tbuckley/cabot-search huggingface dataset:
Mobile Device Use While Driving--United States and Seven European Countries, 2011
Authors: Rebecca B Naumann, Ann M Dellinger
Journal: MMWR Morbidity and Mortality Weekly Report (2013)

Road traffic crashes are a global public health problem, contributing to an estimated 1.3 million deaths annually. Known risk factors for road traffic crashes and related injuries and deaths include speed, alcohol, nonuse of restraints, and nonuse of helmets. More recently, driver distraction has become an emerging concern. To assess the prevalence of mobile device use while driving in Belgium, France, Germany, the Netherlands, Portugal, Spain, the United Kingdom (UK), and the United States, CDC analyzed data from the 2011 EuroPNStyles and HealthStyles surveys. Prevalence estimates for self-reported talking on a cell phone while driving and reading or sending text or e-mail messages while driving were calculated. This report describes the results of that analysis, which indicated that, among drivers ages 18–64 years, the prevalence of talking on a cell phone while driving at least once in the past 30 days ranged from 21% in the UK to 69% in the United States, and the prevalence of drivers who had read or sent text or e-mail messages while driving at least once in the past 30 days ranged from 15% in Spain to 31% in Portugal and the United States. Lessons learned from successful road safety efforts aimed at reducing other risky driving behaviors, such as seat belt nonuse and alcohol-impaired driving, could be helpful to the United States and other countries in addressing this issue. Strategies such as legislation combined with high-visibility enforcement and public education campaigns deserve further research to determine their effectiveness in reducing mobile device use while driving. Additionally, the role of emerging vehicle and mobile communication technologies in reducing distracted driving–related crashes should be explored.
Immune Processes and Infectious Factors in Central Nervous System Disease
Authors: P Y Paterson
Journal: Annual Review of Medicine (1969)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Atlas of intravascular ultrasound Edited by J M Hodgson and H M Sheehan. (Pp 352; $145.) New York, Raven Press, 1993. ISBN 0-7817-0013-2
Authors: A Bryan
Journal: Cardiovascular Research (1995)

Journal Article Atlas of intravascular ultrasound: Edited by J M Hodgson and H M Sheehan. (Pp 352; $145.) New York, Raven Press, 1993. ISBN 0-7817-0013-2 Get access AJ Bryan AJ Bryan Bristol, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 4, April 1995, Page 583, https://doi.org/10.1016/S0008-6363(95)90126-4 Published: 01 April 1995
PWE-193 Antithrombotic therapy and cardiovascular outcomes following upper gastrointestinal bleeding – how are we doing?
Authors: K Siau, J Hannah, M Widlak, N Quraishi, N Bhala, T Iqbal
Journal: Gut (2015)

<h3>Introduction</h3> Upper gastrointestinal bleeding (UGIB) is a recognised risk of antithrombotic therapy. We aimed to investigate whether patients admitted with UGIB whilst on antithrombotic therapy were continued on these following discharge, and to assess bleeding and cardiovascular outcomes. <h3>Method</h3> We performed a retrospective cohort study on consecutive inpatients referred to our university hospital for suspected UGIB over 18 months, who had been prescribed antithrombotic therapy at the point of admission. Patients were identified through our electronic database, and records were scrutinised for co-morbidities, antithrombotic indication (s), endoscopy findings, endotherapy and rebleeding. Primary outcomes included mortality and cardiovascular events at 1 year, whereas secondary outcomes included rebleed rates, and discontinuation of antiplatelet/anticoagulant therapy. Statistical analysis was performed using Fisher’s Exact test. <h3>Results</h3> 133 patients were included in the study, with a median age of 76 years (SD), of which 65.4% were male. Median follow-up was 255 days. Antithrombotic therapy consisted of aspirin monotherapy (44.4%), clopidogrel (9.7%), dual antiplatelet therapy (16.5%), anticoagulant (23.2%), with coronary artery disease (47.5%), atrial fibrillation (18.6%), cerebrovascular disease (9.3%) being the primary indications. Peptic ulcer disease was the commonest lesion on endoscopy (34%), followed by normal endoscopy (28.6%), gastritis (12.8%), and oesophagitis (7.5%). Intervention was performed in 30% of cases. Our 30-day rebleed rate was 5.2%. 30-day and 1-year all-cause mortality rates were 9.0% and 21.0% respectively. Antithrombotic therapy was at least partially discontinued in 55.2% of patients, with no concordance to Rockall scoring or endoscopic findings. Independent predictors of antithrombotic continuation included: metallic heart valve, coronary artery stenting within one year, and recent venous thromboembolism. At 1 year of follow-up, discontinuation of antithrombotic therapy was associated with increased cardiovascular mortality (RR 4.5, p = 0.036), increased all-cause mortality (RR 3.0, p = 0.003), and cardiovascular events (RR 6.1, p = 0.003). Continuation of antithrombotic therapy following haemostasis did not significantly increase bleeding-related mortality. <h3>Conclusion</h3> Patients with cardiovascular comorbidity are at high risk of developing ischaemic events following admission for UGIB. Clinicians should consider careful risk-benefit assessment prior to discontinuing established antithrombotic treatment. <h3>Disclosure of interest</h3> None Declared.
Beta-Adrenergic Blocking Drugs
Authors: J G Gerber, A S Nies
Journal: Annual Review of Medicine (1985)

