tbuckley/cabot-search huggingface dataset:
P1-10-07: Comparing Breast Cancer Screening Guidelines: A Stage-Survival-Cost Model in a Public Hospital.
Authors: DT Friedman, C Raskind-Hood, K Adams, E Becker, I Habtes, C D'Orsi, K Gundry, G Birdsong, S Gabram-Mendola
Journal: Cancer Research (2011)

Abstract Background: Despite advances in diagnosis and treatment of breast cancer in the United States, racial disparities in survival persist. Female breast cancer represented the costliest cancer site in 2010 with further increases projected to 2020. Mammography screening guidelines reflect the inherent difficulty in reconciling mortality reduction with potential harms to patients and cost-effectiveness concerns. Controversy still surrounds the 2009 updated USPSTF recommendations, as critics and advocates alike evaluate lives saved, costs, and how best to compare screening strategies. This study simulates USPSTF and ACS guidelines’ effects on stage, 5-year survival, and cost of treatment vs. usual practice in women treated in an urban public hospital. Methods: Charts of 84 patients diagnosed with Stage I-III breast cancer in 2008 were reviewed. Published tumor doubling times guided a retrospective model to predict size at diagnosis by simulated ACS or USPSTF guidelines. AJCC-7 stages were then assigned to produce 3 distributions: 1) actual stage; 2) stage under ACS; and 3) stage under USPSTF. Survival estimates by stage and year from diagnosis were drawn from NCDB statistics and applied to each stage distribution, yielding average predicted survival for the actual and hypothetical scenarios. Finally, treatment costs for women continuously enrolled in Medicaid for 18 months were calculated from merged claims and registry data and similarly applied. Results: Study patients averaged 55 years; 85% were African American. Forty-nine percent were covered by Medicaid and 23% by Medicare. Comparing actual and predicted stages at diagnosis showed significant shifts in stage distribution between all three scenarios (Table 1). ACS guidelines predicted higher survival (87.5% at 5 years) than actual (85.5%; p&amp;lt;0.01) or USPSTF (84.6%; p&amp;lt;0.0001), while no significant difference was revealed between actual and USPSTF. ACS guidelines also predicted lower costs of treatment relative to USPSTF and actual, while USPSTF guidelines were more expensive than actual (Table 2). Discussion: To our knowledge, no studies have compared the impact of alternative screening guidelines on outcomes in a predominantly African-American, public hospital population. These data support continued use of and adherence to ACS screening recommendations for inner city patients to achieve the best survival and the lowest cost. Given the likelihood of patients to be uninsured or covered by federal programs, this study carries implications for public policy and patient education, especially in low-resource programs caring for underserved patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-10-07.
Inhibition of Prostacyclin and Platelet Thromboxane A<sub>2</sub>after Low-Dose Aspirin
Authors: F. Eric Preston, Susan Whipps, Christine Ann Jackson, Adrian John French, Peter James Wyld, Christopher James Stoddard
Journal: New England Journal of Medicine (1981)

To compare the inhibitory effects of aspirin on prostaglandin synthesized by vessel walls and platelets, we obtained vein segments from five subjects before they were given 150 or 300 mg of aspirin and at various intervals afterward. We then measured prostacyclin (PGI2) synthesis with a radioimmunoassay for its stable metabolite, 6-keto-prostaglandin F1α. Platelet production of thromboxane A2 was measured with a radioimmunoassay for its stable metabolite, thromboxane B2. Two hours after aspirin had been given, 81 to 100 per cent inhibition of PGI2 synthesis was demonstrated; 86 per cent inhibition was still evident in one subject tested eight hours after administration. Simultaneously, platelet production of thromboxane B2 was completely inhibited for more than 24 hours. We conclude that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses of aspirin. Our results also indicate that in male subjects the prolonged template bleeding time after aspirin is not the consequence of selective inhibition of platelet production of thromboxane. (N Engl J Med. 1981; 304:76–9.)
Accurate diagnosis and long term management is problem in epilepsy, not cost of drugs
Authors: J. Coebergh
Journal: BMJ (2013)

