tbuckley/cabot-search huggingface dataset:
First-Line Pemetrexed plus Cisplatin followed by Gefitinib Maintenance Therapy versus Gefitinib Monotherapy in East Asian Never-Smoker Patients with Locally Advanced or Metastatic Nonsquamous Non–Small Cell Lung Cancer: Final Overall Survival Results from a Randomized Phase 3 Study
Authors: James Chih-Hsin Yang, Vichien Srimuninnimit, Myung-Ju Ahn, Chia-Chi Lin, Sang-We Kim, Chun-Ming Tsai, Tony Mok, Mauro Orlando, Tarun Puri, Xin Wang, Keunchil Park
Journal: Journal of Thoracic Oncology (2015)

IntroductionThe primary analysis of this open-label, randomized, multicenter phase 3 study revealed no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) and unknown epidermal growth factor receptor gene (EGFR) mutation status; however, the hazard ratio favored PC/G. This report describes the final overall survival (OS) results.MethodsChemonaive, East Asian light ex-smokers/never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status were randomized (1:1) to PC/G (n = 118) or G (n = 118). EGFR mutation status was retrospectively determined for 76 patients, 52 (68.4%) of whom had EGFR-mutated tumors (exon 19 deletions in 26 and L858R point mutation in 24). OS was analyzed by the Kaplan-Meier method. The study was registered at ClinicalTrials.gov (NCT01017874).ResultsMedian OS was similar in the PC/G (26.9 months) and G (27.9 months) groups (hazard ratio = 0.94, 95% confidence interval: 0.68–1.31, p = 0.717). Median OS was longer with PC/G than with G in patients with EGFR wild-type tumors (28.4 versus 8.9 months) and longer with G than with PC/G in patients with EGFR-mutated tumors (45.7 versus 32.4 months), especially those with exon 19 deletions. Second-line postdiscontinuation therapy was common and included chemotherapy (PC/G, 41 of 118 [34.7%]; G, 73 of 118 [61.9%]) and rechallenge with an EGFR tyrosine kinase inhibitor (PC/G, 27 of 118 [22.9%]; G, 9 of 118 [7.6%]).ConclusionsThe progression-free survival and OS results from this study further demonstrate the importance of determining EGFR mutation status to select the most appropriate first-line treatment for patients with advanced NSCLC.
Effect of Attribution Length on the Use and Cost of Health Care for a Pediatric Medicaid Accountable Care Organization
Authors: Eric W. Christensen, Nathaniel R. Payne
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Little is known about the effect of pediatric accountable care organizations (ACOs) on the use and costs of health care resources, especially in a Medicaid population. <h3>Objective</h3> To assess the association between the length of consistent primary care (length of attribution) as part of an ACO and the use and cost of health care resources in a pediatric Medicaid population. <h3>Design, Setting, and Participants</h3> A retrospective study of Medicaid claims data for 28 794 unique pediatric patients covering 346 277 patient-attributed months within a single children's hospital. Data were collected for patients attributed from September 1, 2013, to May 31, 2015. The effect of the length of attribution within a single hospital system's ACO on the use and costs of health care resources were estimated using zero-inflated Poisson distribution regression models adjusted for patient characteristics, including chronic conditions and a measure of predicted patient use of resources. <h3>Exposures</h3> Receiving a plurality of primary care at an ACO clinic during the preceding 12 months (attribution to the ACO). <h3>Main Outcomes and Measures</h3> The primary outcome measure was the length of attribution at an ACO clinic compared with subsequent inpatient hospitalization and subsequent use and cost of outpatient and ancillary health care resources. <h3>Results</h3> Among the 28 794 pediatric patients receiving treatment covering 346 277 patient-attributed months during the study period, continuous attribution to the ACO for more than 2 years was associated with a decrease (95% CI) of 40.6% (19.4%-61.8%) in inpatient days but an increase (95% CI) of 23.3% (2.04%-26.3%) in office visits, 5.8% (1.4%-10.2%) in emergency department visits, and 15.3% (12.5%-18.0%) in the use of pharmaceuticals. These changes in the use of health care resources combined resulted in a cost reduction of 15.7% (95% CI, 6.6%-24.8%). At the population level, the impact of consistent primary care was muted by the many patients in the ACO having shorter durations of participation. <h3>Conclusions and Relevance</h3> These findings suggest significant and durable reductions of inpatient use and cost of health care resources associated with longer attribution to the ACO, with attribution as a proxy for exposure to the ACO's consistent primary care. Consistent primary care among the pediatric Medicaid population is challenging, but these findings suggest substantial benefits if consistency can be improved.
Global and regional trends in mortality from chronic obstructive pulmonary disease: Their relation to poverty, smoking and population change
Authors: Jaymini Patel, Peter G.J. Burney, Roger B. Newson, Cosetta Minelli, Mohsen Naghavi
Journal: European Respiratory Journal (2014)

Background: Chronic Obstructive Pulmonary Disease (COPD) moved from fourth to third commonest cause of death in the world between 1990 and 2010, but little is known of what is driving this change. COPD has been associated with age, poverty and smoking.