There are currently six beta-adrenoceptor blocking drugs on the market. Although all the drugs competitively interact with the beta-adrenergic receptors, their pharmacokinetics and ancillary properties distinguish them from one another. By understanding these differences, the various beta-adrenoceptor drugs can be rationally used to a therapeutic advantage.
Effective immunotherapy of pre-existing tumor in a stringent rat mammary tumor model by targeting the rat neu, “self”, tumor-associated antigen using an alphavirus replicon based immunotherapy with in-vivo DC tropism
Authors: Kehui Wang, Brandon W. Sur, Kurt I. Kamrud, Bolyn Fralish, Jonathan F. Smith, Edward L. Nelson
Journal: Cancer Research (2005)

6042   Introduction: The majority of human tumor-associated antigens (TAAs) are either minimally altered or malexpressed “self” antigens. Effective anti-tumor immunity must overcome intrinsic tolerance to TAAs and barriers derived from host:tumor interactions to mount a sufficiently potent anti-tumor immune response for tumor cell destruction. The immune system dendritic cell (DC), the most potent antigen-presenting cell, is a logical target for strategies designed to elicit robust immune responses. However, adoptive transfer of ex vivo manipulated DCs must overcome biological and regulatory hurdles. The Venezuelan Equine Encephalitis (VEE)-derived replicon particle (VRP) has in vivo tropism for murine DCs and may be advantageous for eliciting larger magnitude and more efficacious anti-tumor immune responses. Methods: These studies used VRPs encoding the reporter protein dsRed (VRP-dsRed), rat neu target antigen (VRP-rNeu) or an irrelevant antigen influenza hemagglutinin (VRP-HA) and a stringent animal model of a non-mutated “self” TAA in an effort to recapitulate the human clinical state. We used Fisher 344 rats and the syngeneic moderately immunogenic 13762 mammary tumor line, with moderate expression of rat neu. Immunizations, SC or IM administration, q3 weeks x 3 were used to establish anti-tumor immunity for challenge and mechanistic studies. For treatment studies, tumor was established 48 hr prior to initiation of immunizations q10 d. VRPs encoding dsRed were administered SC or in the footpad to evaluate the extent of in-vivo tropism for rat DCs, extending the report of in-vivo murine DC tropism (McDonald & Johnston, J Virol 2000). Data: Administration of VRP-dsRed revealed transfected DCs trafficking to draining lymph nodes DCs within 12 hr and persisting in excess of 84 hr. Immunization with VRP-rNeu resulted in significant antigen-specific, tumor challenge protection (p=0.002), the induction of immunologic memory, low titer antigen-specific antibody responses that were exclusively IgG2 supporting the induction of Th1 biased immune responses, and the ability for cellular transfer immunity by Winn assay. This immunotherapeutic strategy also demonstrated efficacy against pre-established tumor with delayed tumor outgrowth and cure of 20% of animals (p=0.022) by targeting a single TAA. Conclusions: Our findings demonstrate that the VRP vector system has in-vivo tropism for rat DCs that both traffic and remain in secondary lymphoid tissues appropriately. This VRP based, single TAA antigen-specific, immunotherapeutic strategy overcomes tolerance to the “self” antigen neu and elicits very active Th1 anti-tumor immunity. These results support both further evaluation and rapid translation into clinical evaluations of this potent DC tropic vector-based immunotherapy.
Neutrophil oxidative burst activates ATM to regulate cytokine production and apoptosis
Authors: C. J. Harbort, Paulo Vitor Soeiro-Pereira, Horst von Bernuth, Angela M. Kaindl, Beatriz Tavares Costa-Carvalho, Antonio Condino-Neto, Janine Reichenbach, Joachim Roesler, Arturo Zychlinsky, Borko Amulic
Journal: Blood (2015)
Risk factors for treatment-related death in elderly patients with aggressive non-Hodgkin's lymphoma: results of a multivariate analysis.
Authors: H Gómez, M Hidalgo, L Casanova, R Colomer, D L Pen, J Otero, W Rodríguez, C Carracedo, H Cortés-Funes, C Vallejos
Journal: Journal of Clinical Oncology (1998)

