tbuckley/cabot-search huggingface dataset:
Phase III Multicenter Randomized Trial of the Dartmouth Regimen Versus Dacarbazine in Patients With Metastatic Melanoma
Authors: Paul B. Chapman, Lawrence H. Einhorn, Michael L. Meyers, Scott Saxman, Alicia N. Destro, Katherine S. Panageas, Colin B. Begg, Sanjiv S. Agarwala, Lynn M. Schuchter, Marc S. Ernstoff, Alan N. Houghton, John M. Kirkwood
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Several single-institution phase II trials have reported that the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) can induce major tumor responses in 40% to 50% of stage IV melanoma patients. This study was designed to compare the overall survival time, rate of objective tumor response, and toxicity of the Dartmouth regimen with standard dacarbazine treatment in stage IV melanoma patients. PATIENTS AND METHODS: In this multicenter phase III trial, 240 patients with measurable stage IV melanoma were randomized to receive the Dartmouth regimen (dacarbazine 220 mg/m 2 and cisplatin 25 mg/m 2 days 1 to 3, carmustine 150 mg/m 2 day 1 every other cycle, and tamoxifen 10 mg orally bid) or dacarbazine 1,000 mg/m 2 . Treatment was repeated every 3 weeks. Patients were observed for tumor response, survival time, and toxicity. RESULTS: Median survival time from randomization was 7 months; 25% of the patients survived ≥ 1 year.There was no difference in survival time between the two treatment arms when analyzed on an intent-to-treat basis or when only the 231 patients who were both eligible and had received treatment were considered. Tumor response was assessable in 226 patients. The response rate to dacarbazine was 10.2% compared with 18.5% for the Dartmouth regimen (P = .09). Bone marrow suppression, nausea/vomiting, and fatigue were significantly more common in the Dartmouth arm. CONCLUSION: There was no difference in survival time and only a small, statistically nonsignificant increase in tumor response for stage IV melanoma patients treated with the Dartmouth regimen compared with dacarbazine. Dacarbazine remains the reference standard treatment for stage IV melanoma.
Roflumilast potently inhibits CXCL1 mediated neutrophil migration in COPD patients
Authors: Amy Turner, Peter Fenwick, Peter Barnes, Louise Donnelly
Journal: European Respiratory Journal (2011)

Chronic obstructive pulmonary disease (COPD) is associated with glucocorticosteroid insensitive inflammation. Neutrophils from COPD patients migrate more in response to CXCL1 than cells from control subjects. Roflumilast, a PDE4 inhibitor recently approved for COPD in the EU, reduces neutrophil numbers in sputum from COPD patients. The mechanism of this anti-inflammatory effect is not clear, but may be due to inhibition of neutrophil migration. Thus this study investigated the effects of roflumilast N-oxide (RNO), the active metabolite of roflumilast, on neutrophil migration in comparison with another PDE4 inhibitor, rolipram.  Neutrophils were isolated from whole blood samples from healthy subjects and COPD patients. Chemotaxis was measured using 48-well Boyden chambers and [Ca 2+ ] i  by fluorimetry.  Both RNO and rolipram completely inhibited migration of neutrophils from healthy subjects towards CXCL1 (3nM) with EC 50  values of 0.18±0.13 nM and 2.8±0.51 nM, n=4, respectively. A similar response was seen with neutrophils obtained from patients with COPD (EC 50  RNO: 0.74±0.89 nM; rolipram 42±45.9 nM, n=3). Having established that cell migration was attenuated by PDE4 inhibitors, the effects of these compounds on CXCL1 stimulated [Ca 2+ ] i  was investigated. RNO (1μM) inhibited the peak of [Ca  2+ ] i  and area under the curve (AUC) by 83.0±2.6% and 90.3±2.1%, n=6. Rolipram (1μM) also inhibited these responses by 80.7±3.2% and 86.3±2.1%, n=6.  These data indicate that oral PDE4 inhibitors may have added anti-inflammatory effects by reducing CXCL1 stimulated neutrophil migration into the lung via regulation of [Ca 2+ ] i  and this could contribute to the anti-inflammatory effects of roflumilast in the treatment of COPD.
Predictive factors of exercise capacity decline in patients with COPD
Authors: Maria A. Ramon, Jaume Ferrer, Esther Rodriguez, Elena Gimeno-Santos, Judith Garcia-Aymerich
Journal: European Respiratory Journal (2013)

