tbuckley/cabot-search huggingface dataset:
Prioritization of HCV treatment in the direct-acting antiviral era: An economic evaluation
Authors: Natasha K. Martin, Peter Vickerman, Gregory J. Dore, Jason Grebely, Alec Miners, John Cairns, Graham R. Foster, Sharon J. Hutchinson, David J. Goldberg, Thomas C.S. Martin, Mary Ramsay, Matthew Hickman
Journal: Journal of Hepatology (2016)

We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID).A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment.The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage.Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high.
Knocking on molecular alterations in advanced gastric cancer (AGC).
Authors: Fabricio Racca, Cinta Hierro, Debora Moreno, Marta Vilaro, Stefania Landolfi, Ana Vivancos, Jose Jimenez, Teresa Macarulla, Jaume Capdevila, Elena Élez, Guillem Argilés, Tamara Saurí, Cristina Cruz, Analia Azaro, Sandra Castro, Paolo Nuciforo, Jordi Rodón, Josep Tabernero, Maria Alsina
Journal: Journal of Clinical Oncology (2015)

4063 Background: AGC represents the third leading cause of cancer related deaths. Chemotherapy for AGC is active but still of limited efficacy and targeted agents Trastuzumab and Ramucirumab have shown modest activity. Expanded molecular profile may provide critical information on druggable molecular aberrations and treatment options for these patients (pts). Methods: From 11/2010 to 11/2014, 101 pts with AGC underwent genetic/proteomic tumor profiling as part of the VHIO Phase I Trial Molecular Prescreening Program. Detection of mutations (mt) was performed with Multiplex-Single base extension followed by Mass-spect detection (Sequenom) or NGS (Amplicon-seq) (Illumina). Immunohistochemistry was used to assess HER2, PTEN and PDL1 expression. Amplification of HER2, PIK3CA, FGFR1, FGFR2, and METwere analyzed by in situ hybridization. Results: Median age of pts was 59-year, 66% men. Median prior treatment lines were 3 (1-6). Median overall survival was 18 months. As expected, HER2 was deregulated in 20%. PIK3CA mt and PTEN low expression were respectively found in 9% and 30%, with one pt harboring both molecular alterations. KRAS mt were found in 5%. PIK3CA, KRAS, FGFR4 and MSH6 mt coexisted in one pt. Amplification in FGFR2 (5%), MET (2%), and PIK3CA (1%) were also detected. One pt harbored amplification in 10 genes implicated in receptor tyrosine kinase- and cell cycle- pathways. PDL1 was positive in 6%; PIK3CA mt and PDL1 overexpression coexisted in 3%, ARID1A and SMAD4 also coexisted in another pt. Twenty-seven pts (27%) were treated with targeted therapies according to their molecular profile, with modest efficacy. Conclusions: Our molecular data is consistent with TCGA data. Pts. with AGC considered for genetic/proteomic tumor profile seem to derive benefit from this expanded characterization and treatment in phase I/II clinical trials with targeted agents. Molecular aberration Treatment Outcome HER2 deregulated Chemotherapy + HER2/ HER3 inhibitors (inhib) 4 SD (stable disease ≥ 6 months) + 1 PD (progressive disease) HER2/HER3 inhib 2 SD + 3 PD PI3KCA mt Chemotherapy + PI3KCA inhib 2 SD + 2 PD PI3KCA inhib 2 SD + 3 PD PDL1 positive PDL1 inhib 1 SD + 3 PD MET deregulated Chemotherapy + MET inhib 1 SD MET inhib 3 PD HGF inhib 1 PD FGFR4 amplified FGFR4 inhib 2 PD
BMA asks for 53% pay increase
Authors: A E A Joseph, S. Fordham, E M Armstrong
Journal: BMJ (1997)