PURPOSE It has been suggested that age is associated with chemotherapy-related death in patients with non-Hodgkin's lymphoma (NHL) treated with doxorubicin-containing chemotherapy. The purpose of this study was to evaluate the relative influence of increasing age and other clinical parameters on the occurrence of treatment-related death in elderly patients with intermediate- or high-grade NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. METHODS A retrospective study of patients 60 years of age or older with intermediate- or high-grade NHL treated with CHOP chemotherapy in a single cancer center. The following variables were recorded: age (60 to 69, 70 to 79, and 80 to 94 years), histology (Working Formulation [WF] D, E, F, G, and H), Ann Arbor stage, B symptoms, extranodal involvement, bulky disease (&gt; 7 cm), performance status (Eastern Cooperative Oncology Group [ECOG] scale), International Prognostic Index (IPI score), serum lactate dehydrogenase (LDH) level and doxorubicin relative dose-intensity (RDI). The relationship between these features and treatment-related death was assessed in univariate and multivariate logistic regression analysis. RESULTS From 1982 to 1991, 267 consecutive patients were treated. Median age was 70 years (range, 60 to 94 years). There were 35 toxic deaths. Sixty-three percent of the deaths occurred after the first cycle. Infection accounted for 82% of the toxic deaths. In the univariate analysis, the features associated with an increased risk of toxic death were ECOG performance status 2 to 4 (relative risk [RR], 7.82), B symptoms (RR, 3.38), diffuse large-cell histology (RR, 3.06), bulky disease (RR, 2.58), serum levels of LDH (RR, 2.53), and IPI score (RR, 2.46). The age groups did not show significance. In the regression model, performance status 2 to 4 was the only independent predictor of treatment-related death (RR, 3.52; 95% confidence interval [CI], 2.98 to 4.06). CONCLUSION Our results show that in elderly patients with NHL treated with doxorubicin-based chemotherapy the risk for treatment-related death is associated with poor performance status rather than with increasing chronologic age.
Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia.
Authors: C L Loprinzi, J C Michalak, D J Schaid, J A Mailliard, L M Athmann, R M Goldberg, L K Tschetter, A K Hatfield, R F Morton
Journal: Journal of Clinical Oncology (1993)