Methods: We compared COPD mortality among those aged 40 years and older in 1990 and 2010, using data from the Global Burden of Disease programme. Mortality in 2010 was standardised to the 1990 population to quantify the difference in mortality rates attributable to changes in population. Regional COPD mortality rates for 1990 and 2010 were regressed against age, sex, gross national income/capita and an index of cumulative smoking exposure. Finally, we estimated the percentage of change in COPD mortality risk attributable to changes in age distribution, gross national income and smoking index.

Findings: Total deaths over the age of 40 years fell slightly from 2,995,058 in 1990 to 2,837,877 in 2010, though the number would have risen to 5,231,916 if the age-sex specific rates had remained constant. Changes in smoking led to a small increase in age-sex specific rates, but the main association with the changes in age-sex specific COPD mortality rates was a change in gross national income.

Interpretation: The main drivers of changes in COPD mortality between 1990 and 2010 are changes in age distribution, associated with increased deaths, and improving economic conditions, associated with reduced COPD mortality rates.
Abstract 12297: Comparative Effectiveness of Digoxin and Beta Blockers for Supraventricular Tachycardia in Infants
Authors: Christoph P Hornik, Patricia Y Chu, Jennifer S Li, Reese Clark, P Brian Smith, Kevin D Hill
Journal: Circulation (2013)

Background: Supraventricular tachycardia (SVT) is the most common arrhythmia in infants. Prior trials have been underpowered and there is no consensus regarding pharmacotherapy. We sought to evalua...
Use of 5-Hydroxytryptophan Labeled With Carbon 11 in Social Anxiety Disorder—Reply
Authors: Andreas Frick, Mark Lubberink, Tomas Furmark
Journal: JAMA Psychiatry (2015)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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 Psychiatry journal
Abstract #LB-244: Six biomarker panel detects early stage ovarian cancer
Authors: Gil Mor, James Symanowski, Irene Visintin, Michael Birrer, David Ward
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Introduction: Early diagnosis of epithelial ovarian cancer (EOC) would significantly decrease the morbidity and mortality from this disease, but it is difficult in the absence of specific physical symptoms. In the high risk population, the only preventive measure offered is oophorectomy. However, for every 100 surgeries, only 1 or 2 cancers are detected, leading to ~98% unnecessary surgeries. Recently, we reported the development and characterization of a Six Biomarker Panel which can determine the risk of ovarian cancer with a sensitivity of 95% and specificity of 99.4%. The objectives of this study were two fold: 1) to validate the performance of this panel in a larger cohort of stage I I and 2) to determine the performance of the six biomarkers in a sample population obtained from multiple centers in the United States. Methods: Serum samples were obtained from the Gynecologic Oncology Group (GOG), which enrolled the patients under the protocol GOG 136 from nearly 50 institutions in the USA. 193 ovarian cancer patients were evaluated. Ninety-three were diagnosed with stage I and II. One hundred samples were diagnosed with stage III and IV. Tumor type included 130 papillary serous, 6 mucinous, 42 adenocarcinomas, and 15 clear cell carcinomas. Ninety-four samples from normal healthy individuals were also received from the GOG. The six biomarkers were evaluated in a blinded fashion using the Cancer Panel from Millipore. The model described in Visintin et al (ref) was used for sample classification and an independent statistician evaluated the results. Results: From Stage I & II EOC, 86/92 were correctly classified (96.6%) and 97/100 from Stage III & IV (97 %). In the healthy group 3/92 were misclassified (3.2%). The sensitivity and specificity for early stages is 93.5 and 96.8% respectively with an overall error rate of 4.8% and ROC of 0.965. For late stages, at a sensitivity of 95%, the specificity is 98%; overall error rate 3.1% and ROC of 0.979. The classification results for the whole GOG cohort is Sensitivity 95.3% and Specificity 96.8%; overall error rate of 4.2% and ROC of 0.972. Conclusion: The present results demonstrate that the Six Biomarker Panel is able to identify stage I and II ovarian cancer with a sensitivity of 93.5 %. This cohort is unique due to the number of early stage cancers and the fact that the GOG has recruited samples from multiple institutions in the USA. The performance of test is similar to the results reported using samples collected only at Yale University. These results further strengthen the potential utility of this test for the high risk population to accurately detect early stage ovarian cancers and therefore obviate the risk of unnecessary preventive surgeries.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-244.
Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, Fallopian tube, or primary peritoneal cancer (AOC): Results of an international intergroup trial (AGO-OVAR16).
Authors: Andreas Du Bois, Anne Floquet, Jae Weon Kim, Jörn Rau, Jose Maria Del Campo, Michael Friedlander, Sandro Pignata, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Mansoor Raza Mirza, Bradley J. Monk, Pauline Wimberger, Isabelle Ray-Coquard, Rongyu Zang, Ivan Diaz-Padilla, Klaus H. Baumann, Jae Hoon Kim, Philipp Harter
Journal: Journal of Clinical Oncology (2013)

