (n=547) or carcinomas of the colon (n=521), breast (n=1,473), lung (n=907) or ovary (n=312) were prospectively registered at 117 randomly selected US oncology practices between March 2002 and December 2005. Pretreatment characteristics including clinical and sociodemographic factors and practice setting associated with reductions in chemotherapy dose intensity over 4 cycles were evaluated. Results: Chemotherapy regimen standards and intended dose and schedule were defined in 97% and 93% of patients, respectively. Average initial (planned) relative dose intensity (RDI) was 90% while the mean RDI actually delivered over 4 cycles was 83%. Reductions in RDI =15% of standard were planned in 23% of patients and actually occurred over 4 cycles in 38%. Body surface area (BSA) calculated by the method of Mosteller exceeded the BSA utilized by the oncology practices in two-thirds of patients most often due to capping at 2 m 2 . Obese patients with a body mass index (BMI) =30 were more likely to receive planned RDI reductions =15% (30%) than patients with BMI &lt;30 (21%) (P&lt;.0001). Other factors associated with planned reductions in RDI in multivariate analysis included: older age, male gender, lower education, absence of myeloid growth factor prophylaxis and cancers of the lung or ovary as well as the practice setting, size and geographic location. Factors associated with unplanned (subsequent) reductions in RDI included: older age, male gender, poorer Charlson comorbidity index, prior chemotherapy, lung cancer, low baseline hematocrit, white blood or platelet count, poor renal or hepatic function and low serum albumin as well as smaller practice and rural setting. Conclusions: A substantial proportion of patients receiving cancer chemotherapy experience both planned and unplanned reductions in RDI. Further understanding of factors associated with such reductions may provide opportunities for improving the quality of cancer care and clinical outcomes. [Table: see text]
Abstract P131: Optimal Phenomapping Strategy to Identify Novel Subgroups of Patients With Type 2 Diabetes and High Cardiovascular Disease Risk
Authors: Matthew W Segar, Muthiah Vaduganathan, Kershaw V Patel, Melissa Caughey, Mujeeb Basit, Duwayne Willett, Darren K McGuire, Ambarish Pandey
Journal: Circulation (2020)

Introduction: Phenomapping can be used to identify subgroups of patients with similar risk factor profiles; however, there is no widely accepted clustering method. We compared 3 phenomapping strategies to identify groups of individuals with diabetes mellitus (DM) and high cardiovascular disease (CVD) risk. Methods: Participants with DM and no baseline CVD from the ACCORD trial (N = 6591) were included in this study. Among 45 mixed data variables, we used an informed variable selection method with optimization of the Wald index to select the top 20 covariates associated with survival. Gaussian mixture models (GMM), Latent Class Analysis (LCA), and finite mixture model-based clustering (FMM) were performed to identify mutually exclusive phenogroups. Bayesian information criterion (BIC) and Dunn index were calculated for each method and compared. The primary composite endpoint was cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Results: FMM clustering with 3 phenogroups was the optimal clustering strategy as determined by the lowest BIC and highest Dunn index (Figs A-B). Phenogroup 1 had a higher burden of comorbidities and DM complications; phenogroup 2 were older with intermediate CV comorbidity burden, but lowest complications from DM; and phenogroup 3, the largest group, had a lower prevalence of CV-related comorbidities. In adjusted Cox models, over 4.9 years median follow-up, phenogroup 1 and 2 participants (vs. phenogroup 3) had a significantly higher risk of primary composite endpoint (Fig C). In Cox analysis, when group membership was added to 10 optimal predictors of primary composite endpoint, the C -index improved from 0.68 to 0.70 ( P = 0.02). Similar risk patterns were also observed in an external cohort (Look AHEAD trial, N = 4211) with the highest risk of adverse outcome seen in phenogroup 1 (Fig D). Conclusion: Semi-supervised clustering using FMM efficiently identifies phenogroups of patients with DM with distinct clinical characteristics and CVD risk.
Changes in List Prices, Net Prices, and Discounts for Branded Drugs in the US, 2007-2018
Authors: Inmaculada Hernandez, Alvaro San-Juan-Rodriguez, Chester B. Good, Walid F. Gellad
Journal: JAMA (2020)

