tbuckley/cabot-search huggingface dataset:
Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies
Authors: Y. K. Loke, C. S. Kwok, S. Singh
Journal: BMJ (2011)

<b>Objective</b> To determine the comparative effects of the thiazolidinediones (rosiglitazone and pioglitazone) on myocardial infarction, congestive heart failure, and mortality in patients with type 2 diabetes. <b>Design</b> Systematic review and meta-analysis of observational studies. <b>Data sources</b> Searches of Medline and Embase in September 2010. <b>Study selection</b> Observational studies that directly compared the risk of cardiovascular outcomes for rosiglitazone and pioglitazone among patients with type 2 diabetes mellitus were included. <b>Data extraction</b> Random effects meta-analysis (inverse variance method) was used to calculate the odds ratios for cardiovascular outcomes with thiazolidinedione use. The I<sup>2 </sup>statistic was used to assess statistical heterogeneity. <b>Results</b> Cardiovascular outcomes from 16 observational studies (4 case-control studies and 12 retrospective cohort studies), including 810 000 thiazolidinedione users, were evaluated after a detailed review of 189 citations. Compared with pioglitazone, use of rosiglitazone was associated with a statistically significant increase in the odds of myocardial infarction (n=15 studies; odds ratio 1.16, 95% confidence interval 1.07 to 1.24; P&lt;0.001; I<sup>2</sup>=46%), congestive heart failure (n=8; 1.22, 1.14 to 1.31; P&lt;0.001; I<sup>2</sup>=37%), and death (n=8; 1.14, 1.09 to 1.20; P&lt;0.001; I<sup>2</sup>=0%). Numbers needed to treat to harm (NNH), depending on the population at risk, suggest 170 excess myocardial infarctions, 649 excess cases of heart failure, and 431 excess deaths for every 100 000 patients who receive rosiglitazone rather than pioglitazone. <b>Conclusion</b> Among patients with type 2 diabetes, use of rosiglitazone is associated with significantly higher odds of congestive heart failure, myocardial infarction, and death relative to pioglitazone in real world settings.
Occupational Lung Diseases.
Journal: Annals of Internal Medicine (1975)

A Short History of Occupational Lung Diseases. Prevention of Occupational Lung Diseass. The Clinical Approach. Legal Aspects of Industrial Disease. Pulmonary Physiology. Epidemiology and Occupational Lung Disease. The Deposition and Clearance of Dust from the Lungs. Pathological Reactions of the Lung to Dust. The Measurement of Workplace Aerosols. Respiratory Protection. Basic Mechanisms in Occupational Lung Diseases Including Lung Cancer and Mesothelioma. Silicosis. Silicates and Lung Disease. Asbestos-Related Diseases. Coal Workers' Pneumoconiosis. Other Pneumoconiosis. Occupational Asthma. Byssinosis and Related Conditions. Industrial Bronchitis and Other Nonspecific Conditions. Hypersensitivity Pneumonitis. Toxic Gases and Fumes. Barotrauma and Hazards of High Pressure. Infectious Diseases. Occupational Lung Cancer.
Use of Radiation Therapy in the Last 30 Days of Life Among a Large Population-Based Cohort of Elderly Patients in the United States
Authors: B. Ashleigh Guadagnolo, Kai-Ping Liao, Linda Elting, Sharon Giordano, Thomas A. Buchholz, Ya-Chen Tina Shih
Journal: Journal of Clinical Oncology (2012)

Our goal was to evaluate use and associated costs of radiation therapy (RT) in the last month of life among those dying of cancer.We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked databases to analyze claims data for 202,299 patients dying as a result of lung, breast, prostate, colorectal, and pancreas cancers from 2000 to 2007. Logistic regression modeling was used to conduct adjusted analyses of potential impacts of demographic, health services, and treatment-related variables on receipt of RT and treatment with greater than 10 days of RT. Costs were calculated in 2009 dollars.Among the 15,287 patients (7.6%) who received RT in the last month of life, its use was associated with nonclinical factors such as race, gender, income, and hospice care. Of these patients, 2,721 (17.8%) received more than 10 days of treatment. Nonclinical factors that were associated with greater likelihood of receiving more than 10 days of RT in the last 30 days of life included: non-Hispanic white race, no receipt of hospice care, and treatment in a freestanding, versus a hospital-associated facility. Hospice care was associated with 32% decrease in total costs of care in the last month of life among those receiving RT.Although utilization of RT overall was low, almost one in five of patients who received RT in their final 30 days of life spent more than 10 of those days receiving treatment. More research is needed into physician decision making regarding use of RT for patients with end-stage cancer.
Abstract 4992: Zkscan3 facilitates invasion of colorectal cancer associated with ceacam5
Authors: Seon A. Roh, Chan Wook Kim, Ka Hee Tak, Jin Cheon Kim
Journal: Cancer Research (2014)

