tbuckley/cabot-search huggingface dataset:
Review: In COPD, tiotropium improves lung function and reduces adverse events compared with ipratropium bromide
Authors: Diego J. Maselli, Jay I. Peters
Journal: Annals of Internal Medicine (2016)

ACP Journal Club19 January 2016Review: In COPD, tiotropium improves lung function and reduces adverse events compared with ipratropium bromideDiego J. Maselli, MD, Jay I. Peters, MDDiego J. Maselli, MDUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, USA (D.J.M., J.I.P.)Search for more papers by this author, Jay I. Peters, MDUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, USA (D.J.M., J.I.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2016-164-2-006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationCheyne L, Irvin-Sellers MJ, White J. Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015;9:CD009552. https://pubmed.ncbi.nlm.nih.gov/26391969Clinical Impact RatingsGIM/FP/GP: Pulmonology: References1 Barnes PJ. The pharmacological properties of tiotropium. Chest. 2000;117:63S-6S. [PMID: 10673478] Google Scholar2 Salpeter SR, Buckley NS, Salpeter EE. Meta-analysis: anticholinergics, but not beta-agonists, reduce severe exacerbations and respiratory mortality in COPD. J Gen Intern Med. 2006;21:1011-9. [PMID: 16970553] Google Scholar3 Gosens R, Zaagsma J, Meurs H, Halayko AJ. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res. 2006;7:73. [PMID: 16684353] Google Scholar3 Meurs H, Oenema TA, Kistemaker LE, Gosens R. A new perspective on muscarinic receptor antagonism in obstructive airways diseases. Curr Opin Pharmacol. 2013;13:316-23. [PMID: 23643733] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA (D.J.M., J.I.P.)This article was published at Annals.org on 5 January 2016. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 January 2016Volume 164, Issue 2Page: JC6KeywordsAdverse eventsBronchodilatorsChronic obstructive pulmonary diseaseForced expiratory volume in the first second of expirationHospitalizationsLungsMortalityPatientsPneumoniaSteroids ePublished: 19 January 2016 Issue Published: 19 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Photochemical Toxicity: Toxic, Allergic, and Carcinogenic Aspects With Emphasis on Predicting Effects in Humans—an Introduction&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: F. Alan Andersen, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1982)

Photochemical Toxicity: Toxic, Allergic, and Carcinogenic Aspects With Emphasis on Predicting Effects in Humans—an Introduction Get access F. Alan Andersen, Ph.D. F. Alan Andersen, Ph.D. 2Bureau of Radiological Health, Food and Drug Administration, Public Health Service, U.S. Department of Health and Human Services, 8757 Georgia Ave. (HFK-300), Silver Spring, Md. 20910. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 1, July 1982, Pages 151–152, https://doi.org/10.1093/jnci/69.1.151 Published: 01 July 1982
Assessment of lipids and bone-derived resorption products during neoadjuvant therapy with anastrozole (A), v tamoxifen (T), v combination (C) in the IMPACT trial
Authors: I. E. Smith, M. Dowsett
Journal: Journal of Clinical Oncology (2004)

675 Background: Estrogen has a beneficial effect on lipid metabolism and decreased estrogen levels have been associated with a decrease in bone mineral density. The IMPACT trial evaluated neoadjuvant therapy with A, T or C in postmenopausal women with estrogen receptor-positive breast cancer. During the study an assessment was made of the comparative effects of these treatments on serum lipids and bone resorption. Methods: Non-fasting clotted blood samples were taken at baseline and at 3 months. Total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were measured using a timed end-point method on a Synchron CX9. Non-HDL cholesterol levels (N-HDL-C) were calculated. Bone resorption was measured using serum CrossLaps (CTX) One Step ELISA. Estradiol was measured by radioimmunoassay (RIA). Results: Percentage changes in parameters from baseline (using † arithmetic mean; †† geometric mean) are given in the table. Conclusions: The beneficial effects of T on lipids were as expected. Following 3 months treatment with A there was a significant increase in HDL-C, but there was no significant effect on TC. A increased bone resorption, in contrast to T, but there was no significant correlation between the mean % change (from baseline to 3 months) of estradiol and CTX in any of the treatment groups. This suggests either that estrogen levels are only one of the factors affecting bone metabolism in postmenopausal women, or that 3 months is too short a period to assess bone markers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Clinical benefit in oncology trials: Is this a patient-centered or tumor-centered endpoint?
Authors: P. Ohorodnyk, E. A. Eisenhauer, C. M. Booth
Journal: Journal of Clinical Oncology (2009)

