tbuckley/cabot-search huggingface dataset:
Preoperative Delays in the US Medicare Population With Breast Cancer
Authors: Richard J. Bleicher, Karen Ruth, Elin R. Sigurdson, Eric Ross, Yu-Ning Wong, Sameer A. Patel, Marcia Boraas, Neal S. Topham, Brian L. Egleston
Journal: Journal of Clinical Oncology (2012)

Although no specific delay threshold after diagnosis of breast cancer has been demonstrated to affect outcome, delays can cause anxiety, and surgical waiting time has been suggested as a quality measure. This study was performed to determine the interval from presentation to surgery in Medicare patients with nonmetastatic invasive breast cancer who did not receive neoadjuvant chemotherapy and factors associated with a longer time to surgery.Medicare claims linked to Surveillance, Epidemiology, and End Results data were reviewed for factors associated with delay between the first physician claim for a breast problem and first therapeutic surgery.Between 1992 and 2005, 72,586 Medicare patients with breast cancer had a median interval (delay) between first physician visit and surgery of 29 days, increasing from 21 days in 1992 to 32 days in 2005. Women (29 days v 24 days for men; P < .001), younger patients (29 days; P < .001), blacks and Hispanics (each 37 days; P < .001), patients in the northeast (33 days; P < .001), and patients in large metropolitan areas (32 days; P < .001) had longer delays. Patients having breast conservation and mastectomies had adjusted median delays of 28 and 30 days, respectively, with simultaneous reconstruction adding 12 days. Preoperative components, including imaging modalities, biopsy type, and clinician visits, were also each associated with a specific additional delay.Waiting times for breast cancer surgery have increased in Medicare patients, and measurable delays are associated with demographics and preoperative evaluation components. If such increases continue, periodic assessment may be required to rule out detrimental effects on outcomes.
Clinical Implementation of Comprehensive Strategies to Characterize Cancer Genomes: Opportunities and Challenges
Authors: Laura E. MacConaill, Paul Van Hummelen, Matthew Meyerson, William C. Hahn
Journal: Cancer Discovery (2011)

Abstract An increasing number of anticancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Recent evidence suggests that the selection of patients whose tumors harbor specific genetic alterations identifies the subset of patients who are most likely to benefit from the use of such agents. As the number of genetic alterations that provide diagnostic and/or therapeutic information increases, the comprehensive characterization of cancer genomes will be necessary to understand the spectrum of distinct genomic alterations in cancer, to identify patients who are likely to respond to particular therapies, and to facilitate the selection of treatment modalities. Rapid developments in new technologies for genomic analysis now provide the means to perform comprehensive analyses of cancer genomes. In this article, we review the current state of cancer genome analysis and discuss the challenges and opportunities necessary to implement these technologies in a clinical setting. Significance: Rapid advances in sequencing technologies now make it possible to contemplate the use of genome scale interrogation in clinical samples, which is likely to accelerate efforts to match treatments to patients. However, major challenges in technology, clinical trial design, legal and social implications, healthcare information technology, and insurance and reimbursement remain. Identifying and addressing these challenges will facilitate the implementation of personalized cancer medicine. Cancer Discovery; 1(4): 297–311. ©2011 AACR.
Phase II Study of Axitinib in Sorafenib-Refractory Metastatic Renal Cell Carcinoma
Authors: Brian I. Rini, George Wilding, Gary Hudes, Walter M. Stadler, Sinil Kim, Jamal Tarazi, Brad Rosbrook, Peter C. Trask, Laura Wood, Janice P. Dutcher
Journal: Journal of Clinical Oncology (2009)

