tbuckley/cabot-search huggingface dataset:
Reducing Perceived Pain Levels During Nonbreast Lymphoscintigraphy
Authors: Mickaila J. Johnston, James A. Ntambi, Nicki Hilliard, Horace J. Spencer, Rita Vaughn, Shawna S. Owens, Rebecca S. Myrick, Larry D. Parker, Douglas A. Garner, Tracy L. Yarbrough
Journal: Clinical Nuclear Medicine (2015)

The aim of this study was to quantify the reduction of perceived pain levels during lymphoscintigraphy for melanoma by altering the pH of the Tc-sulfur colloid to near the physiologic value of 7.40.This is an institutional review board- and Food and Drug Administration-approved randomized, double-blinded, prospective crossover trial, registered with clinicaltrials.org. Before beginning the procedure and after signing informed consent, 60 serial enrollees presenting for sentinel lymph node imaging of melanoma of the thorax and appendicular structures completed a questionnaire addressing background information, administered by a research support nurse.An investigator (N.H.) prepared the injections to be used and labeled them such that no one else could discover which injections contained standard-of-care solution and which contained the pH-altered solution (buffered to near pH 7.40 using sodium bicarbonate).After each injection, the enrollee was asked by a research support nurse to quantify the pain of each injection using a scale of 0 to 10. The injection site location (head, thorax, appendicular structures, and other) was also recorded.Sixty subjects were enrolled in the study, of which 57 had complete data. On average, there was a significant mean (SD) decrease of 1.42 (2.17) points (95% confidence interval, 0.85-2.00) on a pain scale of 0 to 10 when the buffered injections were used as compared with the standard-of-care injections (P < 0.0001). Ordering of injections did not significantly affect perceived pain scores.The use of sodium bicarbonate to buffer the pH of Tc-sulfur colloid to near the physiologic value of 7.40 significantly reduced perceived pain levels during nonbreast lymphoscintigraphy.
A multicentric observational trial with metastatic breast cancer (MBC) patients on pegylated liposomal doxorubicin (PLD) regimen
Authors: J. B. Huober, W. Fett, A. Nusch, M. Neise, M. Schmidt, A. Wischnik, S. Gerhard, T. Goehler, A. Rost
Journal: Journal of Clinical Oncology (2008)

1139 Background: PLD is approved for the treatment of MBC. In 2 randomized phase III studies in MBC patients (pts), PLD showed equal efficacy vs doxorubicin or vinorelbine in 1st- or 2nd-line setting, respectively. In this observational study, the toxicity profile and efficacy of PLD was analyzed under routine conditions. Methods: 125 MBC pts were recruited from June 03 until Nov 05 at 34 sites. ECOG status was 0–1 in 78% of pts. Median age was 62 years (37–84), median number of metastatic sites was 2 (1–5). 52% of pts were in 1st- or 2nd-line, 46% in 3rd - 6th-line therapy. 56% (n=70) of pts were pretreated with an anthracycline-containing regimen and 71% had previous endocrine treatment. Median PLD dose was 40 mg/m² (15–50 mg/m²) with the administration every 4 weeks being the most frequently used (range 2–5). 649 treatment courses were analyzed, the median number of cycles was 4 (1–12). Results: Leucopenia was the most prominent hematologic toxicity, with 3 pts developing grade 3 and 1 pt developing grade 4 toxicity. Only 2 pts had grade 3/4 thrombocytopenia. The predominant nonhematologic toxicity was skin toxicity, observed in 44 pts (20/16/5/1 pts with grade 1,2,3,4 toxicities respectively). No clinical signs, nor symptoms of cardiovascular toxicity were seen. No grade 3, 4 alopecia occurred. In 22% of pts dose reductions and in 30% of pts treatment delays were recorded. 53 pts (42%) showed response to therapy with 6 pts (4.8%) achieving complete remission (CR) and 47 pts (37.6%) PR; 37 pts (30%) had stable disease (SD), and 28 pts (22%) progression (PD); in 7 pts response was unknown. In anthracycline pretreated pts, in 24 cases (34%) response to therapy was observed (2 CR, 22 PR); 25 pts (36%) had SD and 17 pts (24%) PD. In the overall population, median progression-free interval and overall survival (OS) was 7.2 (95% CI: 5.4–8.6), and 20.8 months (95% CI: 15.4–22.6), respectively. Conclusions: In this observational study, PLD therapy was effective and well tolerated, even in heavily pretreated pts. This data compares favourably with data from published randomized trials. Supported by ESSEX Pharma Germany Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Essex Pharma
Abstract 1140: Chronic Exercise Protects against Macro- and Micro- vascular Endothelial Dysfunction Induced by Acute Hypertension during Exertion
Authors: Shane A Phillips, Lewis B Somberg, Aaron Perme, Emon K Das, David D Gutterman
Journal: Circulation (2007)