Abstract Purpose: ZKSCAN3 is over-expressed in invasive colonic tumor cells and regulate the expression of several genes favoring tumor progression including integrin β4. We evaluated the role of ZKSCAN3 in invasive signaling pathway with stage 4 colorectal cancer (CRC). Materials and methods: 119 metastatic CRC (mCRC) patients who palliatively or curatively resected and 331 sporadic CRC patients who curatively resected from January 2004 to December 2009 were used to identify correlations between single-nucleotide polymorphism (SNP) rs733743 and clinically prognostic parameters. To validation of prior correlation, the genotypes of SNP identified by pyrosequencing using 81 patients (33 with mCRC and 48 CRC patients) and CRC cell lines. We then performed immunohistochemistry (IHC) and Western blot on 36 mCRC patients and 49 CRC patients. Up-regulated putative down-stream targets included genes contributing tumor aggressiveness and invasiveness; VEGF, cyclin D2, Akt, phospho-Akt, integrin β4, KRAS, CEACAM5, and integrin α5β1. To test biological utility assay, ZKSCAN3 mRNA was knocked down by ZKSCAN3 specific siRNA in metastatic CRC cells (LOVO) and ZKSCAN3 cDNA was overexpressed in the low-ZKSCAN3 expressed CRC cells (HCT116). Results: Wild-type alleles (GG) of ZKSCAN3 rs733743 was related with male dominant, family history of malignancy, high CEA concentration, and mCRC. The wild-type alleles of ZKSCAN3 rs733743 using tissue sample was related with lymphvascular invasion. ZKSCAN3 IHC positive tissue was related with lymphovascular invasion. ZKSCAN expression was higher in LOVO and SW620 cell lines which were derived from metastatic site. ZKSCAN3 high groups were related with CEA, integrin β4, VEGF, and AKT and ZKSCAN3 low groups were related with RAS, VEGF, AKT, and PAKT in metastatic tumor tissue. Therefore, ZKSCAN3 seemed to be related with CEA and integrin β4 to metastasis. Additional CEA expression was observed a significant decrease in ZKSCAN3 knockdowned LOVO cell (1.0 vs 0.89, P= 0.046) and invasiveness of the ZKSCAN3 overexpressed HCT116 cells was higher in CEA coated filters (75.6±6.0 vs 91.3±4.5, P=0.023). Conclusion: ZKSCAN3 is related with colorectal tumor progression and invasion. ZKSCAN3 overexpression tumor may facilitate metastasis of colorectal cancer associated with CEACAM5. Citation Format: Seon Ae Roh, Chan Wook Kim, Ka Hee Tak, Jin Cheon Kim. Zkscan3 facilitates invasion of colorectal cancer associated with ceacam5. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4992. doi:10.1158/1538-7445.AM2014-4992
Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma
Authors: D. Koul, R. Shen, Y.-W. Kim, Y. Kondo, Y. Lu, J. Bankson, S. M. Ronen, D. L. Kirkpatrick, G. Powis, W. K. A. Yung
Journal: Neuro-Oncology (2010)

The phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway is critical in glioblastomas. Loss of PTEN, a negative regulator of the PI3K pathway or activated PI3K/Akt pathway that drive increased proliferation, survival, neovascularization, glycolysis, and invasion is found in 70%–80% of malignant gliomas. Thus, PI3K is an attractive therapeutic target for malignant glioma. We report that a new irreversible PI3K inhibitor, PX-866, shows potent inhibitory effects on the PI3K/Akt signaling pathway in glioblastoma. PX-866 did not induce any apoptosis in glioma cells; however, an increase in autophagy was observed. PX-866 inhibited the invasive and angiogenic capabilities of cultured glioblastoma cells. In vivo, PX-866 inhibited subcutaneous tumor growth and increased the median survival time of animals with intracranial tumors. We also assessed the potential of proton magnetic resonance spectroscopy (MRS) as a noninvasive method to monitor response to PX-866. Our findings show that PX-866 treatment causes a drop in the MRS-detectable choline-to-NAA, ratio and identify this partial normalization of the tumor metabolic profile as a biomarker of molecular drug action. Our studies affirm that the PI3K pathway is a highly specific molecular target for therapies for glioblastoma and other cancers with aberrant PI3K/PTEN expression.
Plasma Lipoproteins and Apolipoproteins as Predictors of Cardiovascular Risk and Treatment Benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)
Authors: Chris J. Packard, Ian Ford, Michele Robertson, James Shepherd, Gerard J. Blauw, Michael B. Murphy, Edward L.E.M. Bollen, Brendan M. Buckley, Stuart M. Cobbe, Allan Gaw, Michael Hyland, J. Wouter Jukema, Adriaan M. Kamper, Peter W. Macfarlane, Ivan J. Perry, David J. Stott, Brian J. Sweeney, Cillian Twomey, Rudi G.J. Westendorp
Journal: Circulation (2005)

Background— Statins are important in vascular disease prevention in the elderly. However, the best method of selecting older patients for treatment is uncertain. We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Method and Results— The association of LDLc and HDLc with risk was examined in the 5804 70- to 82-year-old subjects of PROSPER. Baseline LDLc showed no relation to risk of the primary end point in the placebo group ( P =0.27), nor did on-treatment LDLc in the pravastatin group ( P =0.12). HDLc was inversely associated with risk in subjects on placebo ( P =0.0019) but not in those on pravastatin ( P =0.24). Risk reduction on pravastatin treatment was unrelated to baseline LDLc ( P =0.38) but exhibited a significant interaction with HDLc ( P =0.012). Subjects in the lowest 2 quintiles of HDLc (&lt;1.15 mmol/L) had a risk reduction of 33% (hazard ratio, 0.67; 95% confidence limits, 0.55, 0.81; P &lt;0.0001), whereas those with higher HDLc showed no benefit (RR, 1.06; 95% confidence limits, 0.88, 1.27; P =0.53). During follow-up, there was no relation between achieved level of LDLc or HDLc and risk. However, the change in the LDLc/HDLc ratio on statin treatment appeared to account for the effects of therapy. Conclusions— In people &gt;70 years old, HDLc appears to be a key predictor of risk and of treatment benefit. Findings in PROSPER suggest that statin therapy could usefully be targeted to those with HDLc &lt;1.15 mmol/L or an LDLc/HDLc ratio &gt;3.3.
Oncogenic<i>CSF3R</i>Mutations in Chronic Neutrophilic Leukemia and Atypical CML
Authors: Julia E. Maxson, Jason Gotlib, Daniel A. Pollyea, Angela G. Fleischman, Anupriya Agarwal, Christopher A. Eide, Daniel Bottomly, Beth Wilmot, Shannon K. McWeeney, Cristina E. Tognon, J. Blake Pond, Robert H. Collins, Basem Goueli, Stephen T. Oh, Michael W. Deininger, Bill H. Chang, Marc M. Loriaux, Brian J. Druker, Jeffrey W. Tyner
Journal: New England Journal of Medicine (2013)

The molecular causes of many hematologic cancers remain unclear. Among these cancers are chronic neutrophilic leukemia (CNL) and atypical (BCR-ABL1-negative) chronic myeloid leukemia (CML), both of which are diagnosed on the basis of neoplastic expansion of granulocytic cells and exclusion of genetic drivers that are known to occur in other myeloproliferative neoplasms and myeloproliferative-myelodysplastic overlap neoplasms.To identify potential genetic drivers in these disorders, we used an integrated approach of deep sequencing coupled with the screening of primary leukemia cells obtained from patients with CNL or atypical CML against panels of tyrosine kinase-specific small interfering RNAs or small-molecule kinase inhibitors. We validated candidate oncogenes using in vitro transformation assays, and drug sensitivities were validated with the use of assays of primary-cell colonies.We identified activating mutations in the gene encoding the receptor for colony-stimulating factor 3 (CSF3R) in 16 of 27 patients (59%) with CNL or atypical CML. These mutations segregate within two distinct regions of CSF3R and lead to preferential downstream kinase signaling through SRC family-TNK2 or JAK kinases and differential sensitivity to kinase inhibitors. A patient with CNL carrying a JAK-activating CSF3R mutation had marked clinical improvement after the administration of the JAK1/2 inhibitor ruxolitinib.Mutations in CSF3R are common in patients with CNL or atypical CML and represent a potentially useful criterion for diagnosing these neoplasms. (Funded by the Leukemia and Lymphoma Society and others.).
Reduced Olfactory Bulb Volume in Patients With Schizophrenia
Authors: Bruce I. Turetsky, Paul J. Moberg, David M. Yousem, Richard L. Doty, Steven E. Arnold, Raquel E. Gur
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors' goal in this study was to compare the size of olfactory bulbs of patients with schizophrenia and those of healthy subjects.METHOD: Magnetic resonance imaging scans of olfactory bulbs were obtained from 26 patients with schizophrenia and 22 healthy comparison subjects. A reliable region of interest procedure was used to measure olfactory bulb volume.RESULTS: Patients exhibited 23% smaller bilateral bulb volume than comparison subjects, independent of acute clinical, demographic, or treatment measures. Bulb volume correlated with odor detection sensitivity in healthy subjects but not in patients with schizophrenia.CONCLUSIONS: Patients with schizophrenia exhibit structural olfactory deficits as well as functional olfactory deficits. The olfactory system may be a model system in which to study the neurobiology of the disorder.
Association of Chronic Kidney Disease and Anemia with Physical Capacity
Authors: Michelle C. Odden, Mary A. Whooley, Michael G. Shlipak
Journal: Journal of the American Society of Nephrology (2004)