Spence is right that epilepsy is not managed well.1 Rather than focusing on the cost and use of drugs perhaps the problem is with diagnosis and management in general. The recent national audit of seizure management in hospital identified considerable variability.2 The few sites that performed well showed that good care is possible, but, overall, assessment on arrival was …
Abstract 838: Suppression of constitutive and interleukin-6-inducible activation of signal transducer and activator of transcription 3 in human prostate cancer cells by diallyl trisulfide, a cancer chemopreventive constituent of garlic
Authors: Kumar Chandra-Kuntal, Shivendra V. Singh
Journal: Cancer Research (2011)

Abstract Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor implicated in prostate cancer development. The STAT3 is constitutively active in a large fraction of human prostate cancer cells and clinical prostate cancer specimens. Hyperactivity of STAT3 is associated with advanced prostate cancer. Furthermore, STAT3 activation promotes survival and inhibits apoptosis in prostate cancer cells. Agents that are safe but can either suppress activation of STAT3 or overcome STAT3 activation for their anticancer effects are attractive for prevention and treatment of prostate cancer. Natural products have attracted tremendous attention for the discovery of novel agents potentially useful for prevention and treatment of human cancers. The present study demonstrates that diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of processed garlic, inhibits phosphorylation (activation) of STAT3 in prostate cancer cells in culture and in vivo. Exposure of DU145 and LNCaP human prostate cancer cells to growth suppressive and pharmacologically-relevant concentrations of DATS (20 and 40 μmol/L) resulted in suppression of constitutive (DU145) as well as interleukin-6 (IL-6)-induced (LNCaP) phosphorylation of STAT3 (Tyr705). The DATS-mediated suppression of STAT3 activation correlated with inhibition of Janus-activated kinase 2 phosphorylation. Constitutive and/or IL-6-induced nuclear translocation of pSTAT3 as well as STAT3 dimerization was also inhibited markedly on treatment with DATS in both cell lines. Inhibition of prostate cancer development in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice by gavage with DATS correlated with a visible decrease in the levels of pSTAT3. Interestingly, the IL-6-mediated activation of STAT3 failed to confer protection against proapoptotic response to DATS in either cell line. Likewise, the DATS-mediated inhibition of cell migration was either not affected or minimally reversed by the IL-6 treatment or ectopic expression of constitutively active STAT3. In conclusion, the present study indicates that DATS treatment suppresses STAT3 phosphorylation in prostate cancer cells in culture and in vivo, but activation of this oncogenic transcription factor is largely dispensable for cellular responses to DATS. Ability of DATS to overcome STAT3 activation is a therapeutic advantage for this chemopreventive agent. This study was supported by the USPHS grant 2 RO1 CA113363-06, awarded by the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 838. doi:10.1158/1538-7445.AM2011-838
Barrett’s esophagus and reflux disease
Authors: M. di Pietro
Journal: Endoscopy (2010)

Very high quality clinical and translational research has been presented at the Digestive Disease Week (DDW) 2010 in New Orleans (1 – 5 May, New Orleans, Louisiana, USA). Here, a selection of the 16 best abstracts presented from the upper gastrointestinal field are briefly reviewed, with focus on Barrett's esophagus and reflux-related diseases. In selecting the abstracts specific relevance has been given to the following three elements: the impact of studies on daily clinical practice; their contribution to the understanding of the natural history of diseases; and the translational potential to introduce new diagnostic tools.
Abstract P6-06-06: The therapeutic potential and hazard of exposure to <i>Cerbera odollam</i> leaf extracts
Authors: F Chung, K Chan, YY Lim, B Li
Journal: Cancer Research (2012)