Introduction:  Exercise capacity declines over time in patients with Chronic Obstructive Pulmonary Disease (COPD), and this decline is a predictor of mortality. However, the factors associated with this deterioration have been poorly studied.  Aim:  To estimate the prospective association between clinical and functional variables and the decline in exercise capacity in patients with COPD.  Measurements:  Clinical and functional relevant variables were collected for 226 clinically stable COPD patients included in the PAC-COPD Cohort Study. The six-minute walk distance (6MWD) was determined at baseline and after a mean (SD) of 1.7 (0.3) years. The annual rate of change in exercise capacity was calculated for each patient. Multivariate regression was used to analyze predictive factors of exercise capacity decline.  Main Results:  Patients were mostly male (92%), their mean (SD) age was 67.4 (8.3) years, postbronchodilator FEV1 54 (17) % predicted, and 6MWD at baseline 444 (83) meters. During follow-up, 6MWD decreased by 20.4 (39.2) m/year. In the bivariate analysis dyspnea (MRC≥2), quality of life (total score in the Sant George respiratory questionnaire), the level of airway obstruction (FEV1), lung hyperinflation (RV/TLC), and baseline 6MWD were associated with the annual rate of change in exercise capacity. In the multivariate regression model, only dyspnea, RV/TLC and baseline 6MWD remained statistically significant.  Conclusions:  Evaluation of COPD patients in stable condition may be useful to predict their future decline in exercise capacity. Dyspnea and pulmonary hyperinflation are the baseline variables associated with this decline and could be used to select candidates for pulmonary rehabilitation.
Time to diagnostic procedures and treatment in outpatients diagnosed of lung cancer (LC) included in our rapid diagnose protocol (RPD)
Authors: M. Isabel Andrade, Tamara Gutierrez, Amaia Iridoy, Jose Antonio Cascante, Pilar Cebollero, V. Manuel Eguia, J. Javier Hueto
Journal: European Respiratory Journal (2011)

Aim:  To determine the time to diagnose procedures and treatment in outpatients diagnosed of LC in Navarra (Spain) included in a RDP.   Method:  Retrospective analysis of outpatients diagnosed of LC in our RDP from January 2006 to October 2010. The reference date was the day they were sent to our service. We analyzed time to CT, to bronchoscopy, to endobronchial ultrasound transbronchial needle aspiration (RT-EBUS), to transparietal fine needle aspiration (TFNA) and to Positron emission Tomography (PET), time to treatment and the hospitalization average.   Results:  70 patients were diagnosed of LC in our RDP; 80% were men, the mean age was 63.9; 68.5% were remitted from primary care (PC). The mean time to the last diagnostic procedure was 22,5 days from PC and 16,4 from first visit in our RDP (RDPfv).The table reflects time from PC*(or other remission service) or RDPfv to each procedure.  We use PET since 2006 and EBUS since October 2008. 75% of patients didn9t need hospitalization. The mean days, when needed, was 3.1 (1-8). Patients required surgical treatment in 22,8%, oncologic in 68.5% and Palliative Care as first choice in 8,5%. Globally, time from PC* to treatment was 37,4 days (5-103) and from RDPfv to treatment was 31,4days (0-90).   Conclussions:  With our RDP we have achieved a lower time delay to diagnosis and treatment (no difference between kind of treatment)of LC comparing with most of the existing recommendations.  We haven9t need hospitalization in most cases and the mean of days was low.
Nonmedical Prescription Opioid Use and Use Disorders Among Adults Aged 18 Through 64 Years in the United States, 2003-2013
Authors: Beth Han, Wilson M. Compton, Christopher M. Jones, Rong Cai
Journal: JAMA (2015)

