tbuckley/cabot-search huggingface dataset:
Agreement of treatment effects for mortality from routinely collected data and subsequent randomized trials: meta-epidemiological survey
Authors: Lars G Hemkens, Despina G Contopoulos-Ioannidis, John P A Ioannidis
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To assess differences in estimated treatment effects for mortality between observational studies with routinely collected health data (RCD; that are published before trials are available) and subsequent evidence from randomized controlled trials on the same clinical question. <b>Design</b>&nbsp;Meta-epidemiological survey. <b>Data sources</b>&nbsp;PubMed searched up to November 2014. <b>Methods</b>&nbsp;Eligible RCD studies were published up to 2010 that used propensity scores to address confounding bias and reported comparative effects of interventions for mortality. The analysis included only RCD studies conducted before any trial was published on the same topic. The direction of treatment effects, confidence intervals, and effect sizes (odds ratios) were compared between RCD studies and randomized controlled trials. The relative odds ratio (that is, the summary odds ratio of trial(s) divided by the RCD study estimate) and the summary relative odds ratio were calculated across all pairs of RCD studies and trials. A summary relative odds ratio greater than one indicates that RCD studies gave more favorable mortality results. <b>Results</b>&nbsp;The evaluation included 16 eligible RCD studies, and 36 subsequent published randomized controlled trials investigating the same clinical questions (with 17 275 patients and 835 deaths). Trials were published a median of three years after the corresponding RCD study. For five (31%) of the 16 clinical questions, the direction of treatment effects differed between RCD studies and trials. Confidence intervals in nine (56%) RCD studies did not include the RCT effect estimate. Overall, RCD studies showed significantly more favorable mortality estimates by 31% than subsequent trials (summary relative odds ratio 1.31 (95% confidence interval 1.03 to 1.65; I<sup>2</sup>=0%)). <b>Conclusions</b>&nbsp;Studies of routinely collected health data could give different answers from subsequent randomized controlled trials on the same clinical questions, and may substantially overestimate treatment effects. Caution is needed to prevent misguided clinical decision making.
Postsurgical Follow-up of Colorectal Cancer Patients Monitored by the Leukocyte Migration Test&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M Zöller, U Schulz, W Dietze, H Wesch, S Matzku
Journal: JNCI Journal of the National Cancer Institute (1983)

Blood samples from more than 1,000 patients with colorectal cancer were tested in the leukocyte migration test (LMT) and by a radioimmunoassay for carcinoembryonic antigen (CEA) for evaluation of: 1) the correlation of LMT response to the status of disease and 2) the use of LMT and CEA determination in the monitoring of patients after surgical removal of the primary tumor. A total of 320 patients, which were tested repeatedly, constituted the key group of the investigation: Of these, 56 patients developed recurrences or metastases whereas 217 patients showed no sign of reactivated disease. The group of patients with persistent absence of disease showed test profiles of either persistent negativity (50%) or conversion of one or both parameters; persistently positive profiles were rarely encountered. Patients with recurrences and metastases showed either positive profiles or conversion of positivity; only 3 patients were negative in both tests. However, despite significant disease-related response of the LMT, the test is not recommended as an adjunct to postsurgical monitoring, because of its technical complexity.
Audit of indications and rate of re-excision following breast-conserving surgery within a multidisciplinary cancer network (Sussex, Surrey, and West Hampshire [SWSH]) in the United Kingdom.
Authors: D. Westbroek, K. Mann, V. Juniat, R. Daoud, I. J. Laidlaw
Journal: Journal of Clinical Oncology (2010)