Introduction: Exercise is recommended to reduce cardiovascular disease risk. However, exercise-induced hypertension may threaten vascular endothelial health. Previous studies indicate conditioned s...
Abstract 16346: Soluble P-Selectin Predicts Lower Extremity Peripheral Artery Disease Incidence and Change in the Ankle Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Christina L Wassel, Cecilia Berardi, James S Pankow, Nicholas B Larson, Paul A Decker, Naomi Q Hanson, Michael Y Tsai, Michael H Criqui, Matthew A Allison, Suzette J Bielinski
Journal: Circulation (2014)

Background: Given the global burden of peripheral arterial disease (PAD) and the associated morbidity, continuing investigation of potential biomarkers as therapeutic targets for preventing PAD is warranted. The association of P-selectin, an endothelial cell adhesion molecule, with the ankle brachial index (ABI) and PAD is not well established. Thus, we examined the association of circulating P-selectin with prevalent and incident PAD, the ABI, and change in the ABI. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective population-based cohort including 6814 non-Hispanic white, African American, Hispanic and Chinese men and women aged 45-84 at baseline (2000-02). For this analysis, 5700 participants with both P-selectin at Exam 2 (2002-04) and the ABI at Exam 3 (2004-05) were available, with change in ABI from Exam 3 to Exam 5 (2010-12) available on 4276 participants. P-selectin was modeled per standard deviation (SD), while prevalent and incident PAD were defined as ABI ≤ 0.90 after excluding those with ABI&gt;1.4. Linear regression was used for ABI, growth curve models for change in ABI, and logistic regression for prevalent and incident PAD. Results: In models adjusted for demographics, lifestyle factors, comorbidities, blood pressure, lipids, fasting glucose, c-reactive protein (CRP), interleukin-6 (IL-6), D-dimer, and fibrinogen, each SD (13 ng/mL) higher P-selectin was significantly associated with 0.007 lower ABI (95% CI ((-0.011, -0.004)), p&lt;0.001), and an average change in the ABI of -0.006 ((-0.010, -0.003, p&lt;0.001). P-selectin was also significantly associated with a 1.14-fold greater odds of prevalent PAD ((1.00, 1.28), p=0.04), and a 1.30-fold greater odds of incident PAD ((1.10, 1.55), p&lt;0.001). There were no significant interactions of p-selectin by race/ethnicity or gender. Addition of P-selectin to models containing traditional PAD risk factors as well as CRP, IL-6, D-dimer and fibrinogen did not improve the c-statistic or net reclassification for incident PAD. Conclusions: P-selectin appears to be strongly associated with the development of PAD. However, further research is needed in population-based studies to confirm prospective associations of p-selectin with incident PAD and change in the ABI.
Nova et Vetera
Authors: R S FRANCE, A FESSLER
Journal: BMJ (1949)

REPORTS OF SOCIETIESand worry, and lack of rest that played so large a part in causing relapse were aggravated by child-rearing, and the difficulties in bringing up a child must be taken into account when the ques- tion of termination was considered.No tuberculous patient should bring up a child without help in the home, especially at night, for the early months.The mother of the unwanted child
Anti-Inflammatory Effects of Pioglitazone and/or Simvastatin in High Cardiovascular Risk Patients With Elevated High Sensitivity C-Reactive Protein
Authors: Markolf Hanefeld, Nikolaus Marx, Andreas Pfützner, Werner Baurecht, Georg Lübben, Efstrathios Karagiannis, Ulf Stier, Thomas Forst
Journal: Journal of the American College of Cardiology (2007)
Abstract 17304: Dense Genotyping of Candidate Gene Loci Identifies Variants Associated with Soluble E-Selectin Levels
Authors: Mahir Karakas, Jens Baumert, Barbara Thorand, Wolfgang Rottbauer, Christa Meisinger, Thomas Illig, Wolfgang Koenig
Journal: Circulation (2011)

