tbuckley/cabot-search huggingface dataset:
Advancing Insulin Therapy in Type 2 Diabetes Previously Treated With Glargine Plus Oral Agents
Authors: Julio Rosenstock, Andrew J. Ahmann, Gildred Colon, Jamie Scism-Bacon, Honghua Jiang, Sherry Martin
Journal: Diabetes Care (2007)

OBJECTIVE—The purpose of this study was to compare two analog insulin therapies (prandial premixed therapy [PPT] versus basal/bolus therapy [BBT]) in type 2 diabetic patients previously treated with insulin glargine (≥30 units/day) plus oral agents, with the aim of demonstrating noninferiority of PPT to BBT. RESEARCH DESIGN AND METHODS—Patients were randomly assigned to PPT (lispro mix 50/50: 50% insulin lispro protamine suspension and 50% lispro; n = 187) t.i.d. with meals or BBT (glargine at bedtime plus mealtime lispro; n = 187) in a 24-week, multicenter, open-label, noninferiority trial. Investigators could replace lispro mix 50/50 with lispro mix 75/25 at the evening meal if the fasting plasma glucose target was unachievable. RESULTS—Baseline A1C was similar (PPT 8.8%; BBT 8.9%; P = 0.598). At week 24, A1C was lower with BBT (6.78 vs. 6.95%, P = 0.021). A1C was reduced significantly from baseline for both therapies (P &amp;lt; 0.0001). The difference in A1C change from baseline to the end point (BBT minus PPT) was −0.22% (90% CI −0.38 to −0.07). Noninferiority of PPT to BBT was not demonstrated based on the prespecified noninferiority margin of 0.3%. The percentages of patients achieving target A1C &amp;lt;7.0% (PPT versus BBT, respectively) were 54 vs. 69% (P = 0.009) and for target ≤6.5% were 35 vs. 50% (P = 0.01) but did not differ for target ≤6.0% or &amp;lt;7.5%. Rates of hypoglycemia were similar for both groups. CONCLUSIONS—Although noninferiority of PPT to BBT was not demonstrated, findings for A1C reduction, percentage of patients achieving A1C targets, hypoglycemia, and number of required injections should be considered in the individual decision-making process of advancing insulin replacement to PPT versus BBT in type 2 diabetes.
Consumption of Vegetables and Fruits and Risk of Breast Cancer
Authors: Carla H. van Gils
Journal: JAMA (2005)

The intake of vegetables and fruits has been thought to protect against breast cancer. Most of the evidence comes from case-control studies, but a recent pooled analysis of the relatively few published cohort studies suggests no significantly reduced breast cancer risk is associated with vegetable and fruit consumption.To examine the relation between total and specific vegetable and fruit intake and the incidence of breast cancer.Prospective study of 285,526 women between the ages of 25 and 70 years, participating in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, recruited from 8 of the 10 participating European countries. Participants completed a dietary questionnaire in 1992-1998 and were followed up for incidence of cancer until 2002.Relative risks for breast cancer by total and specific vegetable and fruit intake. Analyses were stratified by age at recruitment and study center. Relative risks were adjusted for established breast cancer risk factors.During 1,486,402 person-years (median duration of follow-up, 5.4 years), 3659 invasive incident breast cancer cases were reported. No significant associations between vegetable or fruit intake and breast cancer risk were observed. Relative risks for the highest vs the lowest quintile were 0.98 (95% confidence interval [CI], 0.84-1.14) for total vegetables, 1.09 (95% CI , 0.94-1.25) for total fruit, and 1.05 (95% CI , 0.92-1.20) for fruit and vegetable juices. For 6 specific vegetable subgroups no associations with breast cancer risk were observed either.Although the period of follow-up is limited for now, the results suggest that total or specific vegetable and fruit intake is not associated with risk for breast cancer.
Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the<i>F508del-CFTR</i>mutation
Authors: J P Clancy, Steven M Rowe, Frank J Accurso, Moira L Aitken, Raouf S Amin, Melissa A Ashlock, Manfred Ballmann, Michael P Boyle, Inez Bronsveld, Preston W Campbell, Kris De Boeck, Scott H Donaldson, Henry L Dorkin, Jordan M Dunitz, Peter R Durie, Manu Jain, Anissa Leonard, Karen S McCoy, Richard B Moss, Joseph M Pilewski, Daniel B Rosenbluth, Ronald C Rubenstein, Michael S Schechter, Martyn Botfield, Claudia L Ordoñez, George T Spencer-Green, Laurent Vernillet, Steve Wisseh, Karl Yen, Michael W Konstan
Journal: Thorax (2011)

