tbuckley/cabot-search huggingface dataset:
Phase II trial of vinflunine in patients with relapsed small cell lung cancer
Authors: J. D. Peyton, D. R. Spigel, J. D. Hainsworth, D. A. Yardley, H. A. Burris, E. Vazquez, C. Farley, L. Porter, S. Lunin, F. A. Greco
Journal: Journal of Clinical Oncology (2007)

18091 Background: Vinflunine (VFL) is a novel microtubule inhibitor of the vinca alkaloid class which has demonstrated significant preclinical activity in a small cell lung cancer (SCLC) model and antitumor activity in several other tumor types. This multicenter community- based trial was designed to examine the role of VFL in patients (pts) with relapsed SCLC. Methods: The primary endpoint is objective response rate (ORR). Eligibility criteria: previously treated SCLC (sensitive or refractory relapsed pts; limited to 1 prior platinum or non-platinum therapy for limited- or extensive-stage disease), ECOG PS 0–2, measurable disease, and informed consent. Treatment: VFL 320 mg/m 2 IV over 20 minutes day 1 every 21 days for up to 6 cycles. Pts were restaged every 6 weeks. This 2-stage trial was designed to achieve a 20% ORR in platinum-sensitive pts (per RECIST criteria). Results: 29 pts were enrolled from 3/06 to 12/06 (trial ongoing, n=41 planned). Data are available for 16 pts in this analysis. Baseline characteristics: median age 64 years; male/female, 63%/37%; ECOG PS 0/1/2, 25%/50%/25%; and sensitive relapse, 50%. 3 partial response have been observed (ORR 19%, 95% CI 4%-46%). 3 pts (19%) had stable disease and 7 pts (44%) had progressive disease. 3 pts were not evaluable due to: treatment-related toxicity (sepsis; constipation); declining PS, 1 pt each. With a median follow-up of 5 months, the median progression-free survival and overall survival are 1.7 months and 3.6 months, respectively. Grade (G) 3/4 non-hematologic toxicity occurring in more than 1 pt: constipation, dyspnea, fatigue, and hyponatremia (13% each). G3/4 hematologic toxicity: leukopenia (44%), neutropenia (38%), and thrombocytopenia (6%). There have been no treatment-related deaths. Conclusions: VFL appears active as second-line treatment for SCLC. Additional assessment of myelosuppression is needed to better assess VFL’s role. Completion of accrual is anticipated by 4/07. No significant financial relationships to disclose.
Prospective monitoring of circulating tumor cells in breast cancer patients treated with primary systemic therapy—A translational project of the German Breast Group study GeparQuattro
Authors: V. Mueller, S. Riethdorf, S. Loibl, M. Komor, J. Houber, I. Schrader, U. Conrad, M. Untch, G. vMinckwitz, K. Pantel
Journal: Journal of Clinical Oncology (2007)

21085 Background: The impact of circulating tumor cells (CTC) in patients with primary breast cancer is still unclear. Primary systemic treatment (PST) allows the assessment of therapeutic efficacy in breast cancer patients without long follow-up periods. Here we present first results on the presence of CTC in peripheral blood of patients enrolled in the “GeparQuattro” study. Methods: This study incorporates three different chemotherapy approaches and additional Trastuzumab (Herceptin®) treatment for patients with HER-2/neu-positive tumors. Recruitment finished in November 2006 and not all patients have completed therapy yet. We used the CellSearch ™ system to evaluate CTC before PST from 245 patients and after PST from 67 patients. CTC from 45 samples were also examined for HER-2/neu expression by immunocytochemistry in the CellSearch™ system. Results: Before PST we detected CTC in 54/245 patients (22%). CTC numbers in 7.5 mL blood ranged between 1 and 200 (mean 6.5). In 8 CTC-positive samples (3.3%) = 5 CTC were found. Her-2/neu-positive CTC were observed in 25/45 cases (55.6%). CTC could be detected in 7/67 patients (10.4%) after PST (1 or 2 CTC). Before and after PST blood was analyzed from 43 patients, 27 of them were CTC-negative at both time points. Ten initially CTC-positive cases were CTC-negative after PST whereas 6 cases were detected CTC-positive after PST although no CTC could be found before PST. Conclusions: With the CellSearch™ system CTC can be detected in non-metastatic breast cancer patients at primary diagnosis and also after PST. To our knowledge, this is the largest study evaluating the presence of CTC in this context. With the availability of response information from more patients, it will be possible to examine the correlation between the incidence of CTC and response as well as kinetics of HER-2/neu expression during Trastuzumab treatment. [Table: see text]
Pulse Pressure and Risk of Cardiovascular Disease—Reply
Authors: James D. Neaton, Michael Domanski, Jeremiah Stamler
Journal: JAMA (2003)