<h3>Importance</h3> Since 1999, the United States has experienced increases in morbidity and mortality associated with nonmedical use of prescription opioids. <h3>Objective</h3> To assess national trends in and characteristics of nonmedical prescription opioid use and use disorders and the national trend in related mortality. <h3>Design, Setting, and Participants</h3> Prevalence of nonmedical use and use disorders and related risk factors were based on data from 472 200 persons aged 18 through 64 years who participated in the 2003-2013 National Surveys on Drug Use and Health. Mortality was based on the 2003-2013 National Vital Statistics System's Multiple Cause of Death Files. <h3>Exposures</h3> Prevalence of nonmedical use of prescription opioids. <h3>Main Outcomes and Measures</h3> Nonmedical prescription opioid use and use disorders. <h3>Results</h3> Among adults aged 18 through 64 years, the prevalence of nonmedical use of prescription opioids decreased from 5.4% (95% CI, 5.08%-5.70%) in 2003 to 4.9% (95% CI, 4.58%-5.22%) in 2013 (absolute difference, −0.5%; 95% CI, −0.11% to −0.89%), but the prevalence of prescription opioid use disorders increased from 0.6% (95% CI, 0.54%-0.76%) in 2003 to 0.9% (95% CI, 0.75%-1.01%) in 2013 (absolute difference, 0.3%; 95% CI, 0.03%-0.43%). The 12-month prevalence of high-frequency use (≥200 days) also increased from 0.3% (95% CI, 0.19%-0.35%) in 2003 to 0.4% (95% CI, 0.31%-0.48%) in 2013 (absolute difference, 0.1%; 95% CI, 0.01%-0.29%). Mortality assessed by drug overdose death rates involving prescription opioids increased from 4.5 per 100 000 (95% CI, 4.42-4.61) in 2003 to 7.8 per 100 000 (95% CI, 7.64-7.89) in 2013 (absolute difference, 3.3; 95% CI, 3.09-3.41) among adults aged 18 through 64 years. The mean number of days of nonmedical use of prescription opioids increased from 2.1 (95% CI, 1.83-2.37) in 2003 to 2.6 (95% CI, 2.27-2.85) in 2013 (absolute difference, 0.5, 95% CI, 0.05-0.86). The model-adjusted prevalence of having prescription opioid use disorders among nonmedical users increased to 15.7% (95% CI, 13.87%-17.67%) in 2010, 16.1% (95% CI, 14.36%-17.99%) in 2011, 17.0% (95% CI, 15.07%-19.12%) in 2012, and 16.9% (95% CI, 14.95%-19.03%) in 2013 from 12.7% (95% CI, 11.04%-14.53%) in 2003. <h3>Conclusions and Relevance</h3> During the 2003-2013 years, among adults aged 18 through 64 years, the percentage of nonmedical use of prescription opioids decreased. In contrast, the prevalence of prescription opioid use disorders, frequency of use, and related mortality increased.
The effect of whole cell allogeneic vaccination on the progression of hormone-relapsed prostate cancer
Authors: H. S. Pandha, A. Michael, N. Quatan, F. Wushishi, N. Russell, J. Whelan, M. Whelan
Journal: Journal of Clinical Oncology (2004)

4735 Background: Whole cell allogeneic tumor vaccines are being investigated as an immunotherapy option for a variety of cancers. We report the findings from a Phase ll trial in hormone relapsed prostate cancer (HRPC). Methods: HRPC patients were tested for immuno-competence using delayed type sensitivity and scanned for the absence of bone metastases. Patients were not selected on the basis of their HLA type. Participants were vaccinated with a mixture of 3 allogeneic lines (8x106 of each) supplemented with BCG on weeks 0 and 2, followed by the three lines alone monthly for one year. Endpoints included safety, tolerability, QOL, PSA response, time to disease progression (TTP) and immunological profile. Results: Of 28 patients recruited, 26 were evaluable. Median age was 67, median PSA at presentation was 11.1 and performance status was 0. A statistically significant slowdown in PSA release was seen in 11/26. This was associated with a median TTP of 55 weeks, which compares favourably with published data (20–30 weeks). The vaccine was well-tolerated, most frequent side-effects were fatigue and local injection-site reaction. There were no treatment-related SAEs. Furthermore, patients who showed a clinical slowdown in disease exhibited clear evidence of immunological activation. In particular, we have shown proliferation of patient T cells after vaccination and strong enhancement of cytokine responses. Unusually, responding participants showed a mixed TH1 and TH2 type response rather than simply TH1 activation. Conclusion: Whole cell allogeneic vaccination is a safe and feasible treatment option and can slowdown the progression of HRPC. This provides a strong rationale for initiation of the forthcoming phase III trial. No significant financial relationships to disclose.
Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison.
Authors: J Beyer, N Schwella, J Zingsem, I Strohscheer, I Schwaner, H Oettle, S Serke, D Huhn, W Stieger
Journal: Journal of Clinical Oncology (1995)

