tbuckley/cabot-search huggingface dataset:
Dynamic Changes of Health Utility in Lung Cancer Patients Receiving Different Treatments: A 7-Year Follow-up
Authors: Szu-Chun Yang, Chin-Wei Kuo, Wu-Wei Lai, Chien-Chung Lin, Wu-Chou Su, Sheng-Mao Chang, Jung-Der Wang
Journal: Journal of Thoracic Oncology (2019)

This study aimed to estimate the utility values of all subtypes of lung cancer. The trajectories after different kinds of treatments and their major determinants were explored on the basis of real-world data and repeated measurements.From 2011 to 2017, all patients with lung cancer who visited a medical center were invited to fill out the EuroQol Five-Dimension and WHO Quality of Life-Brief questionnaires at each visit. Utility values of quality of life (QoL) after diagnosis and treatments were depicted using a kernel smoothing method. We constructed linear mixed models to predict health utility in each time period and cross-validated them with domain scores of the WHO Quality of Life-Brief.A total of 1715 patients were enrolled, with 6762 QoL measurements. Utility values were lower in patients with advanced-stage disease and older patients. Patients receiving second-line targeted therapy showed higher utility values at 0 to 3 months, 3 to 6 months, and 6 months and beyond (0.89, 0.90, and 0.88, respectively) than did those undergoing chemotherapy (0.81, 0.85, and 0.80, respectively). After using mixed models to control confounders, including poor performance status and disease progression, patients receiving second-line chemotherapy showed health utility similar to that at quasi-baseline, whereas utility values related to second-line targeted therapy were higher at 3 to 6 months and 6 months and beyond (β = 0.07, p = 0.010 and β = 0.07, p < 0.001, respectively). There was convergent validity between the utility values and scores of the physical and psychological domains.Targeted therapy provided treated patients with a higher health utility value than was provided to those treated with chemotherapy. Development of the longitudinal trajectory may help predict changes in QoL and improve the care of lung cancer survivors.
Prognostic value of epidermal growth factor receptors (EGFR) on overall survival of gastric cancer patients.
Authors: Alexandre A. A. Jácome, Durval R. Wohnrath, Cristovam Scapulatempo Neto, Estela C. Carneseca, Joao Soares Nunes, Luciano S. Viana, Sergio Vicente Serrano, José Sebastião Santos
Journal: Journal of Clinical Oncology (2012)

e14599 Background: The human EGFR family is involved in the pathogenesis and progression of several solid tumors. However, there is no consensus about the prognostic role of HER2 expression and of other members of EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of members of the EGFR family in gastric cancer. Methods: Retrospective study with 201 patients with gastric and esophagogastric junction (EGJ) adenocarcinoma stages 0 to IV (AJCC 6th edition) who underwent primary tumor resection between January 2006 and December 2008 at Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Tissue from primary tumors were analyzed by tissue microarray technology. IHC scores 0 and 1+ were classified as negative and scores 2+ and 3+ as positive, both for membrane and cytoplasmic expression of HER1, HER2, HER3 and HER4. The HER2 scoring system for gastric cancer was used for classification. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to a parametric Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. Results: Membrane expression of HER1, HER2 and HER4 were 9%, 17% and 15%, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3 and HER4 were 45%, 62% and 24%, respectively. Expression of HER2 and HER3 correlated with intestinal-type histology (p: 0.001 and p &lt; 0.001, respectively) and advanced age (p: 0.011 and p: 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage and receptors expressions, only TNM stage showed prognostic influence. Conclusions: Expression of HER2 and other members of EGFR family did not have influence on the overall survival in the gastric cancer population studied. The elaboration of a systematic review with meta-analysis or a prospective study could help elucidate this controversial issue.
Conceptualizing and evaluating replication across domains of behavioral research
Authors: Jennifer L. Tackett, Blakeley B. McShane
Journal: Behavioral and Brain Sciences (2018)

Abstract We discuss the authors' conceptualization of replication, in particular the false dichotomy of direct versus conceptual replication intrinsic to it, and suggest a broader one that better generalizes to other domains of psychological research. We also discuss their approach to the evaluation of replication results and suggest moving beyond their dichotomous statistical paradigms and employing hierarchical/meta-analytic statistical models.
Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke
Authors: Karen C. Johnston, Askiel Bruno, Qi Pauls, Christiana E. Hall, Kevin M. Barrett, William Barsan, Amy Fansler, Katrina Van de Bruinhorst, Scott Janis, Valerie L. Durkalski-Mauldin
Journal: JAMA (2019)

Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown.To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke.The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria.Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours.The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity.Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, -0.83% [95% CI, -5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]).Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting.ClinicalTrials.gov Identifier: NCT01369069.
CALM study: A phase II study of intratumoral coxsackievirus A21 in patients with stage IIIc and stage IV malignant melanoma.
Authors: Robert Hans Ingemar Andtbacka, Howard Kaufman, Gregory A. Daniels, Lynn E. Spitler, Jose Lutzky, Sigrun Hallmeyer, Eric D. Whitman, John J. Nemunaitis, Karl Zhou, Roberta Karpathy, Jeffrey Ira Weisberg, Darren Shafren
Journal: Journal of Clinical Oncology (2013)

TPS3128 Background: Coxsackievirus A21 (CVA21: CAVATAK) is a naturally occurring "common cold" virus. CVA21 displays potent oncolytic activity against both in vitro cultures of cancer cells and against in vivo xenografts of human cancers in mouse models of melanoma, prostate cancer, breast cancer and multiple myeloma, all which exhibit high surface ICAM-1 expression, which is used for viral entry. In mouse human melanoma xenograft CVA21 challenge models, progeny virus released from infected cells is capable of targeting adjacent cells, entering the systemic circulation, and destroying micro-metastatic foci. In a phase 1 study, two intralesional injections of CVA21 were shown to reduce or stabilize the growth of injected melanoma lesions. Methods: The CALM study investigates the efficacy and safety of intratumoral CVA21 in approximately 63 pts with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Pts are treated with up to 3 x 10 8 TCID 50 intratumorally on study days 1, 3, 5 and 8 and then every three weeks for a further 6 injections. Key eligibility criteria are ≥ 18 yrs old, ECOG 0-1, and at least 1 injectable cutaneous, sc, or nodal tumor &gt;1.0 cm. The primary endpoint is irPFS at 6 months following tx; secondary endpoints include durable response rate and OS. A 2-stage Simon’s minimax design will be employed. Based on data from previous trials and literature, a target overall irPFS at 6 months of 22.5% versus a projected rate of 10% in the target population is selected. With an alpha level of 5% and 80% of power, a total of 54 evaluable patients will be required to test the null hypothesis that the true irPFS rate is &lt;10% versus the alternative hypothesis that the true irPFS rate is at least 22.5%. Thirty-five patients will be treated at Stage I. If 3 or more objective responses (CR or PR) are achieved by modified RECIST 1.1 criteria in the first 35 patients, then the study will complete enrollment. Results: Currently, 21 patients have been enrolled on the study and treated with CVA21 injections. The treatment has been well tolerated. The Stage I interim efficacy endpoint of &gt; 3 objective responses has been achieved, and the second stage of the study is proceeding with a planned enrollment of a total of 63 patients. Clinical trial information: NCT01227551.
Pharmacodynamic study using FLT PET/CT in patients treated with axitinib.
Authors: Glenn Liu, Peter Scully, Jill Kolesar, Justine Yang Bruce, Jens C. Eickhoff, Scott Perlman, Lakeesha Carmichael, Jennifer Heideman, Robert Jeraj
Journal: Journal of Clinical Oncology (2013)

2537 Background: Axitinib (AX) is a potent VEGFR2 TKI. The objective of this study was to characterize tumor vascular and proliferative changes in patients treated with AX. Methods: Thirty pts with solid malignancies with at least one target lesion appropriate for FLT PET/CT imaging were enrolled. Pts were treated in Cycle #1 (C1) with AX at 5 mg BID x 2 wks, followed by a 1 wk drug holiday. Subsequent cycles continued the AX BID on a continuous basis until progression or unacceptable toxicity. In cohort A, FLT PET/CT was obtained at baseline, C1D14 (during AX) and C1D21 (AX withdrawal). Cohort B used the same treatment schedule, but FLT PET/CT was obtained on C1D14, C1D16 and C1D21. At each imaging time, peak FLT Standardized Uptake Values (SUV peak ), AX pharmacokinetics and plasma VEGF levels were obtained. Results: Of the 30 total pts, 28 had at least 1 PET/CT scan with 24 completing all planned PET/CT scans (13 in Cohort A; 11 in Cohort B). Strong proliferative flare (36% increase in SUV peak from C1D14 to C1D21) was observed in majority of pts with most of the flare occurred within two days after AX withdrawal (25% increase in SUV peak from C1D14 by C1D16). A robust vascular flare paralleled proliferative flare (R=0.57). A trend linking short progression free survival with high withdrawal flare was seen (44% increase in SUV peak for PFS ≤ 6mo vs 11% increase in SUV peak for PFS &gt; 6 mo; p=0.14). VEGF levels and AX PK levels increased during treatment, followed by decrease during withdrawal. Conclusions: The observed AX pharmacodynamics is consistent with our prior observation with another VEGFR TKI and suggests that acute AX withdrawal results in a robust withdrawal flare. This information suggests that the timing of cytotoxic chemotherapy during the flare may increase the therapeutic index, as opposed to concurrent administration which may be antagonistic. This study also shows the power of quantitative molecular imaging, which can simultaneous evaluate treatment response heterogeneity, as well as compensatory effects that may lead to early treatment failure. Clinical trial information: NCT00859118.
Cigarette Smoking, Smoking Cessation, and Long-Term Risk of 3 Major Atherosclerotic Diseases
Authors: Ning Ding, Yingying Sang, Jingsha Chen, Shoshana H. Ballew, Corey A. Kalbaugh, Maya J. Salameh, Michael J. Blaha, Matthew Allison, Gerardo Heiss, Elizabeth Selvin, Josef Coresh, Kunihiro Matsushita
Journal: Journal of the American College of Cardiology (2019)
Abstract 11655: Can Blood Biomarkers Predict Whose Heart is Healthy? - Discriminatory Capacity of High-sensitivity Troponin T and C-reactive Protein Between Patients With and Without Coronary Atherosclerosis, LV Hypertrophy/Dysfunction and Myocardial Perfusion Abnormalities as Assessed by Cardiac CT and SPECT Imaging
Authors: Christopher L Schlett, Quynh A Truong, Waleed Ahmed, Ron Blankstein, Maros Ferencik, Shanmugam Uthamalingam, Fabian Bamberg, Wolfgang Koenig, James L Januzzi, Udo Hoffmann
Journal: Circulation (2012)

