tbuckley/cabot-search huggingface dataset:
Frequency and Cost of Chemotherapy-Related Serious Adverse Effects in a Population Sample of Women With Breast Cancer
Authors: Michael J. Hassett, A. James O'Malley, Juliana R. Pakes, Joseph P. Newhouse, Craig C. Earle
Journal: JNCI Journal of the National Cancer Institute (2006)

The number, nature, and costs of serious adverse effects experienced by younger women receiving chemotherapy for breast cancer outside of clinical trials are unknown.From a database of medical claims made by individuals with employer-provided health insurance between January 1998 and December 2002, we identified 12,239 women 63 years of age or younger with newly diagnosed breast cancer, of whom 4075 received chemotherapy during the 12 months after the initial breast cancer diagnosis and 8164 did not. Diagnostic codes for eight chemotherapy-related adverse effects were identified. Total hospitalizations for all causes, hospitalizations or emergency room visits for adverse effects that are typically related to chemotherapy, and health care expenditures were compared between the two groups of women. All statistical tests were two-sided.Women who received chemotherapy were more likely than those who did not to be hospitalized or to visit the emergency room for all causes (61% versus 42%; mean difference = 19%, 95% confidence interval [CI] = 16.7% to 21.3%, P<.001) and for chemotherapy-related serious adverse effects (16% versus 5%, mean difference = 11%, 95% CI = 9.6% to 12.4%, P<.001). The percentages of chemotherapy recipients who were hospitalized or visited the emergency room during the year after their breast cancer diagnosis were 8.4% for fever or infection; 5.5% for neutropenia or thrombocytopenia; 2.5% for dehydration or electrolyte disorders; 2.4% for nausea, emesis, or diarrhea; 2.2% for anemia; 2% for constitutional symptoms; 1.2% for deep venous thrombosis or pulmonary embolus; and 0.9% for malnutrition. Chemotherapy recipients incurred large incremental expenditures for chemotherapy-related serious adverse effects (1271 dollars per person per year) and ambulatory encounters (17,617 dollars per person per year).Chemotherapy-related serious adverse effects among younger, commercially insured women with breast cancer may be more common than reported by large clinical trials and lead to more patient suffering and health care expenditures than previously estimated.
Is detection of JC virus DNA in blood a valuable screening test for progressive multifocal leukoencephalopathy in Crohn's disease patients eligible for anti-alpha4 integrin therapy?
Authors: G Pineton de Chambrun, G Vernier-Massouille, N Viget, J-F Colombel, Y Yazdanpanah
Journal: Gut (2008)

We read with interest the article by Verbeeck and colleagues ( Gut 2008; 57 :1393–7) investigating the presence of JC virus DNA in urine and blood as a screening tool for active viral replication in immunosuppressed patients with Crohn’s disease. Based on their data, these authors propose using serial assessments of JC virus DNA in the blood compartment to monitor such patients for the risk of developing progressive multifocal leukoencephalopathy (PML) before and during anti-α4 integrin therapy. They postulated that the presence of JC viraemia may be a risk factor for future progression to PML. Moreover, in agreement with other studies they suggest that the absence of JC virus DNA in blood can be associated …
Evolution patterns of raltegravir-resistant mutations after integrase inhibitor interruption
Authors: F. Canducci, B. Barda, E. Ceresola, V. Spagnuolo, M. Sampaolo, E. Boeri, S. Nozza, F. Cossarin, A. Galli, N. Gianotti, A. Castagna, A. Lazzarin, M. Clementi
Journal: Clinical Microbiology and Infection (2010)
Long-acting -agonists: a review of formoterol safety data from asthma clinical trials
Authors: M. R. Sears, A. Ottosson, F. Radner, S. Suissa
Journal: European Respiratory Journal (2008)