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
Are high-performing health systems resilient against the COVID-19 epidemic?
Authors: Helena Legido-Quigley, Nima Asgari, Yik Ying Teo, Gabriel M Leung, Hitoshi Oshitani, Keiji Fukuda, Alex R Cook, Li Yang Hsu, Kenji Shibuya, David Heymann
Journal: The Lancet (2020)
Bystander IFN-γ activity promotes widespread and sustained cytokine signaling altering the tumor microenvironment
Authors: Ronan Thibaut, Pierre Bost, Idan Milo, Marine Cazaux, Fabrice Lemaître, Zacarias Garcia, Ido Amit, Béatrice Breart, Clémence Cornuot, Benno Schwikowski, Philippe Bousso
Journal: Nature Cancer (2020)
Abstract TS1-3: Proteogenomics and Clinical Translation
Authors: MJ Ellis
Journal: Cancer Research (2020)

Abstract Improvements in breast cancer treatment are being achieved at an increasing pace in all three clinical subsets of the disease, namely ER+ HER2- (luminal), HER2+ (HER2-driven) and ER- PgR- and HER2- (triple negative). While these disease groupings served as useful approximations of the immense diversity of breast cancer when only endocrine therapy, chemotherapy and trastuzumab were available, the inadequacy of this disease classification is readily evident when set against the sophistication of our growing therapeutic armamentarium. What is on the horizon to replace our simple immunohistochemistry-based subtyping approaches to avoid misdiagnosis and consequent mismanagement? In this lecture I will make the argument that the advent of efficient and accurate protein mass spectrometry provides the “missing link” in ‘omics analysis that integrates information derived from next generation DNA and RNA analysis to create a more secure diagnostic conclusion. The new field of “clinical proteogenomics” validates proposed disease drivers, dissects complex amplicons, monitors signaling perturbations in response to targeted treatments and determines the activity of the immune microenvironment. The advent of cloud computing promotes the efficient delivery of individualized proteogenomic therapeutic road maps as a near-term possibility. Citation Format: MJ Ellis. Proteogenomics and Clinical Translation [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr TS1-3.
Systematic Review of the Therapeutic Efficacy of Bladder-preserving Treatments for Non–muscle-invasive Bladder Cancer Following Intravesical Bacillus Calmette-Guérin
Authors: Roger Li, Debasish Sundi, Jingsong Zhang, Youngchul Kim, Richard J. Sylvester, Philippe E. Spiess, Michael A. Poch, Wade J. Sexton, Peter C. Black, James M. McKiernan, Gary D. Steinberg, Ashish M. Kamat, Scott M. Gilbert
Journal: European Urology (2020)
Abstract P468: Geographic and Socioeconomic Inequalities in Poor Cardiovascular Health in Canada
Authors: Sarah Singh, Saverio Stranges, Stephanie J Frisbee
Journal: Circulation (2020)