Purpose To investigate the efficacy and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 in patients with metastatic renal cell carcinoma (mRCC) refractory to prior therapies that included, but were not limited to, sorafenib. Patients and Methods In this multicenter, open-label, phase II study, patients with sorafenib-refractory mRCC received a starting dose of axitinib 5 mg orally twice daily. A one-arm, single-stage design was used to estimate the primary end point of objective response rate (ORR), defined by RECIST (Response Evaluation Criteria in Solid Tumors). Secondary end points included safety, duration of response, progression-free survival (PFS), overall survival (OS), and patient-reported outcomes. Results Of 62 patients recruited, 100% had received prior sorafenib, and 74.2% had received two or more prior systemic treatments. The axitinib dose was titrated to greater than 5 mg twice daily in 53.2% of patients, and 35.5% of patients had the dose modified to less than 5 mg twice daily. In 62 patients evaluable for response, the ORR was 22.6%, and the median duration of response was 17.5 months. Median PFS and OS times were 7.4 months (95% CI, 6.7 to 11.0 months) and 13.6 months (95% CI, 8.4 to 18.8 months), respectively. All-causality grade 3 to 4 adverse events included hand-foot syndrome (16.1%), fatigue (16.1%), hypertension (16.1%), dyspnea (14.5%), diarrhea (14.5%), dehydration (8.1%), and hypotension (6.5%). Conclusion Axitinib has antitumor activity in patients with mRCC refractory to prior VEGF-targeted therapy, including sorafenib. Toxicities were mild to moderate and were manageable. A randomized, phase III trial to compare axitinib with sorafenib in patients who have mRCC refractory to one prior first-line therapy regimen is underway.
Syndromic surveillance to assess the potential public health impact of the Icelandic volcanic ash plume across the United Kingdom, April 2010
Authors: A J Elliot, N Singh, P Loveridge, S Harcourt, S Smith, R Pnaiser, K Kavanagh, C Robertson, C N Ramsay, J McMenamin, A Kibble, V Murray, S Ibbotson, M Catchpole, B McCloskey, G E Smith
Journal: Eurosurveillance (2010)

The Health Protection Agency and Health Protection Scotland used existing syndromic surveillance systems to monitor community health in the UK following the volcanic eruption in Iceland in April 2010.
Prognostic and Predictive Value of Centrally Reviewed Ki-67 Labeling Index in Postmenopausal Women With Endocrine-Responsive Breast Cancer: Results From Breast International Group Trial 1-98 Comparing Adjuvant Tamoxifen With Letrozole
Authors: Giuseppe Viale, Anita Giobbie-Hurder, Meredith M. Regan, Alan S. Coates, Mauro G. Mastropasqua, Patrizia Dell'Orto, Eugenio Maiorano, Gaëtan MacGrogan, Stephen G. Braye, Christian Öhlschlegel, Patrick Neven, Zsolt Orosz, Wojciech P. Olszewski, Fiona Knox, Beat Thürlimann, Karen N. Price, Monica Castiglione-Gertsch, Richard D. Gelber, Barry A. Gusterson, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2008)

Purpose To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. Patients and Methods Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. Results Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). Conclusion Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.
Scientific Concepts, Value, and Significance of Chemical Carcinogenesis Studies
Authors: J Huff, J Haseman, D Rall
Journal: The Annual Review of Pharmacology and Toxicology (1991)

Synthetic chemicals and those naturally occurring chemicals that have be­ come 'man-made' via chemical synthesis and high volume production have only relatively recently been introduced into our way of life, and now have become essential for our adopted and evolved lifestyle. With the growing avalanche of chemicals comes the necessity for more public health prudence to minimize human exposures from these chemicals (derivatives, metabolites, and reaction products) and their myriad formulations during synthesis, man­ ufacture, mixing, packaging, transport, use, and disposal. Toxicologic char­ acterization of chemicals, mixtures of chemicals, and consumer products is essential for deciding policy to best protect public health while retaining the benefits we have come to expect. The profile of biological activities and toxicological effects of these agents or substances can be accomplished by using an array of in vitro and in vivo assays. These experiments are conducted
CHARACTERIZATION OF INFLUENZA ANTIBODIES BY SERUM ABSORPTION
Authors: Keith E. Jensen, Fred M. Davenport, Albert V. Hennessy, Thomas Francis
Journal: The Journal of Experimental Medicine (1956)

