tbuckley/cabot-search huggingface dataset:
Phase I clinical and pharmacologic study of eniluracil plus fluorouracil in patients with advanced cancer.
Authors: R L Schilsky, J Hohneker, M J Ratain, L Janisch, L Smetzer, V S Lucas, S P Khor, R Diasio, D D Von Hoff, H A Burris
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the highest dose of fluorouracil (5-FU) that could be safely administered with Eniluracil (776C85; Glaxo Wellcome Inc, Research Triangle Park, NC), an inactivator of dihydropyrimidine dehydrogenase (DPD), on a daily schedule for 5 days, and to define the toxicities of the combination and the pharmacokinetics of 5-FU when administered with 776C85. PATIENTS AND METHODS Patients with advanced solid tumors refractory to standard therapy were enrolled at two institutions. The study consisted of three periods designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of 776C85 alone (period 1); the effects of 776C85 on the pharmacokinetics of 5-FU (period 2); and the maximum-tolerated dose (MTD) of 5-FU, with or without leucovorin, that could be safely administered with 776C85 (period 3). Cohorts of at least three patients each received oral 776C85 alone at doses of 3.7 mg/m2/d, 18.5 mg/m2/d and 0.74 mg/m2/d. After a 14-day washout period, each patient then received 776C85 daily for 3 days, with a single intravenous (i.v.) bolus dose of 5-FU 10 mg/m2 on day 2. After a second washout period, patients were treated with 776C85 daily for 7 days and 5-FU i.v. bolus on days 2 through 6. The starting dose of 5-FU 10 mg/m2/d was escalated until the MTD was determined. After determination of the MTD of 5-FU given with 776C85, oral leucovorin 50 mg/d on days 2 through 6 was added to determine the MTD of 5-FU with leucovorin in the presence of 776C85. Near the completion of the study, additional cohorts of patients were treated with 776C85 at 50 mg/d and oral 5-FU with or without leucovorin. RESULTS Sixty-five patients were enrolled onto the study and 60 were assessable for toxicity and response. Bone marrow suppression was the primary and dose-limiting toxicity of this regimen. Other toxicities included diarrhea, mucositis, anemia, anorexia, nausea, vomiting, and fatigue. 776C85 suppressed DPD activity in peripheral-blood mononuclear cells (PBMCs) by at least 90% for at least 24 hours at all dose levels tested. In the presence of 776C85, 5-FU half-life was prolonged, clearance was reduced, and the drug displayed linear pharmacokinetics. Recommended doses for further testing on a daily for 5-day schedule are 776C85 10 mg/d with i.v. 5-FU 25 mg/m2/d; 776C85 10 mg/d with i.v. 5-FU 20 mg/m2/d plus leucovorin 50 mg/d; 776C85 50 mg/d with 5-FU given orally at 15 mg/m2/d with leucovorin at 50 mg/d. CONCLUSION 5-FU can be safely administered with 776C85; however, the MTDs are considerably lower than those conventionally used, caused, at least in part, by marked alterations in 5-FU plasma pharmacokinetics.
A Retrospective Single Institution Study Evaluating Clinical Outcome and Prognostic Markers for Endometrial and Ovarian Carcinosarcomas (Cs)
Authors: U.S. Asghar, G. Imseeh, A.A. Kirkwood, M. Widschwendter, A. Olaitan, N. Macdonald, T. Mould, M. McCormack, A. Mitra, J.A. Ledermann, R. Arora, R. Kristeleit
Journal: Annals of Oncology (2014)
Association of metabolic syndrome with reduced survival among men receiving androgen deprivation therapy for nonmetastatic prostate cancer.
Authors: Sarah Maria Rudman, Kathryn P. Gray, Julie Kasperzyk, Michael Pitt, Edward Giovannucci, Massimo Loda, Lorelei Mucci, Christopher Sweeney
Journal: Journal of Clinical Oncology (2012)