e11014 Background: Randomized clinical trials report no difference in oncologic outcomes between breast-conserving surgery and traditional mastectomy in appropriately selected breast cancer patients. Clear resection margins remain the most significant predictor of local recurrence. Network (SWHS) guidelines stipulate margins > 2mm for invasive disease and >5mm for in situ disease. Preoperative work-up, localization, specimen orientation, faxitron radiography, and consistent histopathologic protocols for margin assessment are routine. This study assesses retrospectively the indications and rate of re-excision for clear margins within the local cancer network guidelines. Methods: Data was accrued retrospectively by querying for consecutive operative procedure and subsequent interventions using codes (OPCS)—B28.2, B28.4, and B28 for BCS performed by the two senior authors and specialist breast surgeons (IJL and RD), between 01.11.08 and 01.11.09. Histopathology characteristics including tumor grade, size, nodal status, and receptor expression were were generated from WinPath and TPath hospital databases. Results: The network's historical oncologic outcome data compare favorably with peer-reviewed outcome and quality metrics, i.e., local recurrence rates, overall and breast cancer survival rates. Of patients undergoing margin re-excision, 7 (5.9% ), 5 (4.2%), and 6 (5.1%) were for occult DCIS foci, involved margins, or insufficient resection margins respectively. Conclusions: The indications and rate of re-excision are within the wide variability of peer-reviewed outcomes and consistent with the network's guidelines. We are in the process of assessing adjunctive intra-operative techniques to increase clear margin rates at the primary BCS procedure. No. of patients (%) Patients undergoing BCS (11.08–11.09) 118 Patients undergoing further surgery 33 (27.9) Margin re-excision only 18 (15.2) Completion mastectomy 15 (12.7) Patients needing completion mastectomy after re-excision 2 (1.7)* Patients needing > 3 procedures (including initial bcs) 0 * For Paget's disease and DCIS >40mm. No significant financial relationships to disclose.
An economic analysis of varicella immunization in the Singapore military
Authors: Jake J. K. Goh, Marc Ho, W. M. Koh, Vernon J. Lee
Journal: Military Medical Research (2016)

Varicella outbreaks occur frequently in closed environments such as those of militaries. This paper compares the economic outcomes of varicella vaccination in enlisted servicemen without prior reported varicella infection or vaccination.We analyzed the economic outcomes of a varicella vaccination program on all enlisted servicemen without prior reported varicella infection or vaccination in the Singapore Armed Forces (SAF) between December 11, 2010 - December 20, 2013, compared with the previous program of varicella vaccination only for selected personnel between December 1, 2007 - December 10, 2010.In the at-risk population of all active SAF servicemen, the program of varicella vaccination for all servicemen without prior reported varicella infection or vaccination upon enlistment would save 72.0 work days per 1000 (95 % CI: 61.2 - 82.9), valued at SG$6,544 per 1000 (95 % CI: 6,524 - 6,564), i.e., costing SG$91.5 per work day saved (95 % CI: 78.7 - 107.3). This also results in a reduction of 2.7 varicella cases per 1000 and 5.43 outbreaks per 10000, or a total savings of SG$1,695 per 1000 (95 % CI: -2,730 - 6,834), taking into account the cost of work days lost over a three-year period, compared with the previous regime of vaccinations only for selected individuals.The varicella vaccination strategy targeting all enlisted servicemen without prior reported varicella infection or vaccination is able to prevent varicella infections and outbreaks, thus reducing absenteeism and days lost.
Abstract 13813: Transmural Heterogeneity of Cellular Level Power Output is Reduced in Human Heart Failure
Authors: Premi Haynes, Kristofer E Nava, Benjamin A Lawson, Charles S Chung, Mihail I Mitov, Stuart G Campbell, Arnold J Stromberg, Sakthivel Sadayappan, Mark R Bonnell, Charles W Hoopes, Kenneth S Campbell
Journal: Circulation (2013)

Background: Heart failure is associated with global pump dysfunction and ventricular remodeling. However, it is not known if different transmural regions of the left ventricular wall are affected i...
Association of proliferation and apoptosis resistance in polycythemia vera erythroblasts with abnormal MAPK and PI3K/AKT pathway signaling
Authors: J. Laubach, P. Fu, X. Jiang, M. O. Arcasoy
Journal: Journal of Clinical Oncology (2008)