6564 Background: Clinical benefit (CB) was first successfully used as an endpoint in 1997 in the pivotal study of gemcitabine in advanced pancreas cancer. In the trial by Burris et al (J Clin Oncol. 1997) CB was a composite measure of pain, performance status, and weight. Here we describe how CB has been used in oncology trials since that time. Methods: We performed an electronic search ( www.jco.org ) for reports of all clinical trials (phase I, II, III) published in the Journal of Clinical Oncology 1997–2008 citing ‘clinical benefit.‘ Eligible trials were those reporting clinical benefit as an endpoint. Details related to study methodology, sponsorship, and endpoints were abstracted. Use of CB was classified as patient-centered if it referred to improvement in the clinical parameters used by Burris et al or in other disease-related symptoms. CB was classified as tumor-centered if it related to objective tumor criteria for partial/complete response and/or stable disease. Descriptive statistics were used to summarize findings and the chi-square test used to compare proportions. Results: 71 trials reporting CB as an endpoint were identified: 37 in breast, 8 in pancreas, and 26 in other cancers. The definition of CB was patient-centered in 21 trials (30%) and tumor-centered in 50 trials (70%). Only 20% (14/71) of trials (including all 8 pancreas studies) used the original Burris definition. In the second half of the study period there was an increase in the number of trials using CB as an endpoint (17 to 54 trials) and in the proportion of trials with a tumor-centered definition (10/17, 59% to 41/54, 76%, p = 0.09). Study variables associated with the use of a tumor-centered definition include: disease site (breast 35/37, 95%; all others 16/34, 47%, p &lt; 0.001) and intervention (hormone or targeted agent 38/40, 95%; chemotherapy 13/31, 42%, p &lt; 0.001). There was no association with sponsorship (industry 41/56, 73%; non-industry 10/15, 67%, p = 0.86) or phase of trial (phase I/II 36/48, 75%; phase III 15/23, 65%, p = 0.56). Conclusions: Despite its initial definition, clinical benefit is often used to describe objective tumor findings. Clinical trials should use endpoints in a consistent manner to enable clear communication between investigators, clinicians, and patients about the benefit of novel therapies. No significant financial relationships to disclose.
Abstract 20885: A Novel Mechanism for Cardiac Abnormal Automaticity: Orai-Linked Calcium Signaling
Authors: Paul E Wolkowicz, Jian Huang, Patrick K Umeda, Edlue Tabengwa, Hernan E Grenett, Ferdinand Urthaler
Journal: Circulation (2010)

Objective: The plasma membrane Orai proteins permit cell calcium entry in response to calcium store depletion. We address whether the heart contains these voltage-independent calcium channels & whe...
Diethylaminoethyl-Dextran and Uptake of Nucleic Acids by Mammalian Cells2
Authors: Ellen Borenfreund, Mildred Steinglass, Grace C. Korngold, Aaron Bendich
Journal: JNCI Journal of the National Cancer Institute (1973)

Diethylaminoethyl-dextran did not enter mammalian cells in culture under conditions in which it strongly enhanced uptake of polynucleotides. The polyamine was labeled with tritium, and its interaction with cells in vitro, in the presence or absence of DNA, was followed by autoradiography.
Gemcitabine and oxaliplatin followed by paclitaxel and carboplatin as first line therapy for patients with advanced epithelial ovarian cancer. A phase II trial of sequential doublets. (GO-FIRST)
Authors: K. Chrystal, C. B. Steer, K. A. Cheong, E. Galani, A. Strickland, F. Lofts, C. Gallagher, H. Thomas, P. Harper
Journal: Journal of Clinical Oncology (2004)

