tbuckley/cabot-search huggingface dataset:
Join us at The Lancet Clinic
Authors: Sabine Kleinert, Richard Horton, Elena Becker-Barroso, Niall Boyce, David Collingridge, Justine Davies, Emma Grainger, Peter Hayward, John McConnell, Zoë Mullan, Lan-Lan Smith
Journal: The Lancet Infectious Diseases (2015)

On Oct 5, 2015, we launch the first 45 disease-specific pages of a major new online initiative involving all Lancet journals that will bring together an overview Seminar and relevant Reviews, Clinical Series, Commissions, research, Case Reports, and Clinical Pictures. Over the next 18 months or so when The Lancet Clinic is complete, there will be online pages for 135 diseases, which we have identified by a combination of global burden of disease data and clinical practice needs. We hope that The Lancet Clinic will help practising doctors make better informed decisions that ultimately lead to better lives of people worldwide, and help others who want to educate or update themselves keep abreast of the evolving evidence base. Importantly, these pages will be updated at regular intervals. The authors of newly commissioned Seminars have agreed to provide regular summaries of important new evidence for 4 years. Individual clinical editors will pull together newly published material from across the Lancet journals and post links to these on the page regularly. In addition, we are continuing our regular editorial policies of commissioning more specialised Clinical Reviews and Series across The Lancet Group to provide a more focused and in-depth assessment for key diseases. And beyond providing knowledge and information, we want to encourage academic and practising clinicians to use this knowledge for advocacy and change. In 2014, The Lancet published the first Clinical Commission on liver disease in the UK and in February, 2015, we launched our first Clinical Campaign based on this Commission. A Cancer Campaign as a joint effort between The Lancet and The Lancet Oncology followed in April. Clinical Campaigns aim to effect change based on data, knowledge, and expert interpretation in partnership with others. Further Clinical Commissions on asthma, hypertension, dementia, tuberculosis, traumatic brain injury, psychotherapy, chronic obstructive pulmonary disease, and others are underway across all Lancet journals. With these Clinical Commissions and Campaigns, we hope to extend our goal to publish the best science for better lives to being an active partner in using this science for actual change. Commissions and Campaigns will be part of the disease pages to encourage engagement and actions. The Lancet Clinic invites you to be part of this endeavour.
Targeting the Epidermal Growth Factor Receptor With Tyrosine Kinase Inhibitors: Small Molecules, Big Hopes
Authors: Jose Baselga
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.9.2217 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11980990 Targeting the Epidermal Growth Factor Receptor With Tyrosine Kinase Inhibitors: Small Molecules, Big Hopes Jose BaselgaxJose BaselgaSearch for articles by this author Show More Vall d'Hebron University Hospital, Barcelona, Spain https://doi.org/10.1200/JCO.2002.20.9.2217 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Therapeutic effects of the antivascular agent combretastatin A-1 phosphate on orthotopic and subcutaneous colorectal tumours in nude mice.
Authors: RB Pedley, E El Emir, SK Sharma, U Qureshi, Jab Dearling, Hj R
Journal: Cancer Research (2005)