The safety of long-acting β 2 -agonist (LABA) treatment in asthma has been questioned following reported increased respiratory deaths when salmeterol was added to usual pharmacotherapy. The aim of this study was to examine whether asthma, cardiac or all-cause mortality and morbidity were increased with formoterol use. The analysis included all AstraZeneca randomised controlled parallel-group asthma trials of 3–12-months duration involving formoterol. Risks associated with formoterol use compared with non-LABA treatment, overall and in combination with inhaled corticosteroids (ICS), were assessed using an intention-to-treat analysis of the rates and rate ratios of deaths and serious adverse events (SAEs). The main objective of this study was to compare asthma-related mortality in patients using formoterol and those not using formoterol. There were eight asthma-related deaths (0.34 per 1,000 person-yrs) among 49,906 formoterol-randomised patients (92% using ICS), and two (0.22 per 1,000 person-yrs) among 18,098 patients (83% using ICS) not randomised to formoterol, which was nonsignificant. Asthma-related SAEs (&gt;90% of which were hospitalisations) were significantly fewer among formoterol-randomised patients (0.75 versus 1.10%). There was no increase in asthma-related SAEs with increased daily doses of formoterol (9, 18 or 36 μg). There was no significant difference in cardiac mortality or noncardiac nonasthma-related mortality in formoterol-randomised compared to non-LABA-treated patients. All-cause mortality was similar. In the data set in which all subjects were prescribed ICS at baseline, there were seven asthma-related deaths (0.32 per 1,000 person-yrs) among 46,003 formoterol-randomised patients and one (0.14 per 1,000 person-yrs) among 13,905 patients not randomised to formoterol, which was also nonsignificant. There were few asthma-related or cardiac-related deaths among patients randomised to formoterol, and all differences were nonsignificant compared with non-long-acting β 2 -agonist-randomised patients. However, despite data on &gt;68,000 patients, the power was insufficient to conclude that there was no increased mortality with formoterol. Cardiac-related serious adverse events were not increased, and asthma-related serious adverse events were significantly reduced with formoterol.
Chitosan/siRNA Nanoparticles Targeting Cyclooxygenase Type 2 Attenuate Unilateral Ureteral Obstruction-induced Kidney Injury in Mice
Authors: Chuanxu Yang, Line Nilsson, Muhammad Umar Cheema, Yan Wang, Jørgen Frøkiær, Shan Gao, Jørgen Kjems, Rikke Nørregaard
Journal: Theranostics (2014)

Cyclooxygenase type 2 (COX-2) plays a predominant role in the progression of kidney injury in obstructive nephropathy. The aim of this study was to test the efficacy of chitosan/small interfering RNA (siRNA) nanoparticles to knockdown COX-2 specifically in macrophages to prevent kidney injury induced by unilateral ureteral obstruction (UUO). Using optical imaging techniques and confocal microscopy, we demonstrated that chitosan/siRNA nanoparticles accumulated in macrophages in the obstructed kidney. Consistent with the imaging data, the obstructed kidney contained a higher amount of siRNA and macrophages. Chitosan-formulated siRNA against COX-2 was evaluated on RAW macrophages demonstrating reduced COX-2 expression and activity after LPS stimulation. Injection of COX-2 chitosan/siRNA nanoparticles in mice subjected to three-day UUO diminished the UUO-induced COX-2 expression. Likewise, macrophages in the obstructed kidney had reduced COX-2 immunoreactivity, and histological examination showed lesser tubular damage in COX-2 siRNA-treated UUO mice. Parenchymal inflammation, assessed by tumor necrosis factor-alpha (TNF-α) and interleukin 6 mRNA expression, was attenuated by COX-2 siRNA. Furthermore, treatment with COX-2 siRNA reduced heme oxygenase-1 and cleaved caspase-3 in UUO mice, indicating lesser oxidative stress and apoptosis. Our results demonstrate a novel strategy to prevent UUO-induced kidney damage by using chitosan/siRNA nanoparticles to knockdown COX-2 specifically in macrophages.
Efficacy of Antibodies to Epidermal Growth Factor Receptor Against KB Carcinoma In Vitro and in Nude Mice
Authors: E. Aboud-Pirak, E. Hurwitz, M. E. Pirak, F. Bellot, J. Schlessinger, M. Sela
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Efficacy of Antibodies to Epidermal Growth Factor Receptor Against KB Carcinoma In Vitro and in Nude Mice Get access Esther Aboud-Pirak, Esther Aboud-Pirak Department of chemical Immunology, The Weizmann Institute of ScienceRehovot, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Esther Hurwitz, Esther Hurwitz Department of chemical Immunology, The Weizmann Institute of ScienceRehovot, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael E. Pirak, Michael E. Pirak Life Science Research Israel Ltd.Ness Ziona, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Francoise Bellot, Francoise Bellot Rorer Biotechnology, Inc.King of Prussia, PA Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph Schlessinger, Joseph Schlessinger Department of chemical Immunology, The Weizmann Institute of ScienceRehovot, IsraelRorer Biotechnology, Inc.King of Prussia, PA Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Sela Michael Sela * *Correspondence to: Dr. Michael Sela, Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 20, 21 December 1988, Pages 1605–1611, https://doi.org/10.1093/jnci/80.20.1605 Published: 21 December 1988 Article history Received: 21 July 1988 Revision received: 26 September 1988 Accepted: 27 September 1988 Published: 21 December 1988
Nutritional Prevention of Cancer: New Directions for an Increasingly Complex Challenge
Authors: A. R. Kristal, S. M. Lippman
Journal: JNCI Journal of the National Cancer Institute (2009)