<h3>Background and importance</h3> Albumin is a widely used medication for the treatment of critically ill patients, such as those with cirrhosis, burns patients and neonatal patients. However, its management is still a real challenge because of its high cost and controversial uses. <h3>Aim and objectives</h3> The aim of the study was to determine the frequency of inappropriate albumin prescriptions according to guidelines and scientific data in a teaching hospital. <h3>Material and methods</h3> Over a 4 month period, each prescription of human albumin in our teaching hospital was reviewed according to guidelines and recommendations. Data collected were: indication, clinical healthcare unit, patient sex and age, dosage and treatment times, and albuminaemia. Statistical analysis was performed by PSPP software. <h3>Results</h3> A total of 230 prescriptions were studied during the 4 month period coming from 10 healthcare units. Among them, 201 prescriptions were included in this work concerning 80 patients with a sex ratio of 1.10 and mean age of 45.85±25.84 years. Mean albuminaemia was 20.84±5.14 g/L. The mean dosage was 3±2 vial/day. Median duration of treatment was 2 days (IQI 4). The gastroenterology service ordered the most, with 92 orders (46%), followed by the paediatric service with 38 orders (19%). Seventy prescriptions (35%) were judged as inappropriate. The most frequent inappropriate indication was nephrotic syndrome with albuminaemia &gt;20 g/l without hypovolaemia or pulmonary oedema (19 prescriptions, 9.5%) followed by major surgery indication with serum albumin &gt;20 g/L (15, 7.5%). In total, 1694 vials of human albumin were consumed: 822 vials (48.5%) were consumed according to inappropriate indications. The estimated cost of inappropriate use was 15 000€ for a 4 months period. <h3>Conclusion and relevance</h3> This study suggests that inappropriate use of human albumin is quite common with high costs. Hence adoption of comprehensive guidelines may reduce the inappropriate use and healthcare costs. In addition, audit and educational feedback might strengthen the results. <h3>References and/or acknowledgements</h3> 1. Liumbruno G, Bennardello F, Lattanzio A, Piccoli P, Rossettias G. Recommendations for the use of albumin and immunoglobulins. <i>Blood Transfus</i> 2009;7:216–234. No conflict of interest.
Reply to Erik Rud and Eduard Baco's Letter to the Editor re: Re: Jeffrey C. Weinreb, Jelle O. Barentsz, Peter L. Choyke, et al. PI-RADS Prostate Imaging – Reporting and Data System: 2015, Version 2. Eur Urol 2016;69:16–40
Authors: Jelle O. Barentsz, Peter L. Choyke, Francois Cornud, Masoom A. Haider, Katarzyna J. Macura, Daniel Margolis, Faina Shtern, Anwar R. Padhani, Clare M. Tempany, Harriet C. Thoeny, Sadhna Verma, Jeffrey C. Weinreb
Journal: European Urology (2016)
Case 23-1966
Authors: Janet W. McArthur, Robert E. Scully
Journal: New England Journal of Medicine (1966)

Presentation of Case First admission. A thirty-year-old unmarried school-teacher entered the hospital because of amenorrhea of one year's duration.The menarche had occurred between ten and twelve years of age. The menses had been regular at intervals of thirty days, had been accompanied by cramps and had lasted for four or five days until eight years before entry, when they ceased abruptly soon after the patient entered college. Cyclic administration of diethylstilbestrol produced irregular bleeding during the next five years but was subsequently discontinued. Thyroid medication was instituted and maintained for a year, but the irregular bleeding persisted. An endometrial . . .
International cancer seminars: a focus on kidney cancer
Authors: G. Scelo, J.N. Hofmann, R.E. Banks, P. Bigot, R.S. Bhatt, G. Cancel-Tassin, S.K. Chew, C.J. Creighton, O. Cussenot, I.J. Davis, B. Escudier, T.M. Frayling, C. Häggström, M.A.T. Hildebrandt, I. Holcatova, M. Johansson, W.M. Linehan, D.F. McDermott, K.L. Nathanson, S. Ogawa, E.J. Perlman, M.P. Purdue, P. Stattin, C. Swanton, N.S. Vasudev, X. Wu, A. Znaor, P. Brennan, S.J. Chanock
Journal: Annals of Oncology (2016)
STAT3 Expression and Clinical Implications In De Novo Diffuse Large B-Cell Lymphoma: A Report From The International DLBCL Rituximab-CHOP Consortium Program
Authors: Chi Young Ok, Zijun Y. Xu-Monette, Alexander Tzankov, Carlo Visco, Santiago M. Montes, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W. L. Choi, Joannes H.J.M. Van Krieken, Qin Huang, Jooryung Huh, Weiyun Z. Ai, Maurilio Ponzoni, AndrÉs J.M. Ferreri,, John P. Farnen, Michael B. Moller, Jane N. Winter, Miguel A. Piris, L. Jeffrey Medeiros, Ken H. Young
Journal: Blood (2013)
In Vivo Jak1/Jak2 Inhibition Protects From Acute GvHD While Maintaining Robust Anti-Tumor Activity
Authors: Cristiana Carniti, Silvia Gimondi, Antonio Vendramin, Davide Confalonieri, Camilla Recordati, Anisa Bermema, Jacopo Mariotti, Paolo Corradini
Journal: Blood (2013)
O-010 KRAS and BRAF gene subgroup analysis in the Phase 3 RECOURSE trial of TAS-102 versus placebo in patients with metastatic colorectal cancer
Authors: H. Hochster, S. Hager, J.M. Pipas, N. Tebbutt, S. Laurent, C. Gravalos, M. Benavides, F. Longo Munoz, F. Portales, F. Ciardiello, S. Siena, K. Yamaguchi, K. Muro, T. Denda, Y. Tsuji, A. Ohtsu, E. Van Cutsem, R.J. Mayer
Journal: Annals of Oncology (2015)
Observation prior to systemic therapy in patients with metastatic renal cell carcinoma in the kinase inhibitor era.
Authors: R. A. Fisher, A. Pender, K. Thillai, S. Chowdhury, L. M. Pickering, S. St. Rose, M. E. Gore, J. M. G. Larkin
Journal: Journal of Clinical Oncology (2011)