Background: Elevated soluble (s) E-selectin levels have been associated with various cardiovascular diseases. Recently, genetic variants in the ABO blood group have been related to E-selectin levels in a small cohort of patients with type 1 diabetes. We evaluated whether this association is reproducible in a population-based sample. Methods: We used a high-density genotyping array containing single-nucleotide polymorphisms (SNPs) from E-selectin candidate genes (50K IBC Chip) selected on known biology of E-selectin metabolism, mouse genetic studies, and human genetic association studies. SNP selection was based on tagging SNPs and included low-frequency nonsynonymous SNPs. 1,508 men and women from a randomly drawn subsample of the baseline examination of the MONICA/KORA Augsburg Cohort Study, conducted between 1984 and 1995, with measurements of sE-selectin and genotyping by the 50K IBC Chip comprised the study population. Linear regression analysis with adjustment for age, sex and survey was applied to assess associations between gene variants and sE-selectin levels. The significance level was defined as 5.0e-6 accounting for multiple testing. Results: Twelve SNPs, all from the ABO blood group candidate gene (ABO) were significantly associated with levels of E-selectin. The strongest association was observed for rs651007 with a change of E-selectin level per one copy of the minor allele of -18.59 ng/ml (p=5.79*10-56). All twelve SNPs had minor allele frequencies above 20% showing a substantial gene variation. Conclusions: Our findings indicate that the genetic variants at the ABO locus affect sE-selectin levels. These findings may not only enhance our understanding of adhesion molecule biology, but may also provide a focus for several novel research avenues.
Use of Rapamycin to inhibit VEGF for the treatment of primary effusion lymphoma
Authors: Paola Gasperini, Giovanna Tosato
Journal: Cancer Research (2008)

293   Primary effusion lymphoma (PEL) is a fatal lymphoma associated with Kaposi’s sarcoma herpesvirus (KSHV) infection that typically presents as a malignant effusion in body cavities and later disseminates. There is a need for new therapies for PEL as most patients rapidly succumb in spite of high-dose chemotherapy. We developed a murine model of PEL that closely mimics the human disease to evaluate the anti-tumor activities of Rapamycin, which targets mTOR (mammalian target of Rapamycin), an effector of cell-signaling pathways often deregulated in cancer. We found that Rapamycin markedly delayed PEL development, significantly reduced ascites accumulation (P=0.009), prevented solid tumor formation, and significantly extended mouse survival (P
Abstract 13218: Variation in Interstage Outpatient Care after the Norwood Procedure: Report from the National Quality Improvement Collaborative
Authors: David N Schidlow, Jeffrey B Anderson, Thomas S Klitzner, Robert H Beekman, Kathy J Jenkins, John D Kugler, Gerard R Martin, Steven R Neish, Geoffrey L Rosenthal, Carole Lannon
Journal: Circulation (2010)

The NPC-QIC is the first quality improvement collaborative in pediatric cardiology, and its registry captures information on interstage care and outcomes of infants after the Norwood procedure. The...
Patients have strong input into purchasing decisions in Droitwich
Authors: S. Field, A. Giles
Journal: BMJ (1996)