7086 Background: Polycythemia vera (PV), a myeloproliferative disorder associated with JAK2V617F mutation, is characterized by erythrocytosis due to dysregulated red blood cell (RBC) production. We investigated the hypothesis that RBC accumulation results from increased precursor proliferation and/or apoptosis resistance associated with abnormal signaling via MAPK and PI3K/AKT pathways. Methods: Peripheral blood CD34+ cells were grown in liquid culture to generate primary erythroid precursors (EBLs) from PV patients and normal controls recruited in an IRB-approved protocol. All patients were positive for the JAKV617F mutation. Studies of proliferation, apoptosis, and protein phosphorylation were performed. To determine effects of MAPK and PI3K/AKT inhibition, cells were treated with inhibitors of MEK (PD98059) and PI3K (LY294002). Results: Seventeen patients were recruited to the study. In strict serum-free conditions, survival and proliferation of PV EBLs was growth factor-dependent, requiring both erythropoietin (EPO) and stem cell factor. PV EBLs exhibited increased EPO sensitivity, with a proliferation rate 1.6 fold greater than controls at physiologic EPO concentration (P<0.01). EPO-induced ERK1/2 phosphorylation was markedly increased in PV cells compared to controls. EPO induced phosphorylation of AKT in PV but not normal EBLs. PV EBLs were less sensitive than controls to MEK inhibition by a factor of two (P<0.01). Growth factor withdrawal induced a 5.7 fold increase in apoptosis in normal EBLs but only a 2.2 fold increase in PV cells (P<0.01). Inhibition of PI3K during growth factor withdrawal led to a further 1.5-fold increase in apoptosis of normal EBLs (P<0.01), whereas it did not have a significant effect on apoptosis in PV cells. MEK inhibition during growth factor withdrawal did not increase apoptosis in either normal or PV EBLs. Conclusions: 1) PV EBLs containing the JAK2V617F mutation are not cytokine-independent and exhibit EPO hypersensitivity under strict serum-free conditions, 2) Increased proliferation of PV EBLs is associated with increased EPO-induced ERK1/2 phosphorylation, 3) PV EBLs exhibit apoptosis resistance associated with increased EPO-induced phosphorylation of AKT. No significant financial relationships to disclose.
Hepatitis C reinfection after sustained virological response
Authors: Håvard Midgard, Benedikte Bjøro, Arild Mæland, Zbigniew Konopski, Hege Kileng, Jan K. Damås, Jørn Paulsen, Lars Heggelund, Per K. Sandvei, Jetmund O. Ringstad, Lars N. Karlsen, Kathrine Stene-Johansen, John H.-O. Pettersson, Dagny H. Dorenberg, Olav Dalgard
Journal: Journal of Hepatology (2016)
Safety and effectiveness of outpatient therapy in 596 low-risk patients with febrile neutropenia (FN)
Authors: L. Elting, C. Lu, C. Escalante, S. Giordano, J. Trent, E. Avritscher, R. Gralla, J. Talcott, K. Rolston
Journal: Journal of Clinical Oncology (2005)

8116 Background: Outpatient (Outpt) therapy was a major innovation in treatment of FN, but rapid adoption of this strategy precluded adequately powered clinical trials comparing Outpt with inpatient (Inpt) therapy. Among clinically eligible low-risk patients, non-medical barriers such as lack of a caregiver, mandate treatment in the Inpt setting. We compared the outcomes of low-risk pts with FN treated as Outpts to their low-risk counterparts who were treated as Inpts for non-medical reasons. Pts & Method: We selected 1 episode of FN at random for each of 596 consecutive low-risk pts. 103 pts with no caregiver or telephone at home, a history of non-compliance or residence >30 min from the hospital were treated initially as Inpts; 493 pts were treated initially as Outpts. We collected 6 outcomes from medical records: response to the initial antibiotic (abx) regimen, ultimate response (both defined as resolution of all signs and symptoms of infection), medical complications requiring treatment, and days of hospitalization, fever, and abx therapy. The Inpts and Outpts were similar in performance status, comorbidities, bacteremias, and pneumonias. There was a non-significant trend toward more mucositis in Inpts and they were older than Outpts. Confounding factors were strongly associated with outcomes. Thus, we compared Outpts’ outcomes with Inpts’ using logistic or linear regression (as appropriate) to adjust for these factors. Result: All Inpts and Outpts ultimately responded to abx therapy. After adjustment, there were no significant differences between Inpts’ and Outpts’ responses to initial abxs or rates of complications (Table). 19% of Outpts required hospitalization. Outpts’ mean length of stay was significantly shorter than those treated initially as Inpts. Conclusion: We found no evidence that Outpt therapy of FN in low-risk pts compromises effectiveness or safety. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration American Cancer Society, Bayer, Merck
Abstract A2-54: DNA methylation-dependent transcription regulatory networks elucidate dynamics of transcription regulatory circuitry in cancers
Authors: Yu Liu, Yang Liu, Zhengtao Xiao, Xuerui Yang
Journal: Cancer Research (2015)