<h3>Background</h3> VX-809, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, has been shown to increase the cell surface density of functional <i>F508del-CFTR</i> in vitro. <h3>Methods</h3> A randomised, double-blind, placebo-controlled study evaluated the safety, tolerability and pharmacodynamics of VX-809 in adult patients with cystic fibrosis (n=89) who were homozygous for the <i>F508del-CFTR</i> mutation. Subjects were randomised to one of four VX-809 28 day dose groups (25, 50, 100 and 200 mg) or matching placebo. <h3>Results</h3> The type and incidence of adverse events were similar among VX-809- and placebo-treated subjects. Respiratory events were the most commonly reported and led to discontinuation by one subject in each active treatment arm. Pharmacokinetic data supported a once-daily oral dosing regimen. Pharmacodynamic data suggested that VX-809 improved CFTR function in at least one organ (sweat gland). VX-809 reduced elevated sweat chloride values in a dose-dependent manner (p=0.0013) that was statistically significant in the 100 and 200 mg dose groups. There was no statistically significant improvement in CFTR function in the nasal epithelium as measured by nasal potential difference, nor were there statistically significant changes in lung function or patient-reported outcomes. No maturation of immature <i>F508del-CFTR</i> was detected in the subgroup that provided rectal biopsy specimens. <h3>Conclusions</h3> In this study, VX-809 had a similar adverse event profile to placebo for 28 days in <i>F508del-CFTR</i> homozygous patients, and demonstrated biological activity with positive impact on CFTR function in the sweat gland. Additional data are needed to determine how improvements detected in CFTR function secondary to VX-809 in the sweat gland relate to those measurable in the respiratory tract and to long-term measures of clinical benefit. <h3>Clinical trial number</h3> NCT00865904
Metabolomic profiling of the lung in a murine model of emphysema
Authors: Thomas Conlon, Martin Irmler, Johannes Beckers, Jerzy Adamski, Oliver Eickelberg, Ali Önder Yildirim
Journal: European Respiratory Journal (2014)

COPD is characterized by chronic bronchitis, small airway remodeling and emphysema. Metabolomics offers a powerful new tool for understanding changes in disease pathology. Indeed, increases in ceramide levels have been shown to cause pulmonary cell apoptosis and emphysema in mice. Here we aimed to use targeted metabolomics to fully characterize profiles in serum, lung and BAL of the porcine pancreatic elastase (PPE) induced model of emphysema and relate to changes in the transcriptome.

A single oropharyngeal application of PPE (80U/kg) to C57BL/6 mice resulted in a progressive severe emphysema on d28, 56 & 161 as demonstrated by declining lung function and increased airspace enlargement (d28 64.2±16.2 v 28.0±4.7; d56 71.4±17.2 v 25.6±8.7; d161 74.0±18.5 v 47.2μm (mean±s.d.) for PPE v PBS). Targeted metabolite analysis was subsequently performed on serum, lung and BAL using the AbsoluteIDQ Kit (Biocrates Life Sciences). In parallel microarray analysis of lung tissue was undertaken.

Interestingly, we found a significant time dependent reduction of phosphatidylcholines (67.5%) in BAL, acylcarnitines (38.2%) in lung, sphingomyelins (45.4% & 14.9%) and lysophosphatidylcholines (25.5% & 10.7%) in both BAL and lung respectively of PPE exposed mice. To substantiate, microarray data demonstrated changes in the expression pattern of genes important for the metabolism of sphingolipids (eg Asah1 ), that confirmed the metabolism of sphinogolipids towards ceramide. However, no significant change to the metabolic profile of serum was observed. Thus, changes in the metabolome local to the lung may contribute to disease pathology, lead to the discovery of new biomarkers of emphysema development and raise new therapeutic targets.
S63 Investigation Of Serum Biomarkers In Tuberculosis Diagnosis
Authors: C. Tweed, G. Bothamley
Journal: Thorax (2014)