Absorptions of sera from groups of persons, both normal and after vaccination, resulted in complete removal of antibody to all strains of influenza virus within a type when a strain of antigenic configuration similar to that presumed to be the strain of first experience was employed. Absorption of these sera with strains encountered after the primary antigenic stimulus, removed antibody to strains recently experienced, but failed to absorb the primary antibody. By these methods, three age groups could be distinguished whose characteristic principal antibody was oriented to react with maximal efficiency either with FM1 or PR8 or Swine/1976 influenza viruses. Persons in these age groups had an initial experience with strains of the respective antigenic characteristics found in the variants of influenza virus mentioned. Basis for understanding these results was obtained with sera from successively infected ferrets, when serum absorptions demonstrated all type-specific antibody was oriented to react only with the strain of first infection. In view of this evidence there can now be little doubt as to the marked persistent influence an antigenic experience with influenza virus has upon the antibody-forming mechanisms of the virgin host.
Autism, language, and the folk psychology of souls
Authors: Stephen Flusberg, Helen Tager-Flusberg
Journal: Behavioral and Brain Sciences (2006)

Anecdotal evidence suggests that people with autism, with known impairments in mechanisms supporting a folk psychology of mind or souls, can hold a belief in an afterlife. We focus on the role language plays, not just in acquiring the specific content of beliefs, but more significantly, in the acquisition of the concept of life after death for all people.
PSORIASIS IS A RISK FACTOR FOR ATRIAL FIBRILLATION AND STROKE: A DANISH NATIONWIDE COHORT STUDY
Authors: Ole Ahlehoff, Gunnar H. Gislason, Jesper Lindhardsen, Casper H. Jorgensen, Mette G. Charlot, Steen Z. Abildstrom, Lone Skov, Christian Torp-Pedersen, Peter R. Hansen
Journal: Journal of the American College of Cardiology (2010)
Carotid Endarterectomy Benefits Patients with CKD and Symptomatic High-Grade Stenosis
Authors: Anna Mathew, Michael Eliasziw, P.J. Devereaux, Jose G. Merino, Henry J.M. Barnett, Amit X. Garg
Journal: Journal of the American Society of Nephrology (2009)

Endarterectomy is generally recommended for symptomatic high-grade (70 to 99%) stenosis of the internal carotid artery, but whether this procedure is beneficial among patients with chronic kidney disease (CKD) is unknown. In this re-analysis of data from the North American Symptomatic Carotid Endarterectomy Trial, we included patients with symptomatic stenosis and either stage 3 CKD (<i>n</i> = 524) or preserved kidney function (<i>n</i> = 966; estimated GFR ≥ 60). For medically treated patients with high-grade stenosis, risk for ipsilateral stroke at 2 yr was significantly higher in patients with CKD than in those with preserved renal function (31.6 <i>versus</i> 19.3%; <i>P</i> = 0.042); carotid endarterectomy significantly reduced this risk by 82 and 51%, respectively. To prevent one ipsilateral stroke, the number needed to treat by endarterectomy was four for patients with CKD and 10 for patients with preserved renal function. Compared with patients with preserved renal function, those with CKD had similar rates of perioperative stroke and death but higher rates of cardiac events. In conclusion, patients with stage 3 CKD and symptomatic high-grade carotid stenosis gain a large benefit in stroke risk reduction after endarterectomy.
Miliary tuberculosis during treatment with anti TNF alpha - a report of four cases
Authors: Liliana Alexandrina Grigoriu, Cristina Iacobescu, Ana Maria Sasu, Stefan Rujinski, Adriana Moisoiu, Miron Alexandru Bogdan
Journal: European Respiratory Journal (2013)

