tbuckley/cabot-search huggingface dataset:
Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases
Authors: Ishwaria M. Subbiah, Xiudong Lei, Jeffrey S. Weinberg, Erik P. Sulman, Mariana Chavez-MacGregor, Debu Tripathy, Rohan Gupta, Ankur Varma, Jay Chouhan, Richard P. Guevarra, Vicente Valero, Mark R. Gilbert, Ana M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2015)

Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases.Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index.In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001). In multivariable analysis of the breast-GPA and number of brain metastases (> three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001).The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials.
Current practice patterns of primary care physicians in the management of patients with hepatitis C
Authors: Thomas M. Shehab, Seema S. Sonnad, Mark Jeffries, Naresh Gunaratnum, Anna S. Lok
Journal: Hepatology (1999)

Approximately 4 million Americans are infected with the hepatitis C virus (HCV). Most patients with hepatitis C have no symptoms until cirrhosis is established. Thus, initial diagnosis and management of hepatitis C rely on primary care physicians identifying and screening high-risk individuals. We administered a survey to 1,233 primary care physicians in a health maintenance organization (HMO) in April 1997 to assess their knowledge of the risk factors for HCV infection and approach to the management of 2 hypothetical HCV antibody–positive patients, 1 with elevated and the other with normal alanine transaminase (ALT). Four hundred four (33%) physicians returned the survey. Ninety percent of respondents correctly identified the risk factors for HCV infection, but 20% still considered blood transfusion in 1994 as a significant risk factor for HCV infection. Sixty-two percent of respondents would refer HCV antibody–positive patients with abnormal transaminase levels, but 33% would follow these patients themselves, even though none of the respondents had treated any hepatitis C patient on their own. Forty-three percent of respondents overestimated, while 29% did not know the efficacy of interferon treatment. Sixty-five percent of respondents would retest patients for HCV antibody, regardless of risk factors and transaminase levels. We found that most primary care physicians correctly identified the significant risk factors for HCV infection and appropriately managed the 2 hypothetical patients, but there was considerable confusion about the use of HCV tests and the effectiveness of treatment. Educational programs for primary care physicians are needed to implement hepatitis C screening and to initiate further evaluation and management of those who test positive.
Increased Risk of Subsequent Myocardial Infarction in Patients With Type 2 Diabetes: A Retrospective Cohort Study Using the U.K. General Practice Research Database
Authors: Huifang Liang, Carlos Vallarino, Guiandre Joseph, Sudhakar Manne, Alfonso Perez, Shumin Zhang
Journal: Diabetes Care (2014)

To compare the risk of subsequent myocardial infarction (MI) between patients with and without type 2 diabetes mellitus (T2DM) in a retrospective cohort study.Patients with their first MI recorded in the U.K. General Practice Research Database in 1997-2008 were classified as T2DM, diagnosed before or within 28 days after the date of the first recorded MI (i.e., the index date), or non-T2DM. Patients diagnosed within 28 days after the index date were assumed to have developed T2DM at baseline (i.e., before the index date). The primary outcome was the first subsequent MI. The secondary outcomes were all-cause death and a composite of all-cause death or subsequent MI. Cox proportional hazards models were fit to obtain hazard ratios (HRs) for all outcomes.A total of 7,411 T2DM (median age 72 years; men 63.4%) and 48,726 non-T2DM patients (median age 69 years; men 65.3%) were included. The crude incidences (per 1,000 patient-years) in T2DM vs. non-T2DM were 32.8 vs. 22.8 for subsequent MI, 83.7 vs. 52.1 for all-cause death, and 106.5 vs. 69.9 for the composite end point. The adjusted HRs for subsequent MI, all-cause death, and their combination were 1.41 (95% CI 1.27-1.56), 1.50 (1.41-1.60), and 1.42 (1.34-1.50), respectively, in women and 1.23 (1.14-1.34), 1.40 (1.33-1.47), and 1.33 (1.27-1.39) in men.Compared with non-T2DM, T2DM was associated with an increased risk for subsequent MI, all-cause death, and their composite end point. The risk tends to be higher in women than in men.
Murine L5178Y Cells Resulting in Altered Drug Sensitivities From Fractionated Radiation Exposure In Vitro
Authors: A S Bellamy, B T Hill
Journal: JNCI Journal of the National Cancer Institute (1984)