<h3>Importance</h3> Most studies that have examined drug prices have focused on list prices, without accounting for manufacturer rebates and other discounts, which have substantially increased in the last decade. <h3>Objective</h3> To describe changes in list prices, net prices, and discounts for branded pharmaceutical products for which US sales are reported by publicly traded companies, and to determine the extent to which list price increases were offset by increases in discounts. <h3>Design, Setting, and Participants</h3> Retrospective descriptive study using 2007-2018 pricing data from the investment firm SSR Health for branded products available before January 2007 with US sales reported by publicly traded companies (n = 602 drugs). Net prices were estimated by compiling company-reported sales for each product and number of units sold in the US. <h3>Exposures</h3> Calendar year. <h3>Main Outcomes and Measures</h3> Outcomes included list and net prices and discounts in Medicaid and other payers. List prices represent manufacturers' price to wholesalers or direct purchasers but do not account for discounts. Net prices represent revenue per unit of the product after all manufacturer concessions are accounted for (including rebates, coupon cards, and any other discount). Means of outcomes were calculated each year for the overall sample and 6 therapeutic classes, weighting each product by utilization and adjusting for inflation. <h3>Results</h3> From 2007 to 2018, list prices increased by 159% (95% CI, 137%-181%), or 9.1% per year, while net prices increased by 60% (95% CI, 36%-84%), or 4.5% per year, with stable net prices between 2015 and 2018. Discounts increased from 40% to 76% in Medicaid and from 23% to 51% for other payers. Increases in discounts offset 62% of list price increases. There was large variability across classes. Multiple sclerosis treatments (n = 4) had the greatest increases in list (439%) and net (157%) prices. List prices of lipid-lowering agents (n = 11) increased by 278% and net prices by 95%. List prices of tumor necrosis factor inhibitors (n = 3) increased by 166% and net prices by 73%. List prices of insulins (n = 7) increased by 262%, and net prices by 51%. List prices of noninsulin antidiabetic agents (n = 10) increased by 165%, and net prices decreased by 1%. List price increases were lowest (59%) for antineoplastic agents (n = 44), but discounts only offset 41% of list price increases, leading to 35% increase in net prices. <h3>Conclusions and Relevance</h3> In this analysis of branded drugs in the US from 2007 to 2018, mean increases in list and net prices were substantial, although discounts offset an estimated 62% of list price increases with substantial variation across classes.
Abstract 16115: Air Pollution Associates With Leukopoietic Activity: A Link to Atherosclerotic Inflammation
Authors: Shady Abohashem, Tawseef Dar, Azar Radfar, Brian Tung, Blake Oberfeld, Nicki Naddaf, Tomas Patrich, Ahmed Ghoneem, Parastou Ghazi, James Jaffer, Michael T. Osborne, Ahmed A Tawakol
Journal: Circulation (2019)

Introduction and Hypothesis: Fine particulate matter ≤ 2.5 mm (PM2.5) air pollution poses a pervasive environmental health threat that contributes to cardiovascular disease (CVD). We previously dem...
Abstract P253: Blood Pressure Status Among Current Cigarette, E-cigarette, And Marijuana Users In The United States: An Analysis Of The National Health And Nutrition Examination Surveys, 2013-2016
Authors: Denise C Vidot, Lenette M Jones, Yendelela Cuffee, Amber Johnson, Lizelh Ayala
Journal: Circulation (2020)

Introduction: Tobacco and marijuana have been associated with abnormal blood pressure (BP). Yet, little is known about differences in BP status among individuals who smoke cigarettes, e-cigarettes, and marijuana, independently or in combination. The purpose of this study was to provide prevalence estimates of elevated BP, stage 1 hypertension, and stage 2 hypertension among smokers of varied substances and route of administration. Hypothesis: We hypothesized that cigarette users would have higher BP levels compared to e-cigarette or marijuana users. Methods: Data from adults (20-to-59 years) who completed the National Health and Nutrition Examination Surveys between 2013 and 2016 (N=6,282) were examined. Smoking status was ascertained by self-report of use in the last 30-days via computer assisted questionnaires as: cigarette only, cigarette + marijuana, cigarette + e-cigarette, e-cigarette only, e-cigarette + marijuana, marijuana only, and non-smokers of any product. BP was ascertained by the average of three systolic and diastolic readings. Following the latest BP guidelines, BP was categorized as elevated, hypertension stage 1 (HTN1), or hypertension stage 2 (HTN2). Survey method-appropriate chi-squared analyses were conducted to provide weighted prevalence estimates. Results: Over half (60.6%) of the adults in the sample were current smokers [cigarette only (31.9%); e-cigarette only (1.4%); marijuana only (7.3%); cigarette + marijuana (16.1%), cigarette + e-cigarette (3.1%), e-cigarette + marijuana (0.7%)]. A quarter (25.5%) of the sample had elevated BP; 43.9% had HTN1; and 12.7% had HTN2. Among smokers, cigarette only users had the highest prevalence of elevated BP (7.7%), HTN1 (14.7%), and HTN2 (4.3%); followed by the combined use of cigarettes and marijuana (4.8%, 6.0%, 1.2%, respectively). Marijuana and e-cigarette combination users had the lowest prevalence of HTN1 (0.16%) and HTN2 (0.0%) followed by marijuana only users (2.8%, 0.9%, respectively; p=0.04). Conclusions: This analysis is among the first to leverage population-based data to assess BP status among independent and combination users of cigarettes, e-cigarettes, and marijuana. The majority of the sample had at least elevated BP, which is documented to increase cardiovascular disease risk. Additional studies are needed to evaluate the impact of frequency and duration of use on cardiovascular disease risk after considering other lifestyle behaviors (i.e., diet and physical activity).
Abstract P536: Healthy for Life: A Health Promotion Model Improving Confidence and Dietary Behaviors
Authors: Meg D Yuan, Heather Gavras, Olivia Barnes, Remy Poudel
Journal: Circulation (2020)