PURPOSE Several placebo-controlled randomized clinical trials have demonstrated that megestrol acetate can result in appetite stimulation and nonfluid weight gain in patients with cancer anorexia/cachexia. The present trial was designed to compare megestrol acetate doses ranging from 160 to 1,280 mg/d. METHODS This trial randomized 342 assessable patients with cancer anorexia/cachexia to receive oral megestrol acetate at doses of 160, 480, 800, or 1,280 mg/d. Patients were evaluated monthly by history, examination, patient-completed questionnaires, and serum albumin levels. RESULTS The data demonstrate that there is a positive dose-response effect for megestrol acetate on appetite stimulation (P &lt; or = .02). In concert, there was a trend for more nonfluid weight gain with higher drug doses. Megestrol acetate was well tolerated in this group of patients with advanced malignant disease. CONCLUSION The positive dose-response effect that we observed for megestrol acetate on appetite stimulation supports both our prestudy hypothesis and other available literature. Nonetheless, based primarily on the cost and inconvenience associated with the use of higher doses of this drug, it is reasonable to use 160 mg/d for the initial treatment of cancer anorexia/cachexia in routine clinical practice.
Severe drug allergy: The first 100 cases declared to allergy vigilance network
Authors: G. Kanny, L. Guenard, P. Demoly, C. Ponvert, J. Grand, C. Gallen, P. Chalmet, A. Croizier, J. Jacquier, M. Morisset, A. Auffret, V. Cordebar, C. Debavelaere, C. Debavelaere, J. Devoisins, C. Nootens, N. Petit, F. Pirson, A. Sorlin, A. Andrier-Schmitt, A. Andrier-Schmitt, E. Beaudouin, I. Bossé, M. Buard, C. Chappard
Journal: Journal of Allergy and Clinical Immunology (2005)
Notice of Retraction: Ahimastos AA, et al. Effect of Perindopril on Large Artery Stiffness and Aortic Root Diameter in Patients With Marfan Syndrome: A Randomized Controlled Trial.<i>JAMA</i>. 2007;298(13):1539-1547.
Authors: Bronwyn A. Kingwell, Anuradha Aggarwal, Kellie M. D’Orsa, Melissa F. Formosa, Anthony J. White, Ravi Savarirayan, Anthony M. Dart
Journal: JAMA (2015)

The authors suggested that biosimilar quality might be inconsistent over time and suggested that track-and-trace capabilities might encourage consistent quality.Product quality is tightly regulated by the FDA, both for reference biologics and biosimilars.Each batch of every biologic must meet predetermined release specifications before it can be used to treat patients.These tight regulatory requirements ensure product quality and consistency over time for all biologics.
Effective effector generation of CD8+ T cells and NK cells: A need for T-bet and ZEB-too
Authors: Sara E. Hamilton, Stephen C. Jameson
Journal: The Journal of Experimental Medicine (2015)

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Insight from Sara Hamilton (left) and Stephen Jameson (right)



Both T cells and NK cells employ complex networks of transcriptional regulators to control their differentiation and functional prowess. In this issue, three studies report that the transcription factor ZEB2 is
Report questions FDA approval of controversial anticoagulant
Authors: Michael McCarthy
Journal: BMJ (2015)

Officials of the US Food and Drug Administration lowered its standards to ease approval of the controversial anticoagulant dabigatran (marketed as Pradaxa) and then deflected questions about its safety that arose after the drug entered clinical practice, an independent watchdog group has alleged in a new report.1

In its report the Project on Government Oversight claimed that the FDA gave in on such issues as the standards that the clinical trial used to secure the drug’s approval and what warnings patients should be given about the drug’s potential hazards.

“In judgment call after judgment call involving the prescription blood thinner Pradaxa . . . the FDA took a lax or permissive approach,” the report said.

The drug, manufactured by Boehringer Ingelheim, was approved by the FDA in 2010 to prevent blood clots in patients with atrial fibrillation, a common complication that can lead …
The role of EGF and transactivating agonists in EGFR/c-Src synergy
Authors: Julie L. Boerner, Jacqueline S. Biscardi, Corinne M. Silva, Sarah J. Parsons
Journal: Cancer Research (2005)