Exposure of murine L5178Y cells in vitro to fractionated X-irradiation (DXR) produced a subline that exhibited significantly altered responses to the cytotoxic effects of a range of antitumor drugs. A DXR schedule of 2 Gy per fraction for 10 fractions (total dose, 20 Gy) was used. Characterization of this subline revealed no marked differences when compared with the parent line in terms of growth rate, cloning efficiency, cell volume, chromosome number, macromolecular content, cell cycle distribution, or response to acute DXR exposure. Drug sensitivities were assessed following 24-hour exposures by colony formation in soft agar. Three distinct patterns of response were found: increased sensitivity of DXR-pretreated cells to bleomycin, cis-diamminedichloroplatinum (II), or dibromodulcitol; comparable responses in both lines to doxorubicin, 5-fluorouracil, or hydroxyurea; and decreased sensitivity of DXR-pretreated cells to vincristine or VP 16213.
Effect of Lowering LDL Cholesterol Substantially Below Currently Recommended Levels in Patients With Coronary Heart Disease and Diabetes
Authors: James Shepherd, Philip Barter, Rafael Carmena, Prakash Deedwania, Jean-Charles Fruchart, Steven Haffner, Judith Hsia, Andrei Breazna, John LaRosa, Scott Grundy, David Waters
Journal: Diabetes Care (2006)

The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes.A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke.End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (hazard ratio 0.75 [95% CI 0.58-0.97], P = 0.026). Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (0.69 [0.48-0.98], P = 0.037) and any cardiovascular event (0.85 [0.73-1.00], P = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes.Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg.
Serum Fibroblast Growth Factor-23 Is Associated with Incident Kidney Disease
Authors: Casey M. Rebholz, Morgan E. Grams, Josef Coresh, Elizabeth Selvin, Lesley A. Inker, Andrew S. Levey, Paul L. Kimmel, Ramachandran S. Vasan, John H. Eckfeldt, Harold I. Feldman, Chi-yuan Hsu, Pamela L. Lutsey
Journal: Journal of the American Society of Nephrology (2014)

Fibroblast growth factor-23 is a bone-derived hormone that increases urinary phosphate excretion and inhibits hydroxylation of 25-hydroxyvitamin D. Recent studies suggest that fibroblast growth factor-23 may be an early biomarker of CKD progression. However, its role in kidney function decline in the general population is unknown. We assessed the relationship between baseline (1990-1992) serum levels of intact fibroblast growth factor-23 and incident ESRD in 13,448 Atherosclerosis Risk in Communities study participants (56.1% women, 74.7% white) followed until December 31, 2010. At baseline, the mean age of participants was 56.9 years and the mean eGFR was 97 ml/min per 1.73 m(2). During a median follow-up of 19 years, 267 participants (2.0%) developed ESRD. After adjustment for demographic characteristics, baseline eGFR, traditional CKD risk factors, and markers of mineral metabolism, the highest fibroblast growth factor-23 quintile (>54.6 pg/ml) compared with the lowest quintile (<32.0 pg/ml) was associated with risk of developing ESRD (hazard ratio, 2.10; 95% confidence interval, 1.31 to 3.36; trend P<0.001). In a large, community-based study comprising a broad range of kidney function, higher baseline fibroblast growth factor-23 levels were associated with increased risk of incident ESRD independent of the baseline level of kidney function and a number of other risk factors.
Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies
Authors: Wilhelmina G Melsen, Maroeska M Rovers, Rolf HH Groenwold, Dennis CJJ Bergmans, Christophe Camus, Torsten T Bauer, Ernst W Hanisch, Bengt Klarin, Mirelle Koeman, Wolfgang A Krueger, Jean-Claude Lacherade, Leonardo Lorente, Ziad A Memish, Lee E Morrow, Giuseppe Nardi, Christianne A van Nieuwenhoven, Grant E O'Keefe, George Nakos, Frank A Scannapieco, Philippe Seguin, Thomas Staudinger, Arzu Topeli, Miquel Ferrer, Marc JM Bonten
Journal: The Lancet Infectious Diseases (2013)
Hemostasis and Fibrinolysis in Severe Liver Failure and Their Relation to Hemorrhage
Authors: Anton L. Boks, Emile J.P. Brommer, Solko W. Schalm, Huub H.D.M. Van Vliet
Journal: Hepatology (1986)

