tbuckley/cabot-search huggingface dataset:
Abstract 3730: Feasibility of office hysteroscopy for evaluation of women with postmenopausal bleeding and association with improved pathological diagnosis
Authors: Jacquelyn M. Shaw, Sukrant Mehta, Scott Chudnoff, Mark Levie, Mark H. Einstein, Gary L. Goldberg, Nicole S. Nevadunsky
Journal: Cancer Research (2015)

Abstract Objectives: Endometrial sampling is critical in the evaluation of women for cancers of the uterine corpus. Hysteroscopy in the operating room is associated with monetary and time expense to the patient and health care system. The purpose of this study was to compare histopathological diagnoses of endometrial biopsies obtained by office hysteroscopy (OH) versus endometrial pipelle (EP). Methods: After IRB approval, records of all women with ICD-9 diagnosis (627.1) for postmenopausal bleeding who had OH attempted in the last 5 years at a single medical institution were evaluated. Demographic data collected included age, BMI, medical comorbidities, and histopathologic diagnosis. “Inadequate tissue” for pathologic evaluation was defined as stated in the pathology report or absence of endometrial tissue on biopsy specimen. Statistical analysis was performed using chi-square and Fisher's exact testing with SPSS software. Results: 85 OHs were attempted and 50 had prior attempted EPs. 98% of OHs and 94% of EPs were successfully performed. However, adequate pathology was obtained in 93% of OHs verses 38% of EPs (p&amp;lt;0.01). Median age was 61 years (range 48-85) and median BMI was 32 kg/m2 (range 19-71). 5% had a BMI&amp;lt;25. The prevalence of diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease were 32%, 74%, 44%, and 21% respectively. There was a significant difference in pathologic diagnoses between OH and EP (p &amp;lt;0.01). Six patients were diagnosed with endometrial hyperplasia, and 3 with endometrial cancers by OH that were not identified by EP. Conclusions: OH is a feasible procedure that may enhance clinicians’ ability to diagnose benign, pre-malignant and malignant causes of post-menopausal bleeding. Further research is needed to understand the association of cost and quality of life with OH versus hysteroscopy in the operating room. Table 1.Pathology findings from OH vs. EPPathologyOffice Hysteroscopy (OH)%Endometrial Pipelle Biopsy (EP)%n = 79n = 19Endometrial Cancer34%00%Endometrial Hyperplasia68%00%Benign Endometrium1924%1053%Atrophic Endometrium45%421%Benign Endometrial Polyp4759%526% Citation Format: Jacquelyn M. Shaw, Sukrant Mehta, Scott Chudnoff, Mark Levie, Mark H. Einstein, Gary L. Goldberg, Nicole S. Nevadunsky. Feasibility of office hysteroscopy for evaluation of women with postmenopausal bleeding and association with improved pathological diagnosis. [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 3730. doi:10.1158/1538-7445.AM2015-3730
A randomized phase III Trial of low dose versus intermediate dose interferon alfa (IFN) as front-line therapy in advanced progressive renal cell cancer (RCC)
Authors: N. M. Tannir, X. Wang, C. S. Ng, V. A. Poulter, P. Mathew, A. O. Siefker-Radtke, E. Jonasch, L. C. Pagliaro, L. Cohen, R. E. Millikan
Journal: Journal of Clinical Oncology (2004)