Chronic kidney disease (CKD) and anemia are common conditions in the outpatient setting, but their independent and additive effects on physical capacity have not been well characterized. The association of CKD and anemia with self-reported physical function was evaluated and exercise capacity was measured in patients with coronary disease. A cross-sectional study of 954 outpatients enrolled in the Heart and Soul study was performed. CKD was defined as a measured creatinine clearance <60 ml/min, and anemia was defined as a hemoglobin level of <12g/dl. Physical function was self-assessed using the physical limitation subscale of the Seattle Angina Questionnaire (0 to 100), and exercise capacity was defined as metabolic equivalent tasks achieved at peak exercise. In unadjusted analyses, CKD was associated with lower self-reported physical function (67.6 versus 74.9; P < 0.001) and lower exercise capacity (5.5 versus 7.9; P < 0.001). Similarly, anemia was associated with lower self-reported physical function (62.6 versus 74.3; P < 0.001) and exercise capacity (5.7 versus 7.5; P < 0.001). After multivariate adjustment, CKD (69.4 versus 74.2; P = 0.003) and anemia (67.5 versus 73.6; P = 0.009) each remained associated with lower mean self-reported physical function. In addition, patients with CKD (6.3 versus 7.7; P < 0.001) or anemia (6.5 versus 7.4; P = 0.004) had lower adjusted mean exercise capacities. Participants with both CKD and anemia had lower self-reported physical function and exercise capacity than those with either alone. CKD and anemia are independently associated with physical limitation and reduced exercise capacity in outpatients with coronary disease, and these effects are additive. The broad impact of these disease conditions merits further study.
Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.
Authors: N R Klinman, M R Stone
Journal: The Journal of Experimental Medicine (1983)

To evaluate the role of environmental selective processes, as opposed to variable region gene expression, in the determination of B cell repertoire expression, we have assessed the phosphorylcholine (PC)-specific repertoire of precursor cells that remain in bone marrow cell populations after the removal of surface immunoglobulin (sIg)-bearing cells. Such cells are assumed to represent a stage in B cell maturation before the expression of sIg, and thus at a time when they have not as yet interfaced with environmental influences that operate through sIg receptors such as antigenic stimulation, tolerance, or antiidiotypic regulation. The repertoire as expressed in these cells, therefore, should reflect the readout of immunoglobulin variable region genes as they are expressed in progenitors to B cells. The results of these studies indicate that, as in mature primary B cell pools of BALB/c mice, the majority of PC-responsive sIg- bone marrow cells are of the T15 clonotype. Thus, environmental selective mechanisms would not appear to be required for the high frequency of B cells of the T15 idiotype in the primary B cell repertoire of BALB/c mice. Analysis of the sIg- bone marrow cells in (CBA/N X BALB/c)F1 male mice demonstrated that the deficit of PC-responsive mature B cells, which is a characteristic of this murine strain, must occur after receptor expression, since a normal frequency of PC-responsive and T15-expressing cells is present in their sIg- bone marrow population. Finally, these same mice were used to obtain bone marrow cell preparations from individual leg bones, so as to permit an analysis of the occurrence of T15+ and T15- clonotypes within individual bone marrow populations. The findings from these studies indicate that T15+ B cells occur as a high frequency event within bone marrow generative cell pools. Furthermore, bone marrow populations that are positive for PC-responsive precursor cells often display multiple copies of such precursor cells that are exclusively either T15+ or T15-. This finding indicates that clonal expansion of cells within the B cell lineage apparently occurs before immunoglobulin receptor acquisition.
Physicians' Perceptions, Preparedness for Reporting, and Experiences Related to Impaired and Incompetent Colleagues
Authors: Catherine M. DesRoches
Journal: JAMA (2010)