PURPOSE To compare autologous bone marrow (BM) with peripheral-blood progenitor cells (PBPC) as hematopoietic rescue after high-dose chemotherapy (HDCT). PATIENTS AND METHODS From January 1991 until April 1993, 47 consecutive patients with relapsed or refractory germ cell tumors were randomized to either BM harvest or collection of PBPC mobilized by chemotherapy plus granulocyte colony-stimulating factor (G-CSF). After additional conventional-dose salvage treatment, all patients received HDCT with carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 with either BM or PBPC rescue. RESULTS Forty-six patients were assessable for hematologic reconstitution, and one patient died on day +4 before engraftment. Rescue using PBPC resulted in a significantly shorter recovery time to neutrophil counts more than 500/microL (10.0 v 11.0 days, P &lt; .01), neutrophil counts more than 1,000/microL (10.0 v 12.0 days, P = .001), and platelet counts more than 20,000/microL (10.0 v 17.0 days, P &lt; .01), as well as in fewer days to transfusion independence from RBCs (8.0 v 12.0, P &lt; .05) and platelets (9.0 v 12.0, P &lt; .01) and fewer days of intravenous (IV) antibiotics (9.0 v 11.0, P &lt; .05). However, no statistical differences in transfusion requirements or in other clinical outcome variables were observed. Overall survival and event-free survival also were not different in the two study arms. CONCLUSION We conclude that the use of PBPC mobilized by chemotherapy plus G-CSF results in sustained trilineage reconstitution after HDCT, which occurs more rapidly as compared with BM. The earlier hematologic reconstitution in patients with PBPC rescue significantly reduces the time to transfusion independence.
Construction of a Human-BAC Array for a high resolution analysis of genomic changes in cancer
Authors: Virginia W. Rodriguez, Abdel Elkahloun, Amalia Dutra, Evgenia Pak, Settara Chandrasekharappa
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

169 

A high density BAC array of the human genome will be very useful to assess global genomic DNA changes in cancer cells and deletion syndromes at a very high resolution using CGH (comparative genomic hybridization) techniques. We are generating an array of over 32,000 BAC clones to give comprehensive coverage of the genome. To begin this process on a small scale, a BAC array of chromosome 8 was developed and tested. This array contains 1463 BAC clones creating a tiling path along the chromosome 8 and includes 48 BAC clones from chromosome X. The BAC clones DNA were amplified using the Phi29 DNA polymerase to generate the required amounts; a modified protocol allowed for efficient amplification of large number of BAC clones. Labeling/hybridization protocols were optimized to detect single copy changes using a panel of cell lines with an increasing number of X chromosomes. DNA from a breast cancer cell line (SKBR3) with two known amplified regions in 8q21 and 8q24 was hybridized to evaluate the usefulness of this high density BAC array. We identified 6 distinct amplified and 3 deleted regions in 8q. Each of these regions was verified by q-PCR (quantitative PCR) and FISH (fluorescence in situ hybridization). These techniques were also used to define the precise boundaries of amplicons in an independent manner. In addition, expression of genes that were part of the amplified/deleted regions was evaluated by expression arrays and q-PCR. Similar high-resolution amplification/deletion maps of chromosome 8 of several pancreatic cancer cell lines are generated. The entire 32,000 BAC clone array is now being assembled, and it is anticipated that a high-resolution analysis will help identify hitherto unknown genomic changes that will lead to a better understanding of cancer.
Conservative Surgery for Vesicocolic Fistula
Authors: S L Lewis, G F Abercrombie
Journal: Journal of the Royal Society of Medicine (1984)