4607 Background: IFN has modest clinical efficacy in RCC but its optimal dose/schedule have not been determined. In vivo, low doses of IFN, given twice daily (bid), produce more potent anti-angiogenic effect and superior anti-tumor activity than higher doses given less frequently. Methods: We conducted a phase III trial to evaluate the progression-free survival (PFS), response rate (RR), toxicity and quality of life (QOL) in patients (pts) with RCC. All pts were stratified into favorable, intermediate or poor-risk groups [Motzer, JCO 17(8): 2530–40, 1999] and were randomized to receive IFN at 0.5 million units (MU) subcutaneously (sc) bid (LD2), or 5 MU sc daily (ID1). Pts completed measures of QOL (FACT-BRM) and depression (CES-D) at baseline and 8 wks after the start of IFN. Results: Of a planned accrual of 120 pts (60 per arm), results are reported for 108 pts (55 received LD2and 53 received ID1). Overall median PFS was 3.4 mos (95% C.I., 2.0–4.0). For LD2 and ID1,median PFS was 3.6 and 2.9 mos, respectively (p= .47). There was also no statistically significant difference in PFS between LD2 and ID1 within each prognostic group, but a statistically significant difference in PFS emerged among the 3 prognostic groups. Median PFS was 5.9, 2.4 and 1.8 mos, for favorable, intermediate, and poor-risk groups, respectively (p = .002). The overall 6-mo PFS was 27%. The overall RR was 7.4% (1 durable CR + 2 PR with LD2,5 PR with ID1, p = .48). There were 20 dose-limiting toxic events associated with LD2 and 37 with ID1. Fewer pts receiving LD2 required dose reduction compared with pts receiving ID1 (7.3% vs 32.1%, p = .001). Pts who received LD2 reported significantly better QOL and fewer symptoms of depression than pts who received ID1 (adjusted means: FACT-BRM, 124.5 vs 105.5, p < .005; CES-D, 12.0 vs 17.7, p < .0001). Twice as many pts receiving ID1met the clinical screening criteria for depression than did pts who received LD2(65.5% vs 34.5%, p < .01). Conclusions: The RR and PFS observed with LD2 and ID1in this trial were similar. The lower toxicity and better QOL favor the use of LD2 when designing combinations of IFN and novel targeted agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Novartis Amgen; Astra-Zeneca; Celera; Genentech; IDEC Pharmaceuticals; Imclone Systems; Incoite Pharmaceuticals; Johnson & Johnson; Merck; Millenium; Pfizer; Schering-Plough
Genome‐Wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians
Authors: Michelle S. Yau, Laura M. Yerges‐Armstrong, Youfang Liu, Cora E. Lewis, David J. Duggan, Jordan B. Renner, James Torner, David T. Felson, Charles E. McCulloch, C. Kent Kwoh, Michael C. Nevitt, Marc C. Hochberg, Braxton D. Mitchell, Joanne M. Jordan, Rebecca D. Jackson
Journal: Arthritis & Rheumatology (2016)

A major barrier to genetic studies of osteoarthritis (OA) is the need to obtain large numbers of individuals with standardized radiographic evaluations for OA. To address this gap, we performed a genome-wide association study (GWAS) of radiographically defined tibiofemoral knee OA in 3,898 cases and 3,168 controls from 4 well-characterized North American cohorts, and we performed replication analysis of previously reported OA loci.We performed meta-analysis using a 2-stage design. Stage 1 (discovery) consisted of a GWAS meta-analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and the Johnston County Osteoarthritis Project. Knee OA was defined as definite osteophytes and possible joint space narrowing or total joint replacement in one or both knees. Stage 2 (validation) was performed in the Multicenter Osteoarthritis Study and the Genetics of Osteoarthritis study. We genotyped lead meta-analysis variants (P ≤ 1 × 10-4 ) from stage 1 and tested the association between these variants and knee OA. We then combined results from all cohorts in a meta-analysis.Lead variants from stage 1, representing 49 unique loci, were analyzed in stage 2; none met genome-wide significance in the combined analysis of stage 1 and stage 2. We validated 1 locus (rs4867568 near LSP1P3) with nominal significance (P < 0.05), which was also our top finding in the combined meta-analysis (odds ratio [OR] 0.84 [95% confidence interval (95% CI) 0.79-0.91], P = 3.02 × 10-6 ). We observed nominally significant associations (P < 0.05) with 3 previously reported OA loci: rs143383 in GDF5 (OR 1.12 [95% CI 1.04-1.21], P = 2.13 × 10-3 ), rs835487 in CHST11 (OR 0.93 [95% CI 0.85-0.99], P = 0.03), and rs8044769 in FTO (OR 1.10 [95% CI 1.03-1.19], P = 6.13 × 10-3 ).These findings provide suggestive evidence of a novel knee OA locus and confirm previously reported associations in GDF5, CHST11, and FTO.
Cost-effectiveness of rituximab maintenance therapy for patients with follicular lymphoma: The Spanish perspective
Authors: J. Gómez Codina, M. Provencio, A. Rueda, F. Capote, F. Carbonell, E. Conde, J. Fernandez Rañada, P. Giraldo, E. Rios, C. Varela
Journal: Journal of Clinical Oncology (2007)