Abstract Background: Despite its significance in leading to the reduction of breast cancer mortality rates, therapeutic regiments for breast cancer still face two major problems: (1) the heterogeneity of the tumours and (2) the prevalence of drug resistance towards anti-estrogen therapy. The leaf extracts from Cerbera odollam were screened for active compounds with the potential to overcome these problems. Methods: Hormone responsive (MCF7) and hormone-independent cell lines (MDA-MB-231) were treated with the fractionated methanolic extracts of C. odollam followed by analyses on cell cycle perturbations and gene expression changes resulting from the treatment. The stated analyses were performed by flow cytometry, semi-quantitative RT-PCR, western blotting and immunofluorescence. The active fraction was identified, upon which HPLC separation was performed to identify the putative active compound. Results: Initial experiments revealed that a fractionated extract contains a potent cytostatic agent which is active towards hormone-responsive but not hormone-independent breast cell lines [the Estrogen Receptor-alpha (ERα) positive MCF7 cells remained static in growth for 10 days]. Comparison of the effects of the active and inactive fractions on MCF7 cells revealed key differences in cell growth and expression of ERα and its downstream regulated genes. The active compound was identified to be neriifolin (a cardiac glycoside) which also exhibited prolonged cytostatic effects (for 10 days upon treatment of 18.7 nM) similar to the active fraction. Gene expression analyses suggested that the ERα/Estrogen (E2) regulatory pathway and p53-dependent p21WAF1 transactivaton could be the cellular targets. Conclusion: Although neriifolin could be a potential drug for breast cancer treatment, its severity in down regulation of the ERα/E2 regulatory pathway which is critical during female development indicates the potential health hazard from our exposure to C. odollam. We are now focusing on establishing assay to evaluate whether neriifolin could cause drug resistance (similar to tamoxifen) by silencing ERα expression through hypermethylation of the ERα promoter. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-06-06.
Survival in Medically Treated Patients with Homozygous β-Thalassemia
Authors: Nancy F. Olivieri, David G. Nathan, James H. MacMillan, Alan S. Wayne, Peter P. Liu, Allison McGee, Marie Martin, Gideon Koren, Alan R. Cohen
Journal: New England Journal of Medicine (1994)

The prognosis of patients with homozygous β-thalassemia (thalassemia major) has been improved by transfusion and iron-chelation therapy. We analyzed outcome and prognostic factors among patients receiving transfusions and chelation therapy who had reached the age at which iron-induced cardiac disease, the most common cause of death, usually occurs.
AT-20 * SINGLE INSTITUTION RETROSPECTIVE REVIEW OF PERFORMANCE STATUS AND CORTICOSTEROID USE IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) PATIENTS (PTS) TREATED ON BEVACIZUMAB (BEV)
Authors: A. Desjardins, J. Herndon, F. McSherry, A. Ravelo, E. Lipp, P. Healy, K. Peters, G. Vlahovic, J. Sampson, A. Friedman, H. Friedman
Journal: Neuro-Oncology (2014)

BACKGROUND: Two multicenter phase III trials, RTOG0825 and AVAglio, evaluated the addition of BEV to radiation and temozolomide in newly diagnosed GBM and demonstrated a lack of statistically significant increased survival and discordant health-related quality of life results. We performed a retrospective chart review in newly diagnosed GBM to understand clinical benefit in BEV-treated patients in the community. METHODS: Newly diagnosed adult GBM pts treated at Duke were identified through our "Primary and Recurrent Glioblastoma Registry". We conducted a retrospective chart review of pts who initiated BEV between 1/1/2009 and 5/14/2012. Pts who participated in a clinical trial prior to receiving BEV were excluded. Pts alive on 5/15/2012 consented to the prospective collection of their data. Demographic and clinical data, including corticosteroid use and Karnofsky performance status (KPS), were analyzed. OS, PFS and time to KPS reduction were measured from BEV initiation. RESULTS: A total of 188 pts have been analyzed. At BEV initiation, median age was 57 years, 64% were male, 86% had KPS ≥80, and 46% were on corticosteroids. Median OS was 23.3 months (95% CI, 20.0-26.2 months). Median PFS was 14.8 months (95%CI, 12.2-17.9 months). Median time to KPS reduction ≥10-points and ≥20-points were 10.8 and 34.0 months, respectively. Of 86 pts on steroids pre-BEV, 78% discontinued steroids at a median of 64 days. Of 102 pts not on steroids pre-BEV, 57% did not initiate steroids, 31% initiated steroids while on BEV, and 12% initiated steroids while on another regimen. CONCLUSION: In newly diagnosed GBM pts treated on BEV in clinical practice, this retrospective review suggests a median OS and median PFS of 23.3 and 14.8 months, respectively. A majority of patients discontinued steroids, or remained off steroids during BEV treatment. Initial KPS levels were maintained by 86% of pts through the first year of follow-up.
Hypoxia Imaging of Uterine Cervix Carcinoma With 18F-FETNIM PET/CT
Authors: Laetitia Vercellino, David Groheux, Anne Thoury, Marc Delord, Marie-Hélène Schlageter, Yann Delpech, Emmanuelle Barré, Valérie Baruch-Hennequin, Perrine Tylski, Laurence Homyrda, Francine Walker, Emmanuel Barranger, Elif Hindié
Journal: Clinical Nuclear Medicine (2012)

Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG.We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes.All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 μg/L (median, 102.5 μg/L). Patients with OPN greater than 144 μg/L had reduced progression-free survival compared with those with OPN less than 144 μg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels.Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.
OC-013 Knife Assisted Resection (kar) Of Large And Refractory Colonic Polyps At A Western Centre: Feasibility, Safety And Efficacy Study To Guide Future Practice: Abstract OC-013 Table 1
Authors: R Bhattacharyya, G Longcroft-Wheaton, P Bhandari
Journal: Gut (2014)

The prescribing of psychotropic drugs was studied in a Scottish general practice of five doctors and 8,300 patients; one third of the patients were aged 12 years or less. In 1971, 336 prescriptions for psychotropic drugs were issued to 172 children and 2,583 to the adults. Most children were given only one prescription, but some needed up to ten in one year. The drugs consisted of sedatives (43 per cent), tranquillisers (41 per cent), and hypnotics (17 per cent). Most were given for behaviour disorders and enuresis. The analysis of drugs given by each doctor showed that one had given about one third of the total. This demonstration of comparative over-prescribing was useful in discussing self-audit.
Why pick a fight with junior doctors?
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2016)

Every doctor is a junior doctor at heart. We’ve all worked long and inhumane hours, worried about our ability to maximise patient safety and experienced the dearth of support services at evenings and weekends. Hospital patients know the pressures too, when a scan has to wait until the morning or it’s taken several hours for a busy junior doctor to arrive on a ward to prescribe a simple analgesic.

Junior doctors become hospital consultants, general practitioners, professors and journal editors, but they don’t forget what it was like to be a junior doctor. It’s an experience that shapes and binds us. Doctors are very different people embarking on diverse careers, but we all share the legacy of our time as junior doctors.

Why, then, would England’s Secretary of State for Health pick a fight with junior doctors? Why has Jeremy Hunt imposed a new contract on junior doctors, the manner of which will only further alienate not just junior doctors but also the rest of the profession and patients? While some commentators draw the conclusion that there is a hidden agenda to dismantle the NHS as we know it, only time will unravel the reasons behind Mr Hunt’s baffling war on juniors.

In the meantime, we are left with attempting to understand the consequences of the contract imposition, in a climate of disillusionment in hospital medicine and general practice, against a background of NHS deficits. Azeem Majeed and others with experience of being a junior doctor attempt to make sense of the contract imposition.1

We’ll be in a better place if everybody’s focus shifts to what’s best for patients. Here, in an unusual and fascinating piece of research, a US team attempts to understand the effects of team dynamics on operative efficiency.2 The authors find that the more familiar the team are with the each other the quicker the operating time. The effect of experience is similar but only up to a point. Around 30 years of working together, operative efficiency starts to wane.

If you do not believe this finding rest assured that this is a single-centre study and the hypothesis needs to be retested in other settings. Once several studies are published on this research question it might be time to consider a systematic review? Would you be convinced then? Evidence synthesis dates back centuries but has evolved rapidly in the last 25 years. Mike Clarke, a pioneer of evidence synthesis, provides an effortless history of this important research methodology sprinkled with pearls of wisdom for any aspiring critical thinker.3
Abstract 4364: Mechanism of promotion effect of diphenylarsenic acid on rat liver carcinogenesis
Authors: Takanori Yamada, Min Wei, Naoto Suga, Hideki Wanibuchi
Journal: Cancer Research (2010)