3016  Many common solid tumours possess an extremely heterogeneous pathophysiology, and successful treatment requires a combination of therapeutic strategies. To optimise combined therapies, we need detailed microscopic information on regional tumour response to treatment. The combretastatins are a family of compounds that interact with tubulin at or near the colchicine binding site, producing vascular shut-down and resulting in central haemorrhagic necrosis of up to 95% of the tumour. We have previously studied the effects of combretastatin A4 phosphate (CA-4-P) in combination with antibody-targeted therapies, which has culminated in an on-going clinical trial. The current study investigates the therapeutic efficacy of combretastatin A-1 phosphate (CA-1-P), as a potential candidate for combined studies. CA-1-P was administered intraperitoneally at 40mg/kg to nude mice bearing either subcutaneous or orthotopic (metastatic deposits in the liver) SW1222 colorectal xenografts. Tumours were removed at selected time points, and a range of tumour parameters were studied concomitantly by quantitative fluorescence microscopy in order to demonstrate changes related to vascular shut-down (eg. blood vessels, hypoxia, perfusion). Subcutaneous tumours were studied at 40 min, 1, 3, 6, 24 and 48h post CA-1-P. Untreated tumours were mostly viable, with perfused blood vessels throughout and only small areas of hypoxia. Tumour perfusion had ceased in all but the tumour periphery by 40 min post CA-1-P, widespread hypoxia had developed by 1 h, and the centre of the tumour was becoming necrotic by 6 h after the drug. By 24h, only a thin outer rim of tumour cells survived. These effects were similar to those achieved with CA-4-P, but results were more reproducible and more dramatic. Orthotopic tumours were grown by intrasplenic injection of SW1222 tumour cells, and the effects of CA1P studied at 1 and 24h post treatment. Results were similar to those seen in the s.c. model. Central perfusion had ceased in most of the tumour deposits by 1h after treatment, but with no effect on normal liver. By 24h there was no resumption of perfusion within the tumour, and many of the deposits showed extensive central necrosis. In preliminary therapy experiments groups of 6 mice were given either no treatment, or CA-1-P (40mg/kg) i.p. on days 1, 8 and 21. CA-1-P alone significantly inhibited tumour growth compared with controls, which was not found when CA-4-P was used as a single agent. The potential for this novel antivascular agent to enhance antibody-targeted therapies is therefore promising, and the relevant experiments are currently underway. Supported by CR UK, EU FP6 (STROMA Project), NTRAC. CA1P supplied by Oxigene.
Causality, the menopause, and depression
Authors: M. Petticrew, L. Nicol-Smith
Journal: BMJ (1997)

Interferon beta in multiple sclerosis Reducing frequency and severity of relapses will be of great clinical benefitEditor-Richard G Richards's editorial on interferon beta in multiple sclerosis deals with the "clinical cost effectiveness" of the drug in the disease, but it lacks a fair balance, emphasising the cost effectiveness and minimising the clinical effectiveness of the drug. 1 Richards states that "the studies showed no evidence of any reduction in the more clinically relevant endpoint-the progression of disability, which should be the goal of treatment."This is his personal judgment and does not reflect the needs and wishes of patients with multiple sclerosis and their families.Multiple sclerosis is a distressing, humiliating, and often long drawn out disease with no cure.For this reason, quality of life, for the patients and their families, is paramount.A drug that can reduce the frequency and severity of relapses, whether or not it diminishes the progression of the disease, will be of great clinical benefit to many patients, improving their situation physically, psychologically, and socially.Surely happiness, feeling better, and increased health have great value.This is what many of us believe that the practice of our profession is about.
Synergistic growth inhibitory and differentiating effects of trimidox and tiazofurin in human promyelocytic leukemia HL-60 cells
Authors: T Szekeres, M Fritzer, H Strobl, K Gharehbaghi, G Findenig, HL Elford, C Lhotka, HJ Schoen, HN Jayaram
Journal: Blood (1994)
Siltuximab for Multicentric Castleman Disease—Letter
Authors: Raphael Teipel, Rainer Ordemann, Ulrike Proske, Frank Dietrich, Marika Mende, Gerhard Ehninger, Frank Kroschinsky, Uwe Platzbecker
Journal: Clinical Cancer Research (2015)

We read with great interest the article by Deisseroth and colleagues ([1][1]) focusing on the recent global approval of the monoclonal IL6 antibody siltuximab for the treatment of patients with HHV-8-, HIV-negative multicentric Castleman disease (MCD). Up to now, treatment options for this rare
The effect of food on and the intra-subject variability of the pharmacokinetics of ZD6474, a novel antiangiogenic agent, in healthy subjects
Authors: R. P. Smith, S. Kennedy, J. Robertson, D. Sandall, R. Oliver
Journal: Journal of Clinical Oncology (2004)

