tbuckley/cabot-search huggingface dataset:
Upfront combination therapy: does the AMBITION study herald a new era in the treatment of pulmonary arterial hypertension?
Authors: Steven D Nathan, Paul A Corris
Journal: Thorax (2015)

A new treatment paradigm for pulmonary arterial hypertension (PAH) has emerged, heralded by the recently published results of the AMBITION study in a recent issue of the New England Journal of Medicine .1 While the practice of combination therapy is not new, this has previously been implemented in a sequential fashion. The AMBITION study is the first study comparing the use of upfront combination therapy in patients with treatment-naive incident PAH who were randomised to therapy with ambrisentan plus tadalafil versus ambrisentan or tadalafil monotherapy. The results were initially presented at the European Respiratory Society meeting in September 2014 with the primary publication in the New England Journal of Medicine in August 2015.1

The primary efficacy endpoint of the AMBITION study was time to first clinical failure (TTCF) defined as either death, hospitalisation for worsening PAH, disease progression (>15% decline in 6 min walk test (MWT) from baseline with WHO functional class III or IV symptoms) or unsatisfactory clinical response (WHO functional class III symptoms while in the study for at least 6 months with a decrease in 6 MWT distance from baseline). The latter three events were all adjudicated and multiple secondary endpoints, including change in the 6 min walk distance, were also evaluated. There were 610 patients enrolled in the study of whom 500 constituted the primary analysis set (PAS).1 The other 105 patients were excluded from the PAS after a protocol amendment aimed at excluding those patients with risk factors for left ventricular diastolic dysfunction. Patients were randomised in a 2:1:1 fashion to upfront combination therapy or monotherapy with ambrisentan or tadalafil. The study demonstrated unequivocally that upfront combination therapy was indeed superior to monotherapy with either single agent based on the selected end points of the study. The HR for TTCF for combination therapy compared with the …
Sex or survival: trade-offs between quality and quantity of life.
Authors: P A Singer, E S Tasch, C Stocking, S Rubin, M Siegler, R Weichselbaum
Journal: Journal of Clinical Oncology (1991)

Patients with localized prostate cancer may be treated with either surgery (radical prostatectomy) or radiotherapy. Although controversial, many physicians believe that surgery offers a higher survival rate. However, the surgical treatment may also produce a higher rate of sexual impotency. Our study assessed how men value survival and sexual potency when asked to trade off one for the other. Using the treatment-choice technique, we interviewed 50 men aged 45 to 70 years without known prostate cancer. At hypothetical rates of survival (90% at 5 years for surgery) and impotency (90% for surgery and 40% for radiotherapy) representing published estimates, 32% of respondents were unwilling to trade off any survival, but 68% were willing to trade off a 10% or greater advantage in 5-year survival (by choosing radiotherapy) to maintain sexual potency. The median 5-year survival traded off was 10% (range, 0% to 80%). Willingness to trade off survival for sexual potency was significantly related to level of education, but not to age, interest in sex, frequency of sexual intercourse, or ability to achieve erection. We conclude that some men may choose treatment with lower long-term survival to increase their chance of remaining sexually potent. Because these men may be difficult to identify in clinical practice, physicians should thoroughly discuss both surgery and radiotherapy options with patients who have localized prostate cancer.
The calculation of received dose intensity.
Authors: W M Hryniuk, M Goodyear
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.12.1935 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2230885 The calculation of received dose intensity. W M HryniukxW M HryniukSearch for articles by this author , M GoodyearxM GoodyearSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.12.1935 First Page PDF © 1990 by American Society of Clinical Oncology
Injected nanocrystals for targeted drug delivery
Authors: Yi Lu, Ye Li, Wei Wu
Journal: Acta Pharmaceutica Sinica B (2016)