56 Background: The metabolic syndrome (MS) is a set of risk factors implicated in both the development of prostate cancer (PC) and as a recognized complication of androgen deprivation therapy (ADT). In our previous study of a Veterans’ Administration (VA) cohort of relapsed PC patients (pts) on ADT, MS was associated with a shorter duration of PC control. Methods: We studied 347 patients (72 from VA and 275 from Health Professionals Follow up Study) treated with ADT for non-metastatic PC. 88% for biochemical relapse post definitive local therapy and 12% treated with primary ADT. MS was assessed by the modified Adult Treatment Panel III criteria prior to the commencement of ADT. Cox models tested for association between MS status and time to overall survival (OS) or time to PC specific survival, stratified by cohorts (VA vs. HPFS). Cumulative incidence of PC specific death (accounting for competing risk of death from other causes and co-morbidities) by MS status was estimated. Results: 96 patients (28%) had MS. 62 patients (18%) died of PC during a median follow-up of 9.5 years. The median OS for patients with and without MS was 7.5 and 10.6 years respectively. A multivariate Cox model adjusted for age at start of ADT, diagnosis, stage, Gleason score and primary treatment showed MS was associated with a significant 53% increased risk of death from any cause (HR(95%CI) 1.53(1.05-2.22); p=0.03). MS patients tended to have increased risk of PC specific death (HR(95%CI) 1.6 (0.9-2.84); p=0.11). Individual MS components hypertension, dyslipidemia, obesity and diabetes were not associated with an increased risk of death from any cause or PC. The cumulative incidence of PC specific death did not differ by MS status. Conclusions In men receiving ADT for androgen dependent PC without metastases, the presence of MS at the commencement of ADT is associated with an increased risk of death compared to those pts without MS. The shorter time to death appears to be at least in part due to shorter time to dying from PC.
Abstract 16122: The iHeartchange Website Targeting Transitioning Patients with Congenital Heart Disease: Feasibility Outcomes
Authors: Adrienne H Kovacs, Luke J Burchill, Geraldine Cullen-Dean, Jeanine L Harrison, Jennifer Stinson, Krista N Gruenwald, Candice K Silversides, Erwin N Oechslin
Journal: Circulation (2012)

Introduction: AHA guidelines recommend initiatives to improve the rate of transfer and quality of transition of patients with congenital heart disease (CHD) from pediatric to adult cardiac care. However, (a) there are few published interventions for transitioning patients with CHD, (b) strategies for effectively engaging adolescents are unknown, and (c) proposed initiatives (e.g., transition clinics) are often resource intensive. We thus developed and evaluated the feasibility of a website (iHeartChange) targeting the needs of transitioning CHD patients. Methods: All patients transferring from a pediatric to adult CHD program in a 1-year period were invited to participate in a study by mail and telephone. Feasibility outcomes, in terms of eligibility and participation rates as well as patient acceptance of the website intervention, are reported. Results: A total of 207 CHD patients aged 16-19 were transferred in 1 year, of whom 187 (mean age = 17.7 years, 58% male, 75% with defects of moderate/great compl...
A phase I study of GTI-2040 (G), an antisense to ribonucleotide reductase (RNR), in combination with high-dose AraC (HiDAC) in acute myeloid leukemia (AML)
Authors: G. Marcucci, R. B. Klisovic, W. Wei, S. Liu, P. Paschka, L. Huynh, J. A. Zwiebel, J. C. Byrd, M. R. Grever, K. Chan, W. Blum
Journal: Journal of Clinical Oncology (2006)

6561 Background: RNR converts ribonucleotides to deoxyribonucleotides for DNA synthesis. AraC is converted into AraC triphosphate (AraCTP) and competes with deoxycytidine for DNA incorporation. We hypothesized that RNR downregulation by G leads to lower deoxycytidine levels, preferential AraCTP incorporation into DNA and increased cytotoxicity. A CTEP-sponsored Phase I dose escalation study of G +HiDAC in relapsed / refractory AML tested this hypothesis. Methods: Cohort I (18–59 yrs) received G (dose level (DL) 1: 3.5 mg/m 2 /d) by continuous IV infusion (CIVI) on d 1–6 + AraC IV q12 hrs on d 2, 4, 6 (DL1: 2500 mg/m 2 /dose). Cohort II (≥60 yrs) received G CIVI on d 1–6 +AraC IV on d 2 −6 (DL1: 1500 mg/m 2 /d). An ELISA-based assay measured plasma and intracellular concentration (IC) of G. Results: To date, cohort I included 9 pts with relapsed and 9 with refractory AML; 9 had intermediate and 9 adverse risk cytogenetics (CyG); 8 received prior HiDAC. Cohort II included 10 pts with relapsed and 6 with refractory AML; 8 pts had intermediate and 8 high risk CyG; 5 pts received prior HiDAC. Toxicities were comparable to HiDAC alone. The younger pts had higher AUC and longer t 1/2 . Of 16 pts evaluable in cohort I (median time to 1st relapse 6 mos), 6 had complete remission (CR) and 1 incomplete CR (no disease and incomplete blood count recovery). In cohort II, no responses were observed. At 120 hrs of antisense infusion, median G IC in marrow cells was higher (i.e., 175 vs75 nM) in younger than in older pts. A median 50% decrease in RNR protein was noted in 5/9 and 5/10 pts in cohort I and II, respectively. In cohort I, a median 50% decrease and 200% increase in RNR was noted in CR (n=4) and non-responder (NR; n=9) pts, respectively. In cohort II R2 downregulation did not predict response. In cohort I 62% of the ICs was in nucleus and 21.2% in cytoplasm in CR pts (n=3) vs. 20.3% and 53.5% in NR pts(n=5). Conclusions: G/HiDAC is feasible. Robust plasma and IC levels of G and target downregulation are achievable in vivo. Responses (41%) were observed only in the younger cohort, where CR pts had higher G nuclear IC and target downregulation than NR pts. Dose escalation continues in the younger cohort to establish a dose for Phase II trials. No significant financial relationships to disclose.
App helps to improve contraception uptake in rural India
Authors: Cheryl Travasso
Journal: BMJ (2016)

