tbuckley/cabot-search huggingface dataset:
Cost effectiveness of zoledronic acid in the prevention of skeletal related events in renal cell carcinoma patients with bone metastases: An exploratory analysis for France
Authors: M. Botteman, S. Kaura, J. Stephens, I. Foley, Y. Chen
Journal: Journal of Clinical Oncology (2008)

16085 Background: Previous European analyses have shown that zoledronic acid (ZOL) is cost effective in patients with bone metastases secondary to breast cancer, lung cancer, and other solid tumors. A recent analysis suggests that ZOL significantly reduce the risk of new skeletal related events (SREs) such as spinal cord compression, pathological fracture, radiation or surgery to bone, in renal cell carcinoma (RCC) patients with bone metastases. The present study assessed the cost effectiveness of ZOL in this population, adopting a French health care payer perspective. Methods: This analysis was based on a retrospective analysis of a trial of ZOL which randomized RCC patients with bone metastases to ZOL (n=27) or placebo (n=19) plus concomitant antineoplastic therapy for 9 months. A model was developed to simulate the costs and quality-adjusted life-years (QALYs) of the trial patients. SRE costs were estimated by pooling data from SRE studies in the Netherlands and Portugal. These estimates were supplemented with literature-based costs. Drug costs were obtained from French tariffs. Consistent with similar economic analyses, it was assumed that quality of life decreased for 1 month after each SRE experienced. Uncertainty was addressed via bootstrapping and multivariate probabilistic sensitivity analyses (PSA), which involved 10,000 model simulations using input values drawn from probability distributions. Results: ZOL and placebo patients experienced an estimated 0.527 vs. 0.402 discounted QALYs, respectively. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (€3,754 v. €10,531, respectively). After taking into consideration drug therapy costs, ZOL saved €4,732 and increased QALYs by 0.125. Thus, ZOL is preferred over placebo both in terms of costs and quality of life. In the PSA, therapy with ZOL saved costs in 93% of simulations. The cost per QALY gained was below the €50,000 per QALY gained threshold in 97% of PSA simulations. Conclusions: The present analysis suggests that ZA is cost saving and increases QALYs compared to placebo in RCC patients with bone metastases in France. These results may need to be confirmed via a larger prospective clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis
A randomized, open-label, phase 2 study of emibetuzumab plus erlotinib (LY+E) and emibetuzumab monotherapy (LY) in patients with acquired resistance to erlotinib and MET diagnostic positive (MET Dx+) metastatic NSCLC.
Authors: D. Ross Camidge, Teresa Moran, Ingel Demedts, Heidrun Grosch, Jean-Pierre Di Mercurio, Kathryn Finch Mileham, Julian R. Molina, Oscar Juan Vidal, Gerold Bepler, Jonathan Wade Goldman, Conrad Lewanski, Keunchil Park, Johan Wallin, Sameera R. Wijayawardana, Xuejing Aimee Wang, Volker Wacheck, Egbert F. Smit
Journal: Journal of Clinical Oncology (2016)