In a study of severe, decompensated liver failure, we tried to find a correlation between hemorrhage and parameters ofhemostasis and fibrinolysis. Three groups of patients were studied: alcoholic cirrhosis; nonalcoholic cirrhosis, and acute liver failure without known prior liver disease. The two cirrhotic groups did not differ significantly from each other in coagulation or in fibrinolytic parameters, although liver function was more impaired in nonalcoholic cirrhosis. The levels of clotting factors, antithrombin III, prekallikrein, plasminogen and α 2 -antiplasmin were significantly lower in the third group. Mean values of fibrinolytic activity (fibrin plate method) were slightly reduced as compared to normal in all three groups. Tissue plasminogen activator–related antigen tended to be elevated especially in alcoholic cirrhosis. The free fast–acting plasminogen activator inhibitor showed extremely high and extremely low levels in some patients among all three groups. Nonvariceal, capillary–type bleeding, including mucosal bleeding, hematomas and bleeding from puncture sites correlated with low thrombotest and normotest levels (p &lt; 0.01), low fibrinogen concentration (p &lt; 0.05) and with a high quotient of fibrinolytic activity (square root of lysis area) and normotest (p &lt; 0.001). The ratio between fibrinformation and dissolution appears to be an important parameter of hemorrhagic tendency in liver disease. Variceal bleeding appeared not to be related to impairment of hemostasis or fibrinolysis.
Monitoring Kidney Function and Albuminuria in Patients With Diabetes
Authors: Hiddo J. Lambers Heerspink, Frank A. Holtkamp, Dick de Zeeuw, Mordchai Ravid
Journal: Diabetes Care (2011)

It is beyond doubt that patients with diabetes are at high risk of developing renal and cardiovascular disease. Both outcomes have significant clinical implications and are associated with high additional costs. Several traditional (blood pressure, HbA1c, cholesterol) and novel cardiovascular biomarkers (C-reactive protein, pro-brain natriuretic peptide) are at hand to identify those individuals who will develop end-stage renal or cardiovascular disease, as early as possible. The traditional biomarkers have been successfully applied in clinical practice and have proven their clinical usefulness. Renal biomarkers, in particular, albuminuria and estimated glomerular filtration rate (eGFR), have been added to the biomarker armamentarium. Both are indeed associated with renal and cardiovascular disease in individuals with diabetes and may be used to identify individuals at risk of long-term complications. Although identifying individuals at risk is important, even more important is the question whether we can lower this risk by changing renal biomarkers through pharmacological (or other) intervention. This overview describes the performance of albuminuria and eGFR in predicting renal and cardiovascular disease. In the second part, the relationship between treatment-induced changes in these two renal biomarkers and renal and cardiovascular outcome will be described.

### Albuminuria

The relationship between albuminuria and renal and cardiovascular disease has been well established. Its association was first described in patients with type 1 diabetes (1,2). Several studies followed these initial reports and confirmed the significance of albuminuria in predicting long-term renal prognosis. Data from prospective trials showed that patients with type 2 diabetes appear to progress from micro- to macroalbuminuria to end-stage renal disease (ESRD), similar to the earlier reports of patients with type 1 diabetes. The Reduction in End Points in Non-Insulin Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan (RENAAL) showed that albuminuria is the most critical baseline predictor for ESRD (3). Similar data …
The cost of physical inactivity: moving into the 21st century
Authors: Michael Pratt, Jeffrey Norris, Felipe Lobelo, Larissa Roux, Guijing Wang
Journal: British Journal of Sports Medicine (2012)

Physical inactivity is increasingly being recognised as a major problem in global health. The WHO estimates that 3.3 million people die around the world each year due to physical inactivity, making it the fourth leading underlying cause of mortality.1 Physical activity has beneficial effects on 23 diseases or health conditions.2 However, in most countries fewer than half of adults are active enough to reap most of these benefits.3 ,4 Given that inactivity increases the risk for many of the most costly medical conditions such as type 2 diabetes, stroke, ischaemic heart disease, falls and hip fractures, and depression, it is not surprising that physical inactivity has a substantial cost burden in addition to a large health burden.

Despite impressive health and economic consequences, it is only recently that addressing physical inactivity has become a mainstream part of public health and health policy.5 However, this is clearly occurring. The WHO Global Action Plan for NCDs emphasises physical activity as an important element of primary and secondary prevention, WHO released a global recommendations for physical activity in 2010,6 the September 2011 United Nations General Assembly Summit on NCDs prominently include physical activity4 and national public health policy in influential countries such as Brazil and the USA substantively incorporates physical activity promotion.7 ,8 However, these are initial steps in addressing a global epidemic of NCDs and inactivity. The gap between the size of the problem and the scale of the public health response remains large. In such situations, effective advocacy is called for9 and often times this means economic data which highlight the costs of not taking action. This seems to be an argument for more and better analyses and research publications on the costs of physical inactivity. However, in the following paragraphs …
Recent progress in pancreatic cancer
Authors: Christopher L. Wolfgang, Joseph M. Herman, Daniel A. Laheru, Alison P. Klein, Michael A. Erdek, Elliot K. Fishman, Ralph H. Hruban
Journal: CA A Cancer Journal for Clinicians (2013)