8092 Background: In patients with relapsed or refractory follicular lymphoma (FL) who attain a response with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or Rituximab + CHOP, maintenance treatment with Rituximab has shown to significantly improve overall survival (OS) (85% at 3 years vs. 77%, p=0.011) and progression free survival (PFS) (51,5 vs. 14.9 months, p&lt;0.001) as compared to observation alone (OA). We analyzed the cost-effectiveness, from a Spanish perspective, of Rituximab maintenance therapy (375mg/m 2 every 3 months until progression or for 2 years) versus OA according to the population and data described for the European Organization for Research Treatment of Cancer (EORTC) 20981 study (van Oers MHJ Blood 2006). Methods: Incremental cost-effectiveness was assessed through a deterministic, three health states model (disease-free, progression and death) transition model. Base case model: PFS and OS were extrapolated from EORTC 20981 data using a Weibull distribution, Rituximab maintenance benefit was assumed to last 5 years, 10 years time horizon, 3.5% discount rate on costs and benefits, and Spanish National Health Service perspective (direct costs only). Resource use was estimated from a Spanish expert panel and EORTC 20981 study. Unit costs were obtained from local databases (May 2006 €). Health states utility values were derived from an ad hoc study. Sensitivity analyses were performed for all mentioned variables. Results: For the base case, more quality-adjusted life years (QALY), life-years (LY) and progression-free survival years per patient on maintenance therapy were obtained versus OA (incremental values of 0.85, 0.94 and 1.46, respectively). Total cost per patient was higher with Rituximab than with OA (+8,026€). Incremental cost per QALY gained was 9,358€, with a cost per LY gained of 8.493€ and a cost per PFS year gained of 5,485€. In the sensitivity analysis, values ranged between 7.263€ and 22.160€ per QALY gained. Conclusions: This study confirms that in patients with relapsed /refractory FL who attain a response with further therapy, maintenance treatment with Rituximab compared to observation alone is cost-effective. No significant financial relationships to disclose.
Ixazomib, an oral proteasome inhibitor, induces rapid mobilization of hematopoietic progenitor cells in mice
Authors: Armin Ghobadi, Michael P. Rettig, Matthew S. Holt, Julie K. Ritchey, Krista Kennerly, Ezhilarasi Chendamarai, Linda Eissenberg, John F. DiPersio
Journal: Blood (2018)
胃消化管間質腫瘍(GIST):新しく提案されたUICC TNMシステムは,NIHのコンセンサス基準よりも優れた予後機能を提供するか?
Authors: Yi Ha Woo, OH Seung Jong, Hong Jenny Jimmy, Kim Dae Hoon, Choi Min Gew, Noh Jae Hyung, Sohn Tae Sung, Bae Jae Moon, Kim Sung
Journal: Annals of Oncology (2011)
Canada releases documents showing secrets of tobacco industry
Journal: BMJ (1999)

Canada's health minister, Allan Rock, has released 1200 pages of documents from a six million page tobacco industry cache in Guildford, England, that show how tobacco companies used advertising to get young people to smoke and investigated ways to encourage people addicted to tobacco to continue smoking.