The anti-TNFs alpha have proven effective in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriasis, Crohn s disease. Among the side effects is well known the risk of developing infections, particularly tuberculosis. We present four cases of miliary tuberculosis with mediastinal lymphadenopathy which occurred during treatment with anti-TNF alpha, diagnosed in 7 Department of “M Nasta” Institute of Pneumology in 2011-2012. Two male patients aged 56 and 41 years, were treated with infliximab for ankylosing spondylitis. One male patient aged 32 and one female aged 47 years were treated with adalimumab for psoriasis. All patients performed chest X-ray, tuberculin skin test, quantiferon TB test for latent TB. The clinical signs of disease were febrile syndrome, dyspnoea, cough and weight loss. In the first case, the positive diagnosis was performed on lung biopsy and culture positive for BK in sputum. In the second case, were revealed AFB in bronchial aspirate. In the third and fourth case, the diagnosis was performed on lung and mediastinal lymphnode biopsy. In all cases we observe an aspect of miliary and mediastinal lymphadenopathy on chest CT. Three patients developed hepatic cytolysis during anti TB treatment. The evolution was slowly favorable in three cases and complicated with bone TB, psoas abscess, meningitis TB and death in one case, proved with HRS chemoresistance. Conclusions: All four cases are severe forms of miliary tuberculosis occurred during treatment with anti TNF alpha. There was a dramatic clinical syndrome with persistent fever, significant weight loss and death in one case. The regression of pulmonary and mediastinal lesions has been very slow.
Evaluation of guidelines for community-acquired pneumonia: a story of confounders, surprises and challenges
Authors: S. Ewig, T. Welte
Journal: European Respiratory Journal (2008)

Maybe guidelines are our fate. With the widespread acknowledgement of the principles of evidence-based medicine as the major basis for medical research, the number of evidence-based guidelines following a predefined methodological approach is steadily increasing. Community-acquired pneumonia (CAP) was one of the first diseases to be covered by guidelines. Since then, in addition to the most authoritative American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) 1, European Respiratory Society (ERS) 2 and British Thoracic Society (BTS) 3 guidelines, multiple national guidelines have been released and repeatedly updated. Without doubt, the ongoing discussion among international experts covering diverse specialties has substantially stimulated clinical research. Searching the world literature of the last 50 yrs, reviewing and rating every meaningful paper, and putting together the available evidence revealed that there are far more questions than answers regarding even the simplest clinical objectives. Some of these were successfully worked on, with the most impressive result being the derivation and validation of tools for severity assessment as the basis for decisions on treatment settings 4. But, do guidelines on CAP actually improve routine clinical practice?

Several studies have tried to approach this issue. The populations studied were very different: some included all hospitalised patients 5–12, whereas others included subgroups such as outpatients 13 and intensive care unit (ICU) patients 14. Most studies were retrospective in design 5–9, 14 and one relied on a pre–post intervention design 10. The selected outcomes usually covered length of hospital stay and mortality 5–11, 14. Most studies focused on antimicrobial treatment as an intervention variable 6, 8, 9, 11, 14, while others evaluated clinical pathways 5. This heterogeneity of study design means conflicting results are not surprising, although most studies …
An Address on Ophthalmology in its Relation to General Medicine
Authors: J. H. Jackson
Journal: BMJ (1877)

stable phosphorised material.For it may be noticed that, whereas lecithin is a very unstable matter, kephalin has been shown by Dr. Thudichum to be remarkably indisposed to decomposition.The presence of such a phosphorised matter in large quantity would cause combustibility, as well as give rise to the singular microscopical reaction described.
The Nosology of Depression: The Endogenous-Reactive Concept
Authors: JOE MENDELS, CARL COCHRANE
Journal: American Journal of Psychiatry (1968)

Controversies surrounding the distinctions between endogenous and reactive types have characterized the literature on depression. Reviewing seven pertinent factor analytic studies, these authors found sufficient consensus to support the independence of the endogenous and reactive factors. It is suggested, however, that these factors may not represent two etiologically distinct types of depression. The endogenous factor may reflect a "classical" depressive syndrome, whereas the reactive factor may reflect a psychiatric disorder in which depression is only one symptom "contaminated" by other nondepressive clinical features.
Prospective Analysis of Eosinophilic Esophagitis (EoE) in Pediatric Patients Living in Rural, Southeastern United States
Authors: Robbie D. Pesek, Troy Gibbons, Amy M. Scurlock, Mallikarjuna Rettiganti, Erin O'Brien, Caroline Daniel, Maria Melguizo Castro, C. Luo, Peggy L. Chandler, Audrey Fendley, Tamara T. Perry, Matthew C. Bell, Josh L. Kennedy, Stacie M. Jones
Journal: Journal of Allergy and Clinical Immunology (2015)
Opioid-Induced Second Window of Cardioprotection
Authors: Ryan M. Fryer, Anna K. Hsu, Janis T. Eells, Hiroshi Nagase, Garrett J. Gross
Journal: Circulation Research (1999)