JNCI | Editorials 363 The prospects for cancer prevention through micronutrient supplementation have never looked worse. Several large, randomized cancer prevention trials have recently reported no reduced risk from micronutrient supplementation ( 1 – 4 ), and the short report by Figueiredo et al. in this issue of the Journal adds to a growing body of evidence that micronutrient supplementation may be harmful. Figueiredo et al. have conducted a secondary analysis from a trial that reported previously that folate (1 mg/d) increased the risk of recurrence of an advanced colorectal adenoma by 67% ( 5 ). They have found that folate increased the risk of prostate cancer by 163%. Among studies addressing micronutrient supplementation for the prevention of cancer, only a single randomized trial, testing 1200 mg of calcium for preventing the recurrence of colorectal polyps, has reported a statistically significant and positive result for its primary cancer outcome ( 6 ), whereas large trials testing supplementation with multivitamins, Nutritional Prevention of Cancer: New Directions for an Increasingly Complex Challenge
Association between Critical Care Physician Management and Patient Mortality in the Intensive Care Unit
Authors: Mitchell M. Levy, John Rapoport, Stanley Lemeshow, Donald B. Chalfin, Gary Phillips, Marion Danis
Journal: Annals of Internal Medicine (2008)

Background: Critically ill patients admitted to intensive care units (ICUs) are thought to gain an added survival benefit from management by critical care physicians, but evidence of this benefit is scant. Objective: To examine the association between hospital mortality in critically ill patients and management by critical care physicians. Design: Retrospective analysis of a large, prospectively collected database of critically ill patients. Setting: 123 ICUs in 100 U.S. hospitals. Patients: 101 832 critically ill adults. Measurements: Through use of a random-effects logistic regression, investigators compared hospital mortality between patients cared for entirely by critical care physicians and patients cared for entirely by non–critical care physicians. An expanded Simplified Acute Physiology Score was used to adjust for severity of illness, and a propensity score was used to adjust for differences in the probability of selective referral of patients to critical care physicians. Results: Patients who received critical care management (CCM) were generally sicker, received more procedures, and had higher hospital mortality rates than those who did not receive CCM. After adjustment for severity of illness and propensity score, hospital mortality rates were higher for patients who received CCM than for those who did not. The difference in adjusted hospital mortality rates was less for patients who were sicker and who were predicted by propensity score to receive CCM. Limitation: Residual confounders for illness severity and selection biases for CCM might exist that were inadequately assessed or recognized. Conclusion: In a large sample of ICU patients in the United States, the odds of hospital mortality were higher for patients managed by critical care physicians than those who were not. Additional studies are needed to further evaluate these results and clarify the mechanisms by which they might occur.
PWE-025 Increased Adenoma Detection In The Right Colon At Surveillance Colonoscopy Compared To Index Colonoscopy Within The Bcsp: Abstract PWE-025 Table 1
Authors: A Kamora, K Kandiah, G Smith, J Martin
Journal: Gut (2014)