LBA5503 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Mismatch repair deficiency associated with complete remission to combination programmed cell death ligand immune therapy in a patient with sporadic urothelial carcinoma: immunotheranostic considerations
Authors: Michael P. Castro, Neal Goldstein
Journal: Journal for ImmunoTherapy of Cancer (2015)

Mismatch repair deficiency (MMRD) is a common pathway of malignant transformation accounting for approximately 15-20 % of human carcinogensis. It has been postulated that MMRD increases tumor antigenicity and highlights a role for immunotherapeutic approach MMR-deficient cancers. This strategy was pursued in a patient with upper tract urothelial carcinoma, and the results are reported here.Molecular profiling was performed using next generation DNA sequencing and (IHC) testing for MMR and PD-L1. A patient with sporadic, high grade urothelial carcinoma of the renal pelvis was found to have a hypermutator genotype with 73 mutations occurring amidst 62 known drivers of malignancy, and 340 VUS alterations. MMR deficiency phenotype was confirmed by the absence of MSH2 and MSH6 as well as deleterious mutations in these genes. IHC staining for programmed cell death ligand-1 [PD-L1] revealed 2+ staining in 80 % of cells. The patient gained access to combination immunotherapy trial utilizing MEDI4736 and MEDI0680 through a clinical trial. The patient achieved a prolonged, complete remission within two months and had no severe ill effects from the treatment.Given their ability to generate neo-antigens, MMR-deficient cancers may be uniquely susceptible to immune checkpoint inhibitor strategies, including urothelial tract cancers. Screening for MMR deficient cancers has the potential to become a routine strategy for evaluating the role of PD-L1 inhibitors for patient with advanced disease. (Clinicaltrials.gov NCT00938834. Registered 13 July 2009).
Plenty of moustaches but not enough women: cross sectional study of medical leaders
Authors: Mackenzie R Wehner, Kevin T Nead, Katerina Linos, Eleni Linos
Journal: BMJ (2015)

To draw attention to sex related disparities in academic medical leadership by investigating the representation of female leaders compared with leaders with moustaches.Cross sectional analysis.Academic medical departments in the United States.Clinical department leaders (n=1018) at the top 50 US medical schools funded by the National Institutes of Health (NIH).The proportions of female leaders and moustachioed leaders across institutions and specialties (n=20). Additionally, the moustache index: the proportion of women compared with the proportion of moustaches, analyzed with multinomial logistic regression models.Women accounted for 13% (137/1018) of department leaders at the top 50 NIH funded medical schools in the US. Moustachioed leaders accounted for 19% (190/1018). The proportion of female department leaders ranged from 0% (0/20) to 26% (5/19) across institutions and 0% (0/53) to 36% (19/53) across specialties. Only seven institutions and five specialties had more than 20% of female department leaders. The overall moustache index of all academic medical departments studied was 0.72 (95% confidence interval 0.58 to 0.90; P=0.004). Only six of 20 specialties had more women than moustaches (moustache index >1).Moustachioed individuals significantly outnumber women as leaders of medical departments in the US. We believe that every department and institution should strive for a moustache index ≥1. Known, effective, and evidence based policies to increase the number of women in leadership positions should be prioritized.
Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites
Authors: Lingli Mu, Rui Zhou, Fang Tang, Xingling Liu, Sanwang Li, Feifan Xie, Xiang Xie, Jie Peng, Peng Yu
Journal: Acta Pharmaceutica Sinica B (2015)

Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5'-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t 1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t 1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable.
Bombing Syria without protecting civilians won’t counter extremism or reduce refugees
Authors: Ayman S Jundi
Journal: BMJ (2015)

Without a plan to protect civilians, UK military involvement may be counterproductive

While you are reading this, British Royal Air Force bombers may be carrying out air strikes against targets in Syria. Civilians may well be affected. RAF bombers started their campaign within hours of a parliamentary vote authorising the extension of air strikes to Syria. But limited strikes against so called Islamic State (ISIS, ISIL, Daesh) are not a sustainable long term solution, and they do not tackle the root causes of extremism or the refugee crisis.

