tbuckley/cabot-search huggingface dataset:
Population-Based Study to Determine the Health System Costs of Using the 21-Gene Assay
Authors: Nicole Mittmann, Craig C. Earle, Stephanie Y. Cheng, Jim A. Julian, Farah Rahman, Soo Jin Seung, Mark N. Levine
Journal: Journal of Clinical Oncology (2017)

Purpose The 21-gene assay Oncotype Dx (Genomic Health, Redwood City, CA) test is used to aid the decision about chemotherapy in patients with hormone receptor-positive breast cancer who received endocrine therapy. Economic studies to support test adoption used decision-analytic models with assumptions and data derived from disparate sources. The objective was to evaluate whether the 21-gene assay test resulted in an overall cost expense or saving to the health system. Patients and Methods One thousand participants enrolled in a field evaluation study, were linked to population-level health system administrative databases, and were observed for 20 months. The cost for the cohort, which included the cost of the test, subsequent treatments received, and health care encounters, was determined. The cost in the absence of the test was compared with the pretest recommendation about chemotherapy from the field study for a base case and under scenarios that reflected different adjuvant chemotherapy use. Overall health system costs and incremental costs were calculated. Results The 21-gene assay resulted in a net decrease in chemotherapy use of 23%. For the base case incremental analysis, the actual overall health system cost of this cohort, including the cost of 21-gene assay, was $29.2 million compared with $26.2 million in the absence of the test-an increase of $3.1 million. For three of the four scenario analyses, the actual overall cost to the health system exceeded the estimated cost in the absence of the test. Results showed that, when at least half of the population received adjuvant chemotherapy, the cost increased to $30.2 million. Conclusion The use of real-world administrative data showed that, despite lower rates of chemotherapy use, the 21-gene assay test results in an overall incremental cost to the health care system in the short-term under most assumptions.
First-in-human phase 1 dose-escalation study of AV-203, a monoclonal antibody against ERBB3, in patients with metastatic or advanced solid tumors.
Authors: John Sarantopoulos, Michael S. Gordon, R Donald Harvey, Kamalesh Kumar Sankhala, Laeeq Malik, Devalingam Mahalingam, Taofeek Kunle Owonikoko, Colleen Margaret Lewis, Francis Payumo, Jim Miller, Christine Powell, Zhigang Weng, Philip B. Komarnitsky, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2014)

11113 Background: AV-203 is an IgG1k humanized monoclonal antibody with high affinity and specificity for the anti-v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3) receptor. Based on promising preclinical activity and resistance prevention data, a phase 1 study was conducted (NCT01603979). Methods: A phase 1 study using a 3+3 dose-escalation design evaluated the safety, tolerability, recommended phase 2 dose (RP2D), pharmacokinetics (PK) and pharmacodynamics of AV-203. AV-203 was given IV at 2, 5, 9, 14 or 20 mg/kg once every 2 wks (1 cycle = 28 days, 2 doses per cycle). Included patients (pts) had advanced solid tumors and progressed on standard therapies or had no proven treatment options. Results: AV-203 was administered to 22 pts (15M/7F; median age 68 y, range 31-82; ECOG PS 0/1: 8/13). Enrolled tumor types included colorectal (4), non–small-cell lung (NSCLC; 4), squamous cell carcinoma of the head and neck (2) and other solid tumors (12). There was a single dose-limiting toxicity of inability to tolerate the study drug (serious Grade 3 diarrhea and multiple concurrent adverse events [AEs]) at 2 mg/kg in an 80-y-old pt. The maximum administered dose of 20 mg/kg was well tolerated. All grade AEs observed in ≥25% of pts were: diarrhea (68%); decreased appetite (41%); hypokalemia, dry skin and hypomagnesemia (36% each); headache, dehydration, dizziness and dyspnea (27% each). Grade 3 and 4 AEs of anemia, diarrhea and hypokalemia occurred in ≥2 pts. The most common treatment-related AEs were diarrhea (59%), dry skin and decreased appetite (32% each), hypomagnesemia (27%) and pruritus (23%). No deaths were attributed to AV-203. Preliminary data show approximately dose proportional PK and no detection of anti-drug antibodies. Median time on treatment for all pts was 43 days (range: 1-491), with 15 pts discontinuing due to progressive disease during this time. There was one confirmed partial response (PR; 6 cycles) in a pt with squamous NSCLC which expressed high levels of neuregulin 1. Conclusions: AV-203 was well tolerated in the dose range tested; RP2D is 20 mg/kg IV every 2 wks. The PR in a pt with squamous cell NSCLC warrants further testing of AV-203 in this indication. Clinical trial information: NCT01603979.
Abstract IA19: Targeting the PRC2 complex through EED for anti-cancer therapy
Authors: Peter W. Atadja
Journal: Cancer Research (2017)

