tbuckley/cabot-search huggingface dataset:
Clinical pharmacology
Authors: N. Bateman, S. Maxwell
Journal: BMJ (1999)

Clinical pharmacology and therapeutics is a relatively young specialty borne out of the rapidly increasing contribution that drug treatments have made to medical practice in the second half of the century. This, in turn, has been driven by a thriving pharmaceutical industry, much of which is UK based. Its development has been underpinned by the recognition that newly available drugs must be assessed in unbiased controlled clinical trials designed, conducted, and analysed to the highest possible standards. Meanwhile, improved measurement techniques of both drugs and their metabolites, and the body's response to them, have increased understanding of pharmacokinetics and pharmacodynamics. Understanding of the potential mechanisms of drug action has increased, increasing the number of target sites for new drug development. Drugs are also used as tools to understand physiological and pathophysiological processes.

The arrival of molecular genetics with mapping of the human genome is set to revolutionise the specialty in the next century. The latest scientific techniques will lead to the discovery of many hitherto unknown target sites and, subsequently, to the design of specific drugs modelled to interact with them. Doctors can expect new, highly specific drugs to progressively replace the blunter pharmacological approaches of past decades. The next generation of clinical pharmacologists will be involved in developing methods to measure the effects of these new drugs in patients.

Training in clinical pharmacology provides the opportunity to develop a career in many different areas of medical practice, with all clinical pharmacologists sharing the traits of enthusiasm and expertise in the development, evaluation, and use of drugs. As well as practising medicine in the NHS, clinical pharmacologists also fulfil a wide variety of other roles (see box).

Traditionally, clinical pharmacologists have combined their specialist interest with a commitment to general internal medicine, usually in a teaching hospital. However, the future …
Independent prognostic impact of lympho-vascular invasion in cutaneous melanoma patients with sentinel lymph node biopsy
Authors: R. Luca, M. Rizzo, P. Mando, C. Perez de La Puente, A. Blanco, S. Rivero, G. Lutter, F. Cappuccio, M. Amat, J. Kaplan, R. Chacon, M. Chacon
Journal: Annals of Oncology (2017)
Development of a web-based application using machine learning algorithms to facilitate systematic literature reviews
Authors: H-L. Wong, T. Luechtefeld, A. Prawira, Z. Patterson, J. Workman, D. Day, N. Chooback, L. Nappi, H.H. Samawi, J-M. Lavoie, A. Spreafico, A.R. Hansen, S. Sahebjam, L.L. Siu, S.P. Ivy, C. Paller, D. Renouf
Journal: Annals of Oncology (2017)
Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes
Authors: Ming-Wai Yeung, Grace Lai-Hung Wong, Kai Chow Choi, Andrea On-Yan Luk, Raymond Kwok, Sally She-Ting Shu, Anthony Wing-Hung Chan, Eric Siu Him Lau, Ronald Ching Wan Ma, Henry Lik-Yuen Chan, Juliana Chung-Ngor Chan, Vincent Wai-Sun Wong, Alice Pik-Shan Kong
Journal: Journal of Hepatology (2017)
GW28-e0748 Where is the lumen of the coronary artery in acutely or chronically occluded artery (during primary PCI for ST segment Elevation Myocardial Infarction or during PCI for CTO)?
Authors: Thach Nguyen, Le Thi Thuy Linh, Thai Ba Anh Minh, Luong Ngoc Tuyet Nhi, Gianluca Rigatelli
Journal: Journal of the American College of Cardiology (2017)
The investigate relationship between severe neutropenia and ABCB1and ABCG2 gene polymorphisms with esophageal cancer patients receiving docetaxel, cisplatin and 5-fluorouracil chemotherapy
Authors: H. Nomura, D. Tsuji, K. Demachi, S. Suzuki, N. Mochizuki, T. Yano, H. Daiko, S. Fujii, T. Kojima, K. Ito, M. Yamaguchi
Journal: Annals of Oncology (2017)
Spotlight on measles 2010: Measles outbreak in the Provence-Alpes-Côte d’Azur region, France, January to November 2010 - substantial underreporting of cases
Authors: C Six, J Blanes de Canecaude, J L Duponchel, E Lafont, A Decoppet, M Travanut, J M Pingeon, L Coulon, F Peloux-Petiot, P Grenier-Tisserant, J C Delarozière, F Charlet, P Malfait
Journal: Eurosurveillance (2010)