Nanocrystals are pure drug crystals with sizes in the nanometer range. Due to the advantages of high drug loading, platform stability, and ease of scaling-up, nanocrystals have been widely used to deliver poorly water-soluble drugs. Nanocrystals in the blood stream can be recognized and sequestered as exogenous materials by mononuclear phagocytic system (MPS) cells, leading to passive accumulation in MPS-rich organs, such as liver, spleen and lung. Particle size, morphology and surface modification affect the biodistribution of nanocrystals. Ligand conjugation and stimuli-responsive polymers can also be used to target nanocrystals to specific pathogenic sites. In this review, the progress on injected nanocrystals for targeted drug delivery is discussed following a brief introduction to nanocrystal preparation methods, i.e., top-down and bottom-up technologies.
Vaccination Against Poliomyelitis with Live Virus Vaccines--6
Authors: D. S. Dane, G. W. A. Dick, M. Briggs, R. Nelson, J. McAlister, J. H. Connolly, M. Haire, F. McKeown, C. M. B. Field
Journal: BMJ (1961)

Many countries using inactivated (Salk) poliovirus vaccine on a large scale have been maintaining a continuing field surveillance of vaccine safety.If and when these countries embark on programmes involving the use of oral poliovirus vaccines they will almost cer- tainly wish to conduct a similar type of surveillance.The assessment of field safety of live virus vaccines is com- plicated by the fact that oral vaccines are infectious and therefore the safety of the vaccine to contacts of vaccinees and to the community as a whole requires consideration.This would be particularly true in countries which chose a gradual introduction of live vaccine in preference to, mass " area feeding " where the opportunities for vaccine virus spread would be more limited.Knowledge of the changes which occur in the character of the vaccine viruses after human passage is essential for laboratories assisting in surveil- lance work, because they may be required to distinguish between naturally occurring viruses and viruses of vaccine origin.In this trial of Sabin type II oral poliovirus vaccine we have attempted to define some of the more common changes which occur in the virus after human passage. Materials and MethodsVaccine Virus.-Sabintype II attenuated vaccine virus was obtained through the Medical Research Council's Poliomyelitis Vaccines Committee.The virus was stored at -300 C. and diluted in Earle's salt solution just prior to use.Both the original vaccine virus and the human-passage vaccine virus which was fed *The five.previous papers on "Vaccination Against Polio- myelitis with Live Virus Vaccines " were as follows.(1) " Trial of TN Type II Vaccine " (Dane et al., Brit.med.
Abstract 8947: Preoperative Anemia is an Independent Predictor of Postoperative Mortality and Adverse Cardiac Events in Elderly Patients Undergoing Elective Vascular Operations
Authors: Prateek K Gupta, Himani Gupta, Abhishek Sundaram, Jason N MacTaggart, Jason M Johanning, Xiang Fang, R. Armour Forse, Marcus Balters, G. Matthew Longo, Jeffrey T Sugimoto, Thomas G Lynch, Iraklis I Pipinos
Journal: Circulation (2012)

Background: Preoperative anemia is associated with adverse outcomes after cardiac surgery, but its association with postoperative outcomes after open and endovascular procedures is not well established. Elderly patients have a decreased tolerance to anemia and are at high risk for complications after vascular procedures. The objective of this study was to assess the impact of preoperative anemia (hematocrit&lt;39%) on postoperative 30-day mortality and adverse cardiac events in patients ≥65 years of age undergoing elective vascular procedures. Methods and Results: Patients (n=31,857) were identified from the American College of Surgeons' 2007-09 National Surgical Quality Improvement Program (NSQIP) - a prospective, multicenter (&gt;250) database maintained across the United States. The primary and secondary outcomes of interest were 30-day mortality and a composite end point of death or cardiac event (cardiac arrest or myocardial infarction), respectively. Forty-seven percent of the study population was anemic. Anemic patients had a postoperative mortality and cardiac event rate of 2.4% and 2.3% in contrast to the 1.2% and 1.2%, respectively, in patients with hematocrit within the normal range (p&lt;0.0001). On multivariate analysis, we found a 4.2% (95% confidence interval, 1.9%-6.5%) increase in the adjusted risk of 30-day postoperative mortality for every percentage point of hematocrit decrease from the normal range. Conclusions: The presence and degree of preoperative anemia are independently associated with 30-day death and adverse cardiac events in patients ≥ 65 years undergoing elective open and endovascular procedures. Identification and treatment of anemia should be an important component of preoperative care for patients undergoing vascular operations.
Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction
Authors: James S. Meabon, Bertrand R. Huber, Donna J. Cross, Todd L. Richards, Satoshi Minoshima, Kathleen F. Pagulayan, Ge Li, Kole D. Meeker, Brian C. Kraemer, Eric C. Petrie, Murray A. Raskind, Elaine R. Peskind, David G. Cook
Journal: Science Translational Medicine (2016)