Background: High-sensitivity troponin T (hsTnT) and C-reactive protein (hsCRP) are associated with cardiovascular events and structural heart disease. However, it is unclear whether these biomarker...
Abstract 12253: Disruption of Endothelial Adherens Junction by High Glucose Concentration is Mediated by HRas/PKC-β-Dependent VE-cadherin Tyrosine Phosphorylation
Authors: Mehran Haidari, Wei Zhang, Zhenping Chen, James T T Willerson, Richard A Dixon
Journal: Circulation (2012)

Hyperglycemia has been recognized as a primary factor in the development of diabetic Micro- and macrovascular diseases and endothelial barrier dysfunction, but the underlying biochemical mechanisms...
Characteristics, treatment and outcome of patients with hepatocellular carcinoma (HCC) in the United States: An analysis of 328 patients from 1998–2005
Authors: Z. K. Stadler, K. E. Stuart
Journal: Journal of Clinical Oncology (2007)

4615 Background: International studies have described the clinical characteristics and outcomes of patients with HCC. However, patient demographics, tumor characteristics, extent of liver disease, risk factors, treatment and outcome are less well established in the United States (US) where HCC remains rare. Methods: We identified 328 patients presenting to Beth Israel Deaconess Medical Center with a new diagnosis of HCC from 1998–2005. Characteristics including risk factors, underlying liver disease, tumor morphology and treatment were entered into a retrospective database. Child-Pugh grade and Cancer of the Liver Italian Program (CLIP) score were determined. Survival analysis was performed and data compared to our previously published HCC cohort from 1985–1995. Results: Patient characteristics were: Median age: 62; Male: 81%; Alcohol use (EtOH): 44%; Hepatitis C (HCV): 38%; Hepatitis B (HBV): 21%; No Risk Factor: 15%. EtOH was more common in HCV (57%) than in HBV (18%) patients. Treatment modality was: liver transplantation (LT) 14.4%, surgical resection 7.8%, chemoembolization or radiofrequency ablation (CE/RFA) 36%, chemotherapy 22%, no treatment 16%. Median overall survival was 13.5 months. Significantly better median survival was associated with Child-Pugh grade A (20.3 mos.), uninodular tumor in &lt;50% of liver (34.3 mos.), absence of portal vein thrombosis (19.2 mos.), CLIP score of 0 (42.5 mos.), background of HBV (32.9 mos.) and No EtOH (16.2 mos.). Treatment correlated with survival: LT, resection, or CE/RFA showed significantly better survival than chemotherapy or no treatment. In comparison to the 1985–95 cohort, median survival improved from 10 to 13.5 months. The 1998–05 cohort had more HBV/HCV (57% versus 20%), more favorable tumor characteristics, less severe liver disease, and more LT (14.4% versus 2.8%). Conclusions: In this single US institution, survival of HCC patients improved by 35% over two decades. Our results are consistent with nationwide trends of increased prevalence of viral infection, screening to find earlier disease, and more widespread use of aggressive treatments. Changing patterns of approaching the cirrhotic patient with HCC may be leading to slightly better results. No significant financial relationships to disclose.
Abstract 19242: No Difference in Skill Acquisition and Retention When Teaching Laypersons Recovery Position Using Four-stage and Two-stage Teaching Technique: A Randomized Comparison
Authors: Katrine Bjørnshave, Lise Q Krogh, Svend B Hansen, Mette A Nebsbjerg, Stinne E Rasmussen, Troels Thim, Bo Løfgren
Journal: Circulation (2015)