5238   The EGFR is overexpressed and correlates with poor prognosis and advanced disease in many types of solid tumors including breast, prostate, colon, lung, head and neck, and gliomas. In addition to EGFR overexpression, c-Src is overexpressed in many types of solid tumors, with identified co-overexpression of EGFR/c-Src in 20 to 30% of breast cancers. Our laboratory has developed a mouse model system in which co-overexpression of the EGFR and c-Src leads to synergistic increases in cell growth, transformation, and tumorigenesis. In part, this synergy has been shown to be dependent on the c-Src mediated phosphorylation of a tyrosine found within the kinase domain of the EGFR (Y845). Mutating this tyrosine to a phenylalanine (Y845F) results in an inhibition of EGF-induced DNA synthesis without affecting classical EGFR signaling pathways, but involving STAT5b and cytochrome c oxidase subunit II. Others recently have reported a role for phosphorylation of Y845 in integrin mediated cell migration and sensitivity to targeted drug therapy. Here we demonstrate in addition to EGF-induced DNA synthesis, that Y845 phosphorylation is critical for DNA synthesis stimulated by growth hormone, endothelin, lysophosphatic acid (LPA), and estrogen. Furthermore, phosphorylated peptides corresponding to Y845 on the EGFR when microinjected into cells, inhibited EGF-induced DNA synthesis. These results implicate the phosphorylation of Y845 on the EGFR as a central conduit for growth and tumorigenesis. To further study the role of Y845 phosphorylation in human cancer, we developed stable human breast cancer cells lines that inducibly express wild type or Y845F-EGFR. Characterizing these cell lines biologically and biochemically to assess the importance of Y845 phosphorylation has shown that as seen with the transient transfection assays described above, Y845F-EGFR expression in MCF7 cells decreased cell growth and prevented the phosphorylation of Stat5b. In addition, Y845F-EGFR expressing cells displayed an altered time course of MAPK phosphorylation and did not induce soft agar colony growth as did cells expressing the wild type receptor. Taken together these data suggest a role for the phosphorylation of Y845 in EGFR mediated transformation of human breast cancer cells and suggest that this tyrosine residue is a potential target of future therapeutics.
Registers for clinical trials already exist
Authors: J A M. Gray
Journal: BMJ (1995)

The alleged roles of passive smoldng in causing lung cancer and excess salt in causing hypertension have been endorsed by many medical bodies, incorporated into public policy, and presented to the -public as scientific facts that should be acted on.It is a revealing commentary on the intellectual status of public health epidemiology that the statistical fiction on which this and similar mis- leading advice is derived should have gone un- challenged for so long.
Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain.
Authors: E Bruera, M Belzile, E Pituskin, R Fainsinger, A Darke, Z Harsanyi, N Babul, I Ford
Journal: Journal of Clinical Oncology (1998)

PURPOSE Use of oxycodone for chronic cancer pain has been hampered by its short elimination half-life. This study was designed to compare the efficacy and safety of controlled-release formulations of oxycodone and morphine for cancer pain. PATIENTS AND METHODS Thirty-two adult patients with cancer pain and a &gt; or = 3-day history of stable analgesia with oral opioids provided written informed consent and were randomized to controlled-release oxycodone or controlled-release morphine for 7 days. To blind the study using available tablet strengths, the dose ratio of oxycodone to morphine was set at 1:1.5. On day 8, patients were crossed over to the alternate drug for 7 days. Pain intensity was assessed using a visual analog scale (VAS 0 to 100 mm) and a categorical scale (CAT 0 to 4). Side effects were assessed using a checklist (four-point categorical severity) and a nondirected questionnaire. Patients and investigators made blinded global ratings of efficacy and treatment preference. RESULTS Twenty-three patients completed the study (10 men, 13 women). The VAS and CAT scores were (mean+/-SD) 23+/-21 and 1.2+/-0.8 on controlled-release oxycodone, and 24+/-20 (P=.43) and 1.3+/-0.7 (P=.36) on controlled-release morphine. No period or carryover effect was detected. There were no significant differences in adverse effects (P=.40) or ratings of efficacy and preference. The median oxycodone/morphine dose ratio was 1.5 and the maximum was 2.3. CONCLUSION Controlled-release oxycodone is as safe and effective as controlled-release morphine in the treatment of cancer pain.
BCX-4161, a Small Molecule and Orally Bioavailable Plasma Kallikrein Inhibitor for the Treatment of Hereditary Angioedema
Authors: Shanta Bantia, Jianwen Zhang, Ramanda Wilson, Cynthia D. Parker, Debra Kellogg, Pravin Kotian, Y.S. Babu
Journal: Journal of Allergy and Clinical Immunology (2013)