Rationing health carePoliticians do not want to duck the issues EDrIOR,-Richard Smith's view that British political leaders will not accept the challenge of leading the debate on health care rationing is, I suspect, widely held.'However, like many widely held views, it is not wholly accurate.The ration- ing of health services was the focus of the most wide ranging inquiry by the House of Commons Select Committee on Health in this parliament.In 1994, we spent 10 weeks taking evidence on priority setting in the NHS from a variety of bodies, including health authorities, fundholding general practitioners, academics, royal colleges, and, of course, the BMA.2Our subsequent report was an attempt to stimu- late public debate on the subject.3Central to our conclusions were that the availability of NHS serv- ices should always be founded on the principles of equity, public choice, and the effective use of resources.It was also central that purchasers' decision making processes should be systematic; be transparent; take full account of the views of the public, health professionals, and other interested parties; be based on a firm assessment ofneed; and make full use of effectiveness and cost effectiveness data.We did indeed talk of increasing the effective- ness of health care, but we also recognised that the need to set priorities in the NHS has been, and will be, always with us.Any attempt to examine the question of NHS rationing in a serious and systematic manner, by health professionals, academics, and the public at large is to be welcomed.However, it is politicians who will be called on to oversee the rationing process, and politicians should not, as you rightly suggest, attempt to duck the issue.I believe that our report will provide a useful starting point for anybody who wants to move the debate on health care rationing forward.
NCCN Task Force Report: mTOR Inhibition in Solid Tumors
Authors: Robert A. Figlin, Elizabeth Brown, Andrew J. Armstrong, Wallace Akerley, Al B. Benson, Harold J. Burstein, David S. Ettinger, Phillip G. Febbo, Matthew G. Fury, Gary R. Hudes, Merrill S. Kies, Eunice L. Kwak, Robert J. Morgan, Joanne Mortimer, Karen Reckamp, Alan P. Venook, Frank Worden, Yun Yen
Journal: Journal of the National Comprehensive Cancer Network (2008)

The mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving cell cycle progression, proliferation, and angiogenesis. These pathways are frequently dysregulated in cancer, and therefore mTOR inhibition is a potentially important antitumor target. Commercially available mTOR inhibitors include rapamycin (i.e., sirolimus) and temsirolimus. Other agents under investigation include everolimus and deforolimus. mTOR inhibition has been studied in various solid tumors, including breast, gynecologic, gastrointestinal, prostate, lung, and head and neck cancers. Studies have focused on mTOR inhibition as a monotherapy or in combination with other drugs based on the principle that inhibiting as many targets as possible reduces the emergence of drug resistance. Temsirolimus is currently the only mTOR inhibitor that is specifically labeled for treatment of solid tumors. However, preclinical studies and early-phase trials are rapidly evolving. Additionally, research is further defining the complicated mTOR pathways and how they may be disordered in specific malignancies. To address these issues, NCCN convened a task force to review the underlying physiology of mTOR and related cellular pathways, and to review the current status of research of mTOR inhibition in solid tumors. (JNCCN 2008;6[Suppl 5]:S1—S20)
Abstract 15183: Do Two Scoring Systems of Coronary Stenosis, Syntax Score and Gensini Score, Similarly Predict Clinical Outcome After Pci in Patients With Stable Angina Pectoris?
Authors: Naoto Murakami, Nobuaki Kokubu, Junichi Nishida, Mamoru Hase, Takefumi Fujito, Mina Kawamukai, Atsushi Mochizuki, Hidemichi Kouzu, Atsuko Muranaka, Shinya Shimoshige, Satoshi Yuda, Akiyoshi Hashimoto, Kazufumi Tsuchihashi, Tetsuji Miura
Journal: Circulation (2014)

Background: Few studies have examined if two score systems of coronary stenosis, SYNTAX score and Gensini score, are different as predictors of prognosis in patients with coronary artery disease (CAD). Here we examined this issue in patients with stable CAD after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed 795 consecutive patients who underwent coronary angiography for suspected stable CAD from January 2007 to August 2012. One hundred fifty-nine patients received PCI according to consensus of the Heart Team in our institute and patients’ consents. Overall severity of coronary stenosis and complexity in each patient was quantified by both the SYNTAX score and Gensini score, and patients were divided into high score group and low score group by the mean of the score in overall patients. Follow-up period was 15.9 ± 14.4 months, and MACE was defined as a composite of cardiac death, myocardial infarction, target vessel revascularization and/or congestive heart failure. Results: The mean SYNTAX score and Gensini score were 19.0 ± 12.4 and 47.8 ± 26.9, respectively. Long-term MACE in a group with high SYNTAX score (≧19, n=71) tended to be higher than a group with low SYNTAX score (&lt;19, n=78), but not significant (Figure 1). However, long-term MACE was significantly higher in a group with high Gensini score (≧48, n=62) than that in a group with low Gensini score (&lt;48, n=97) (Figure 2). In receiver operating characteristic curve analysis, optimal cut-off value of Gensini score to predict MACE was 66.5, of which sensitivity and specificity were 41.2% and 85.6%, respectively (area under curve 0.63, p=0.008). Conclusion: Gensini score is not inferior to SYNTAX in prediction of the clinical outcome after PCI in patients with stable CAD. Prognosis after PCI is favorable in patients with low Gensini score (especially those with GS&lt;66.5).
Lapatinib plus Capecitabine in Breast Cancer
Authors: Guru Sonpavde
Journal: New England Journal of Medicine (2007)