Peer monitoring and reporting are the primary mechanisms for identifying physicians who are impaired or otherwise incompetent to practice, but data suggest that the rate of such reporting is lower than it should be.To understand physicians' beliefs, preparedness, and actual experiences related to colleagues who are impaired or incompetent to practice medicine.Nationally representative survey of 2938 eligible physicians practicing in the United States in 2009 in anesthesiology, cardiology, family practice, general surgery, internal medicine, pediatrics, and psychiatry. Overall, 1891 physicians (64.4%) responded.Beliefs about and preparedness for reporting and experiences with colleagues who practice medicine while impaired or who are incompetent in their medical practice.Sixty-four percent (n = 1120) of surveyed physicians agreed with the professional commitment to report physicians who are significantly impaired or otherwise incompetent to practice. Nonetheless, only 69% (n = 1208) of physicians reported being prepared to effectively deal with impaired colleagues in their medical practice, and 64% (n = 1126) reported being so prepared to deal with incompetent colleagues. Seventeen percent (n = 309) of physicians had direct personal knowledge of a physician colleague who was incompetent to practice medicine in their hospital, group, or practice. Of those with this knowledge, 67% (n = 204) reported this colleague to the relevant authority. Underrepresented minorities and graduates of non-US medical schools were less likely than their counterparts to report, and physicians working in hospitals or medical schools were most likely to report. The most frequently cited reason for taking no action was the belief that someone else was taking care of the problem (19% [n = 58]), followed by the belief that nothing would happen as a result of the report (15% [n = 46]) and fear of retribution (12% [n = 36]).Overall, physicians support the professional commitment to report all instances of impaired or incompetent colleagues in their medical practice to a relevant authority; however, when faced with these situations, many do not report.
Design Issues for Conducting Cost-Effectiveness Analyses Alongside Clinical Trials
Authors: Scott D Ramsey, Martin McIntosh, Sean D Sullivan
Journal: Annual Review of Public Health (2001)

▪ Abstract In response to rising demands for timely economic data on new medical technologies, cost-effectiveness studies are increasingly being conducted alongside clinical trials. Because of the historical differences in perspective and methods between cost-effectiveness studies and clinical trials, the design phase of these hybrid trials requires special consideration. Cost-effectiveness studies require more comprehensive evaluations of outcomes than the endpoints typically measured in clinical trials. Often, these comprehensive outcome measures (such as quality of life) prove useful for interpreting the other endpoints measured in the trial, as well as for estimating the cost-effectiveness of the intervention. In this manuscript, we discuss several aspects related to the design of joint clinical/economic trials, including study perspective, hypothesis testing, sample size estimation, and methods for collecting cost and outcome data. We also discuss issues that may limit the external validity of the cost-effectiveness results of these trials. Many potential threats to external validity can be successfully addressed if they are identified and accounted for in the design phase of the study.
Cost-effectiveness of hepatitis A vaccination in children, adolescents, and adults
Authors: Philip Rosenthal
Journal: Hepatology (2003)

Hepatitis A is a major public health problem in the United States and other developed countries, largely because decreased natural immunity allows for increased susceptibility. To evaluate the cost-effectiveness of routine vaccination of children, adolescents, and certain high-risk adults against hepatitis A, economic analyses of hepatitis A vaccination were identified through searches of MEDLINE, EMBASE, and BIOSIS (February, 1992, to December, 2001) for studies, reviews, editorials, and letters from peer-reviewed journals published in English, French, German, Italian, or Spanish. Experts were also contacted. Articles conforming to accepted standards of quality for health-economic studies were used to compile data on vaccination of children, and results were synthesized in a narrative review. This review of economic analyses of vaccine use in several developed countries shows cost-effectiveness comparable with that of other vaccines in children and within accepted boundaries for adolescents and high-risk adults.