Binary file ES_Abstracts_Final_ECDC.txt matches
Phase 1/2 study of the selective TRK inhibitor larotrectinib, in pediatric patients with cancer
Authors: S. Gallego Mélcon, M. Casanova, S. Bielack, J. Chisholm, C.S. van Tilburg, N. Federman, C.M. Albert, L. Mascarenhas, B. Turpin, R. Nagasubramanian, N. Shukla, S. Spunt, M.C. Cox, D.S. Hawkins, A.S. Pappo, F. Doz, G. Bisogno, S.G. Dubois, T.W. Laetsch, B. Geoerger
Journal: Annals of Oncology (2017)
Abstract 16695: Percutaneous Coronary Intervention and Antiplatelet Therapy on Apixaban or Warfarin: Insights From the ARISTOTLE Trial
Authors: David Kopin, Matthew W Sherwood, W. Schuyler Jones, Daniel M Wojdyla, Basil S Lewis, Freek Verheugt, Lars Wallentin, Christopher B Granger, Renato D Lopes, John H Alexander
Journal: Circulation (2016)

Background:  Few data exist about the combination of dual antiplatelet therapy (DAPT) and direct oral anticoagulants. Patients on DAPT were excluded from ARISTOTLE, but those who underwent percutaneous coronary intervention (PCI) during follow-up were allowed to continue study drug in addition to antiplatelet therapy.   Methods:  All patients in the intention-to-treat group of ARISTOTLE were included. Groups were divided based on performance of PCI during follow-up. Baseline clinical characteristics, PCI frequency, rates of concomitant antiplatelet therapy use, and post-PCI outcomes including stroke/SE and bleeding were reported.   Results:  Of 18,201 patients, 318 (1.7%) underwent PCI (apixaban group [n=153], warfarin group [n=165]) during the trial. Those who underwent PCI were more likely to have valvular heart disease, a history of TIA, and a higher CHADS 2  score but had similar rates of diabetes, prior MI, and CHF. Patients were on study drug at the time of PCI 78.3% of the time (n=249). Of these, 42 (16.8%) did not stop study drug, 78 (31.3%) stopped study drug at time of PCI and restarted >5 days after PCI, and 129 (51.8%) stopped and restarted  30 days) was used in 34.9% of patients, aspirin without P2Y12 was used in 23.1%, P2Y12 therapy without aspirin was used in 12.8%, and 29.2% reported using neither. In the post-PCI subgroup, apixaban-assigned patients had numerically similar rates of ISTH major bleeding (5.93 vs 5.82 events/100 pt-yrs) and stroke (2.74 vs 2.49 events/100 pt-yrs) compared with warfarin-assigned patients.   Conclusions:  In patients in ARISTOTLE, PCI occurred infrequently during follow-up. A majority of patients were on study drug at time of PCI and 17% of patients never stopped drug despite PCI. DAPT was used only one-third of the time. Bleeding and stroke rates were numerically similar between apixaban and warfarin groups in the post-PCI subgroup. Additional data are needed to guide apixaban use in patients undergoing PCI.
<i>Vital Signs</i>: Trends in Incidence of Cancers Associated with Overweight and Obesity — United States, 2005–2014
Authors: C. Brooke Steele, Cheryll C. Thomas, S. Jane Henley, Greta M. Massetti, Deborah A. Galuska, Tanya Agurs-Collins, Mary Puckett, Lisa C. Richardson
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Overweight and obesity are associated with increased risk of at least 13 different types of cancer.Data from the United States Cancer Statistics for 2014 were used to assess incidence rates, and data from 2005 to 2014 were used to assess trends for cancers associated with overweight and obesity (adenocarcinoma of the esophagus; cancers of the breast [in postmenopausal women], colon and rectum, endometrium, gallbladder, gastric cardia, kidney, liver, ovary, pancreas, and thyroid; meningioma; and multiple myeloma) by sex, age, race/ethnicity, state, geographic region, and cancer site. Because screening for colorectal cancer can reduce colorectal cancer incidence through detection of precancerous polyps before they become cancerous, trends with and without colorectal cancer were analyzed.In 2014, approximately 631,000 persons in the United States received a diagnosis of a cancer associated with overweight and obesity, representing 40% of all cancers diagnosed. Overweight- and obesity-related cancer incidence rates were higher among older persons (ages ≥50 years) than younger persons; higher among females than males; and higher among non-Hispanic black and non-Hispanic white adults compared with other groups. Incidence rates for overweight- and obesity-related cancers during 2005-2014 varied by age, cancer site, and state. Excluding colorectal cancer, incidence rates increased significantly among persons aged 20-74 years; decreased among those aged ≥75 years; increased in 32 states; and were stable in 16 states and the District of Columbia.The burden of overweight- and obesity-related cancer is high in the United States. Incidence rates of overweight- and obesity-related cancers except colorectal cancer have increased in some age groups and states.The burden of overweight- and obesity-related cancers might be reduced through efforts to prevent and control overweight and obesity. Comprehensive cancer control strategies, including use of evidence-based interventions to promote healthy weight, could help decrease the incidence of these cancers in the United States.
Um surto de hepatite A em HSH em ligação com relações sexuais ocasionais e saunas gays em Copenhague, Dinamarca
Authors: A Mazick, M Howitz, S Rex, I P Jensen, N Weis, T L Katzenstein, J Haff, K Mølbak
Journal: Eurosurveillance (2005)