4630 Background: Patients with metastatic renal cell carcinoma (mRCC) are heterogenous, with significant variation in clinical course. The use of vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin (mTOR) kinase inhibitors has dramatically changed the prognosis for these patients. However, these treatments are non-curative, necessitating chronic therapy. There is a cohort of patients with indolent disease in whom the initiation of systemic therapy is often deferred. It is inferred that the planned deferment of systemic therapy does not negatively impact on clinical benefit, but there is a lack of published data in the ‘kinase inhibitor era’ to support this contention. Methods: This was a retrospective study. Patients with mRCC treated with sunitinib who had a planned period of observation prior to the initiation of systemic therapy because of asymptomatic or slowly progressive disease were analysed. The primary objective was to determine the progression free survival (PFS) of patients on deferred first-line systemic therapy. Results: Records of 251 patients treated with sunitinib between 2005 and 2010 were reviewed; 64 patients who met the criteria were identified. The median age at diagnosis was 56 years and 75% were male; 80% had clear cell mRCC. All patients but one had a favourable or intermediate prognosis (Heng). The median time from diagnosis of metastases to starting treatment was 14.7 months (95% CI 10.4-16.3) Initial systemic therapy was interferon for 28% of patients and sunitinib for 65% of patients. Interferon patients had a median PFS of 6.3 months (95% CI 3.3-9.9), and sunitinib patients had a median PFS of 4.3 months (95% CI 3.6-7.3). Patients who received a VEGFR kinase inhibitor as second-line therapy after interferon had a median PFS of 7 months (95% CI 4.3-12.5). The median overall survival for all patients was 35 months (95% CI 26-42.3). Conclusions: In this cohort of patients with indolent favourable or intermediate prognosis mRCC, systemic treatment was deferred by a median of over one year but the efficacy of delayed sunitinib treatment was less than expected. Further study is required to define the group of patients for whom delayed systemic therapy is optimal.
TCTAP A-043 Left Main Versus Non-Left Main Intervention in Acute Myocardial Infarction Patients Received Triple or Newer Dual-Antiplatelet Therapy
Authors: Jah Yeon Choi, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Min Shim, Sung Hun Park, Eun Jin Park, Jae Joong Lee, Sunki Lee, Li Hu, Jin Oh Na, Cheolung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2016)
Ibuprofen and Other Arylpropionic Acid Derivatives Can be Responsible for Immediate Selective Responses to Nsaids
Authors: Diana Perez-Alzate, Natalia Blanca-López, Inmaculada Doña, Maria Luisa Somoza, Maria J. Torres, Gador Bogas, Jose A. Cornejo-Garcia, Gabriela Canto, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract 3673: High-density lipoprotein-like nanoparticles target SR-B1 and inhibit the cellular uptake of melanoma-cell derived exosomes
Authors: Michael P. Plebanek, Alexandre Matov, Kannan Mautharasan, Jesse Gatlin, C. Shad Thaxton
Journal: Cancer Research (2015)