5034 Background: Gemcitabine and oxaliplatin are active in epithelial ovarian cancer with minimal overlapping toxicity, and in pre-clinical studies have shown synergy. The primary objective of this prospective phase II study is to evaluate the response rate (RR) and toxicity of gemcitabine and oxaliplatin (GO) administered sequentially with paclitaxel and carboplatin (PC). Secondary objectives were time to progression, quality of life outcomes and overall survival. Methods: Patients with histologically proven epithelial ovarain cancer, FIGO stage II-IV, measurable disease (RECIST), and PS 0–2 were eligible. Treatment consisted of gemcitabine 1250mg/m2 D1, D8 and oxaliplatin 135mg/m2 D8 q21days for 4 cycles followed by carboplatin AUC6 and paclitaxel 175mg/m2 D1 q21days for 4 cycles. Interval debulking was permitted after 4 cycles. Results: 20 patients are enrolled. Median age 62 yrs (range 39–78), FIGO III-IV (16/4). 12/20 pts were only able to have an initial biopsy and of these, 7 were subsequently debulked. 4 cycles of GO were given prior to the planned 4 cycles of PC. The RR to 4 cycles of GO was 80% (CR4/PR12). With subsequent debulking surgery and further chemotherapy (PC) the final RR was 85% (13 CR/4 PR). One pt died of a PE and one progressed on GO and died. At a median F/U of 21 mths 15 pts are still alive, 6 without progression. The median TTP was 15.2 mths. Grade 3/4 toxicities for GO: nausea and vomiting 4pts (20%), neutropenia 4pts (20%). PC: alopecia 14 (70%), neutropenia 2 (10%), thrombocytopenia 1 (5%). Peripheral neuropathy was the major toxicity. 4 pts developed G2 and a further 1pt G3 on GO. With sequential PC, 8 pts developed G2 and 5 pts G3 neuropathy requiring dose reduction in 3 pts and cessation of paclitaxel in 6 pts. Conclusions: GO is a new doublet with activity in ovarian cancer, but sequential PC should not be used given the cumulative neurotoxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly
Relative Efficiencies of the Fitch-Margoliash, Maximum-Parsimony, Maximum-Likelihood, Minimum-Evolution, and Neighbor-joining Methods of Phylogenetic Tree Construction in Obtaining the Correct Tree
Authors: Naruya Saitou, Tadashi Imanishi
Journal: Molecular Biology and Evolution (1989)

The relative efficiencies of several tree-making methods for obtaining the correct phylogenetic tree were studied by using computer simulation.The methods examined were the Fitch-Margoliash (FM), maximum-parsimony (MP), maximumlikelihood (ML), minimum-evolution (ME), and neighbor-joining (NJ) methods.We simulated the evolutionary changes of six DNA sequences each with a length of either 300 or 600 nucleotides.Both constant and varying rates of nucleotide substitution were considered.The DNA sequences generated were used to reconstruct phylogenetic trees by applying the five tree-making methods, and the trees obtained were compared with the model (correct) tree.This process was repeated 50 times for each case, and the following results were obtained: ( 1) The efficiency of obtaining the correct tree for the FM method was considerably lower than those for the other methods.(2) The NJ and ME methods showed a high performance in obtaining the correct tree, and their relative efficiencies were similar to each other.( 3) For distance methods (NJ, FM, and ME), the results obtained by using corrected nucleotide substitutions were much better than those obtained by using nucleotide differences when the rate of substitution varied greatly among different branches.(4) The ML method was slightly inferior to the NJ and ME methods when a constant rate of nucleotide substitution was assumed, but it was slightly better than the latter two methods when the evolutionary rate varied drastically among branches.If one considers the computational time involved, the NJ method seems to be a method of choice.1.
Objective improvement in lung cancer patient care by the development of a multidisciplinary clinic (MDC) in the community
Authors: W. Mayfield, R. Bordoni, R. Holder, M. Waldman, A. Muster, M. McLaughlin, R. Hermann
Journal: Journal of Clinical Oncology (2006)

17086 Background: Medical resources allocated to lung cancer management are limited, scattered and uncoordinated, resulting in sub-optimal care. The MDC offers patients access to multi-disciplinary care (Pulmonary Medicine, Thoracic Surgery, Medical and Radiation Oncology) to operate in an efficient, cost effective way. Methods: 2004 Cancer Registry data on time to treatment (TTT) for lung cancer was 53 days. A project with the primary endpoint of reducing the TTT from 53 to 30 days was designed. Secondary endpoints were improvement in treatment planning; enhancement in clinical trials referral, and patient satisfaction. On 9/15/05 the MDC open its doors. The project was assigned to this clinic including patients with solitary lung nodules, lung, esophageal, and mediastinal cancers, mesothelioma, and other thoracic malignancies. Results: 54 pts were seen in the first 90 days; median age 60 (range 41–82), 29 males; 32 (59%) lung cancer (94% NSCLC), 8 (15%) esophageal cancer, 6 other diagnosis, and 6 abnormal radiological findings without diagnosis. The TTT of 30 evaluable patients is 26.36 days. Of the 30 NSCLC the TNM stage was: 4 IA, 5 IB, 2 each IIA/IIB, 8 (27%) IIIA, 3 (10%) IIIB, and 6 (20%) IV. Fifteen of the cases had pathologic staging. Out of 9 pts with cstage I, 7 (78%) had definitive surgery; 4 pts confirmed to have pstage IB, were evaluated for adjuvant chemo. Four pts with cstage II had surgery, 2 of them adjuvant chemo. Of the 11 pts with cstage III, 5 (46%) received concurrent CHRT, 1 (stage IIIA) underwent surgery f/b chemo, 2 received chemo alone and 2 refused therapy. Out of 6 pts with stage IV, 5 (83%) received systemic therapy. Conclusions: The TTT of 26.36 days represents a 50.26% improvement from our institutional benchmark of 53 days. Updated and expanded data on our project primary and secondary endpoints will be presented at the meeting. No significant financial relationships to disclose.
Central venous access port devices (cvapds) for cancer patients placed by medical oncologist at the oncology day hospital (odh). A prospective study
Authors: J. M. Campos, O. Juan Vidal, A. Albert, V. Caranyana, I. Rico, J. Flores, J. L. Arce
Journal: Journal of Clinical Oncology (2004)