Abstract The Polycomb Repressive Complex-2 (PRC2) plays important roles in regulating gene expression through its histone H3 lysine methyl transferase activity. Dysregulation of PRC2 is observed in multiple cancers. For example, gain of function mutations of the EZH2 catalytic subunit of PRC2 have been reported in B-cell lymphomas, melanoma and parathyroid carcinoma. Components of the complex are also overexpressed in a number of cancers. The PRC2-complex have therefore become a major target for anti-cancer drug discovery. We and others, have reported anti-tumor activity of small molecular weight agents targeting the SAM-binding pocket of EZH2 in preclinical models and a number of EZH2 inhibitors ore showing promising activity in clinical trials. EED and SUZ12 are two additional components of the PRC2 core complex required for regulation of its catalytic function. High resolution structures and other reports have showed that binding of EED to tri-methylated histone H3 Lysine 27 (H3K27Me3) further stimulates the catalytic effect of EZh2. This suggests that small molecular weight compounds binding to and interfering with the EED stimulatory effect on Ezh2 may be able to modulate PRC2 activity. Following this possibility, we launched a comprehensive effort to discover non-catalytic site PRC2 binders. The discovery and characterization of EED226, a highly potent and selective EED-binding inhibitor of PRC2 will be presented. Data will be presented to demonstrate that EED226 inhibits PRC2 function via a distinct allosteric mechanism by binding to the H3K27Me3 binding pocket of EED. Furthermore, EED226 potently inhibits cellular H3K27Me3 levels, modulates target gene expression similar to the SAM competitive Ezh2 inhibitors and inhibits the proliferation of cell lines carrying mutant Ezh2. Oral administration of EED226 to EZH2-mutant tumor bearing mice leads to profound tumor regression. Our data therefore demonstrates that the multi-subunit PRC2 complex can be targeted at non-catalytic binding pockets to achieve anti-tumor activity. Some unique features of the anti-tumor activity achieved through targeting PRC2 will be discussed. Citation Format: Peter W. Atadja. Targeting the PRC2 complex through EED for anti-cancer therapy [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA19.
Disparities in Adjuvant Endocrine Therapy
Authors: Elizabeth J. Cathcart-Rake, Kathryn J. Ruddy
Journal: Journal of the National Comprehensive Cancer Network (2017)

Multiple competing factors (economic, environmental, social, and personal) influence health outcomes.For many patients, the lack of adequate insurance coverage is an obstacle to timely and appropriate medical care.Cancer survivors may be particularly vulnerable to the ill effects of insufficient insurance benefits.In one recent study comparing cancer survivors with their unaffected siblings, cancer survivors were more likely to lack employer-sponsored coverage, have been denied coverage, have Medicaid, and have high out-of-pocket costs.They were also more likely than their siblings to borrow money for medical expenses, worry that they would not receive a medical procedure, and not fill a prescription. 1Uninsured survivors suffered even greater disparities when compared with insured survivors, and were less likely to have a primary care provider or fill a prescription, and more likely to postpone preventive care. 1
Radiofrequency Denervation for Chronic Low Back Pain
Authors: Yakov Vorobeychik, Milan P. Stojanovic, Zachary L. McCormick
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 19013: Longitudinal Changes in Ankle and Brachial Pressures in a Community Dwelling Population: Results From the Baltimore Longitudinal Study of Aging
Authors: Majd AlGhatrif, Matt T Oberdier, Edward Lakatta, Stephani Studenski, Luigi Ferrucci
Journal: Circulation (2015)