Introduction: Resuscitation guidelines recommend that unconscious and spontaneously breathing persons are placed in the recovery position to secure airway patency. Techniques for teaching the recovery position require evaluation. Aim: To evaluate acquisition and retention of recovery position skills among laypersons taught using a four-stage and two-stage teaching technique. Methods: Laypersons were randomized to a standardized European Resuscitation Council (ERC) courses in BLS/AED including training in recovery position using a four-stage teaching technique compared to modified course with the same content using a two-stage teaching technique. Participants were tested immediately after training and three months (±five days) later to assess acquisition and retention of recovery position skills. Tests were video recorded and reviewed by two assessors blinded to teaching technique. A skill checklist in accordance with the ERC guidelines representing the eight steps of the recovery position was used. The primary endpoint was passing the test (8 out of 8 skills). Result: In total, 160 participants were included. Total average number of steps of eight performed correctly was 7.3±1.0 (n=70) vs 7.1±1.1 (n=72) (p=0.5) immediately after the course and 4.1 ±2.3 (n=64) vs 3.8 ±2.3 (n=64) (p=0.4) three month later when using the four-stage and the two-stage technique, respectively. Correct final recovery position was obtained by 91% vs 93% immediately after the course and 49% vs 42% three month later. Each separate step of the recovery position is shown in Table 1. Conclusion: There was no difference in skill acquisition and retention when teaching laypersons recovery position using the four-stage and two-stage teaching technique. There was a marked decrease in skill level three months after training, particularly keeping the airway patent by head tilt and checking breathing regularly in both groups.
Technic of Controlled Drug Assay
Authors: Stanley E. Rosenbloom, Richard P. Shapera, Robert S. Goldbloom, Jack Pincus, Alvin P. Shapiro, Martin Goldstein
Journal: New England Journal of Medicine (1961)

THE following report describes an assay and evaluation of chlorothiazide, hydrochlorothiazide and a placebo in a group of ambulatory patients with mild to moderately severe hypertension. The purpose of the study was threefold: to compare the action on blood pressure of these two diuretics as compared to a placebo in a "double-blind study," this being of importance in view of the well known impact of nonpharmacologic variables on blood pressure1 and the fact that adequately controlled studies of these two agents have been few; to determine if the greater weight-for-weight potency of hydrochlorothiazide as compared with chlorothiazide2 offered any advantage . . .
Once-Weekly Efpeglenatide Dose-Range Effects on Glycemic Control and Body Weight in Patients With Type 2 Diabetes on Metformin or Drug Naive, Referenced to Liraglutide
Authors: Julio Rosenstock, Christopher H. Sorli, Michael E. Trautmann, Cristóbal Morales, Ulrich Wendisch, George Dailey, Marcus Hompesch, In Young Choi, Jahoon Kang, John Stewart, Kun-Ho Yoon
Journal: Diabetes Care (2019)

To explore the efficacy, safety, and tolerability of once-weekly efpeglenatide, a long-acting glucagon-like peptide 1 receptor agonist (GLP-1 RA), in early type 2 diabetes (T2D) (drug naive or on metformin monotherapy).EXCEED 203 was a 12-week, randomized, placebo-controlled, double-blind, parallel-group, dose-ranging study of efpeglenatide once weekly referenced to open-label liraglutide 1.8 mg (exploratory analysis). Participants, ∼90% on metformin monotherapy, were randomized to one of five efpeglenatide doses (0.3, 1, 2, 3, or 4 mg q.w.; n = 181), placebo (n = 37), or liraglutide (≤1.8 mg daily; n = 36). The primary efficacy end point was change in HbA1c from baseline to week 13.From a baseline HbA1c of 7.7-8.0% (61.0-63.9 mmol/mol), all efpeglenatide doses ≥1 mg significantly reduced HbA1c versus placebo (placebo-adjusted least squares [LS] mean changes 0.6-1.2%, P < 0.05 for all) to a final HbA1c of 6.3-6.8% (45.4-50.6 mmol/mol); masked efpeglenatide 4 mg was noninferior to open-label liraglutide. Greater proportions treated with efpeglenatide ≥1 mg than placebo achieved HbA1c <7% (61-72% vs. 24%, P < 0.05 for all), and greater reductions in body weight were observed with efpeglenatide 3 and 4 mg versus placebo (placebo-adjusted LS mean differences -1.4 and -2.0 kg, respectively, P < 0.05 for both). Rates of nausea and vomiting were consistent with other GLP-1 RAs and rapidly subsided after the initial 2 weeks. No neutralizing antibodies were detected with efpeglenatide.Efpeglenatide once weekly led to significant reductions in HbA1c and weight, with a safety profile consistent with the GLP-1 RA class in patients with early T2D mostly on metformin monotherapy.