8247 Background: To assess the efficacy, safety and indications of ambulatory CVAPDs implanted by medical Oncologist at ODH. Methods: A prospective study of cancer pts who requiring during the evolution of their disease a CVAPDs. Ports were implanted via subclavian vein to out-patients at the ODH bed under local anaesthesia, without fluoroscopic guidance, by the Medical Oncologists. Chest radiography was performed after the implantation. Results: One hundred forty consecutive cancer patients received implantable ports (Healthport®) at the ODH between January 2001 and October 2003. ECOG: 0 (14 pts), 1 (99 pts), 2 (25 pts), 3 (2 pts). Median age was 58.5 years (range 29–82). 78 were male. Diagnostic: 65 pts (46.4%) had colo-rectal cancer, 18 pts (12.8%) gastric cancer, 14 pts (10%) breast cancer, 8 pts (5,7%) lung cancer 6 pts (4,2%) esophagous cancer, 5 pts (3.5%) head and neck cancer and 24 pts (17,14%) other cancers such as ovary, bladder, sarcomas… Complications: \(\underline{\mathrm{During\ device\ insertion\ (15{\%})}}\): arterial puncture 6, local hematomas 4, insertion difficulty 6, local irritation 3, and pneumothorax < 5% 2 pts. \(\underline{\mathrm{Mechanical\ (5,7{\%})}}\): catheter tip malposition 3, thrombosis 3, drug extravasation 1, flexura catheter 1. \(\underline{\mathrm{Device-related\ infections\ (4,2{\%})}}\): Subcutaneous port pocket infections 3, phlebitis 1, and port-related bacteremia by coagulasa-negative Staphylococcus aureus in 2. \(\underline{\mathrm{Device\ was\ removal\ in}}\) 7 occasions (5%), 3 due to thrombosis and 3 due to infection and 1 due to patient's request after end of treatment. One patient died of documented Staphylococcus aureus infection despite device was removed. Conclusions: CVAPDs implanted by oncologist in out-patients is safe, efficient (no room surgery is required and hospitalization can be avoided) and confortable for the patients. Very few serious complications during the insertion and during chemotherapy administration were observed. Removal was due to thrombosis in 3 patients and infection in 2. Patients, as well as hospital staff were satisfed about the easy implantation of these devices No significant financial relationships to disclose.
Timing of adjuvant chemotherapy by menstrual cycle phase and risk of secondary amenorrhea in women with early breast cancer: Preliminary results
Authors: A. Alimonti, S. Di Cosimo, G. Ferretti, P. Carlini, P. Papaldo, A. Fabi, A. Gelibter, I. Sperduti, L. Di Lauro, F. Cognetti
Journal: Journal of Clinical Oncology (2004)