Reduction in ankle-brachial index (ABI) is a marker of peripheral arterial disease (PAD) and is attributed to flow limiting lesions. It is unclear whether the major changes in blood pressure with aging affect ankle and brachial pressures differently and result in changes in ABI with advancing age. We studies 719 participants (2176 observations) from the Baltimore Longitudinal Study of Aging who were free of clinical cardiovascular (CV) disease at baseline. Ankle and brachial systolic blood pressures (SBP) and their index (ABI) were measured in both sides using oscillometric device (Colin VP2000) and averages of both sides were calculated. Linear mixed effects models were used with age expressed as Entry-Age and Follow up Time (Time) to test for non-linear longitudinal changes in these parameters. About 15% of the sample had diabetes at baseline, 3.5% were current and 38% were former smokers. Adjusting for diabetes, smoking status and anti-hypertensive medications, men had greater ABI than women (B= 0.02, P=&lt;0.001) with no statistically significant differences in trajectories. ABI changed with aging with statistically significant Entry-age X Time terms (P&lt;0.01). Model predicted values (Figure 1) shows a longitudinal decline in ABI after the age of 65. In men, this decline was a result of a longitudinal decline in ankle SBP vs plateauing brachial SBP. In women, the decline in ABI was a result of a greater increase in brachial SBP compared to ankle SBP. In conclusion, aging is independently associated with a decline in ABI in a healthy population free of clinical C disease. There were gender different in the pressure profiles yielding this reduction in ABI. A pathological reduction in ABI could represent an exaggerated age-associated hemodynamic alterations and not exclusively due to flow limiting lesions. Further studies are needed to understand the underlying alterations in arterial properties and the clinical significance of this subclinical reduction in ABI.
Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer
Authors: John H. Strickler, Jonathan M. Loree, Leanne G. Ahronian, Aparna R. Parikh, Donna Niedzwiecki, Allan Andresson Lima Pereira, Matthew McKinney, W. Michael Korn, Chloe E. Atreya, Kimberly C. Banks, Rebecca J. Nagy, Funda Meric-Bernstam, Richard B. Lanman, AmirAli Talasaz, Igor F. Tsigelny, Ryan B. Corcoran, Scott Kopetz
Journal: Cancer Discovery (2017)

Abstract “Liquid biopsy” approaches analyzing cell-free DNA (cfDNA) from the blood of patients with cancer are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cohorts of patients with cancer can detect genomic alterations at frequencies similar to those observed by direct tumor sequencing, and whether this approach can generate novel insights. Here, we report next-generation sequencing data from cfDNA of 1,397 patients with colorectal cancer. Overall, frequencies of genomic alterations detected in cfDNA were comparable to those observed in three independent tissue-based colorectal cancer sequencing compendia. Our analysis also identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding of anti-EGFR antibodies. Patients with EGFR ECD mutations displayed striking tumor heterogeneity, with 91% harboring multiple distinct resistance alterations (range, 1–13; median, 4). These results suggest that cfDNA profiling can effectively define the genomic landscape of cancer and yield important biological insights. Significance: This study provides one of the first examples of how large-scale genomic profiling of cfDNA from patients with colorectal cancer can detect genomic alterations at frequencies comparable to those observed by direct tumor sequencing. Sequencing of cfDNA also generated insights into tumor heterogeneity and therapeutic resistance and identified novel EGFR ectodomain mutations. Cancer Discov; 8(2); 164–73. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 127
Abstract P116: High Depressive Symptoms May Represent a Barrier to Reach Ideal Cardiovascular Health. A Cross-Sectional Analysis in 10 154 Participants From the Paris Prospective Study III
Authors: Bamba Gaye, Christof Prugger, Pierre Boutouyrie, Frédérique Thomas, Catherine Guibout, Marie C Perrier, Bruno Pannier, Xavier Jouven, Jean P Empana
Journal: Circulation (2015)