Ventral regions of the cerebellum in combat veterans and mice are vulnerable to long-term traumatic brain injury caused by repetitive blast exposure.
Identification and isolation of high avidity tumor-specific CD8 T cells by experimentally assessing pMHC-TCR binding parameters with soluble pMHC complexes
Authors: Julien Schmidt, Michael Hebeisen, Philippe Guillaume, Morgane Magnin, Nathalie Rufer, Immanuel Luescher
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive transfer of high avidity tumor-specific CD8 T cells is a promising treatment for late stage cancers. Because most tumor antigens are self-antigens, tumor-specific T cells typically express low affinity T cell antigen receptors (TCR) due to thymic negative selection, which
Acute Gastroenteritis on Cruise Ships — United States, 2008–2014
Authors: Amy L. Freeland, George H. Vaughan, Shailendra N. Banerjee
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

From 1990 to 2004, the reported rates of diarrheal disease (three or more loose stools or a greater than normal frequency in a 24-hour period) on cruise ships decreased 2.4%, from 29.2 cases per 100,000 travel days to 28.5 cases (1,2). Increased rates of acute gastroenteritis illness (diarrhea or vomiting that is associated with loose stools, bloody stools, abdominal cramps, headache, muscle aches, or fever) occurred in years that novel strains of norovirus, the most common etiologic agent in cruise ship outbreaks, emerged (3). To determine recent rates of acute gastroenteritis on cruise ships, CDC analyzed combined data for the period 2008-2014 that were submitted by cruise ships sailing in U.S. jurisdiction (defined as passenger vessels carrying ≥13 passengers and within 15 days of arriving in the United States) (4). CDC also reviewed laboratory data to ascertain the causes of acute gastroenteritis outbreaks and examined trends over time. During the study period, the rates of acute gastroenteritis per 100,000 travel days decreased among passengers from 27.2 cases in 2008 to 22.3 in 2014. Rates for crew members remained essentially unchanged (21.3 cases in 2008 and 21.6 in 2014). However, the rate of acute gastroenteritis was significantly higher in 2012 than in 2011 or 2013 for both passengers and crew members, likely related to the emergence of a novel strain of norovirus, GII.4 Sydney (5). During 2008-2014, a total of 133 cruise ship acute gastroenteritis outbreaks were reported, 95 (71%) of which had specimens available for testing. Among these, 92 (97%) were caused by norovirus, and among 80 norovirus specimens for which a genotype was identified, 59 (73.8%) were GII.4 strains. Cruise ship travelers experiencing diarrhea or vomiting should report to the ship medical center promptly so that symptoms can be assessed, proper treatment provided, and control measures implemented.
miR‐28‐5p‐IL‐34‐macrophage feedback loop modulates hepatocellular carcinoma metastasis
Authors: Shao‐Lai Zhou, Zhi‐Qiang Hu, Zheng‐Jun Zhou, Zhi Dai, Zheng Wang, Ya Cao, Jia Fan, Xiao‐Wu Huang, Jian Zhou
Journal: Hepatology (2016)