9070 Background: MET signaling represents one mechanism of resistance to EGFR inhibition in EGFR mutant (mt) NSCLC. Emibetuzumab (LY2875358, LY) is a humanized IgG4 monoclonal bivalent MET antibody (mAb) blocking ligand dependent and independent HGF/MET signaling. This study tested whether acquired resistance to erlotinib (E) in MET Dx+ NSCLC pts enriched for EGFRmt can be overcome by LY+E or LY. Methods: Stage IV NSCLC pts with acquired resistance to E, ECOG PS ≤ 2, and MET Dx+ ( ≥ 10% of cells ≥ 2+ by DAKO IHC) tumor sample (archival or fresh) were enrolled in this open-label phase 2 study (NCT01900652). Pts received LY 750mg IV Q2W with or without E 150 mg QD on a 28-day cycle after a maximum E washout period of ≤ 28 days. The primary objective was to evaluate the overall response rate (ORR) in both arms relative to historical control (10%), with a co-primary objective of ORR in pts with MET Dx-high ( ≥ 60% of cells ≥ 2+) in the mandatory post E progression biopsy. Additional objectives included DCR, PFS, safety, PK, and exploratory biomarker analysis. Results: 111 MET Dx+ pts were randomized at a 3:1 ratio to receive LY+E or LY. Median number of prior therapies was 2, 69% of pts had ECOG PS 1, 77% known activating EGFRmt, and 27% known T790M+. The ORR in pts with MET Dx+ NSCLC based on post E progression biopsies (n = 89) was 3.0% for LY+E (95% CI: 0.4, 10.5) and 4.3% for LY (95% CI: 0.1, 21.9). In MET Dx-high pts (n = 74), ORR was 3.8% for LY+E and 4.8% for LY. DCR and PFS were higher for LY+E (50%/3.3mo) than for LY (26%/1.6mo). No unexpected safety signals emerged. Related AEs in ≥ 15% of pts were reported for LY+E only and included fatigue, diarrhea, nausea, dermatitis acneiform, and edema. PK exposure of LY and E were comparable to historical data and no emergence of anti-LY antibody was detected. Exploratory biomarker analysis showed clinical PRs in pts with and without EGFRmt or MET amplification. Conclusions: Acquired resistance to E in MET Dx+ or MET Dx high pts was not reversed by LY+E or LY. LY was well tolerated and a subset of pts in both arms obtained clinical benefit. Further studies are warranted to identify pts benefiting most from emibetuzumab Clinical trial information: NCT01900652.
A Measles Outbreak in an Underimmunized Amish Community in Ohio
Authors: Paul A. Gastañaduy, Jeremy Budd, Nicholas Fisher, Susan B. Redd, Jackie Fletcher, Julie Miller, Dwight J. McFadden, Jennifer Rota, Paul A. Rota, Carole Hickman, Brian Fowler, Lilith Tatham, Gregory S. Wallace, Sietske de Fijter, Amy Parker Fiebelkorn, Mary DiOrio
Journal: New England Journal of Medicine (2016)

Although measles was eliminated in the United States in 2000, importations of the virus continue to cause outbreaks. We describe the epidemiologic features of an outbreak of measles that originated from two unvaccinated Amish men in whom measles was incubating at the time of their return to the United States from the Philippines and explore the effect of public health responses on limiting the spread of measles.
Abstract 2331: CD271 defines a cancer-initiating cell population in hypopharyngeal cancer
Authors: Nobuyuki Tanaka, Takayuki Imai, Mai Mochizuki, Keiichi Tamai, Kazunori Yamaguchi, Kennichi Satoh, Kazuto Matsuura, Ikuro Sato, Shigeru Saijo, Kazuo Sugamura
Journal: Cancer Research (2015)

Abstract Cancer stem cells (CSCs) or Cancer initiating cells (CICs) contribute to the malignant phenotypes of a variety of cancers, but markers to identify human hypopharyngeal cancer (HPC) stem cells remain poorly understood. We found that the CD271+ but not CD271- cell population sorted from xenotransplanted HPCs possesses tumor-initiating capability in immunodeficient mice. Tumors generated from the CD271+ cells contained both CD271+ and CD271- cells, indicating that the population could undergo differentiation. Immunohistological analyses of the tumors revealed that the CD271+ cells localized to a perivascular niche near CD34+ vasculature, to invasive fronts, and to the basal layer. In accordance with these characteristics, a stemness marker, Nanog, and matrix metaloproteinases (MMPs), which are implicated in cancer invasion, were significantly up-regulated in the CD271+ compared to the CD271- cell population. Furthermore, using primary HPC specimens, we demonstrated that high CD271 expression was correlated with a poor prognosis for patients. Furthermore, RNA interference of CD271 in CD271+ cells decreased efficiency of tumor initiation and migration phenotypes, suggesting that CD271 is indeed functional. Taken together, our findings indicate that CD271 is a novel marker for cancer initiating cells and for HPC prognosis. Citation Format: Nobuyuki Tanaka, Takayuki Imai, Mai Mochizuki, Keiichi Tamai, Kazunori Yamaguchi, Kennichi Satoh, Kazuto Matsuura, Ikuro Sato, Shigeru Saijo, Kazuo Sugamura. CD271 defines a cancer-initiating cell population in hypopharyngeal cancer. [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 2331. doi:10.1158/1538-7445.AM2015-2331
Phylogenetic Tools for Generalized HIV-1 Epidemics: Findings from the PANGEA-HIV Methods Comparison
Authors: Oliver Ratmann, Emma B Hodcroft, Michael Pickles, Anne Cori, Matthew Hall, Samantha Lycett, Caroline Colijn, Bethany Dearlove, Xavier Didelot, Simon Frost, A S Md Mukarram Hossain, Jeffrey B Joy, Michelle Kendall, Denise Kühnert, Gabriel E Leventhal, Richard Liang, Giacomo Plazzotta, Art F Y Poon, David A Rasmussen, Tanja Stadler, Erik Volz, Caroline Weis, Andrew J Leigh Brown, Christophe Fraser
Journal: Molecular Biology and Evolution (2016)

Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled. Here, we show that viral phylogenetic tools can be adapted and used to estimate epidemiological quantities of central importance to HIV-1 prevention in sub-Saharan Africa. We used a community-wide methods comparison exercise on simulated data, where participants were blinded to the true dynamics they were inferring. Two distinct simulations captured generalized HIV-1 epidemics, before and after a large community-level intervention that reduced infection levels. Five research groups participated. Structured coalescent modeling approaches were most successful: phylogenetic estimates of HIV-1 incidence, incidence reductions, and the proportion of transmissions from individuals in their first 3 months of infection correlated with the true values (Pearson correlation > 90%), with small bias. However, on some simulations, true values were markedly outside reported confidence or credibility intervals. The blinded comparison revealed current limits and strengths in using HIV phylogenetics in challenging settings, provided benchmarks for future methods' development, and supports using the latest generation of phylogenetic tools to advance HIV surveillance and prevention.
Expression of RHAMM and WT1 As Well As T Cell Responses to These Antigens Before and After Allogeneic Stem Cell Transplantation in Patients with Leukemia
Authors: Rosaely Casalegno-Garduño, Claudia Meier, Jiju Mani, Kersten Borchert, Inken Hilgendorf, Yvonne Gross, Anna Filipowska, Dirk Koczan, Alf Spitschak, Michael Linnebacher, Anita Schmitt, Jochen Greiner, Mathias Freund, Brigitte M Püutzer, Michael Schmitt
Journal: Blood (2011)
Treatment and prevention of acute and recurrent ankle sprain: an overview of systematic reviews with meta-analysis
Authors: Cailbhe Doherty, Chris Bleakley, Eamonn Delahunt, Sinead Holden
Journal: British Journal of Sports Medicine (2016)

Ankle sprains are highly prevalent with high risk of recurrence. Consequently, there are a significant number of research reports examining strategies for treating and preventing acute and recurrent sprains (otherwise known as chronic ankle instability (CAI)), with a coinciding proliferation of review articles summarising these reports.To provide a systematic overview of the systematic reviews evaluating treatment strategies for acute ankle sprain and CAI.Overview of intervention systematic reviews.Individuals with acute ankle sprain/CAI.The primary outcomes were injury/reinjury incidence and function.46 papers were included in this systematic review. The reviews had a mean score of 6.5/11 on the AMSTAR quality assessment tool. There was strong evidence for bracing and moderate evidence for neuromuscular training in preventing recurrence of an ankle sprain. For the combined outcomes of pain, swelling and function after an acute sprain, there was strong evidence for non-steroidal anti-inflammatory drugs and early mobilisation, with moderate evidence supporting exercise and manual therapy techniques. There was conflicting evidence regarding the efficacy of surgery and acupuncture for the treatment of acute ankle sprains. There was insufficient evidence to support the use of ultrasound in the treatment of acute ankle sprains.For the treatment of acute ankle sprain, there is strong evidence for non-steroidal anti-inflammatory drugs and early mobilisation, with moderate evidence supporting exercise and manual therapy techniques, for pain, swelling and function. Exercise therapy and bracing are supported in the prevention of CAI.
Long Term Results of Allogeneic Stem Cell Transplant for CML in Pediatric Patients: A Study of 50 Cases Transplanted over 20 Years in a Single Institution.
Authors: Vaneuza A.M. Funke, Claudia Pettengil, Carmem M.S. Bonfim, Jefferson Ruiz, Marco A. Bitencourt, Daniela C. Setubal, Elenaide C. Nunes, Michel M. Oliveira, Ana Paula Azambuja, Denise H. Lima, Keiko T. Kojo, Heliz Regina A. Neves Datamanager, Jose Zanis Neto, Carlos R. Medeiros, Ricardo Pasquini
Journal: Blood (2006)
Long-Term Results of the GIMEMA LAP AIDA 0493 Amended Protocol in Elderly Patients with Acute Promyelocytic Leukemia (APL).
Authors: R. Latagliata, M. Breccia, P. Fazi, M. Vignetti, A. Cupri, M. Sborgia, D. Vincelli, A. Candoni, F. Salvi, S. Rupoli, G. Martinelli, M.G. Kropp, N. Di Rienzo, V. Zampaglione, A. Venditti, L. Melillo, G. Cimino, M.C. Petti, G. Avvisati, F. Lo Coco, F. Mandelli
Journal: Blood (2005)
Asthma--expiratory dyspnoea?
Journal: BMJ (1981)