Abstract Context-dependent DNA methylation plays a critical role in regulating gene transcription, thereby serving as an important epigenetic marker or regulator in many biological activities such as pluripotency, development, and complex diseases such as cancer. However, previously in most of the de novo reconstructions of cancer type-specific transcription regulatory networks (TRN), DNA methylation has rarely been taken into account as a significant factor in regulating transcription factor activity and controlling gene expression. The present study was set to systematically assess the involvement of DNA methylation in transcription regulatory circuitry in cancer. We took advantages of the multi-dimensional profiling data of DNA methylations and gene expressions in tumor samples of different cancers in The Cancer Genome Atlas (TCGA) consortium, and developed an integrative analysis pipeline based on conditional mutual information theory, to quantify the cooperative regulatory effects of CpG site methylations and transcription factors on gene expressions, in a genome-wide scale. Our analysis showed that DNA methylation and transcription factors indeed control gene expressions often in duet. To map the interplay between these two major defining factors of gene expression, DNA Methylation-dependent Transcription Regulatory Network (MeTRN), the first of its kind, was assembled for each of 19 major cancer types in TCGA. MeTRN provides a comprehensive view specifically on DNA methylation-dependent transcription events in each cancer type, and has been largely validated by public ChIP-seq and DNaseI-seq data. Comparison of these networks across cancer types showed that context-specificity of transcriptional circuits can be largely attributed to the context-dependent nature of DNA methylation patterns. Therefore, by assembling the cooperative effects of transcription factors and DNA methylations on gene transcription, MeTRN recapitulates an epigenetic scheme that implements dynamics of transcription regulatory circuitry across cancers via context-dependent DNA methylation marks. Supported by extensive cross-validations and experimental evidence, this epigenetically marked and dynamic transcription regulatory circuitry serves as a new basis for further mechanistic studies of gene expression dysregulations in cancers. Citation Format: Yu Liu, Yang Liu, Zhengtao Xiao, Xuerui Yang. DNA methylation-dependent transcription regulatory networks elucidate dynamics of transcription regulatory circuitry in cancers. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-54.
With better adjuvant therapy, does breast cancer stage still matter?
Authors: Ines Vaz-Luis, Harold J Burstein
Journal: BMJ (2015)

Catching cancers when they are small still makes a difference to survival

Breast cancer mortality is declining throughout the Western world.1 2 3 If, as J F Kennedy said, “victory has a thousand fathers,” then progress in breast cancer surely has a lot of parents. In the late 1970s, guidelines recommended screening mammography for women over the age of 40, resulting in implementation of national and regional screening programmes in most developed countries. Soon after, adjuvant endocrine therapy and chemotherapy were found to reduce the risk of breast cancer recurrence and death.4 5 Meanwhile, the combination of early detection and effective radiation therapy enabled breast conserving surgery as an option for most women.6 The implementation of these truly multidisciplinary treatment programmes, combining local and systemic treatments with public health screening initiatives and health awareness campaigns, revolutionised and improved breast cancer care.