MicroRNAs (miRNAs) play a critical role in regulation of tumor metastasis. However, the role of these molecules in hepatocellular carcinoma (HCC) has not been fully elucidated. In this study, we employed miRNA‐sequencing and identified 22 miRNAs involved in HCC metastasis. One of these, miR‐28‐5p, was down‐regulated in HCCs. This down‐regulation correlated with tumor metastasis, recurrence, and poor survival. Biofunctional investigations revealed that miR‐28‐5p deficiency promoted tumor growth and metastasis in nude mice without altering the in vitro biological characteristics of HCC cells. Through gene expression profiles and bioinformatics analysis, we identified interleukin‐34 (IL‐34) as a direct target of miR‐28‐5p, and the effects of miR‐28‐5p deficiency on HCC growth and metastasis was dependent on IL‐34‐mediated tumor‐associated macrophage (TAM) infiltration. Moreover, we found that TAMs induced by miR‐28‐5p‐IL‐34 signaling inhibit miR‐28‐5p expression on HCC cells by transforming growth factor beta 1, resulting in an miR‐28‐5p‐IL‐34‐macrophage‐positive feedback loop. In clinical HCC samples, miR‐28‐5p levels were inversely correlated with IL‐34 expression and the number of TAMs. Patients with low miR‐28‐5p expression, high IL‐34 levels, and high numbers of TAMs had a poor prognosis with shorter overall survival and time to recurrence. Conclusion : A miR‐28‐5p‐IL‐34‐macrophage feedback loop modulates HCC metastasis and serves as a novel prognostic factor as well as a therapeutic target for HCC. (H epatology 2016;63:1560‐1575)
Implementation of pharmacy services in 22 oncology clinics.
Authors: Ashley Feldt, Jennifer Godden
Journal: Journal of Clinical Oncology (2014)

145 Background: Our integrated health care system consisted of 15 hospitals and 159 clinics. Since 2011, 22 private practice oncology clinics transitioned to hospital-based clinics. This presented an opportunity to standardize safe and effective pharmacy services at these locations. Methods: Using patient volumes, system leaders determined six pharmacists would serve the 22 new clinics via telepharmacy. Baseline pharmacy services to be offered were prospective order verification, product checking and drug information dissemination. To prepare for the transition, over 25 physicians agreed to standardize electronic order sets and develop one formulary. Vial sizes were consolidated and a uniform way to prepare each chemotherapy agent was designated. Over 75 policies were reviewed and updated. Education was provided to all caregivers prior to the transition. Once baseline services were integrated, additional patient-focused services such as supportive care counseling, follow-up phone calls, medication reconciliation and chemotherapy education were offered. Results: Pharmacists verified over 66,000 physician-ordered chemotherapy prescriptions in 2013, intervening on about 6% by suggesting adjustments for potential organ dysfunction or toxicity. For the past year pharmacists counseled nearly 90 patients a month regarding their supportive care medications. Survey results revealed a consistent increase in overall understanding, although the sample size did not allow for statistical significance. In addition, pharmacists made about 25 follow-up phone calls to patients to assess control of nausea and vomiting, completed medication histories for about 10 patients new to chemotherapy and were consulted for about 5 chemotherapy teachings per month. Conclusions: Integration of pharmacy services in our oncology clinics has allowed for development of a streamlined and safe process for ordering and preparing chemotherapy. It also has increased patient access to pharmacists and education related to supportive care medications.
Three Treasures Healing
Authors: Sally Lipton Derringer
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 15520: Tadalafil Attenuates Ischemic Cardiomyopathy and Improves Left Ventricular Function in Mice
Authors: Fadi N Salloum, Vinh Q Chau, Nicholas N Hoke, Rakesh C Kukreja
Journal: Circulation (2012)