Industrial bladder cancer SIR,-In a leading article on industrial bladder cancer (27 February, p 614) Robin Glashan claims that evidence from a study by Vineis et al purports to show that engineering workers using lubricating oil are at risk.'The paper by Vineis gives the results of a study into the incidence of larynx, bladder, and infantile tumours occurring among residents of towns in the province of Turin in the period 1965-9 and is in Italian.A careful reading of the paper, and the English abstract, reveals no reference to lubricating oil, greases, or lubricant in any form.I feel it is important to put this correction on record as there is no evidence either from this article or elsewhere that workers using lubricant oils are at any special risk of bladder cancer.
ABVD versus EVAP as first line therapy for Hodgkin’s Lymphoma: Result from a phase III trial
Authors: A. Sharma, S. Bakhshi, V. Raina, S. Thulkar, D. N. Sharma, G. Karthik, L. Kumar
Journal: Journal of Clinical Oncology (2008)

8533 Background: Majority of HL patients can be cured with available protocols. Goal of treatment is to reduce acute and late toxicity without compromising outcome. Earlier we have shown that bleomycin and DTIC in ABVD may be replaced by etoposide and prednisone. Method: We conducted a prospective single center phase III trial to test non-inferiority of EVAP as compared to ABVD as first line therapy. From September 2004 to January 2007, 100 newly diagnosed cases of HL were randomized to ABVD standard doses (Arm A) or EVAP- etoposide 60 mg/m2 infusion day 1–3, vinblastine 6 mg/m2 and doxorubicin 25 mg/m2 both IV day 1 and 8, and prednisone 40 mg/m2 PO day 1- 14 every 4 week (Arm B). IFRT was given to initial bulky sites or residual disease. The endpoints were RR, OS, PFS, and toxicity in 2 groups. Local ethics committee approved the project. Results: One patient in Arm A (n= 51) and 4 patients in Arm B (n=49) didn’t receive treatment and were excluded from analysis. The results are: CR rates 86% (ORR-88%) Vs 80% (ORR 82.2%); on treatment PD 4% Vs 8.9% in arm B. Five patients in arm A (2 lung and 1 cardiac) and 4 patients in arm B (1 cardiac) died of toxicity during treatment. During follow up 6% and 17.8% patients in two arms progressed (p=0.07). With median follow up of 20 months 3 years OS in arm A & B is 86% and 83% respectively (p=0.11) while PFS is 39 months and 29.3 months respectively (p=0.053). Currently 84% and 86.7% patients are alive in arm A and B respectively. Conclusion: This trial has demonstrated that though more patients progressed after EVAP but were able to be salvaged with PBSCT. EVAP may be at least choice of therapy in patients where lung toxicity because of bleomycin is a concern. No significant financial relationships to disclose.
Bevacizumab and gliobastoma of the elderly: A single-center retrospective analysis.
Authors: Eduardo Barrascout, Michele Lamuraglia, Bertrand Baussart, Stephan Gaillard, May Mabro, Aymen Lagha, Rolande Nguefack, Julie Gachet, Christine Theodore
Journal: Journal of Clinical Oncology (2015)