<h3>Introduction</h3> In screening for tuberculosis (TB), we need to distinguish between active and latent TB. In those with a positive interferon-gamma release assay (IGRA) additional tests are required to identify active TB. Proteomic fingerprinting suggested that four proteins (C-reactive protein (CRP), transthyretin, neopterin, and serum amyloid A (SAA)) might be able to distinguish active from latent disease.<sup>1</sup> <h3>Methods</h3> Patients were grouped to reflect different stages of infection and those with latent TB were followed for over eight years. These groups were: 1) Smear-positive TB (n = 20), 2) Smear-negative/culture-positive TB (n = 12), 3) Recent TB contacts with positive interferon-gamma release assay (IGRA) (n = 15), and 4) No TB detected with firm alternative diagnosis (n = 12). All patients in groups 1 to 3 and 25% of group 4 were IGRA positive. Serum samples were collected and enzyme-linked immunosorbent assays (ELISAs) were performed to measure C-reactive protein, transthyretin, neopterin, and serum amyloid A found in the serum samples from each group. Standard cut-off values were used for each protein and results labelled as either positive or negative. Chi-square calculations were used to determine the significance of the results in differentiating between active TB, latent TB, and absence of TB infection. <h3>Results</h3> All four biomarkers were positive in smear-positive TB, but SAA and CRP were less sensitive in smear-negative TB (see attached table). Even in the control group, there were positive tests for the four biomarkers. None of those with latent TB developed active disease, even though a proportion had a positive test. <h3>Conclusion</h3> These four biomarkers did not distinguish between active and latent disease, and did not predict the development of active disease in those with latent TB infection. <h3>Reference</h3> Agranoff D, Fernandez-Reyes D, Papadopoulos MC, Rojas SA, Herbster M, Loosemore A, Tarelli E, Sheldon J, Schwenk A, Pollok, Rayner CF, Krishna S. Indentification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum.<i> Lancet</i> 2006;368:1012–21
Ischemic Postconditioning During Primary Percutaneous Coronary Intervention
Authors: Joo-Yong Hahn, Young Bin Song, Eun Kyoung Kim, Cheol Woong Yu, Jang-Whan Bae, Woo-Young Chung, Seung-Hyuk Choi, Jin-Ho Choi, Jang-Ho Bae, Kyung Joo An, Jong-Seon Park, Ju Hyeon Oh, Sang-Wook Kim, Jin-Yong Hwang, Jae Kean Ryu, Hun Sik Park, Do-Sun Lim, Hyeon-Cheol Gwon
Journal: Circulation (2013)

Background— Ischemic postconditioning has been reported to reduce infarct size in patients with ST-segment–elevation myocardial infarction. However, cardioprotective effects of postconditioning have not been demonstrated in a large-scale trial. Methods and Results— We performed a multicenter, prospective, randomized, open-label, blinded end-point trial. A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction within 12 hours after symptom onset were randomly assigned to the postconditioning group or to the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow as follows: The angioplasty balloon was positioned at the culprit lesion and inflated 4 times for 1 minute with low-pressure (&lt;6 atm) inflations, each separated by 1 minute of deflation. The primary end point was complete ST-segment resolution (percentage resolution of ST-segment elevation &gt;70%) measured at 30 minutes after PCI. Complete ST-segment resolution occurred in 40.5% of patients in the postconditioning group and 41.5% of patients in the conventional PCI group (absolute difference, −1.0%; 95% confidence interval, −8.4 to 6.4; P =0.79). The rate of myocardial blush grade of 0 or 1 and the rate of major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group (17.2% versus 22.4% [ P =0.20] and 4.3% versus 3.7% [ P =0.70], respectively). Conclusion— Ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment–elevation myocardial infarction undergoing primary PCI with current standard practice. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00942500.
The burden of infectious diseases in Europe: a pilot study
Authors: E A van Lier, A H Havelaar, A Nanda
Journal: Eurosurveillance (2007)