Introduction Colonoscopy has been shown to be effective in reducing the incidence of colorectal cancer (CRC), presumably resulting from the removal of premalignant adenomas. There are data, however, to suggest that colonoscopy is less effective at preventing malignancy in the right colon, when compared to the left colon. A proposed explanation for this observation is that right-sided adenomas may be missed at colonoscopy, either due to inadequate bowel preparation or, alternatively, due to the presence of serrated adenomas that are more difficult to visualise. Within the Bowel Cancer Screening Programme (BCSP) patients found to have adenomas are entered into a surveillance programme, based on predefined guidelines. This study compares the findings at surveillance colonoscopy with the index colonoscopy in these individuals. Methods All patients having surveillance colonoscopies at the West London Bowel Cancer Screening Centre between 1st January 2009 and 28th February 2013 were included in the study. The results of the initial index procedure and subsequent surveillance procedures were retrieved from the endoscopy reporting system (Scorpio) and the histology of all polyps resected and retrieved was obtained from the hospital pathology system. The site of all adenomas removed for all procedures was recorded and the distribution of the adenomas found in the left and right colon were compared for the index and surveillance procedures (Chi squared). Results 242 patients were included in the study. In total 848 adenomas were found during the index colonoscopies and 379 adenomas were found during the surveillance procedures. 143 (59.1%) surveillance colonoscopies were performed at 1 year and 99 (40.9%) were performed at 3 years. The table below shows the number and percentage of adenomas found in the left colon (up to and including the splenic flexure) and the right colon (proximal to the splenic flexure) in both the index and surveillance procedures. View this table: Abstract PWE-025 Table 1 Significantly more adenomas were identified within the right colon at the surveillance procedures than were in the index examinations (p = 0.0001). Conclusion This study suggests that more proximal adenomas are found during surveillance colonoscopies than on initial screening colonoscopies. As approximately 60% of the surveillance examinations were at one year it is likely that these lesions were missed at the initial examination. Greater care needs to be taken at initial colonoscopy to visualise the proximal bowel and clear it of neoplasia, particularly in those individuals with multiple polyps. Disclosure of Interest None Declared.
Effects of Papaverine upon Ectopic Ventricular Tachycardia Produced by Myocardial Infarction
Authors: A. SIDNEY HARRIS, ANTONIO ESTANDÍA, ABDO BISENI, HERBERT T. SMITH
Journal: Circulation (1953)

Papaverine hydrochloride exhibited some ectopic impulse suppressor effect which was brief in duration and could not be maintained. Additional doses led to toxic reactions including increased ectopic activity. No consistent correlation was found between changes in blood pressure and decreases or increases in ectopic frequency. Vasodilator potency of drugs apparently bears no intimate relation to ectopic impulse suppressor effect.
Regulation of inflammatory responses by the commensal microbiota: Figure 1
Authors: Benjamin J Marsland
Journal: Thorax (2011)

It is well established that dysregulation of the interactions between the immune system and commensal bacteria is one factor that underpins the development and chronicity of a number of inflammatory diseases. Certain phyla of bacteria within the microbiota have been associated with 'health', but the mechanisms by which the presence of these bacteria supports a healthy environment are still being unravelled. Recent evidence indicates that one such mechanism involves the anti-inflammatory properties of fermentation products of fibre, short-chain fatty acids and their signalling through the G-protein coupled receptor GPR43. Recent findings also indicate that, even in health, bacterial communities harbour in the airways, indicating that direct exposure to bacterial products at this site may provide a further explanation for how commensal bacteria can regulate chronic airway inflammation.
Promoting environmental health
Authors: J. D Williamson
Journal: BMJ (1996)

The British government's white paper, Health of the Nation, received a cautious welcome on its publication in 1992.1 Its critics believed that its approach to health was limited, that it omitted many important issues such as the effects of environment and poverty, and that it implied ditching the World Health Organisation's comprehensive Health For All strategy.2 Since then, WHO has met with the European Union in Helsinki in 1994 and approved a model environmental health action plan,3 which Britain has been asked to pilot.4 The result gives us a clear view of the British government's segmental approach to Health For All.5 It also raises issues about who should do what in promoting environmental health.