e13060 Background: The primary objective of this study was to determine any difference in progression free survival (PFS), overall survival (OS), clinical benefit and tolerability between elderly and non-elderly patients receiving bevacizumab at recurrence for glioblastoma in a single center. Methods: We retrospectively analyzed 47 patients with recurrent glioblastoma receiving bevacizumab (10 mg/kg every 14 days) between January 2011 and January 2014 in second line. Bevacizumab was introduced for all patients at recurrence after a treatment of first line by temozolomide. A cohort of 19 patients was older than 70 years against 28 patients were under 70 years Results: No statistically significant difference was detected in terms of PFS and OS. PFS was 3.4 months for elderly patients against 5 for non-elderly patients (p > 0.5). OS from recurrence in elderly and non-elderly patients was respectively 6.7 and 4.6 months (p > 0.5). A significant statistical (p = 0.01) improvement of Karnofky Performance Status Scale was observed in young patients. Contrarely, non Karnofky Performance Status Scale was change in ederly patients. Regarding toxicity, 2 of the 19 elderly patients presented hypertension. In younger patients, 7 adverse events have been observed (1 proteinuria, 2 hypertension, 1 hemorrhage and 1 anal abscess). Conclusions: Despite small number of patients in this retrospective study, the efficacy and safety of bevacizumab in recurrent glioblastoma appears similar in elderly and non-elderly patients. However, clinical benefit seemed to be less important in younger patients. A prospective multicentric study integrating geriatric assessment tools and quality of life would be interesting in this patient’s population.
Comparing Non–Vitamin K Oral Anticoagulants
Authors: Anna L. Parks, Rita F. Redberg
Journal: JAMA Internal Medicine (2016)

David J. Graham, MD, MPH; Marsha E. Reichman, PhD; Michael Wernecke, BA; Ya-Hui Hsueh, PhD; Rima Izem, PhD; Mary Ross Southworth, PharmD; Yuqin Wei, MS; Jiemin Liao, MA; Margie R. Goulding, PhD; Katrina Mott, MHS; Yoganand Chillarige, MPA; Thomas E. MaCurdy, PhD; Chris Worrall, BS; Jeffrey A. Kelman, MD, MMSc
Interventions to reduce sedentary behaviour in 0–5-year-olds: a systematic review and meta-analysis of randomised controlled trials
Authors: Katherine L Downing, Jill A Hnatiuk, Trina Hinkley, Jo Salmon, Kylie D Hesketh
Journal: British Journal of Sports Medicine (2016)

To evaluate the effectiveness of behavioural interventions that report sedentary behaviour outcomes during early childhood.Systematic review and meta-analysis.Academic Search Complete, CINAHL Complete, Global Health, MEDLINE Complete, PsycINFO, SPORTDiscus with Full Text and EMBASE electronic databases were searched in March 2016.Inclusion criteria were: (1) published in a peer-reviewed English language journal; (2) sedentary behaviour outcomes reported; (3) randomised controlled trial (RCT) study design; and (4) participants were children with a mean age of ≤5.9 years and not yet attending primary/elementary school at postintervention.31 studies were included in the systematic review and 17 studies in the meta-analysis. The overall mean difference in screen time outcomes between groups was -17.12 (95% CI -28.82 to -5.42) min/day with a significant overall intervention effect (Z=2.87, p=0.004). The overall mean difference in sedentary time between groups was -18.91 (95% CI -33.31 to -4.51) min/day with a significant overall intervention effect (Z=2.57, p=0.01). Subgroup analyses suggest that for screen time, interventions of ≥6 months duration and those conducted in a community-based setting are most effective. For sedentary time, interventions targeting physical activity (and reporting changes in sedentary time) are more effective than those directly targeting sedentary time.Despite heterogeneity in study methods and results, overall interventions to reduce sedentary behaviour in early childhood show significant reductions, suggesting that this may be an opportune time to intervene.CRD42015017090.
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Walther F. Goebel, Oswald T. Avery
Journal: The Journal of Experimental Medicine (1929)

It has been demonstrated that many multiples of minimal doses of Bacillus typhosus reacting factors can be neutralized by specific immune sera. The potency of a given serum can be conveniently titrated against increasing amounts of reacting factors. If the immune serum is diluted or if the amount of the reacting factors is too large for a given amount of serum, there is obtained neutralization but only irregularly. Normal and heterologous sera (therapeutic meningococcus and erysipelas horse sera) free of normal agglutinins or possessing normal agglutinins of a low titer (1:16) for Bacillus typhosus are not able to neutralize the reacting factors. There is obtained questionable neutralization with a serum possessing normal Bacillus typhosus agglutinins in dilution 1:64. The titer of the neutralizing antibodies increases in the course of immunization. Immune sera exercise a definite protection against the mortality induced by intravenous injection of Bacillus typhosus culture filtrates.