The main objectives of this pilot study were to test the potential use of the disease burden concept in the field of infectious diseases, including data quality and availability; to recommend future studies; and to stimulate a debate. The disease burden of seven infectious diseases (influenza, measles, HIV, campylobacteriosis, infection with enterohaemorrhagic Escherichia coli, salmonellosis and tuberculosis) in Europe was estimated by calculating Disability Adjusted Life Years (DALYs), a composite measure that attempts to combine mortality, incidence and sequelae, taking duration and severity into account. The results show that the relative burden of diseases as measured by DALYs differs from that only measured by incidence or mortality. Several limitations regarding data availability and quality have been identified, resulting in an underestimation of the true burden of disease in this pilot. Notwithstanding these, HIV-infection, tuberculosis (TB) and influenza are estimated to cause the highest burden in Europe among the selected diseases. The burden of foodborne diseases (campylobacteriosis, infection with enterohaemorrhagic Escherichia coli and salmonellosis) and in particular of measles is lower. A consideration of the relative comparison of burden between diseases can be useful when tackling the difficult, sensitive but necessary task of identifying priority actions. A low burden stresses the need for continued support for prevention and control whereas a high burden indicates the need for additional interventions. Following this pilot project, a generalised burden of disease study for infectious diseases in Europe is recommended. Such a study would benefit from an approach that identifies and combines several methods of investigation, including epidemiological modelling, and it should be done in collaboration with other international efforts in this field.
Therapy-Dependent Influence of Time-to-Treatment Interval on Myocardial Salvage in Patients With Acute Myocardial Infarction Treated With Coronary Artery Stenting or Thrombolysis
Authors: Albert Schömig, Gjin Ndrepepa, Julinda Mehilli, Markus Schwaiger, Helmut Schühlen, Stephan Nekolla, Jürgen Pache, Stefan Martinoff, Hildegard Bollwein, Adnan Kastrati
Journal: Circulation (2003)

Background— The relationship between myocardial salvage and time-to-treatment interval in patients with acute myocardial infarction (AMI) treated with coronary artery stenting or thrombolysis has not been studied. Methods and Results— This study analyzed 264 patients with AMI randomized to coronary stenting (133 patients) or thrombolysis (131 patients) in the setting of 2 randomized trials. Patients were divided into the following 3 groups defined by tertiles of the time-to-treatment interval: lower tertile (&lt;165 minutes), middle tertile (165 to 280 minutes), and upper tertile (&gt;280 minutes). Paired scintigraphic examinations were performed to obtain salvage index, which was the primary end point of the study. In the group with thrombolysis, the salvage index (median [25th; 75th] percentile) was 0.45 (0.16; 0.83) in the lower, 0.29 (0.17; 0.48) in the middle, and 0.20 (0.04; 0.46) in the upper tertile ( P =0.03). In the group with stenting, the salvage index was 0.56 (0.49; 0.75) in the lower, 0.57 (0.36; 0.73) in the middle, and 0.57 (0.32; 0.75) in the upper tertile ( P =0.59). In patients treated with stenting, the salvage index was greater than in patients treated with thrombolysis in the lower (0.56 versus 0.45, P =0.09), middle (0.57 versus 0.29, P =0.0003), and upper (0.57 versus 0.20, P =0.0005) tertiles of the time-to-treatment interval. Conclusions— The influence of the time-to-treatment interval on the myocardial salvage in patients with AMI depends on the type of reperfusion therapy. Coronary artery stenting was superior to thrombolysis independent of the time-to-treatment intervals, and the difference in benefit increased with more prolonged time from symptom onset.
Intra-arterial hepatic fotemustine for the treatment of liver metastases from uveal melanoma: experience in 101 patients
Authors: S. Peters, V. Voelter, L. Zografos, S. Pampallona, R. Popescu, M. Gillet, W. Bosshard, G. Fiorentini, M. Lotem, R. Weitzen, U. Keilholz, Y. Humblet, S. Piperno-Neumann, R. Stupp, S. Leyvraz
Journal: Annals of Oncology (2006)
Medical Oncologists' Perceptions of Financial Incentives in Cancer Care
Authors: Jennifer L. Malin, Jane C. Weeks, Arnold L. Potosky, Mark C. Hornbrook, Nancy L. Keating
Journal: Journal of Clinical Oncology (2012)