Background: Poor cardiovascular health (CVH), characterized by clinical risk and unhealthy lifestyle habits, is a leading cause of death and disease worldwide. Despite advances in healthcare and policy, there remains an inequitable burden of poor CVH among Canadian sub-populations based on socioeconomic status and geographic region. Using recently published data and a national toolkit, this study aimed to quantify inequalities in poor CVH across the Canadian population. Methods: We conducted a cross-sectional study on Canadian adults, ≥20 years, from the nationally representative Canadian Community Health Survey 2017. Using the American Heart Association’s CVH Index, CVH was defined for each individual as a summed score of 7 components, where 1 point was awarded for achieving ideal health in each component. A total score of 0-2 points indicated poor overall CVH. The Canadian Institute for Health Information (CIHI) Measuring Health Inequalities Toolkit, a standardized methodological approach to analyzing health inequalities in population-based data using pre-defined stratifications and second-level interactions, was used to quantify inequalities in poor CVH based on Toolkit-defined stratifications in sex, income, urban/rural status, and region of residence. The regional distribution of CVH was mapped using ArcGIS software. Results: Approximately 7% of Canadians had poor CVH, representing 2 million Canadians. Poor dietary habits were noted in 99.0% of the population, with poor body mass index and poor physical activity noted in 58.1% and 42.3%, respectively. The eastern provinces of Newfoundland and Labrador and New Brunswick had the greatest proportion of health regions with poor CVH. An examination of the largest CVH inequalities across provinces revealed that females in the lowest income tercile residing in Prince Edward Island were 8-times more likely to experience poor CVH than females in the highest income tercile (RR 8.43, 95%CI 7.09-10.04). Additionally, females in New Brunswick residing in rural regions were almost 3-times more likely to experience poor CVH than females residing in urban regions (RR 3.07, 95%CI 1.07-4.87). In most provinces, income and urban/rural inequalities among males were observed but were of smaller magnitude than the inequalities among females. Conclusion: The greatest inequalities in poor CVH were experienced by females in the lowest income groups. Urban/rural inequalities in CVH were complex and varied by geographic region. The CIHI toolkit is a robust and systematic approach to understanding health inequalities that will enable comparison between studies and health/disease states, and thus facilitate comparative policy evaluation and population health priority setting.
Covid-19: roundup of latest news
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The vast majority of NHS emergency departments in England don’t have adequate isolation facilities for containing the spread of infectious diseases such as covid-19, one of the country’s most senior emergency doctors told The BMJ . Chris Moulton, consultant in emergency medicine at the Royal Bolton Hospital and former vice president of the Royal College of Emergency Medicine, said he had visited and observed around 80 emergency departments in his current role as joint emergency medicine lead for the NHS’s Getting it Right First Time (GIRFT) programme. He said, “I don’t think I’ve seen …
A clinical trial design applying Bayesian adaptive randomization for targeted therapy development in lung cancer: A step toward personalized medicine
Authors: X. Zhou, E. S. Kim, R. S. Herbst, S. Liu, I. I. Wistuba, L. Mao, J. Lewis, S. M. Lippman, W. K. Hong, J. J. Lee
Journal: Journal of Clinical Oncology (2007)

7697 Background: Multiple axes of signaling pathways are associated with lung carcinogenesis. These signaling axes are different in pts (pts) and their cancers. Utilization of molecularly targeted agents may inhibit these specific aberrant pathways and lead to clinical efficacy. Biomarkers expressions can be used as indicators for the aberrant signaling to identify effective targeted therapy. Methods: The program, “Biomarker-integrated Approaches of Targeted Therapy of Lung Cancer Elimination (BATTLE),” consists of an umbrella screening trial and 4 parallel phase II targeted therapies trials (with erlotinib, sorafenib, vandetanib, and the combination of erlotinib and bexarotene) in advanced non-small cell lung cancer pts with prior chemotherapy. All pts will have biopsy samples taken for biomarker profile assessment prior to the randomization. A ‘surrogate response‘ to treatment is defined as progression free at 8 weeks after randomization. The Bayesian ordinal probit model is used to characterize the response rate. Pts with certain biomarker profile will be adaptively randomized (AR) to one of the 4 treatment arms with the randomization rate based on the updated response rate based on accumulated data in the trial. For each biomarker profile, better performing arms will have higher randomization rates and vise versa. Early stopping rules are set so that low-performing arms may be suspended for new patient entry. Results: Based on extensive simulation studies, the proposed design with a total of 200 pts has desirable operating characteristics to: (1) identify effective agents with high probability; (2) suspend ineffective agents; and (3) treat more pts with effective agents according to their biomarker profiles. The Bayesian design incorporates prior data and findings from the current pts to form better estimates of the treatment efficacy for pts with different biomarker profiles. The design continues to “learn” and improve the estimates as the trial moves along. Conclusion: The Bayesian AR design is a smart and ethical design and ideally suitable for the development of targeted therapy. It may help in identifying effective agents based on pts’ tumor biomarker profile and thus treat more pts with effective therapies. No significant financial relationships to disclose.
Relative Efficiencies of Simple and Complex Substitution Models in Estimating Divergence Times in Phylogenomics
Authors: Qiqing Tao, Jose Barba-Montoya, Louise A Huuki, Mary Kathleen Durnan, Sudhir Kumar
Journal: Molecular Biology and Evolution (2020)