Background:  The Ideal Cardiovascular Health is a new tool defined by the American Heart Association with the aim to promote cardiovascular health by assessing 7 modifiable health behaviors and biological risk factors.   Hypothesis:  We investigated the hypothesis that high depressive symptoms represent a barrier to reach ideal cardiovascular health. We further explored the relationship of depressive symptoms on the behavioral and biological components of ICVH.   Methods:  Between 2008 and 2012, 10 154 men and women 50-75 years of age were examined in a large health center and enrolled in the Paris Prospective Study III. Ideal cardiovascular health comprises 4 behavioral components (nonsmoking, body mass index >18 kg/m2 and  7 on the 13-item Questionnaire of Depression 2nd version, Abridged (QD2A) or the use of antidepressants. Polytomous logistic regression analysis was applied to quantify the association of high depressive symptoms with intermediate and ideal cardiovascular health with poor cardiovascular health used as the reference category. Separate linear regression analyses were performed to examine the relationship of the QD2A scale with the behavioral and the biological cardiovascular health components. Regression models were adjusted for age, sex, living status, educational level and perceived health.   Results:  Mean age of participants was 59.1 (SD 6.3) years and 60.2% were males. A total of 851 (8.6%) showed high depressive symptoms, 5.0% in men and 14.2% in women. Poor, intermediate and ideal cardiovascular health was observed in respectively 32.3% (39.9% in men and 20.0% in women), 51.3% (49.7% in men and 54.0% in women) and 16.4% (10.7% in men and 26.0% in women) of study participants. Individuals with high depressive symptoms had a 35% (odds ratio [OR] 0.65; 95% confidence interval [CI] 0.54-0.78) and 43% (OR 0.57; 95% CI 0.44-0.74) decreased chance of having an intermediate and ideal cardiovascular health, respectively. The QD2A scale was significantly associated with the behavioral components β linear regression =-0.38, p   Conclusion:  Participants with high depressive symptoms have a substantially reduced chance of reaching ideal cardiovascular health, especially its behavioral components. High depressive symptoms may represent a barrier to reach ideal cardiovascular health.
PD-1 Modulates Radiation-Induced Cardiac Toxicity through Cytotoxic T Lymphocytes
Authors: Shisuo Du, Lin Zhou, Gregory S. Alexander, Kyewon Park, Lifeng Yang, Nadan Wang, Nicholas G. Zaorsky, Xinliang Ma, Yajing Wang, Adam P. Dicker, Bo Lu
Journal: Journal of Thoracic Oncology (2017)
Deep Learning Algorithms for Detection of Lymph Node Metastases From Breast Cancer
Authors: Jeffrey Alan Golden
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association Between Treatment by Locum Tenens Internal Medicine Physicians and 30-Day Mortality Among Hospitalized Medicare Beneficiaries
Authors: Daniel M. Blumenthal, Andrew R. Olenski, Yusuke Tsugawa, Anupam B. Jena
Journal: JAMA (2017)