The linked paper by Saadatmand and colleagues brings that progress forward into the 21st century.1 Using a population based cohort of 173 797 patients and comparing patterns of care and outcomes in two time periods (1999-2005 v 2006-12), they document steadily improving survival for women with breast cancer in the Netherlands. Dutch …
Cell Death and Cancer Therapy: Don't Forget to Kill the Cancer Cell!
Authors: Anthony Letai
Journal: Clinical Cancer Research (2015)

Abstract In our current age of targeted therapies, there is understandably considerable attention paid to the specific molecular targets of pharmaceutical intervention. For a targeted drug to work, it must bind to a target selectively and impair its function. Monitoring biomarkers of the impaired target function can provide vital in vivo pharmacodynamic information. Moreover, genetic changes to the target are often the source of resistance to targeted agents. However, for the treatment of cancer, it is necessary that the therapy not only provide efficient binding and inhibition of the target, but also that this intervention reliably kills the cancer cell. In this CCR Focus section, four articles make the connection between therapies that target T-cell activation, autophagy, IAP proteins, and BCL-2 and the commitment of cancer cells to cell death. Before addressing those exciting classes of targeted therapies, however, an overview is provided to discuss cell death induced by what is arguably still the most successful set of drugs in the history of medical oncology, conventional chemotherapy. Clin Cancer Res; 21(22); 5015–20. ©2015 AACR. See all articles in this CCR Focus section, "Cell Death and Cancer Therapy."
Primary lung sarcomas and sarcomatoid carcinomas - Clinicopathological prognostic factors in operated patients
Authors: Yanina Slavova, Dora Marinova, Emil Astroukov, Vladimir Stanoev, Danail Petrov
Journal: European Respiratory Journal (2013)

Aim: To study the prognostic significance of T- and N-status, pTNM stage, cytokeratin, desmin and CD15 expression in operated for primary lung sarcomas (PLSs) or sarcomatoid carcinomas (SCs) patients.  Material and Methods: Surgically resected specimen (men n=38; women n=19) from 18 PLSs and 39 SCs patients were studied. The T- and N-status, pTNM stage and immunohistochemical expression of cytokeratin, desmin, CD15 were evaluated. Statistical methods used: chi-square, Kaplan-Meier, Cox regression analysis.  Results: Cytokeratin expression is characteristic for SCs – it is found in 38 (97%) cases and in only 7 (39%) cases of PLS (p  Conclusions: Cytokeratin and CD15 expressions are characteristic for SCs while Desmin is found only in PLSs. T1/2 status and pTNM I/II stage may represent favorable prognostic factors in PLSs and SCs.
The use of pulmonary embolism severity index (PESI) score in identifying patients suitable for ambulatory treatment or early hospital discharge following diagnosis of pulmonary embolism
Authors: Veronica Smith, Rossana Salinas-Abedalaziz, Muriel Shannon, Brendan Madden
Journal: European Respiratory Journal (2012)

Introduction: International treatment guidelines for pulmonary embolism (PE) recommend that patients with low-risk of mortality should be considered for early discharge or ambulatory care. The Pulmonary Embolism Severity Index (PESI) has been validated to assess probability of 30 and 90 day mortality post PE. The aim of this study was to determine whether avoiding hospital admission, or facilitating early discharge, in low-risk patients could be achieved safely using the PESI score.  Methods: Since May 2010, St George9s Hospital has implemented a PE Assessment pathway. The PESI score was used to risk stratify patients in order to determine suitability for early discharge or ambulatory care. A dedicated PE specialist nurse collected patient data and selected appropriate patients. Low-risk patients with PESI score I-II were given education, and taught self-administration of low molecular weight heparin.  Results: Over a twenty-one month period, 119 of 346 patients with confirmed PE on computed tomography pulmonary angiogram (CTPA) were discharged within 24-48 hours of diagnosis. A further 25 patients were able to avoid hospital admission altogether. No readmissions or mortalities were noted in these groups, within up to 90 days of diagnosis.  Conclusions: The PESI score can be utilised effectively by a specialist nurse to treat patients with low-risk PE (PESI score class I-II) in the community.
High-Rate Cancers Among Low-Risk Populations&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Fraumeni, Joseph F.
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article High-Rate Cancers Among Low-Risk Populations Get access Joseph F. Fraumeni, Jr., M.D. Joseph F. Fraumeni, Jr., M.D. 3Environmental Epidemiology Branch, Division of Cancer Cause and Prevention, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, Bethesda, Md. 20205. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 65, Issue 5, November 1980, Pages 1187–1189, https://doi.org/10.1093/jnci/65.5.1187 Published: 01 November 1980