The conventional wisdom in molecular evolution is to apply parameter-rich models of nucleotide and amino acid substitutions for estimating divergence times. However, the actual extent of the difference between time estimates produced by highly complex models compared with those from simple models is yet to be quantified for contemporary data sets that frequently contain sequences from many species and genes. In a reanalysis of many large multispecies alignments from diverse groups of taxa, we found that the use of the simplest models can produce divergence time estimates and credibility intervals similar to those obtained from the complex models applied in the original studies. This result is surprising because the use of simple models underestimates sequence divergence for all the data sets analyzed. We found three fundamental reasons for the observed robustness of time estimates to model complexity in many practical data sets. First, the estimates of branch lengths and node-to-tip distances under the simplest model show an approximately linear relationship with those produced by using the most complex models applied on data sets with many sequences. Second, relaxed clock methods automatically adjust rates on branches that experience considerable underestimation of sequence divergences, resulting in time estimates that are similar to those from complex models. And, third, the inclusion of even a few good calibrations in an analysis can reduce the difference in time estimates from simple and complex models. The robustness of time estimates to model complexity in these empirical data analyses is encouraging, because all phylogenomics studies use statistical models that are oversimplified descriptions of actual evolutionary substitution processes.
Abstract P206: Diet Quality is Lower Among Adolescents Who Skip Lunch
Authors: Spencer M Clason, Lori Spruance, Leann Myers, Keelia O'Malley, Carolyn Johnson
Journal: Circulation (2020)

Introduction: A healthy diet is key in preventing chronic diseases and black adults have higher rates of hypertension, obesity, and heart disease death rates compared to their white counterparts. Because dietary habits track from adolescence to adulthood, it is important to understand dietary habits of adolescents. This study aimed to examine the dietary quality among adolescents who skip lunch compared to those who do not. Methods: Data were collected in 2012 from 718 adolescents attending schools in New Orleans, Louisiana. Schools were high-poverty and closed-campus. Adolescents participated in a 24-hour dietary recall using the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Tool and data were converted into Healthy Eating Index (HEI-10) scores (range 0-100; higher scores reflect higher quality diet). Mean scores were compared between students who skipped lunch and those who did not. Results: Of the 718 respondents, 88.3% were black and 15.3% of students skipped lunch. Students who ate lunch had a mean HEI score of 46.6 compared to a mean score of 41.7 for students who skipped lunch (p&lt;0.001). Students who skipped lunch also had significantly lower intake of total vegetables, whole fruits, total dairy, total protein, and higher intake of empty calories (Solid fats, alcohols, and added sugars (SoFASS)). Conclusions: Skipping lunch was associated with lower quality diet, though diet quality was low among all students. Students who skip lunch are less likely to consume vegetables, whole fruits, whole grains, and proteins and have higher intake of SoFASS. Considering over 15% of the sample did not eat lunch in a closed-campus school setting, further research should consider how to encourage students to participate in the National School Lunch Program. Table 1. HEI score comparisons between those who skip and do not skip lunch.
A trial of vaccination with the carcinoembryonic antigen (CEA) peptide CAP 1–6D with montanide ISA 51 adjuvant or granulocyte- macrophage colony stimulating factor (GM-CSF) in HLA-A2+ patients with CEA producing adenocarcinomas of gastrointestinal (GI) track
Authors: R. P. Whitehead, K. Jantz, A. Simmons
Journal: Journal of Clinical Oncology (2007)