Em 2004, em Copenhague, na Dinamarca, durante um surto de hepatite A principalmente relacionado com homens que tem relacoes sexuais com outros homens, um estudo caso-controle foi feito para identificar os factores de risco de infeccao. Um caso foi definido como um HSH de mais de 17 anos, vivendo em Copenhaga, infectado pelo virus da hepatite A com IgM positivos diagnosticados entre junho e agosto de 2004 e que nao tiveram contacto com um caso de hepatite A entre os seus parentes antes da doenca aparecer. Os controles foram seleccionados no Festival da Gay Pride de Copenhague. O estudo incluiu 18 casos e 64 controles. Dezesseis casos e 36 controles tinham parceiros sexuais ocasionais (ORMH 5,6, 95% CI 1,2-26,9). Onze casos e 14 controles tinham tido relacoes sexuais nos saunas gays (ORMH 4,2, 95% CI 1,5-11,5). Parece que relacoes que tinham ocorrido em casas privadas fossem protectoras (ORMH 0,2, 95% CI 0,1-0,7). As relacoes occasionais incluindo relacoes em saunas gays eram um factor de risco importante para a disseminacao do VHA em HSH em Copenhague. Os resultados concordem com aqueles que foram observados em outros surtos na Europa. A immunidade geral frente a hepatite A tendo baixado e o potencial epidemico crescido, recomendamos uma educacao sobre estes assuntos de saude, como tambem a vacina contre a hepatite A para todos os homens homosexuais que nao vivem em casais estaveis, particularmente se visitarem saunas gays ou outros lugares aonde cambios de parceiro sao frequentes. Para parar a disseminacao da hepatite A nos homens homosexuais na Europa, um consenso ao nivel europeu- sobre as medidas de prevencao e controle poderia ser necessario.
AB0438 Body Mass Index and Response to Tocilizumab in Rheumatoid Arthritis: A Real Life Study
Authors: A. Gardette, S. Ottaviani, J. Sellam, F. Berenbaum, F. Lioté, A. Meyer, B. Fautrel, E. Palazzo, P. Dieudé
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Several studies have suggested that obesity could have a negative influence on the response to anti-TNFα, including infliximab, in rheumatoid arthritis (RA) and spondyloarthritis. Little is known about the impact of body mass index (BMI) on other biologic agents. <h3>Objectives</h3> The purpose of this study was to evaluate the influence of BMI on response to tocilizumab (TCZ) in RA. <h3>Methods</h3> A total of 115 RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After six months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, tender and swollen joints, and consumption of corticosteroids were analyzed. The primary endpoint was decrease in DAS28 ≥1.2. Secondary outcomes were good EULAR response and EULAR remission. <h3>Results</h3> At baseline, the median [interquartile range] BMI was 25.4 [22.0-28.8] kg/m<sup>2</sup>. The number of patients with normal weight, overweight and obesity was 53, 37 and 25, respectively. Baseline characteristics did not differ between the three subgroups of BMI. After six months, the number of RA patients with DAS28 decrease ≥1.2, EULAR good response and remission was 83 (72.2%), 44 (38.3%) and 37 (32.2%), respectively. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1-29.9] <i>vs.</i> 24.9 [22.0-27.1], P=0.38), EULAR good response (25.9 [22.8-30.0] <i>vs.</i> 25.4 [22.0-28.4], P=0.61) and remission (25.1 [22.5-28.6] <i>vs.</i> 25.4 [22.0-28.9], P=0.76). <h3>Conclusions</h3> In contrast to anti-TNFα agents, this study did not show any influence of BMI on response to TCZ in RA. However, prospective studies are needed to confirm these results that could be useful for the selection of biologics in obese RA patients. <h3>Disclosure of Interest</h3> None declared
Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes
Authors: Peiman Nazerian, Christian Mueller, Alexandre de Matos Soeiro, Bernd A. Leidel, Sibilla Anna Teresa Salvadeo, Francesca Giachino, Simone Vanni, Karin Grimm, Múcio Tavares Oliveira, Emanuele Pivetta, Enrico Lupia, Stefano Grifoni, Fulvio Morello, Elisa Capretti, Matteo Castelli, Simona Gualtieri, Federica Trausi, Stefania Battista, Paolo Bima, Federica Carbone, Maria Tizzani, Maria G. Veglio, Patrick Badertscher, Jasper Boeddinghaus, Thomas Nestelberger, Raphael Twerenbold
Journal: Circulation (2017)