A smartphone app that uses videos to tackle concerns about—and illustrate the benefits of—family planning has improved the uptake of contraceptives among women in rural India, researchers from the Johns Hopkins Center for Communication Programs have found.

The research, presented at the International Conference on Family Planning in Nusa Dua, Indonesia, on 28 January, found that women in Bihar who had watched the videos were 4.5 times more likely to use contraceptive methods such as intrauterine devices, injectable contraceptives, or oral contraceptive pills.

The app, called Gyan Jyoti, or “light of …
Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas
Authors: J. Moon, J. Kim, S. Sohn, D. Yang, J. Lee, H. Kim, H. Shin, J. Chung, W. Lee, Y. Joo, S. Oh
Journal: Journal of Clinical Oncology (2007)

8069 Background: The present study was conducted to evaluate the safety and efficacy of alemtuzumab plus CHOP chemotherapy for patients with peripheral T-cell lymphomas (PTCLs). Methods: Twenty patients with newly diagnosed PTCLs were enrolled. The treatment consisted of classical CHOP plus alemtuzumab (10 mg/m 2 i.v on day 1 and 20 mg/m 2 i.v on day 2 in the first cycle, then 30 mg/m 2 i.v on day 1 in the subsequent cycles) based on 3-week intervals. Results: Thirteen complete responses (65.0%) and 3 partial responses (15.0%) were confirmed, giving an overall response rate of 80.0 %. The estimated event-free survival at 1 year was 43.3%. The most severe hematologic adverse event was neutropenia, which occurred with a grade 4 intensity in 18 patients (90.0%). Plus, febrile neutropenia was observed in 11 patients (55.0%). Five patients (25%) experienced CMV (cytomegalovirus) reactivation, while 3 patients developed CMV diseases, such as pneumonitis or retinitis. There were 2 treatment-related deaths. Conclusions: The alemtuzumab plus CHOP chemotherapy seemed to produce active antitumor activity in terms of the complete response rates in patients with PTCLs. However, since high infectious and hematologic toxicities were observed, careful monitoring and early treatment to prevent treatment-related mortality are needed. No significant financial relationships to disclose.
Family perspectives on aggressive cancer care near the end of life.
Authors: Alexi A. Wright, Nancy Lynn Keating, John Ayanian, Elizabeth A. Chrischilles, Katherine Leslie Kahn, Christine Ritchie, Craig Earle, Mary Beth Landrum
Journal: Journal of Clinical Oncology (2015)

6517 Background: Advanced cancer patients are receiving increasingly aggressive medical care near death, despite growing concerns that the use of hospital-based services at the end of life (EOL) reflects poor quality of care. Methods: We surveyed bereaved family members of 1,159 older patients participating in the Cancer Care Outcomes Research and Surveillance study (CanCORS; a national, prospective, observational cohort study) who were diagnosed with or recurred with advanced lung or colorectal cancer, and who died by 2011. We assessed whether bereaved family members’ perceptions of the quality of patients’ EOL care were associated with claims-based measures of aggressive medical care before death, adjusted for patients’ demographic and clinical characteristics, mental illness, and treatment preferences. Results: Bereaved family members of patients who enrolled in hospice ≥ 3 days before death (n = 601) were more likely to report excellent quality of EOL care compared with those who enrolled later or did not receive hospice care (n = 558; adjusted proportion: 58.5% vs. 42.7%, P < 0.001). In contrast, family members of patients admitted to the ICU within 30 days of death (n = 153) were less likely to report excellent quality of EOL care than those who were not (n = 1,006; adjusted proportion 44.4% vs. 52.9%, P = 0.03), as were family of patients who died in the hospital (n = 467; adjusted proportion 41.8% vs. 57.1%, P < 0.001). Frequent use of the emergency department in the last month of life was not associated with lower family-reported ratings of EOL care quality (n = 92 with ≥ 2 visits; adjusted proportion 50.5% vs. 50.9%, P = 0.79); nor was the receipt of chemotherapy within 2 weeks of death (n = 77; adjusted proportion 48.7% vs. 51.1%, P = 0.80). Conclusions: Our findings suggest that efforts to improve earlier hospice enrollment, reduce ICU admissions at the EOL, and avoid terminal hospitalizations are important to improve the quality of cancer care and families’ experiences. While existing quality measures characterize the repeated use of emergency visits and chemotherapy near death as poor quality care, we could not detect a difference in family ratings of care by these measures.
Evolution of behavior disorders into adolescence
Authors: A Thomas, S Chess
Journal: American Journal of Psychiatry (1976)