Canadian health officials, who travelled last May to British American Tobacco's Guildford headquarters, examined documents relating to Imperial Tobacco, a subsidiary of the company and Canada's largest tobacco firm. The documents were housed in a depository established in 1998 …
A Markov model to evaluate cost-effectiveness of the PARP inhibitor, olaparib, for fourth-line treatment of recurrent ovarian cancer.
Authors: Juliet Elizabeth Wolford, Jiaru Bai, Ramez Hassef Eskander, Robin Keller, Lindsey Minion, John K. Chan, Bradley J. Monk, Krishnansu Sujata Tewari
Journal: Journal of Clinical Oncology (2016)

5563 Background: Evaluate cost-effectiveness of olaparib, an oral PARP inhibitor, which unlike many other drugs administered via IV infusion, is outside the sphere of Medicare coverage. Methods: With the exception of olaparib, only IV drugs approved for recurrent ovarian cancer were studied, including platinum-based, non-platinum, and bevacizumab-based regimens. Registration trial data was reviewed to estimate toxicity and PFS rates for the different agents. Medicare data for 2015 was used to determine the costs of IV chemotherapy as well as for managing toxicities, infusions, and supportive care. A Markov model was created in TreeAge Pro 2015. Nodes in the Markov chain allowed patients to transition through response, hematological complications, non-hematological complications, progression, and death. Incremental cost-effectiveness ratios (ICER) were calculated for each group. Survival for ovarian cancer was reported in quality adjusted life months, with the adjustment occurring from a baseline of having recurrent ovarian cancer during a given month. Results: Platinum-based combinations were most cost-effective at $1,672/PFS mo as compared to non-platinum agents ($6,688/mo), olaparib ($10,291/mo), and bevacizumab-containing regimens ($12,482/mo). By adding $81,108 prior to progression, costs associated with olaparib therapy were 5.3X more than platinum-based combinations. When using 4th line data, the only positive ICER using 4th line data was for non-platinum drugs ($35,567 extra cost for 1 PFS month). Using probability adjusted to 2ndline olaparib treatment, olaparib’s ICERs’ are $5,225 for bevacizumab, $16,347 for non-platinum, and $51,935 for platinum treatment. Conclusions: Despite an uncommonly high 34% response rate among germline BRCA+ patients with measurable, recurrent ovarian cancer, the high cost of olaparib was not balanced by costs of infusion and managing toxicities of IV drugs typically associated with 20% RR and hypothetically shorter time to progression in the 4th line setting. Reconciliation of incremental clinical benefits with new cost prohibitive therapies remains problematic.
Combination Melphalan and Bortezomib Conditioning with Autologous Hematopoietic Stem Cell Support in Patients with Advanced Multiple Myeloma. A Phase I/II Study.
Authors: Scott D. Rowley, David Siegel, Michele L. Donato, Andrew L. Pecora, Tatyana Feldman, Stuart Goldberg, Andre Goy, Aisha Masood
Journal: Blood (2009)
A randomized and double‐blind controlled trial evaluating the safety and efficacy of rituximab for warm auto‐immune hemolytic anemia in adults (the RAIHA study)
Authors: Marc Michel, Louis Terriou, Francoise Roudot‐Thoraval, Mohamed Hamidou, Mikael Ebbo, Guillaume Le Guenno, Lionel Galicier, Sylvain Audia, Bruno Royer, Anne‐Sophie Morin, Jean Marie Michot, Arnaud Jaccard, Laurent Frenzel, Mehdi Khellaf, Bertrand Godeau
Journal: American Journal of Hematology (2016)