Introduction: Poor diet is the leading risk factor for death globally. Community-based programs can have a positive impact on promoting healthy dietary attitudes and behaviors. The American Heart Association and Aramark’s initiative, Healthy for Life 20 by 20 aims to change food and health confidence and behaviors, equipping individuals with new skills for healthy living. The program includes healthy cooking demonstrations, hands-on skills practice and nutrition and heart health workshops. Objectives: To examine the effectiveness of the Healthy for Life program over time, specifically: -Changes in participant confidence in the preparation of healthy foods at home -Changes in participant consumption of fruits, vegetables, and whole grains -Changes in participant frequency of healthy shopping habits Methods: A community engagement program was implemented and evaluated in 22 community centers. Sessions were focused on enhancement of confidence and behaviors around healthy shopping, cooking and consumption. Two delivery methods were offered: 10 classes over 24 weeks or 4 classes over 8-12 weeks. Community center facilitators administered the same paper survey to participants at the first educational experience, and then again at the final experience or every 3 months following the first educational experience. Results: Analysis was conducted with 418 participants to measure change in healthy behaviors and confidence over time. Participants were predominately female (83%), 55 or older (55.9%), African American (68.4%) and non-Hispanic (81.6%). About half (44.7%) had a college degree or higher, nearly a fifth (17.9%) received benefits from SNAP and almost half (48.3%) indicated they are the only person in their household preparing meals. Almost half (42%) of respondents attended 4 or more educational experiences. On average, respondents statistically significantly increased their daily fruit &amp; vegetable consumption by .43 serving(s). After taking classes, 119 of 394 (30.2%) respondents increased their level of confidence to prepare healthy meals at home and 128 of 379 (33.8%) respondents increased their level of confidence to substitute healthier cooking and food preparation methods. Similarly, 120 of 385 (31.2%) respondents reported increased frequency of reading food labels and checking the nutritional values when purchasing food. Conclusions: The Healthy for Life community program involving a skills-based format can be an effective health promotion model in improving confidence and dietary behaviors over time. However, additional research studies are required to further assess the long-term health impacts of this type of intervention.
Abstract P471: Citizenship Status and the Prevalence, Treatment, and Control of Cardiovascular Disease Risk Factors Among Immigrants in United States, 2011-2016
Authors: Jenny S Guadamuz, Ramon A Durazo-Arvizu, Martha L DAVIGLUS, Gregory Calip, Edith Nutescu, Dima Qato
Journal: Circulation (2020)

Introduction: Immigrants without US citizenship, i.e., noncitizens, encounter barriers in accessing care which may contribute to disparities in cardiovascular disease (CVD), the leading cause of death among immigrants in the US. Despite this, little is known about whether the prevalence, treatment, and control of CVD risk factors differ by citizenship status This study estimates the prevalence, treatment, and control of CVD risk factors (hypercholesterolemia, hypertension, and diabetes) among US immigrants by citizenship status. Methods: We used nationally representative, cross-sectional data from the National Health and Nutrition Examination Survey (2011/12 to 2015/16), restricted to 5,306 immigrant adults (≥20 years). Citizenship status (exposure) was categorized as either citizen or noncitizen. CVD risk factor prevalence (age-standardized), treatment, and control were defined per national guidelines and determined using examinations and prescription-medication inventories. Treatment was estimated among persons with relevant conditions and control was estimated among persons who were receiving treatment. Associations were evaluated using Poisson regressions (prevalence ratios, PR). Results: Hypercholesterolemia (42.0%), hypertension (29.0%), and diabetes (15.7%) were common among immigrants and marginal differences were observed between citizens and noncitizens. However, noncitizens were less likely to be treated for hypercholesterolemia (16.4% vs. 43.3%, PR 0.38 [CI 0.31-0.46], P &lt;0.001), hypertension (60.3% vs. 79.6%, PR 0.76 [CI 0.70-0.84], P &lt;0.001), and diabetes (51.2% vs. 66.6%, PR 0.77 [CI 0.66-0.90], P &lt;0.001) than citizens. Because noncitizens disproportionally lack a usual source of care (30.2% vs. 16.6%, P &lt;0.001) and health insurance (48.8% vs. 19.1%, P &lt;0.001), adjusting for access to care largely explained differences in the treatment of CVD risk factors. Among those treated for CVD risk factors, citizens and noncitizens achieved similar control of hypercholesterolemia (36.2%) and hypertension (67.5%), but disparities in diabetes control were observed (35.3% vs. 46.9% , P =0.04). Conclusions: While CVD risk factors were common in citizens and noncitizens, treatment rates were significantly lower among noncitizens due to poor access to care. Efforts to prevent CVD morbidity and mortality among immigrants should address the undertreatment of risk factors by ensuring access to care among immigrants, regardless of citizenship status.
Amplifying the impact of clinical pharmacology and therapeutics
Authors: Emma H Baker, Jamie Coleman, David Webb
Journal: BMJ (2020)

As clinical pharmacologists representing a truly generalist specialty, spanning all ages and organs, we welcome the call for rebalancing of specialist and generalist skills to improve care for patients with multimorbidity.1

Clinical pharmacology and therapeutics (CPT) arose in the last century in response to the explosive development of new drugs and parallel evolution of medicines regulation. In the 1970s, the …