The New York longitudinal study has followed the development of 136 subjects from infancy into adolescence. The authors report the distribution of diagnoses and outcome of 43 children who developed behavior problems before the adolescent period and the characteristics of 5 new cases diagnosed in adolescence and discuss issues of prediction. The analysis of the longitudinal data for subjects with and without behavior disorders permits discussion of two of the general issues in the literature: the significance of adolescent turmoil and the distinctness of adolescence as a developmental stage.
Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study
Authors: Liping Hou, Urs Heilbronner, Franziska Degenhardt, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Raffaella Ardau, Bárbara Arias, Lena Backlund, Claudio E M Banzato, Antoni Benabarre, Susanne Bengesser, Abesh Kumar Bhattacharjee, Joanna M Biernacka, Armin Birner, Clara Brichant-Petitjean, Elise T Bui, Pablo Cervantes, Guo-Bo Chen, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Scott R Clark, Francesc Colom, David A Cousins, Cristiana Cruceanu, Piotr M Czerski, Clarissa R Dantas, Alexandre Dayer, Bruno Étain, Peter Falkai, Andreas J Forstner, Louise Frisén, Janice M Fullerton, Sébastien Gard, Julie S Garnham, Fernando S Goes, Paul Grof, Oliver Gruber, Ryota Hashimoto, Joanna Hauser, Stefan Herms, Per Hoffmann, Andrea Hofmann, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Nina Lackner, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G Leckband, Carlos A López Jaramillo, Glenda MacQueen, Mirko Manchia, Lina Martinsson, Manuel Mattheisen, Michael J McCarthy, Susan L McElroy, Marina Mitjans, Francis M Mondimore, Palmiero Monteleone, Caroline M Nievergelt, Markus M Nöthen, Urban Ösby, Norio Ozaki, Roy H Perlis, Andrea Pfennig, Daniela Reich-Erkelenz, Guy A Rouleau, Peter R Schofield, K Oliver Schubert, Barbara W Schweizer, Florian Seemüller, Giovanni Severino, Tatyana Shekhtman, Paul D Shilling, Kazutaka Shimoda, Christian Simhandl, Claire M Slaney, Jordan W Smoller, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Sarah K Tighe, Alfonso Tortorella, Gustavo Turecki, Julia Volkert, Stephanie Witt, Adam Wright, L Trevor Young, Peter P Zandi, James B Potash, J Raymond DePaulo, Michael Bauer, Eva Z Reininghaus, Tomas Novák, Jean-Michel Aubry, Mario Maj, Bernhard T Baune, Philip B Mitchell, Eduard Vieta, Mark A Frye, Janusz K Rybakowski, Po-Hsiu Kuo, Tadafumi Kato, Maria Grigoroiu-Serbanescu, Andreas Reif, Maria Del Zompo, Frank Bellivier, Martin Schalling, Naomi R Wray, John R Kelsoe, Martin Alda, Marcella Rietschel, Francis J McMahon, Thomas G Schulze
Journal: The Lancet (2016)
Abstract MP032: Greater Physical Activity Assessed by Accelerometry is Associated with Favorable Adipokine Profile in the Community: Cross-sectional Observations from The Framingham Third Generation Cohort
Authors: Nicole L Glazer, Kerrie Nelson, Lisa M Sullivan, Joanne M Murabito, Ramachandran S Vasan
Journal: Circulation (2012)