Acute aortic syndromes (AASs) are rare and severe cardiovascular emergencies with unspecific symptoms. For AASs, both misdiagnosis and overtesting are key concerns, and standardized diagnostic strategies may help physicians to balance these risks. D-dimer (DD) is highly sensitive for AAS but is inadequate as a stand-alone test. Integration of pretest probability assessment with DD testing is feasible, but the safety and efficiency of such a diagnostic strategy are currently unknown.In a multicenter prospective observational study involving 6 hospitals in 4 countries from 2014 to 2016, consecutive outpatients were eligible if they had ≥1 of the following: chest/abdominal/back pain, syncope, perfusion deficit, and if AAS was in the differential diagnosis. The tool for pretest probability assessment was the aortic dissection detection risk score (ADD-RS, 0-3) per current guidelines. DD was considered negative (DD-) if <500 ng/mL. Final case adjudication was based on conclusive diagnostic imaging, autopsy, surgery, or 14-day follow-up. Outcomes were the failure rate and efficiency of a diagnostic strategy for ruling out AAS in patients with ADD-RS=0/DD- or ADD-RS ≤1/DD-.A total of 1850 patients were analyzed. Of these, 438 patients (24%) had ADD-RS=0, 1071 patients (58%) had ADD-RS=1, and 341 patients (18%) had ADD-RS >1. Two hundred forty-one patients (13%) had AAS: 125 had type A aortic dissection, 53 had type B aortic dissection, 35 had intramural aortic hematoma, 18 had aortic rupture, and 10 had penetrating aortic ulcer. A positive DD test result had an overall sensitivity of 96.7% (95% confidence interval [CI], 93.6-98.6) and a specificity of 64% (95% CI, 61.6-66.4) for the diagnosis of AAS; 8 patients with AAS had DD-. In 294 patients with ADD-RS=0/DD-, 1 case of AAS was observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1.9) and an efficiency of 15.9% (95% CI, 14.3-17.6) for the ADD-RS=0/DD- strategy. In 924 patients with ADD-RS ≤1/DD-, 3 cases of AAS were observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1) and an efficiency of 49.9% (95% CI, 47.7-52.2) for the ADD-RS ≤1/DD- strategy.Integration of ADD-RS (either ADD-RS=0 or ADD-RS ≤1) with DD may be considered to standardize diagnostic rule out of AAS.URL: https://www.clinicaltrials.gov. Unique identifier: NCT02086136.
Pathological response in a triple-negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann’s refined classification (TNBCtype-4)
Authors: I. Echavarria Diaz-Guardamino, A.C. Picornell, S. López-Tarruella, Y. Jerez, K. Hoadley, E. Alvarez, M. del Monte-Millán, J. Gayarre, R. Ramos-Medina, T. Massarrah, I. Ocaña, M. Cebollero, F. Moreno Antón, J.A. García-Saenz, H. Gomez Moreno, H. Fuentes, A.I. Ballesteros Garcia, U. Bohn Sarmiento, C. Perou, M. Martin Jimenez
Journal: Annals of Oncology (2017)
GW28-e1142 Thrombin-loaded alginate-calcium microspheres: a novel hemostatic embolic material for transcatheter arterial embolization
Authors: Jingjing Rong, Ming Liang, Fengqi Xuan, Jingyang Sun, Lijun Zhao, Huizhen Zheng, Xiaoxiang Tian, Dan Liu, Quanyu Zhang, Chengfei Peng, Fei Li, Xiaozeng Wang, Yaling Han, Weiting Yu, Wang Shuang
Journal: Journal of the American College of Cardiology (2017)
Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma
Authors: Eunice Del Rosario, Stephanie Florez-Pollack, Lucio Zapata, Katia Hernandez, Andrea Tovar-Garza, Michelle Rodrigues, Linda S. Hynan, Amit G. Pandya
Journal: Journal of the American Academy of Dermatology (2017)
A Phase I/II study everolimus in combination with paclitaxel-carboplatin in patients with advanced adenocarcinoma of the stomach
Authors: H.H. Loong, F. Mo, L. Li, C. Lee, K-C. Lam, J. Koh, P. Chiu, A. Teoh, A.T.C. Chan, E. Ng, W. Yeo
Journal: Annals of Oncology (2017)
Limits on working hours may be relaxed after Brexit, warns employment expert
Authors: Anne Gulland
Journal: BMJ (2017)