In fact, if anything, they are likely to make these two problems even worse. The US led coalition has been bombing ISIS targets in Iraq and Syria for more than a year, with limited …
Impact of sentinel lymph node biopsy on staging of early cervical cancer: Results of a prospective, multicenter study
Authors: F. Lecuru, A. Bats, P. Mathevet, D. Querleu, E. Leblanc, P. Morice, E. Darai, H. Marret, C. Collin, G. Chatellier, F. Gilaizeau
Journal: Journal of Clinical Oncology (2009)

CRA5506 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Omalizumab reduces cysteinyl leukotriene and 9α,11β-prostaglandin F2 overproduction in aspirin-exacerbated respiratory disease
Authors: Hiroaki Hayashi, Chihiro Mitsui, Eiji Nakatani, Yuma Fukutomi, Keiichi Kajiwara, Kentaro Watai, Kiyoshi Sekiya, Takahiro Tsuburai, Kazuo Akiyama, Yoshinori Hasegawa, Masami Taniguchi
Journal: Journal of Allergy and Clinical Immunology (2015)
Differences in Underlying Culprit Lesion Morphology Between Men and Women
Authors: Lin Wang, Gary S. Mintz, Bernhard Witzenbichler, D. Christopher Metzger, Michael J. Rinaldi, Peter L. Duffy, Giora Weisz, Thomas D. Stuckey, Bruce R. Brodie, Shinji Inaba, Ke Xu, Ajay J. Kirtane, Gregg W. Stone, Akiko Maehara
Journal: JACC. Cardiovascular imaging (2015)
Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials
Authors: Salvatore Cassese, Robert A Byrne, Gjin Ndrepepa, Sebastian Kufner, Jens Wiebe, Janika Repp, Heribert Schunkert, Massimiliano Fusaro, Takeshi Kimura, Adnan Kastrati
Journal: The Lancet (2015)
Clofarabine administration weekly to adult patients with advanced solid tumors in a phase I dose-finding study
Authors: C. C. Cunningham, J. Nemunaitis, N. Senzer, S. Vukelja, D. Richards, V. Vukovic, S. Weitman
Journal: Journal of Clinical Oncology (2005)

7109 Background: Clofarabine (CLOLAR), a next-generation nucleoside analogue that inhibits DNA synthesis, has demonstrated activity in acute leukemia. Clofarabine has also shown potent preclinical activity in a wide range of solid tumor cell lines and murine tumor models, so a Phase I study in patients (pts) with solid tumors is warranted. Methods: A Phase I study is ongoing to determine the maximum tolerated dose (MTD) of clofarabine in adult pts with advanced solid tumors. Clofarabine is administered IV on days 1, 8, and 15 of a 28-day cycle in escalating doses starting at 4 mg/m2. Results: To date, a total of 57 patients have been treated. Preliminary demographic and adverse event (AE) data are available for 38 pts, 22 males/16 females, median age 66 years (range 24 to 79), treated in 11 cohorts with doses up to 103 mg/m2. Tumor types include colorectal (9), lung (8), transitional cell bladder (3), pancreas (3), prostate (3), SCC larynx (2), cholangiocarcinoma (2), and others. Most pts (29) received at least 2 cycles; 11 pts received ≥3 cycles. Drug-related AEs in >20% of pts include nausea (55%), vomiting (32%), fatigue (32%), and weakness (24%). Drug-related serious AEs include Grade (Gr) 2 anemia (3) and vomiting (1), Gr 3 neutropenic fever (1) and hypotension (1), and Gr 4 thrombocytopenia (1) and acute myocardial infarction (1). Preliminary response data shows substantial improvement of target lesion by PET scan in a pt with SCCL, 1 PR, and 13 SD; notably, 1 prostate cancer pt had a PSA drop from 7975 ng/mL to 934 ng/mL at end of study. Pharmacokinetic (PK) data up to 129 mg/m2 imply that Cmax and AUC(0–6) are dose-proportional. Drug clearance (∼18 L/h/m2), half-life (∼4 h), and volume of distribution at steady state (∼71 L/m2) are consistent with PK in adult leukemia pts. Conclusions: Clofarabine administered weekly for 3 weeks (days 1, 8, and 15) every 28 days to adult pts with solid tumors up to 129 mg/m2 is well tolerated and shows clinical activity. Enrollment is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ilex Products Ilex Products Ilex Products Ilex Products