Abstract Exosomes play a crucial role in the progression of cancer through the transport of a variety molecular cargo, including proteins, lipids, and nucleic acids, to and from cells as a means of intercellular communication. Unraveling mechanisms of exosome-cell interactions may open avenues for studying cellular communication and lead to new therapies. Cellular exosome uptake depends on cholesterol-rich membrane microdomains called lipid rafts. Non-specific depletion of lipid raft cholesterol reduces cellular exosome uptake; however, to our knowledge, no targeted mechanism of inhibiting cellular exosome uptake has been reported. Scavenger receptor type B-1 (SR-B1) localizes to lipid rafts, and is a high-affinity receptor for cholesterol-rich high-density lipoproteins (HDL). SR-B1 is an intriguing therapeutic target because it is upregulated in many different cancers due to the high need for cholesterol of rapidly dividing cancer cells. Therefore, we hypothesized that specific targeting of SR-B1 and modulation of cholesterol flux through this receptor with biomimetic HDL-like nanoparticles (HDL NPs) would disrupt cellular exosome uptake. As a model, we explored exosomes derived from melanoma cells as they have been shown to promote angiogenesis and immunosuppression both crucial events in melanoma progression. Melanoma exosomes have also been shown to actively prepare metastatic sites, creating a suitable microenvironment allowing for the development of metastasis. Because of this, targeting exosomes and intercellular signaling could be beneficial for the treatment of metastatic melanoma. Using a variety of techniques including confocal microscopy, flow cytometry and automated image analysis, data demonstrate that HDL NPs specifically target SR-B1 in lipid rafts in melanoma cells and modulate cholesterol flux through this receptor. This leads to a clustering of SR-B1 at the cell membrane and potent inhibition of the cellular uptake of melanoma cell-derived exosomes. Citation Format: Michael P. Plebanek, Alexandre Matov, Kannan Mautharasan, Jesse Gatlin, C. Shad Thaxton. High-density lipoprotein-like nanoparticles target SR-B1 and inhibit the cellular uptake of melanoma-cell derived exosomes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3673. doi:10.1158/1538-7445.AM2015-3673
Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study
Authors: Won Park, Dae Hyun Yoo, Pedro Miranda, Marek Brzosko, Piotr Wiland, Sergio Gutierrez-Ureña, Helena Mikazane, Yeon-Ah Lee, Svitlana Smiyan, Mie-Jin Lim, Vladimir Kadinov, Carlos Abud-Mendoza, HoUng Kim, Sang Joon Lee, YunJu Bae, SuYeon Kim, Jürgen Braun
Journal: Annals of the Rheumatic Diseases (2016)

Objectives To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). Methods This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). Results Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. Conclusions This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment. Trial registration number NCT01571206; Results.
Age-Specific Trends From 2000–2011 in All-Cause and Cause-Specific Mortality in Type 1 and Type 2 Diabetes: A Cohort Study of More Than One Million People
Authors: Jessica L. Harding, Jonathan E. Shaw, Anna Peeters, Susan Davidson, Dianna J. Magliano
Journal: Diabetes Care (2016)