Background: Phosphodiesterase-5 inhibitors including sildenafil, vardenafil and tadalafil induce anti-ischemic effect in the heart in various animal species. Since tadalafil is a long-acting and mo...
Phase I and Pharmacokinetic Study of the Differentiating Agent Vesnarinone in Combination With Gemcitabine in Patients With Advanced Cancer
Authors: Amita Patnaik, Eric K. Rowinsky, Brinda K. Tammara, Manuel Hidalgo, Ronald L. Drengler, Allison M. Garner, Lillian L. Siu, Lisa A. Hammond, Sally A. Felton, Suresh Mallikaarjun, Daniel D. Von Hoff, S. Gail Eckhardt
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetic profile of vesnarinone given once daily in combination with gemcitabine. PATIENTS AND METHODS: Twenty-six patients were treated with oral vesnarinone once daily on a continuous schedule at doses of 60, 90, 120, 150, and 180 mg in combination with intravenous (IV) gemcitabine at a dose of 1,000 mg/m 2 on days 1, 8, and 15 every 4 weeks. To determine whether biologically relevant concentrations were being achieved, predose concentrations (C min ) of vesnarinone were obtained weekly. Plasma gemcitabine and 2′,2′-difluorodeoxyuridine concentrations were obtained during courses 1 and 2. RESULTS: Twenty-six patients were treated with 92 courses of vesnarinone/gemcitabine. The principal toxicities of the regimen consisted of neutropenia and thrombocytopenia, which were dose-limiting in two of eight heavily pretreated new patients treated at the 90 mg/1,000 mg/m 2 dose level and one of 10 minimally pretreated new patients at the 120 mg/1,000 mg/m 2 dose level. None of three patients treated with 15 courses at the vesnarinone/gemcitabine dose levels of 60 mg/1,000 mg/m 2 experienced DLT. Pharmacokinetic studies of vesnarinone revealed significant interpatient variability at any given dose level. There was evidence of a linear relationship between vesnarinone dose and mean C min at dosages of vesnarinone less than 150 mg, with plateauing of mean C min values at higher dosages. There was no impact of vesnarinone on gemcitabine concentrations, and the vesnarinone pharmacokinetics did not change with gemcitabine between weeks 1 and 2. Two partial responses occurred in patients with refractory breast and non–small-cell lung carcinoma. CONCLUSION: When combined with gemcitabine, the recommended dose of vesnarinone for phase II evaluations is 90 mg orally once daily with gemcitabine 1,000 mg/m 2 IV on days 1, 8, and 15 every 4 weeks. There is no evidence of pharmacokinetic interaction between vesnarinone and gemcitabine. Further studies of vesnarinone as a single agent or in combination with gemcitabine and other antineoplastic agents are warranted.
Impact of histology and smoking status on survival outcome of patients with advanced non-small cell lung cancer (NSCLC): West Japan Oncology Group (WJOG) study 3906L.
Authors: Y. Kogure, M. Ando, Y. Chiba, N. Yamamoto, K. Asami, T. Hirashima, K. Sugio, N. Ikeda, H. Saka, K. Nakagawa
Journal: Journal of Clinical Oncology (2010)

e18013 Background: Although adenocarcinoma (Ad) histology and smoking status are now recognized as possible prognostic factors in advanced NSCLC, the distribution of both extensively overlaps. We aim to assess the impact and possible interaction of these factors on survival among advanced NSCLC patients receiving chemotherapy in a practical setting. Methods: Clinical information was retrospectively assembled for stage IIIb or IV NSCLC patients who started first-line systemic chemotherapy at affiliated institutions of WJOG between January 1, 2004 and December 31, 2005. As for smoking status, we obtained detailed information including the number of cigarettes smoked per day, years of smoking, and years since cessation. Overall survival (OS) was compared using log-rank test, and Cox regression analysis was performed to identify independent prognostic factors. Results: 2542 consecutively treated patients were collected at 40 institutions. Among them, 71 were excluded because of unknown smoking history. Patient characteristics were: median age 66 years (range: 25-92); male/female, 1,697/774; Ad/non-Ad, 1,731/740; smoker/nonsmoker, 1,733/738. The median OS of Ad in nonsmokers (593 days) was longer than that of Ad in smokers, non-Ad in nonsmokers, and non-Ad in smokers (384, 374, and 319 days, respectively, p < 0.001). In the Cox model including sex, age, stage, performance status, and treatment as covariates, we found a significant interaction (p = 0.039) between histology (Ad/non-Ad) and smoking status (smoker/nonsmoker); smoking conferred a hazard ratio of 1.34 (95% CI, 1.15-1.55) in Ad, in contrast to 0.99 (0.75-1.31) in non-Ad. In detailed analyses, larger pack-years and shorter period since cessation showed a significant trend for poorer survival in Ad (p < 0.001), but not in non-Ad (p ≥ 0.434). Conclusions: This survey demonstrated that Ad histology is associated with a better prognosis and that smoking status has a prognostic impact only in patients with Ad. The differences in survival outcome imply the necessity to investigate whether the nonsmoking Ad patients is a distinct cohort in NSCLC in terms of tumor biology and disease behavior. No significant financial relationships to disclose.