Britain's environmental health action plan is a simple list of what the government is doing or planning to do about environmental health.5 It is not a new agenda and therefore contains no new policy initiatives. …
Prognostic Factors in Resected Stage I Non–Small-Cell Lung Cancer: A Multivariate Analysis of Six Molecular Markers
Authors: Charles Lu, Jean-Charles Soria, Ximing Tang, Xiao-Chun Xu, Luo Wang, Li Mao, Reuben Lotan, Bonnie Kemp, B. Nebiyou Bekele, Lei Feng, Waun K. Hong, Fadlo R. Khuri
Journal: Journal of Clinical Oncology (2004)

To analyze the prognostic significance of six molecular biomarkers (death-associated protein kinase [DAPK] promoter methylation, interleukin-10 [IL-10] protein expression, cyclooxygenase-2 [COX-2] mRNA expression, human telomerase reverse transcriptase catalytic subunit [hTERT] mRNA expression, retinoic acid receptor-beta [RAR-beta] mRNA expression, and K-ras mutational status) in stage I non-small-cell lung cancer (NSCLC) patients.Biomarker analyses were performed on tumors from 94 patients with stage I NSCLC who underwent surgical resection at our institution. A minimum follow-up period of 5 years was required. DAPK methylation was assessed by methylation-specific polymerase chain reaction (PCR). RAR-beta, COX-2, and hTERT mRNA levels were determined by in situ hybridization with digoxigenin-labeled antisense riboprobes. K-ras mutation status was determined by the PCR-primer introduced restriction with enrichment for mutant alleles method. IL-10 protein expression was analyzed by immunohistochemistry using a polyclonal antihuman IL-10 antibody. Cancer-specific survival was analyzed with a Cox proportional hazards model. To identify independent prognostic factors, a stepwise selection method was used.DAPK methylation, IL-10 lack of expression, COX-2 expression, hTERT expression, RAR-beta expression, and K-ras mutations were observed in 46.8%, 29.8%, 59.6%, 34.0%, 23.4%, and 34.0% of patients, respectively. In the final model, DAPK methylation and IL-10 lack of expression were significant negative prognostic factors for cancer-specific survival, whereas COX-2 expression was of borderline significance.In this cohort of resected stage I NSCLC patients, molecular markers that independently predict cancer-specific survival have been identified. The prognostic roles of DAPK methylation, IL-10, and other biomarkers in NSCLC merit further investigation.
Baseline Predictors of Renal Disease Progression in the African American Study of Hypertension and Kidney Disease
Authors: Keith C. Norris, Tom Greene, Joel Kopple, Janice Lea, Julia Lewis, Mike Lipkowitz, Pete Miller, Annie Richardson, Stephen Rostand, Xuelei Wang, Lawrence J. Appel
Journal: Journal of the American Society of Nephrology (2006)

Patients with chronic kidney disease have an increased risk for progression to ESRD. The purpose of this study was to examine factors that predict increased risk for adverse renal outcomes. Cox regression was performed to assess the potential of 38 baseline risk factors to predict the clinical renal composite outcome of 50% or 25-ml/min per 1.73 m2 GFR decline or ESRD among 1094 black patients with hypertensive nephrosclerosis (GFR 20 to 65 ml/min per 1.73 m2). Patients were trial participants who had been randomly assigned to one of two BP goals and to one of three antihypertensive regimens and followed for a range of 3 to 6.4 yr. In unadjusted and adjusted analyses, baseline proteinuria was consistently associated with an increased risk for adverse renal outcomes, even at low levels of proteinuria. The relationship of proteinuria with adverse renal outcomes also was evident in analyses that were stratified by level of GFR, which itself was associated with adverse renal outcomes but only at levels <40 ml/min. Other factors that were significantly associated with increased renal events after adjustment for baseline GFR, age, and gender, both with and without adjustment for baseline proteinuria, included serum creatinine, urea nitrogen, and phosphorus. In black patients with hypertensive nephrosclerosis, increased proteinuria, reduced GFR, and elevated levels of serum creatinine, urea nitrogen and phosphorus were directly associated with adverse clinical renal events. These findings identify a subset of this high-risk population that might benefit from even more aggressive treatment.