<h3>Importance</h3> Use of locum tenens physicians has increased in the United States, but information about their quality and costs of care is lacking. <h3>Objective</h3> To evaluate quality and costs of care among hospitalized Medicare beneficiaries treated by locum tenens vs non–locum tenens physicians. <h3>Design, Setting, and Participants</h3> A random sample of Medicare fee-for-service beneficiaries hospitalized during 2009-2014 was used to compare quality and costs of hospital care delivered by locum tenens and non–locum tenens internal medicine physicians. <h3>Exposures</h3> Treatment by locum tenens general internal medicine physicians. <h3>Main Outcomes and Measures</h3> The primary outcome was 30-day mortality. Secondary outcomes included inpatient Medicare Part B spending, length of stay, and 30-day readmissions. Differences between locum tenens and non–locum tenens physicians were estimated using multivariable logistic regression models adjusted for beneficiary clinical and demographic characteristics and hospital fixed effects, which enabled comparisons of clinical outcomes between physicians practicing within the same hospital. In prespecified subgroup analyses, outcomes were reevaluated among hospitals with different levels of intensity of locum tenens physician use. <h3>Results</h3> Of 1 818 873 Medicare admissions treated by general internists, 38 475 (2.1%) received care from a locum tenens physician; 9.3% (4123/44 520) of general internists were temporarily covered by a locum tenens physician at some point. Differences in patient characteristics, demographics, comorbidities, and reason for admission between locum tenens and non–locum tenens physicians were not clinically relevant. Treatment by locum tenens physicians, compared with treatment by non–locum tenens physicians (n = 44 520 physicians), was not associated with a significant difference in 30-day mortality (8.83% vs 8.70%; adjusted difference, 0.14%; 95% CI, −0.18% to 0.45%). Patients treated by locum tenens physicians had significantly higher Part B spending ($1836 vs $1712; adjusted difference, $124; 95% CI, $93 to $154), significantly longer mean length of stay (5.64 days vs 5.21 days; adjusted difference, 0.43 days; 95% CI, 0.34 to 0.52), and significantly lower 30-day readmissions (22.80% vs 23.83%; adjusted difference, −1.00%; 95% CI −1.57% to −0.54%). <h3>Conclusions and Relevance</h3> Among hospitalized Medicare beneficiaries treated by a general internist, there were no significant differences in overall 30-day mortality rates among patients treated by locum tenens compared with non–locum tenens physicians. Additional research may help determine hospital-level factors associated with the quality and costs of care related to locum tenens physicians.
Efficacy and Safety of ITCA 650, a Novel Drug-Device GLP-1 Receptor Agonist, in Type 2 Diabetes Uncontrolled With Oral Antidiabetes Drugs: The FREEDOM-1 Trial
Authors: Julio Rosenstock, John B. Buse, Rehan Azeem, Prakash Prabhakar, Lise Kjems, Holly Huang, Michelle A. Baron
Journal: Diabetes Care (2017)

ITCA 650 (exenatide in osmotic mini-pump) continuously delivers exenatide subcutaneously for 3-6 months. Two doses of ITCA 650 were compared with placebo in patients with uncontrolled type 2 diabetes.This 39-week, phase 3, double-blind, placebo-controlled trial randomized 460 patients aged 18-80 years with glycated hemoglobin (HbA1c) 7.5-10% [58-86 mmol/mol] 1:1:1 to placebo, ITCA 650 40 μg/day, or ITCA 650 60 μg/day. Primary end point was change in HbA1c at 39 weeks.Least squares (LS) mean change from baseline HbA1c was -1.1% [-12.2 mmol/mol] and -1.2% [-13.2 mmol/mol] for ITCA 650 40 and 60 μg/day, respectively (P < 0.001 vs. placebo -0.1% [-1.3 mmol/mol]). In a prespecified analysis, greater HbA1c reductions occurred in patients not receiving sulfonylureas (SUs) versus those receiving SUs (-1.7% vs. -1.2% [-18.6 and -13.1 mmol/mol]). At week 39, HbA1c <7% [53 mmol/mol] was attained in 37%, 44%, and 9% of ITCA 650 40 μg/day, ITCA 650 60 μg/day, and placebo groups, respectively (P < 0.001 each dose vs. placebo). LS mean change from baseline body weight was -2.3 kg and -3.0 kg for ITCA 650 40 and 60 μg/day, respectively (P ≤ 0.015 vs. placebo -1.0 kg). Nausea was the most common adverse event (AE) and subsided over time. Discontinuation for gastrointestinal AEs occurred in 7.2% with ITCA and 1.3% with placebo. Most AEs associated with procedures to place and remove ITCA 650 were mild and transient.ITCA 650 significantly reduced HbA1c and weight compared with placebo and was well tolerated in patients with uncontrolled type 2 diabetes on oral antidiabetes medications.