n engl j med 356;14 www.nejm.org april 5, 2007 1471 cies. Nonstandardized empirical antibiotic therapy has confounded the interpretation of findings in some previous trials of the diagnosis of ventilator-associated pneumonia. Therefore, the initial antibiotic therapy in our trial, consisting of meropenem with or without ciprofloxacin, served to standardize empirical treatment until culture results became available. Patients with known pathogens not susceptible to these drugs were excluded; thus, differences observed in outcomes could be better attributed to the diagnostic strategy. It is important not to interpret the use of these antibiotics as clinical recommendations for the treatment of ventilator-associated pneumonia. The treatment guidelines of the American Thoracic Society were published after our trial had been completed.1 Daren Heyland, M.D. Queen’s University Kingston, ON K7L 2V7, Canada dkh2@post.queensu.ca
Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin
Authors: Jessica L Mega, David A Morrow, Alison Brown, Christopher P Cannon, Marc S Sabatine
Journal: Circulation (2008)

Background : LDL cholesterol (LDL-C) reduction in response to statins varies widely, with many patients not reaching target goals. We hypothesized that polymorphisms in LDL-C metabolism and statin pharmacokinetic genes would be associated with magnitude of LDL-C reduction with statin therapy. Methods : 49 tagging and candidate polymorphisms were selected in 9 genes and their associations with statin efficacy were tested in 1507 post-ACS subjects randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d. Results : Two variants in APOE (rs7412 and rs429358 ) were significantly associated with baseline LDL-C (P=7.9×10 −9 and P=0.0032) and determine the isoforms ϵ2, ϵ3, and ϵ4 of apolipoprotein E. After adjustment for baseline LDL-C and clinical features, the percent reduction in LDL-C from baseline to day 30 was greatest in ϵ2 carriers, intermediate in ϵ3/ϵ3 individuals, and least in ϵ4 carriers with atorvastatin (P trend =0.00039) and pravastatin (P trend =0.00038), (Fig , Top). The percent of subjects achieving an LDL-C of ≤70 mg/dl was higher for ϵ2 carriers than ϵ4 carriers (atorvastatin P trend =0.00037 and pravastatin P trend =0.0084) (Fig , Bottom). The HR for CV death, MI, or stroke over 2 yrs for ϵ2 carriers vs ϵ3/ϵ3 individuals was 0.78 (95% CI 0.40 – 1.51). Conclusion : Evaluating genetic variants in 9 genes, we found that carriers of APOE ϵ2 versus ϵ4 had significantly lower baseline LDL-C, greater LDL-C reduction with atorvastatin or pravastatin, and more frequently achieved a goal of LDL-C ≤70 mg/dl. These findings add to the understanding of the genetic mechanisms that influence statin efficacy and suggest that common variants, such as the ones in APOE , may help tailor treatments.
Formal measurement of clinical uncertainty: prelude to a trial in perinatal medicine
Authors: R Lilford
Journal: BMJ (1994)

Clinical trials are ethical when there is collective and balanced uncertainty about the best treatment among informed clinicians. This uncertainty can be identified either by observing differences in practice or, as explored here, by formal measurement of clinical belief.

Fetomaternal medicine is largely concerned with timing delivery of preterm fetuses that are failing to thrive. Delivery is indicated when prematurity is judged preferable to continued intrauterine life, but often the relative risks of these alternatives are unknown.1 During the planning of a trial to compare early with delayed delivery under different circumstances 10 specialists in fetomaternal medicine were interviewed about their beliefs.

The specialists were presented with four scenarios, one practice and three substantive, in each of which the decision between immediate and delayed delivery was difficult (see figure). They recorded their opinions on an analogue dial connected to a microcomputer. For each scenario respondents were asked what they thought the relative risk of permanent morbidity …