Legal protections ensuring that doctors do not breach limits on safe working hours could be eroded after the UK leaves the European Union, an employment expert has warned.

Jason Heyes, professor of employment relations at Sheffield University, told a meeting discussing Brexit’s effect on healthcare that the European Union’s working time regulations, which ensure that doctors do not work for more than an average of 48 hours a week and guarantee rights such as rest breaks and holidays, might be targeted by a Conservative government when the UK leaves the EU.

“Once UK policy makers have the ability to start tinkering with working time regulations they will start doing so,” he told the meeting, organised by …
GW28-e0751 Clinical Characteristics, Microbiological Profile And Risk Factors For In-Hospital Mortality Of Infective Endocarditis
Authors: Hoang Minh Tran, Vien Thanh Truong, Pham Phuong Linh, Nguyen Minh Tri Nhan, Thach Nguyen, Gianluca Rigatelli
Journal: Journal of the American College of Cardiology (2017)
Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials
Authors: Alex Tsodikov, Roman Gulati, Eveline A.M. Heijnsdijk, Paul F. Pinsky, Sue M. Moss, Sheng Qiu, Tiago M. de Carvalho, Jonas Hugosson, Christine D. Berg, Anssi Auvinen, Gerald L. Andriole, Monique J. Roobol, E. David Crawford, Vera Nelen, Maciej Kwiatkowski, Marco Zappa, Marcos Luján, Arnauld Villers, Eric J. Feuer, Harry J. de Koning, Angela B. Mariotto, Ruth Etzioni
Journal: Annals of Internal Medicine (2017)

The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction.To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO.Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models.Randomized controlled trials in Europe and the United States.Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization.Prostate cancer screening.Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began.Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening.The MLT is a simple metric of screening and diagnostic work-up.After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality.National Cancer Institute.
RNA Regulations and Functions Decoded by Transcriptome-Wide RNA Structure Probing
Authors: Meiling Piao, Lei Sun, Qiangfeng Cliff Zhang
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract RNA folds into intricate structures that are crucial for its functions and regulations. To date, a multitude of approaches for probing structures of the whole transcriptome, i.e., RNA structuromes, have been developed. Applications of these approaches to different cell lines and tissues have generated a rich resource for the study of RNA structure–function relationships at a systems biology level. In this review, we first introduce the designs of these methods and their applications to study different RNA structuromes. We emphasize their technological differences especially their unique advantages and caveats. We then summarize the structural insights in RNA functions and regulations obtained from the studies of RNA structuromes. And finally, we propose potential directions for future improvements and studies.
Long‐term safety of intravenous cardiovascular agents in acute heart failure: results from the European Society of Cardiology Heart Failure Long‐Term Registry
Authors: Alexandre Mebazaa, Justina Motiejunaite, Etienne Gayat, Maria G. Crespo‐Leiro, Lars H. Lund, Aldo P. Maggioni, Ovidiu Chioncel, Eiichi Akiyama, Veli‐Pekka Harjola, Petar Seferovic, Cecile Laroche, Marisa Sanz Julve, Eulalia Roig, Frank Ruschitzka, Gerasimos Filippatos
Journal: European Journal of Heart Failure (2017)