This Phase 3 multicentre randomized double‐blind and placebo‐controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously received corticosteroids for less than 6 weeks could be included. At inclusion, all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, and then tapered according to a pre‐defined recommended reduction scheme. Besides prednisone, eligible patients received 2 infusions of RTX or placebo at a fixed dose of 1,000 mg 2‐week apart. The primary endpoint was overall response rate (complete response [CR] + partial response [PR]) in an intent‐to‐treat (ITT) analysis at 1 year. A total of 32 patients (17 females [53%], mean age at inclusion 71 ± 16 years) were enrolled and randomized. In all, 27 patients were followed for at least 1 year and their data were evaluable for response. With an ITT analysis, the overall response rate at 1 year was 75% [95%CI: 47.6‐92.7] with 11 CR and 1 PR with RTX versus 31% [11.0‐58.7] (5 CR) with placebo ( P = 0.032). At 2 years, 10/16 patients with RTX versus 3/16 with placebo still showed CR ( P = 0.011). Overall, eight severe infections occurred during follow‐up, six with placebo and two with RTX ( P = 0.39). At 2 years, six patients with placebo had died, but none with RTX ( P = 0.017). Compared to placebo, RTX combined with prednisone may be effective and safe for treating newly‐diagnosed wAIHA in adults. Am. J. Hematol. 92:23–27, 2017. © 2016 Wiley Periodicals, Inc.
PTH-254 Unexpected findings in magnetic resonance enterography (MRE) and their clinical significance: Abstract PTH-254 Table 1
Authors: S Ravindran, N Barlow, A Dunk, D Howlett
Journal: Gut (2015)

The clinical and pathological features of five sporadic cases of enteric infection caused by Escherichia coli O157 (enterohaemorrhagic or Vero cytotoxin-producing E coli showed a range of features. These included one case with pseudomembranous colitis, one with an acute exacerbation of ulcerative colitis, and three with enterocolitis. Diagnostic difficulties encountered initially in four of the five cases were finally resolved by correlating the results of microbiological with histopathological investigations. In view of the heterogeneity of clinical and histological signs and symptoms, it is concluded that all patients with abdominal pain and diarrhoea or rectal bleeding should have early microbiological investigation.
Targeting Hypoxic Prostate Tumors Using the Novel Hypoxia-Activated Prodrug OCT1002 Inhibits Expression of Genes Associated with Malignant Progression
Authors: Heather Nesbitt, Niall M. Byrne, S. Nicole Williams, Louise Ming, Jenny Worthington, Rachel J. Errington, Laurence H. Patterson, Paul J. Smith, Stephanie R. McKeown, Declan J. McKenna
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To understand the role of hypoxia in prostate tumor progression and to evaluate the ability of the novel unidirectional hypoxia-activated prodrug OCT1002 to enhance the antitumor effect of bicalutamide. Experimental Design: The effect of OCT1002 on prostate cancer cells (LNCaP, 22Rv1, and PC3) was measured in normoxia and hypoxia in vitro. In vivo, tumor growth and lung metastases were measured in mice treated with bicalutamide, OCT1002, or a combination. Dorsal skin fold chambers were used to image tumor vasculature in vivo. Longitudinal gene expression changes in tumors were analyzed using PCR. Results: Reduction of OCT1002 to its active form (OCT1001) decreased prostate cancer cell viability. In LNCaP-luc spheroids, OCT1002 caused increased apoptosis and decreased clonogenicity. In vivo, treatment with OCT1002 alone, or with bicalutamide, showed significantly greater tumor growth control and reduced lung metastases compared with controls. Reestablishment of the tumor microvasculature following bicalutamide-induced vascular collapse is inhibited by OCT1002. Significantly, the upregulation of RUNX2 and its targets caused by bicalutamide alone was blocked by OCT1002. Conclusions: OCT1002 selectively targets hypoxic tumor cells and enhances the antitumor efficacy of bicalutamide. Furthermore, bicalutamide caused changes in gene expression, which indicated progression to a more malignant genotype; OCT1002 blocked these effects, emphasizing that more attention should be attached to understanding genetic changes that may occur during treatment. Early targeting of hypoxic cells with OCT1002 can provide a means of inhibiting prostate tumor growth and malignant progression. This is of importance for the design and refinement of existing androgen-deprivation regimens in the clinic. Clin Cancer Res; 23(7); 1797–808. ©2016 AACR.
Efficacy and safety of paclitaxel and carboplatin with bevacizumab for the first-line treatment of patients with nonsquamous non-small cell lung cancer (NSCLC): Analyses based on age in the phase III PointBreak and E4599 trials.
Authors: Corey J. Langer, Mark A. Socinski, Jyoti D. Patel, Alan Sandler, Joan H. Schiller, Larry Leon, Shailaja Uttamsingh, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2013)