To analyze changes by age-group in all-cause and cause-specific mortality rates from 2000-2011 in people with diabetes.A total of 1,189,079 (7.3% with type 1 diabetes) Australians with diabetes registered on the National Diabetes Service Scheme between 2000 and 2011 were linked to the National Death Index. Mortality rates in the total population were age standardized to the 2001 Australian population. Mortality rates were calculated for the following age-groups: 0 to <40 years, ≥ 40 to <60 years, and ≥60 to ≤85 years. Annual mortality rates were fitted using a Poisson regression model including calendar year as a covariate and age and sex where appropriate, with Ptrend reported.For type 1 diabetes, all-cause, cardiovascular disease (CVD), and diabetes age-standardized mortality rates (ASMRs) decreased each year by 0.61, 0.35, and 0.14 per 1,000 person-years (PY), respectively, between 2000 and 2011, Ptrend < 0.05, while cancer mortality remained unchanged. By age, significant decreases in all-cause, CVD, and diabetes mortality rates were observed in all age-groups, excluding diabetes mortality in age-group 0-40 years. For type 2 diabetes, all-cause, CVD, and diabetes ASMRs decreased per year by 0.18, 0.15, and 0.03 per 1,000 PY, respectively, Ptrend < 0.001, while cancer remained unchanged. By age, these decreases were observed in all age-groups, excluding 0-40 years, where significant increases in all-cause and cancer mortality were noted and no change was seen for CVD and diabetes mortality.All-cause, CVD, and diabetes ASMRs in type 1 and type 2 diabetes decreased between 2000 and 2011, while cancer ASMRs remained unchanged. However, younger populations are not benefiting from the same improvements as older populations. In addition, the absence of a decline in cancer mortality warrants urgent attention.
A single centre retrospective review of oral cyclophosphamide in hormone-refractory prostate cancer
Authors: K. A. Cheong, K. Chrystal, J. Spicer, P. G. Harper
Journal: Journal of Clinical Oncology (2005)

4781 Background: Chemotherapy for hormone refractory prostate cancer (HRPC) has until recently demonstrated improvement in QoL and symptom control but little effect on survival. Many patients due to co-morbidity and age would be unsuitable for taxane-based chemotherapy. We have retrospectively analyzed a group of patients treated with daily oral cyclophosphamide with relatively high PSA (>700), whose co-morbidity made other chemotherapies unsuitable. Low dose oral cyclophosphamide (50mg) administered on a metronomic schedule has been associated with anti-angiogenic activity. Previous studies have used it in combination with steroids or other cytotoxics with moderate activity and no severe toxicities. Methods: A retrospective review of patients with HRPC unsuitable for “standard” chemotherapy treated with oral cyclophosphamide 50mg daily at our institution between 1/2002 and 8/2004 (results updated 12/2004). Results: 21 men were identified, mean age 71 (58–81), 15/6 PS ½, median baseline PSA 725ng/ml (35–2800). All patients had progressed through standard hormonal therapies (LHRH analogues, antiandrogen and stilboestrol). 1 had prior chemotherapy. Baseline PSA doubling time: ≤3 mths 10, 4–6 mths 8, >6mths 2, 1 unspecified. 3 pts achieved a ≥50% PSA reduction, 1 pt a flare and return to baseline, 6 pts progressed within 3 months. 7 pts remain on treatment (3 - 16 mths) with 1 pt not assessable. Median duration of treatment 5.3 mths. Estimated median time to PSA progression (>25% increase from baseline) is 4.0 mths. Estimated median survival is 12.9 mths. No dose modification were required. No G3/4 toxicity was observed. No pts ceased treatment due to toxicity. 3 pts received concurrent steroids, 1 of which had a PSA response. 4 pts had a flare response, 2 of whom responded. Conclusions: Oral cyclophosphamide is a well tolerated regimen with demonstrable activity in HRPC. It should be considered as a therapeutic option particularly in the elderly and frail. No significant financial relationships to disclose.
Paediatrics, ethics, outcome research and critical care organization, sedation, pharmacology and miscellanea.
Authors: Massimo Antonelli, Enric Azoulay, Mark Bonten, James Chastre, Giovanni Citerio, Giorgio Conti, D De Backer, Francois Lemaire, Hugo Gerlach, James Groeneveld, George Hedenstierna, Daniel Macrae, James Mancebo, Salvatore Maurizio Maggiore, Albert Mebazaa, Paul Metnitz, John Pugin, Joseph Wernerman, Hugo Zhang
Journal: Intensive Care Medicine (2009)
Nontuberculous Pneumonia Complicating Pulmonary Tuberculosis
Authors: Gerald F. Hogan
Journal: New England Journal of Medicine (1945)

FOR many years, certain clinicians have discussed the relation between pulmonary tuberculosis and pneumonia occurring in the same patient. Opinion has been unanimous concerning the low incidence of the combined diseases, but when explanations have been offered concerning the reasons for the low incidence, much diversity has appeared. There has been similar disagreement about the effect that either disease has on the other. In only a few cases have opinions been supported by case reports. This study was therefore undertaken in an attempt to answer the following questions: What is the incidence of these two diseases occurring in the same . . .