Vesicocolic fistula due to diverticular disease of the colon is conventionally treated by resection of the diseased bowel and closure of the vesical defect. Three cases are described in which separation of the viscera and simple suture of the vesical and colonic defects was carried out. A greater omental graft was interposed between the rectum and bladder. Two of the patients are well 12 and 26 months postoperatively. The third patient died a year postoperatively from a complication of her diverticular disease.
Prevention of Emesis from Multiple-Day and High-Dose Chemotherapy Regimens
Authors: Rudolph M. Navari
Journal: Journal of the National Comprehensive Cancer Network (2007)

The prevention of chemotherapy-induced nausea and vomiting (CINV) has improved significantly with the introduction of the 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists combined with dexamethasone. Most studies have reported on patients undergoing single-day highly or moderately emetogenic chemotherapy. There have been fewer studies and much less success in preventing CINV in patients undergoing multiple-day chemotherapy or high-dose chemotherapy with stem cell transplant. Current practice guidelines suggest the use of a first-generation 5-HT3 receptor antagonist and dexamethasone daily for each day of the multiple-day chemotherapy regimens. This practice seems to control acute CINV, but delayed CINV remains poorly controlled with a complete response (e.g., no emesis, no rescue) of less than 50% in most studies. Three new agents—palonosetron, aprepitant, and olanzapine— have shown high efficacy in preventing acute and delayed CINV in patients undergoing single-day chemotherapy. These agents have high potential for preventing CINV in patients undergoing multiple-day chemotherapy. This article proposes recommendations for their use in clinical trials and in practice.
Understanding Conflicting Neuropathological Findings in Patients Clinically Diagnosed as Having Alzheimer Dementia
Authors: Stephen Salloway, Reisa Sperling
Journal: JAMA Neurology (2015)

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Abstract 3357: Superiority of ApoB/ApoA1 Ratio for Predicting Cardiovascular Risk in Pooled Analyses of the Incremental Decrease in Endpoints through Aggressive Lipid-Lowering (IDEAL) and Treating to New Targets (TNT) Trials
Authors: John J Kastelein, Ingar Holme, Philip Barter, Anders G Olsson, Nilo B Cater, David A DeMicco, Michael Gaffney, Michael Szarek, John C LaRosa, Terje R Pedersen
Journal: Circulation (2006)
Impact of antifungal prescription on relative distribution and susceptibility of Candida spp. – Trends over 10 years
Authors: Sébastien Bailly, Danièle Maubon, Pierre Fournier, Hervé Pelloux, Carole Schwebel, Claire Chapuis, Luc Foroni, Muriel Cornet, Jean-François Timsit
Journal: Journal of Infection (2015)
Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541.
Authors: G L Rosner, J B Hargis, D R Hollis, D R Budman, R B Weiss, I C Henderson, R L Schilsky
Journal: Journal of Clinical Oncology (1996)

PURPOSE We examined data from a large clinical trial to determine if chemotherapy dosing according to actual body weight places obese patients at greater risk of toxicity. PATIENTS AND METHODS Cancer and Leukemia Group B (CALGB) study 8541, a randomized study of schedule and dose of adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) for stage II breast cancer patients with positive regional lymph nodes, provided data on 1,435 women for analysis. Using body-mass index (BMI), we classified a woman as obese if her BMI was &gt; or = 27.3 kg/m2; doses were considered weight-based if within 5% of values calculated using actual weight. Our primary analysis concerned toxicity risks during cycle 1. RESULTS Among women who received weight-based doses of the most dose-intensive CAF regimen, 47% of obese and 51% of nonobese women experienced severe hematologic toxicity (grade &gt; or = 3) during cycle 1 (P = .51, two-tailed). The overall risk ratio (obese v nonobese) of treatment failure among women who received weight-based doses during cycle 1 was 1.02 (95% confidence interval, 0.83 to 1.26), stratified by treatment and adjusted for number of positive nodes, menopausal status, hormone receptor status, and tumor size. The overall adjusted failure risk ratio (weight-based v reduced initial doses) was 0.73 (95% confidence interval, 0.53 to 1.00) among obese women. CONCLUSION Obese patients initially dosed (within 5%) by actual weight did not experience excess cycle 1 toxicity or worse outcome compared with nonobese women dosed similarly. The data suggest that obese women who received reduced doses in cycle 1 experienced worse failure-free survival. We recommend that initial doses of CAF be computed according to actual body weight.