Background: Adipokines, produced by adipose tissues, contribute to the development of obesity-related metabolic traits. It is unclear, however, if greater physical activity favorably affects cardiometabolic profiles by influencing levels of key adipokines. We related physical activity, as measured by accelerometry, to circulating levels of novel adipokines, including retinol binding protein-4 (RBP4), adipocyte-fatty acid binding protein (A-FABP), adiponectin, leptin and leptin-receptor (LEP-R), in a large community-based sample. Methods: We evaluated 2063 participants in the 3rd generation Framingham Heart Study cohort (mean age 47 years, 55% female) who underwent objective assessment of moderate-to-vigorous physical activity (MVPA) by an accelerometer. MVPA was measured in total minutes, and in bouts ≥10 minutes (MVPA10) and nonbouts (MVPA&lt;10 minutes). Blood adipokine levels were log-transformed and related to MVPA, using separate regression models for each adipokine, adjusted for age, sex, smoking, and season. Results: On average, participants engaged in 28 minutes/day of MVPA, 19 minutes/day of nonbout MVPA and 9 minutes/day of MVPA10. Mean adipokine levels were 40.7 ± 10.7 ng/ml for RBP-4, 18.6 ± 10.3 ng/ml for A-FABP, 11.4 ± 12.9 ng/ml for leptin, 19.6 ± 8.6 ng/ml for LEP-R, and 8.7 ± 5.5 ng/ml for adiponectin. Total MVPA, as well as MVPA10 and nonbout MVPA, were inversely related to leptin and A-FABP and positively associated with levels of adiponectin (See Table). The directionality of the observed associations - positive for adiponectin and negative for leptin and A-FABP- were consistent with greater physical activity being related to a more favorable cardiometabolic profile. Conclusions: In our cross-sectional study of a large community-based sample, both bout and nonbout MVPA were significantly related to a favorable adipokine profile. Additional longitudinal observations are warranted to assess if physical activity influences cardiometabolic health through alterations in adipokine levels.
Is a punch biopsy reliable in subtyping basal cell carcinoma? A systematic review
Authors: D.J. Kadouch, A. van Haersma de With, J. Limpens, A.C. van der Wal, A. Wolkerstorfer, M.W. Bekkenk, M.A. de Rie
Journal: British Journal of Dermatology (2016)

Basal cell carcinoma (BCC) is the most prevalent type of skin cancer. Numerous studies have reported on the rising incidence of BCC causing a major burden on current health care systems (1) . Current management relies on the histopathological subtype of a punch biopsy and this becomes more and more relevant due to the increasing use of non-surgical treatments. However the reliability of a punch biopsy in subtyping BCC has been questioned. The aim of this systematic review was to judge the reliability of a punch biopsy in accurately subtyping primary BCC. This article is protected by copyright. All rights reserved
Platinum-based combination chemotherapy in the treatment of older non-small cell lung cancer (NSCLC) patients (pts): Is there a role for Complete Geriatric Assessment (CGA)? Final results from the prospective multicenter NVALT-3 study
Authors: M. Wymenga, B. Biesma, A. Vincent, O. Dalesio, H. Groen
Journal: Journal of Clinical Oncology (2009)

e20547 Background: Nearly 50% of NSCLC pts are aged over 70 years, but only few receive combination chemotherapy. CGA is often advocated to assess the benefits and risks of chemotherapy in older pts. Methods: A total of 182 NSCLC pts ≥ 70 years with stage IIIb/IV disease were randomized to 4 cycles carboplatin/gemcitabine (CG) or carboplatin/paclitaxel (CP). Primary endpoint was change in QoL at week18. At baseline, CGA was performed with nine different tests. Toxicity (tox) was scored using NCI-CTC v2. Tox related outcomes were defined as all grade III/IV tox, SAEs, ≥ grade II neurological or neuropsychiatric (NP) tox and the ability to finish all cycles. Relationship of CGA and QoL scores with tox endpoints were investigated. Results: Median age was 74 yrs (70–87). PS was 0 in 30%, 1 in 54% and 2 in 17%. Median OS was 8.6 mo (95% CI, 7.2–10.2) for CG and 6.9 mo (95% CI, 5.6–10.0) for CP. Median PFS was 4.7 mo (95% CI, 3.9–5.8) for CG and 4.5 mo (95% CI, 4.1–5.3) for CP. One year survival was 29% (95% CI, 21–41%) for CG and 23% (95% CI, 16–35%) for CP. There was no difference in the change in global QoL between arms. Quality-adjusted survival curves were not different. PS was prognostic, but not different for both arms. Pts with better Activities of Daily Living (ADL), instrumental ADL, or physical functioning were more likely to finish all chemotherapy cycles. Pts with worse emotional or role functioning or Geriatric Depression Score were more likely to experience NP tox. None of the CGA or QoL summary scores were associated with the occurrence of the other tox endpoints at p&lt; 0.01. Conclusions: Carboplatinum based combination chemotherapy in older NSCLC pts is feasible. The choice for adding paclitaxel or gemcitabine to carboplatin cannot be made based on effects on QoL. CGA predicts toxicity to a limited extent but does not add substantial information to PS. No significant financial relationships to disclose.