780 Background: Chemotherapy-induced amenorrhea (CIA), with resulting infertility and prolonged exposure to risks and symptoms of menopause, has been receiving increasing attention in recent years. Our purpose was to characterize the factors associated with CIA and examine whether the phase of menstrual cycle at chemotherapy start can affect the rate of CIA in premenopausal early breast cancer women. Methods: CIA was defined as the cessation of menses for at least 3 months during or soon after chemotherapy. Menstrual phase was defined as days 1–6; follicular phase as days 7–14; luteal phase as days 15–20 and premenstrual phase as days 21–28. Type and duration of adjuvant therapy were recorded. Results: Among 88 premenopausal patients, univariate analysis showed no significant correlation between CIA and age, tumor size, number of axillary nodes, stage of disease and receptor status. CIA occurred in 45% and 47% of patients receiving intravenous CMF (Cyclophosphamide 600 mg/m2, Methotrexate 40 mg/m2, 5-Fluorouracil 600 mg/m2 days 1 and 8 q 28 x 6 cycles) and FEC/EC respectively (5-Fluorouracil 600 mg/m2, Epirubicin 75 mg/m2, Cyclophosphamide 600 mg/m2 day 1 q 21 x 6 cycles/Epirubicin 90 mg/m2, Cyclophosphamide 600 mg/m2 day 1 q 21 x 4 cycles)(p=0.88), with a median time to onset of 85.5 (range 42–140) and 52.6 (range 21–84) days (p=0.15), respectively. Women aged less than 40 years or more than or equal to 40 years developed CIA on average after 2.8 and 3.1 courses, respectively (p=0.71). The duration of chemotherapy (more or less than 6 courses) affected neither the rate nor the time of CIA development. The incidence of CIA was higher for patients treated in the follicular phase rather than in the other menstrual cycle phases (68% and 43%, p=0.02). By multivariate analysis this difference reached values close to statistical significance (p=0.06). Conclusions: An enhanced ability to predict the likelihood of CIA may facilitate decision-making facing the tradeoffs between beneficial and detrimental effects of adjuvant therapy, especially in young patients with good prognosis. The final results will be presented at the meeting. No significant financial relationships to disclose.
Management of testicular neoplasms in France and compliance with national guidelines.
Authors: S. Culine, S. Hoppe, C. Hennequin, M. Saves, N. Mottet
Journal: Journal of Clinical Oncology (2010)

4580 Background: Testicular neoplasms (TN) are uncommon and curable tumors with standardized treatment. Guidelines are available. Treatments may lead to adverse effects (long-term severe toxicities, secondary cancer), occurring among young men. Our aim was to describe the primary TN management in France and to evaluate compliance with the national guidelines. Methods: Cases of TN diagnosed in 2003-2004 were identified from 11 general official exhaustive cancer registries. A detailed medical chart was used to collect individual data on tumor description and management. National guidelines published in 2002 were used as reference (Progrès en Urologie 2002;12:71-78). A conformity list was defined by a group of experts. Each criterion could be in accordance with the recommendations, severely noncompliant (disagreement with the recommendations with a potential impact on outcome), marginally noncompliant (no effect on patient outcome) and noncompliant but justifiable (noncompliance explained by patient or tumor characteristics). Results: 256 patients with testicular seminoma (TS) and 197 with testicular nonseminoma (TNS) were included: 69% had a stage I, 16% a stage II, 16% a stage III and 11% an undetermined one. Globally only 10% of patients with TS and 12% with TNS received a totally conform management (all stages combined). When restricting to therapeutic steps only, conformity to standard guideline was 44% and 28% respectively for TS and TNS. Most severe noncompliance are summarized in the Table. Conclusions: Based on exhaustive French cancer registries, the real-life TN management is quite disappointing, specially for pretherapeutic step, surveillance for TNS, chemotherapy for TNS and TS and post chemotherapy surgery. This study highlights the need for larger guidelines diffusion on every contributor (pathologist, urologist, medical oncologist and radio-oncologist). It might also be considered as a plea for patients’ centralization in reference centers. TS TNS Tumor markers at diagnosis 40% 33% Histology report 35% 46% Radiotherapy 31% / Chemotherapy 62% 58% Active surveillance only / 95% Postchemotherapy lymph node dissection / 70% No significant financial relationships to disclose.
A Phase 2 Study Of Brentuximab Vedotin In Patients With Relapsed Or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results In Patients With DLBCL and Other B-Cell Lymphomas
Authors: Nancy L. Bartlett, Jeff P. Sharman, Yasuhiro Oki, Ranjana H. Advani, Celeste M. Bello, Jane N. Winter, Yin Yang, Dana A. Kennedy, Eric D. Jacobsen
Journal: Blood (2013)
Phase III Study of Palbociclib in Combination with Exemestane Vs. Capecitabine, in Hormonal Receptor (Hr) Positive/Her2 Negative Metastatic Breast Cancer (Mbc) Patients with Resistance to Non-Steroidal Aromatase Inhibitors (Nsai): Pearl Study (Geicam/2013-02_Cecog/Bc.1.3.006)
Authors: M. Martin, S. Beslija, E. Carrasco, Z. Kahan, M.J. Escudero, I. Láng, C.H. Bartlett, B. Bermejo, M. Inbar, J.I. Chacón, D.C. Jinga, J.A. García-Sáenz, J.La De Haba, M. Koehler, S. Morales, J.M. Gil, A. Antón, M. Ruiz-Borrego, L. Murillo, C. Zielinski
Journal: Annals of Oncology (2014)