3167 Background: ZD6474 is an orally available, vascular endothelial growth factor (VEGF) receptor-2 tyrosine kinase inhibitor that also has activity against epidermal growth factor receptor (EGFR) tyrosine kinase, which is currently under Phase II evaluation in a range of tumor types. The effect of food on the absorption characteristics of ZD6474 are not known, therefore these studies have a restriction on dosing with food. The effect of food on the pharmacokinetics of ZD6474 has now been assessed in healthy male volunteers. In the same study intra-subject variability in pharmacokinetics was also determined to ensure correct sizing of future clinical pharmacology studies. Methods: Sixteen volunteers were randomized to receive a single oral dose of ZD6474 (300 mg) on each of three occasions: once 30 minutes after a standard high-fat breakfast and twice under fasted conditions, or once under fasted conditions and twice 30 minutes after a standard high-fat breakfast. Due to the long half-life of approximately 10 days there was a 6-week washout between each treatment period. The effect of food on the absorption of ZD6474 compared with fasted conditions was assessed using the criteria for establishing bio-equivalence based on the end-points of Cmax and AUC. These parameters were also used to assess the intra-subject variability. Results: Statistical analysis of provisional data showed there was no clinically significant effect on either Cmax or AUC of ZD6474 when dosed with food compared with the fasted state. In addition, the overall intra-subject variability of ZD6474 was small (coefficients of variation [CVs] of 8% and 11% for AUC and Cmaxrespectively), and appears to decrease when ZD6474 is taken with food (AUC CVs of 5% and 10% and Cmax 10% and 13% for fed and fasted respectively). Conclusions: These data indicate that the restriction on dosing with food can be removed from patient studies with the assurance that the day to day variability in exposure to ZD6474 will not increase as a result of patients taking their daily ZD6474 dose with or without food. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy
Authors: An Moonen, Vito Annese, Ann Belmans, Albert J Bredenoord, Stanislas Bruley des Varannes, Mario Costantini, Bertrand Dousset, J I Elizalde, Uberto Fumagalli, Marianne Gaudric, Antonio Merla, Andre J Smout, Jan Tack, Giovanni Zaninotto, Olivier R Busch, Guy E Boeckxstaens
Journal: Gut (2015)

<h3>Objective</h3> Achalasia is a chronic motility disorder of the oesophagus for which laparoscopic Heller myotomy (LHM) and endoscopic pneumodilation (PD) are the most commonly used treatments. However, prospective data comparing their long-term efficacy is lacking. <h3>Design</h3> 201 newly diagnosed patients with achalasia were randomly assigned to PD (n=96) or LHM (n=105). Before randomisation, symptoms were assessed using the Eckardt score, functional test were performed and quality of life was assessed. The primary outcome was therapeutic success (presence of Eckardt score ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for re-treatment, lower oesophageal sphincter pressure, oesophageal emptying and the rate of complications. <h3>Results</h3> In the full analysis set, there was no significant difference in success rate between the two treatments with 84% and 82% success after 5 years for LHM and PD, respectively (p=0.92, log-rank test). Similar results were obtained in the per-protocol analysis (5-year success rates: 82% for LHM vs 91% for PD, p=0.08, log-rank test). After 5 years, no differences in secondary outcome parameter were observed. Redilation was performed in 24 (25%) of PD patients. Five oesophageal perforations occurred during PD (5%) while 12 mucosal tears (11%) occurred during LHM. <h3>Conclusions</h3> After at least 5 years of follow-up, PD and LHM have a comparable success rate with no differences in oesophageal function and emptying. However, 25% of PD patients require redilation during follow-up. Based on these data, we conclude that either treatment can be proposed as initial treatment for achalasia. <h3>Trial registration numbers</h3> Netherlands trial register (NTR37) and Current Controlled Trials registry (ISRCTN56304564).
Racial Differences in and Prognostic Value of Biomarkers of Hyperglycemia
Authors: Christina M. Parrinello, A. Richey Sharrett, Nisa M. Maruthur, Richard M. Bergenstal, Morgan E. Grams, Josef Coresh, Elizabeth Selvin
Journal: Diabetes Care (2015)