Abstract —Opioids have been previously shown to confer short-term cardioprotection against a prolonged ischemic insult. Therefore, the present study was designed to determine whether opioids can induce a delayed or “second window” of cardioprotection and to assess the potential involvement of the mitochondrial K ATP channel. All rats were subjected to 30 minutes of ischemia and 2 hours of reperfusion (I/R). Control animals, injected with saline 24 hours before I/R, elicited an infarct size/area at risk (IS/AAR) of 62.9±3.4. TAN-67, a δ1-opioid receptor agonist, was administered 10 or 30 mg/kg IP 12, 24, 48, or 72 hours before I/R. TAN-67 (10 mg/kg) 12- or 24-hour pretreatment did not significantly reduce IS/AAR (62.1±6.3 and 43.3±7.3, respectively). Similarly, 12-hour pretreatment with TAN-67 (30 mg/kg) did not reduce IS/AAR (60.0±5.6); however, 24-hour pretreatment significantly reduced IS/AAR (34.5±5.9). Forty-eight–hour pretreatment with TAN-67 maximally reduced IS/AAR (29.2±7.0), and opioid-induced cardioprotection was lost after 72-hour pretreatment (61.7±3.8). TAN-67–induced cardioprotection could be abolished by pretreatment with the selective δ 1 -opioid receptor antagonist 7-benzylidenenaltrexone, BNTX, administered either 30 minutes before TAN-67 given 48 hours before I/R or 10 minutes before I/R in rats previously treated for 48 hours with TAN-67 (59.6±3.1 and 58.7±3.5, respectively). The involvement of the K ATP channel was investigated with 2 inhibitors: glibenclamide, a nonselective K ATP channel inhibitor, and 5-hydroxydecanoic acid, selective for the mitochondrial K ATP channel in rabbits. Glibenclamide, administered 30 minutes before I/R in 48-hour TAN-67–pretreated rats, completely abolished cardioprotection (60.4±3.2). Similarly, 5-hydroxydecanoic acid, administered 5 minutes before I/R in rats pretreated 48 hours previously with TAN-67, completely abolished cardioprotection (57.8±2.5). These results suggest that δ 1 -opioid receptor stimulation, 24 to 48 hours before an ischemic insult, produces a delayed cardioprotective effect that is possibly the result of mitochondrial K ATP channel activation.
Double-Blind, Randomized Trial of Docetaxel Plus Vandetanib Versus Docetaxel Plus Placebo in Platinum-Pretreated Metastatic Urothelial Cancer
Authors: Toni K. Choueiri, Robert W. Ross, Susanna Jacobus, Ulka Vaishampayan, Evan Y. Yu, David I. Quinn, Noah M. Hahn, Thomas E. Hutson, Guru Sonpavde, Stephanie C. Morrissey, Geoffrey C. Buckle, William Y. Kim, Daniel P. Petrylak, Christopher W. Ryan, Mario A. Eisenberger, Amir Mortazavi, Glenn J. Bubley, Mary-Ellen Taplin, Jonathan E. Rosenberg, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2011)

Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy.The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m(2) intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided α at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives.In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months.In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.
Mammalian Gcm genes induce Hes5 expression by active DNA demethylation and induce neural stem cells
Authors: Seiji Hitoshi, Yugo Ishino, Akhilesh Kumar, Salma Jasmine, Kenji F Tanaka, Takeshi Kondo, Shigeaki Kato, Toshihiko Hosoya, Yoshiki Hotta, Kazuhiro Ikenaka
Journal: Nature Neuroscience (2011)