13513 Advances in drug therapy have improved the survival of patients with GI tumors but most patients with metastatic disease are not cured. Immunotherapy is an additional modality of treatment. In this trial, the CEA peptide, CAP 1–6D, was combined with either GM-CSF or montanide ISA 51 as adjuvants and used to vaccinate patients with CEA producing GI tumors. End points were development of peptide responsive immunity, toxicity, and anti-tumor effects. To be eligible, patients were required to have a histologic diagnosis of adenocaricnoma of GI tract origin with a life expectancy of at least 6 months and to have either metastatic disease or to have completed standard adjuvant therapy after resection. Patients were required to have a CEA producing tumor, be HLA-A2 positive, have a performance status of 0–1, test negative for HIV, hepatitis B and C, and have adequate bone marrow, liver and kidney function. Treatment consisted of 1 mg of CAP 1–6D peptide combined with either 250 ug of GM-CSF given intradermally, or 2 ml of Montanide ISA 51 given subcutaneously every 3 weeks for 6 treatments. Blood was drawn for ELISpot assay at each visit. Nine (out of a planned 10) patients, 8 with colorectal cancer and 1 with pancreatic cancer, were entered before the peptide was deemed expired and withdrawn from clinical use by the NCI. Of five colorectal patients with metastatic disease at baseline 4 progressed and 1 had stable disease. The pancreatic cancer patient was treated adjuvantly but progressed during therapy. Three colorectal cancer patients treated adjuvantly were free of disease at baseline and at the completion of therapy. Treatments were well tolerated. ELISpot data on 5 patients showed that 4 patients developed peptide responsive immunity. Responsive patients included those receiving either GM-CSF or Montanide ISA 51 and both adjuvantly treated and progressive metastatic colorectal patients and the progressed pancreatic cancer patient. This vaccine regimen can be safely given to cancer patients and can produce peptide responsive immunity in the ELISpot assay but this does not correlate with clinical anti-tumor effect. No significant financial relationships to disclose.
Methods matter: exploring the ‘too much, too soon’ theory, part 1: causal questions in sports injury research
Authors: Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Merete Møller, Adam Hulme, Mohammad Ali Mansournia, Marti Casals, Erik Thorlund Parner
Journal: British Journal of Sports Medicine (2020)

It is widely accepted that athletes sustain sports injury if they train 'too much, too soon'. However, not all athletes are built the same; some can tolerate more training than others. It is for this reason that prescribing the same training programme to all athletes to reduce injury risk is not optimal from a coaching perspective. Rather, athletes require individualised training plans. In acknowledgement of athlete diversity, it is therefore essential to ask the right causal research question in studies examining sports injury aetiology.In this first part of a British Journal of Sports Medicine educational series, we present four different causal research questions related to the 'too much, too soon' theory and critically discuss their relevance to sports injury prevention.If it is true that there is no 'one size ﬁts all' training programme, then we need to consider by how much training can vary depending on individual athlete characteristics. To provide an evidence-base for subgroup-specific recommendations, a stronger emphasis on the following questions is needed: (1) How much training is 'too much' before athletes with different characteristics sustain sports-related injury? and (2) Does the risk of sports injury differ among athletes with a certain characteristic (eg, high experience) compared with athletes with other characteristics (eg, low experience) depending on how much training they perform? CONCLUSION: We recommend that sports injury researchers aiming to examine the 'too much, too soon' theory should carefully consider how they, assisted by coaches, athletes and clinicians, pose their causal research question. In the light of the limitations of population-based prevention that intends to provide all athletes with the same advice, we argue that a stronger emphasis on research questions targeting subgroups of athletes is needed. In doing so, researchers may assist athletes, clinicians and coaches to understand what training advice/programme works best, for whom and under what circumstances.