OBJECTIVE We compared levels and associations of traditional (fasting glucose, HbA1c) and nontraditional (fructosamine, glycated albumin, and 1,5-anhydroglucitol [1,5-AG]) biomarkers of hyperglycemia with incident cardiovascular disease (CVD), incident end-stage renal disease (ESRD), and prevalent retinopathy in black and white adults. RESEARCH DESIGN AND METHODS We included 10,373 participants without (8,096 white, 2,277 black) and 727 with diagnosed diabetes (425 white, 302 black) from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox proportional hazards models to compare hazards ratios of CVD and ESRD among blacks and whites from baseline (1990–1992) through 2012. We compared the odds ratios (from logistic regression) of retinopathy among blacks and whites. We tested for the interaction of each biomarker with race. RESULTS Median values of biomarkers were higher among blacks versus whites (all P &amp;lt; 0.001). Relative risks for each biomarker with incident CVD and ESRD, and odds ratios for each biomarker with prevalent retinopathy, were similar by race (all P values for interaction by race &amp;gt;0.10). CONCLUSIONS The prognostic value of HbA1c, fructosamine, glycated albumin, and 1,5-AG with incident CVD, incident ESRD, and prevalent retinopathy were similar by race. Our results support similar interpretation of HbA1c and nontraditional biomarkers of hyperglycemia among black and whites with respect to long-term complications.
High-dose therapy followed by autologous hematopoietic stem-cell infusion for patients with multiple myeloma.
Authors: W I Bensinger, S D Rowley, T Demirer, K Lilleby, K Schiffman, R A Clift, F R Appelbaum, A Fefer, T Barnett, R Storb, T Chauncey, R T Maziarz, J Klarnet, P McSweeney, L Holmberg, D G Maloney, C H Weaver, C D Buckner
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate the outcome of patients with multiple myeloma (MM) who received high-dose therapy followed by autologous bone marrow (BM) or peripheral-blood stem-cell (PBSC) infusion. PATIENTS AND METHODS Sixty-three consecutive patients with MM received autologous BM (n = 13) or PBSC with or without BM (n = 50) following regimens that contained busulfan (Bu) and cyclophosphamide (Cy) (n = 18), modified total-body irradiation (TBI) followed by Bu and Cy (n = 36), or Bu, melphalan, and thiotepa (n = 9). Two thirds of the patients had resistant disease and 69% had received more than 6 months of previous chemotherapy. RESULTS AND CONCLUSION Recovery of peripheral-blood cell counts was more rapid in patients who received PBSC with or without BM than in patients who received BM alone. Sixteen of 63 patients (25%) died of complications of treatment within 100 days. Nineteen (40%) of 48 assessable patients achieved a complete response (CR), 23 (48%) had a partial response (PR), and six (12%) had no response. The probabilities of survival and survival without relapse or progression for all 63 patients at 3.0 years were .43 and .21, respectively. The probability of relapse or progression at 3 years was .69, and 17 patients (27%) have died of progressive MM. The probabilities of survival and relapse-free survival at 3 years for the 19 patients who achieved a CR were .42 and .17, respectively. In the multivariate analysis, beta2-microglobulin levels more than 2.5 micrograms/mL, more than two regimens of prior therapy and eight cycles of treatment, time to transplant longer than 3 years from diagnosis, and prior radiation were associated with adverse outcomes. Additional strategies, such as intervention earlier in the disease course, improved treatment regimens, sequential high-dose treatments, and posttransplant therapies may improve outcome of selected patients with MM.
Evaluation of Platelet Inhibition by Tirofiban in Patients Stratified According to Aspirin and Clopidogrel Responsiveness
Authors: Gianluca Campo, Marco Valgimigli, Alice Frangione, Serena Luccarelli, Elisa Cangiano, Caterina Cavazza, Luca Fileti, Roberto Ferrari
Journal: Journal of the American College of Cardiology (2010)
Abstract 18813: Prevalence and Distribution of Behavioral Cardiovascular Disease Risk Factors in Sub-Saharan Africa: The World Health Organization’s World Health Survey
Authors: Mercy W Kamau, Eileen Stuart-Shor, Ling Shi, Laura Hayman
Journal: Circulation (2013)