Abstract Diphenylarsinic acid (DPAA) is an enviromental degradation of product of diphenylarsine chloride or diphenylarsine cyanide, which were chemical warfare agents produced by Japan during the World War II. DPAA is now considered a dangerous environmental pollution in Kamisu, Japan, where it is suspected of inducing health effect that include articulation disorders, involuntary movements, and sleep disorders. We previously showed that GST-P (Glutathione S-transferase P) positive foci which is precancerous condition increased the number and the area at DPAA 20 ppm but not at below on rat liver carcinogenesis in medium-term bioassay (Ito test), suggesting that DPAA had promotion activities. However, the mechanism of its promotion activities is unclear. The purpose of present study is to clarify the mechanism of DPAA-induced promotion activity in rat liver carcinogenesis. We found that DPAA at 20 ppm but not at below increased significantly in oxidative DNA damage, mRNA expression of CYP1B1, cyclin D1, and c-Myc, and protein level and transcriptional activity of AhR (Arylhydrocarbon receptor) which is implicated in most of the biological responses to the environmental contaminant (e.g. TCDD). Proteome analysis showed that 69 proteins were differentially up or down-regulated in DEN-DPAA 20ppm group compared with DEN alone including 18 proteins of AhR pathway. These results suggested that activity of AhR pathway and oxidative DNA damage on rat liver carcinogenesis involved in promotion activity of DPAA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4364.
B12
Authors: Nizar A. Mullani, Jesus M. Gaeta, Richard A. Goldstein, Richard W. Smalling, Robert D. Ekas, Lance K. Gould
Journal: Clinical Nuclear Medicine (1984)

Mullani, Nizar A.; Gaeta, Jesus M.; Goldstein, Richard A.; Smalling, Richard W.; Ekas, Robert D.; Gould, Lance K. Author Information
Lupus Erythematosus Treated with a Combination of Quinacrine, Hydroxychloroquine and Chloroquine*
Authors: Mauray J. Tye, Herbert White, Bernard Appel, Harvey B. Ansell
Journal: New England Journal of Medicine (1959)

THIS study was undertaken as a clinical evaluation of the treatment of lupus erythematosus with a tablet composed of quinacrine, 25 mg., hydroxychloroquine, 50 mg., and chloroquine, 65 mg.¶ Certain antimalarial drugs have been shown to be more effective than any therapy previously available in treatment of chronic discoid lupus erythematosus. The literature on the use of quinacrine,1 , 2 hydroxychloroquine3 , 4 and chloroquine5 is already extensive. We have studied therapeutic and maintenance doses, relapses and side effects of this combination.The action of and the rationale for the use of these antimalarial drugs in lupus erythematosus have been the subject of some . . .
1158 PEG-IFNA/RIBAVIRIN/PROTEASE INHIBITOR COMBINATION IS HIGHLY EFFECTIVE IN HCV-MIXED CRYOGLOBULINEMIA VASCULITIS
Authors: D. Saadoun, S. Pol, P. Lebray, F. Blanc, G. Pialoux, A. Karras, D. Bazin-Kara, E. Plaisier, P. Cacoub
Journal: Journal of Hepatology (2012)
Enzyme Replacement Therapy by Renal Allotransplantation in Fabry's Disease
Authors: J. T. R. Clarke, R. D. Guttmann, L. S. Wolfe, J. G. Beaudoin, D. D. Morehouse
Journal: New England Journal of Medicine (1972)

Serial measurements of the neutral glycosphingolipids in the plasma and urine of a man who underwent renal allotransplantation because of renal failure due to Fabry's disease were done to evaluate the contribution of the donor organ to the correction of the basic metabolic defect. The concentration of galactosylgalactosylglucosylceramide in the plasma transiently decreased after the renal transplantation (from 0.76 to 0.48 μmoles per 100 ml). The variations in concentration of this lipid closely paralleled similar changes in the concentration of its precursor, N-acetylgalactosaminylgalactosylgalactosylglucosylceramide (from 0.23 to 0.07 μmoles per 100 ml), suggesting that the alterations in galactosylgalactosylglucosylceramide were the result of changes in the rate of formation of the lipid rather than increased catabolism by the graft. The data do not support the hypothesis that enzyme replacement by renal transplantation is effective in correcting the basic metabolic defect in patients with Fabry's disease.
1096 ENHANCED ANTITUMORAL EFFECTS BY COMBINING ADENOVIRUS-MEDIATED ANTI-ANGIOGENESIS WITH Ad-flk1 AND VACCINATION WITH AFP-PULSED DENDRITIC CELLS IN AN ORTHOTOPIC MURINE HCC MODEL
Authors: A. Vogt, F. Al-Awad, N. Meumann, T. Sauerbruch, C.P. Strassburg, H. Büning, M.A. Gonzalez-Carmona
Journal: Journal of Hepatology (2013)