Answer questions and earn CME/CNE Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in the understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. CA Cancer J Clin 2013;63:318‐348. © 2013 American Cancer Society.
Wheeze, asthma diagnosis and medication use: a national adult survey in a developing country
Authors: R I Ehrlich
Journal: Thorax (2005)

<b>Background:</b> As relatively little is known about adult wheeze and asthma in developing countries, this study aimed to determine the predictors of wheeze, asthma diagnosis, and current treatment in a national survey of South African adults. <b>Methods:</b> A stratified national probability sample of households was drawn and all adults (&gt;14 years) in the selected households were interviewed. Outcomes of interest were recent wheeze, asthma diagnosis, and current use of asthma medication. Predictors of interest were sex, age, household asset index, education, racial group, urban residence, medical insurance, domestic exposure to smoky fuels, occupational exposure, smoking, body mass index, and past tuberculosis. <b>Results:</b> A total of 5671 men and 8155 women were studied. Although recent wheeze was reported by 14.4% of men and 17.6% of women and asthma diagnosis by 3.7% of men and 3.8% of women, women were less likely than men to be on current treatment (OR 0.6; 95% confidence interval (CI) 0.5 to 0.8). A history of tuberculosis was an independent predictor of both recent wheeze (OR 3.4; 95% CI 2.5 to 4.7) and asthma diagnosis (OR 2.2; 95% CI 1.5 to 3.2), as was occupational exposure (wheeze: OR 1.8; 95% CI 1.5 to 2.0; asthma diagnosis: OR 1.9; 95% CI 1.4 to 2.4). Smoking was associated with wheeze but not asthma diagnosis. Obesity showed an association with wheeze only in younger women. Both wheeze and asthma diagnosis were more prevalent in those with less education but had no association with the asset index. Independently, having medical insurance was associated with a higher prevalence of diagnosis. <b>Conclusions:</b> Some of the findings may be to due to reporting bias and heterogeneity of the categories wheeze and asthma diagnosis, which may overlap with post tuberculous airways obstruction and chronic obstructive pulmonary disease due to smoking and occupational exposures. The results underline the importance of controlling tuberculosis and occupational exposures as well as smoking in reducing chronic respiratory morbidity. Validation of the asthma questionnaire in this setting and research into the pathophysiology of post tuberculous airways obstruction are also needed.
Weekly monitoring of children with asthma for infections and illness during common cold seasons
Authors: Jaime P. Olenec, Woo Kyung Kim, Wai-Ming Lee, Fue Vang, Tressa E. Pappas, Lisa E.P. Salazar, Michael D. Evans, Jack Bork, Kathleen Roberg, Robert F. Lemanske, James E. Gern
Journal: Journal of Allergy and Clinical Immunology (2010)

Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity.We sought to evaluate rhinovirus infections during peak seasons in children with asthma and to analyze relationships between viral infection and illness severity.Fifty-eight children aged 6 to 8 years with asthma provided 5 consecutive weekly nasal lavage samples during September and April; symptoms, medication use, and peak flow were recorded. Rhinoviruses were identified by using multiplex PCR and partial sequencing of viral genomes.Viruses were detected in 36% to 50% of the specimens, and 72% to 99% of the viruses were rhinoviruses. There were 52 different strains (including 16 human rhinovirus C) among the 169 rhinovirus isolates; no strains were found in more than 2 collection periods, and all but 2 children had a respiratory tract infection. Virus-positive weeks were associated with greater cold and asthma symptom severity (P < .0001 and P = .0002, respectively). Furthermore, virus-positive illnesses had increased duration and severity of cold and asthma symptoms and more frequent loss of asthma control (47% vs 22%, P = .008). Although allergen-sensitized versus nonsensitized children had the same number of viral infections, the former had 47% more symptomatic viral illnesses (1.19 vs 0.81 per month, P = .03).Rhinovirus infections are nearly universal in children with asthma during common cold seasons, likely because of a plethora of new strains appearing each season. Illnesses associated with viruses have greater duration and severity. Finally, atopic asthmatic children experienced more frequent and severe virus-induced illnesses.