Introduction: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally accounting for 30% of total deaths worldwide with 82% of these deaths occurring in low/middle income countries (LMIC). WHO targeted 4 behavioral risk factors (physical inactivity, unhealthy diet, tobacco use, harmful use of alcohol) as the foundation of the WHO framework on prevention and control of CVD in LMIC. The purpose of this study was to examine the prevalence, distribution and association of these 4 risk factors in selected countries of Sub-Saharan Africa (SSA). Methods: Secondary analysis was conducted on data from the population-based WHO World Health Survey using data from 4 countries in SSA to reflect low (Senegal), middle (Ghana, Kenya), and high (South Africa) GDP. The data was weighted to account for country-specific sample sizes and pooled to provide regional prevalence estimates. The analysis controlled for age, gender, living location (rural/urban) and education. Analysis included Chi-square and logistic regression. Results: The pooled data among 13,850 subjects revealed high prevalence of unhealthy diet (67%), with lower prevalence of physical inactivity, tobacco use and harmful alcohol (12%, 14%, 6%, respectively). Country-specific analysis revealed that prevalence of behavioral CVD risk factors varied by socio-demographic variables within the countries of interest. Physical inactivity and unhealthy diet was higher among older individuals (p&lt;.05) and female (p&lt;.05). Tobacco use and harmful use of alcohol was higher in middle age men (p&lt;.001) with a trend for higher use in rural locations. Among the selected countries significant differences include: Kenya had the highest prevalence of unhealthy diet (OR=12.5, 95%CI=11.1-14.3). South Africa had the highest prevalence of physical inactivity (OR=7.8, 95%CI=6.8-9.1) and tobacco use (OR=2.8, 95%CI=2.4-3.3). Ghana had the highest prevalence of harmful use of alcohol (OR=3.8, 95%CI=3.1-4.6). Conclusions: This study demonstrates within and between-country differences in the prevalence and distribution of the 4 CVD behavioral risk factors. These results highlight the necessity of local and region-specific data to tailor policy, resource allocation and prevention measures.
NOA-08 randomized phase III trial of 1-week-on/1-week-off temozolomide versus involved-field radiotherapy in elderly (older than age 65) patients with newly diagnosed anaplastic astrocytoma or glioblastoma (Methusalem).
Authors: W. Wick, C. Engel, S. E. Combs, G. Nikkhah, J. Steinbach, R. Kortmann, M. Simon, C. Wille, G. Reifenberger, M. Weller
Journal: Journal of Clinical Oncology (2010)

LBA2001 Background: The median survival time for elderly patients (pts) with malignant gliomas is in the range of a few months. Radiotherapy (RT) is the standard treatment and superior to best supportive care both with respect to progression-free and overall survival. The benefit derived from surgery and RT is modest, and both treatments are less well tolerated in elderly pts than in the young. The availability of a potentially effective pharmacological agent, temozolomide (TMZ), for malignant glioma, which exhibits a favorable safety profile, necessitated a reconsideration of the widespread therapeutic nihilism with malignant glioma in the elderly. Methods: The NOA-08 trial of the Neurooncology Working Group (NOA) of the German Cancer Society compared standard postsurgical involved-field RT to a dose of 54-60 Gy, in pts with anaplastic astrocytoma or glioblastoma &gt; 65 ys with a Karnofsky performance score ≥ 60, to TMZ in an one week on/one week off schedule at 100 mg/m 2 with dose modification in 25 mg steps in both directions. The primary endpoint was the median survival time (OS) during the follow-up in the 12 months after date of operation. The trial sought to demonstrate the non-inferiority of TMZ compared with RT. Regarding a maximal difference of 25% between both treatment arms in OS as being equivalent, 2 x 206 pts were randomized between May 15, 2005 and Nov 2, 2009 in 22 German and one Suisse sites to provide 80% power to achieve significance at a one-sided level of 0.05. Thirty-nine patients were excluded from the intention-to-treat (ITT) population because no therapy was applied (n=22) or withdrawal of informed consent (n=17). Results: All histological diagnoses were centrally confirmed. Pts characteristics were balanced between arms in the ITT population (n=373) except for more resections and more anaplastic astrocytomas in the RT arm. The non-inferiority of TMZ was not shown. In contrast, pts in the TMZ arm had an increased risk of death (HR=1.24 [95% CI: 0.94-1.63]) compared to pts in the RT arm. The rate of adverse and serious adverse events was higher in the TMZ arm. Conclusions: This trial fails to show the non-inferiority of dose-intensified TMZ alone compared with RT alone in the primary treatment of older pts with malignant glioma. Unlike anaplastic glioma in the younger patient population, RT cannot be safely deferred in the treatment of elderly patients with anaplastic astrocytoma or glioblastoma. Whether RT plus TMZ is superior to RT alone, is addressed in the ongoing companion trial conducted by NCIC, EORTC and TROG. [Table: see text] [Table: see text]