8073 Background: A post hoc analysis of NSCLC (pts) ≥70 y in the pivotal E4599 trial found increased adverse events (AEs) and numerically decreased survival benefit associated with bevacizumab (BEV) vs pts &lt;70 y. We evaluated the efficacy and safety of BEV by age in pts in a pooled dataset from the E4599 and PointBreak (PB) trials. Methods: Pts randomized to the PC (paclitaxel and carboplatin ) + BEV arms of E4599 and PB received P 200 mg/m 2 , C AUC 6, and BEV 15 mg/kg q3w for 6 (E4599) or 4 (PB) cycles; 1 pt in PB received 6 cycles. Eligible pts received maintenance BEV q3w until disease progression or unacceptable toxicity. Overall survival (OS), progression-free survival (PFS), and safety were assessed in pts grouped according to age (&lt;65 y, 65–75 y, 70–75 y, &lt;75 y, and ≥75 y). Pt-level data from the PC + BEV arms of E4599 and PB were pooled and compared with data from pts in the PC-alone arm of E4599. Results: PB and E4599 randomized 467 pts and 434 pts to PC + BEV, respectively. Baseline characteristics were balanced between age groups. OS and PFS hazard ratios (HRs) and increases in grade ≥3 AEs for the pooled pt cohort relative to E4599 PC-alone arm are shown (Table). Outcomes were similar in pts &lt;70 y and ≥70 y, and data from the pooled population were similar to those seen in each individual trial (data not shown). Conclusions: In a pooled exploratory analysis of pt data from E4599 and PB, the statistically significant benefit associated with the addition of BEV to PC appeared consistent across all age groups &lt;75y. Pts ≥75 y receiving BEV had a higher incidence of grade ≥3 AEs relative to PC alone with no statistically significant survival benefit, although an increase in grade ≥3 AEs was observed in all age groups. Clinical trial information: NCT00762034 and NCT00021060. [Table: see text]
Antidepressant treatment during breast-feeding
Authors: K L Wisner, J M Perel, R L Findling
Journal: American Journal of Psychiatry (1996)

The primary purpose of this article is to review critically the literature about use of antidepressants during lactation. Strategies for the clinical management of depressed breast-feeding mothers are also suggested.The authors conducted a computerized search of MEDLINE for articles. The review includes studies in which serum levels of drugs were obtained from nursing infants.Fifteen published reports were located that provided information for the following nine antidepressants: amitriptyline, nortriptyline, desipramine, clomipramine, doxepin, dothiepin, fluoxetine, sertraline, and bupropion.Amitriptyline, nortriptyline, desipramine, clomipramine, dothiepin, and sertraline were not found in quantifiable amounts in nurslings, and no adverse effects were reported. Therefore, these are the drugs of choice for breast-feeding women. Adverse effects were described in some young infants whose mothers had been treated with doxepin or fluoxetine during breast-feeding. The collective serum level data suggest that infants older than 10 weeks are at low risk for adverse effects of tricyclics, and there is no evidence of accumulation. Research needs include an expanded database of mother-baby serum levels, behavioral assessments of infants during nursing, and longitudinal developmental evaluation of nurslings. Prescription of an antidepressant for a breast-feeding woman is a case-specific risk-benefit decision.