The cost of cancer care continues to increase at an unprecedented rate. Concerns have been raised about financial incentives associated with the chemotherapy concession in oncology practices and their impact on treatment recommendations.The objective of this study was to measure the physician-reported effects of prescribing chemotherapy or growth factors or making referrals to other cancer specialists, hospice, or hospital admissions on medical oncologists' income. US medical oncologists involved in the care of a population-based cohort of patients with lung or colorectal cancer from the Cancer Care Outcomes Research and Surveillance (CanCORS) study were surveyed regarding their perceptions of the impact of prescribing practices or referrals on their income.Although most oncologists reported that their incomes would be unaffected, compared with salaried oncologists, physicians in fee-for-service practice, and those paid a salary with productivity incentives were more likely to report that their income would increase from administering chemotherapy (odds ratios [ORs], 7.05 and 7.52, respectively; both P < .001) or administering growth factors (ORs, 5.60 and 6.03, respectively; both P < .001).A substantial proportion of oncologists who are not paid a fixed salary report that their incomes increase when they administer chemotherapy and growth factors. Further research is needed to understand the impact of these financial incentives on both the quality and cost of care.
Atrial natriuretic peptide in stable and decompensated chronic obstructive pulmonary disease.
Authors: K Skwarski, M Lee, L Turnbull, W MacNee
Journal: Thorax (1993)

BACKGROUND--Plasma levels of atrial natriuretic peptide (ANP) are elevated in patients with chronic obstructive pulmonary disease (COPD) and may have a role in preventing oedema formation in these patients. METHODS--Plasma ANP levels were measured in 60 patients with COPD and these measurements were related to pulmonary haemodynamics, response to treatment during exacerbations, and clinical patterns of the stable disease. RESULTS--Plasma ANP levels did not correlate significantly with right atrial or pulmonary arterial pressures but did correlate significantly with both the right ventricular end diastolic volume and right ventricular wall volume measured by magnetic resonance imaging. Oxygen (2 1/min by nasal prongs for 30 minutes) did not change the mean pulmonary arterial pressure or the level of plasma ANP. In 20 patients with an acute exacerbation of COPD plasma ANP levels were higher in those with oedema (302 (185) pg/ml) than in those without oedema (87 (43) pg/ml). Oxygen given for one hour had no effect on plasma levels of ANP. However, plasma ANP levels fell over the first three days during treatment in those with oedema, the fall correlating with the change in body weight. In a further 20 stable patients with hypoxic COPD, those with hypercapnia and previous episodes of oedema had higher levels of plasma ANP (120 (50) pg/ml) than normocapnic patients with no previous oedema (54 (15) pg/ml). CONCLUSIONS--The level of ANP is high in the plasma of patients with COPD, particularly during exacerbations in those with oedema. The association of a high plasma ANP level and volume overload is shown by the fall in ANP levels with treatment of the oedema, and the correlation between levels of ANP and right ventricular end diastolic or wall volumes.
Molecular Genetics of Lung Cancer
Authors: Yoshitaka Sekido, Kwun M. Fong, John D. Minna
Journal: Annual Review of Medicine (2003)

Lung cancer results from multiple changes in the genome of susceptible pulmonary cells caused by exposure to carcinogens found in tobacco smoke, the environment, or the workplace. Recent studies suggest that histologically apparent lung cancer is due to the sequential accumulation of specific genetic and morphologic changes to the normal epithelial cells of the lung. Positive signallers, such as those mediated by the oncogene RAS, and negative signallers, such as those mediated by the tumor suppressor retinoblastoma protein (RB), contribute to unchecked cell growth and proliferation. Other key molecular derangements can also be considered hallmarks of cancer, including evasion of apoptosis and senescence, angiogenesis, tissue invasion, and metastases. Epigenetic inactivation of genes via DNA methylation provides another novel way of evading normal cellular control mechanisms. The new knowledge of the human genome coupled with global methods of detecting genetic abnormalities and profiling gene expression in tumor cells may enable us to understand the signaling pathways of lung cancer cells. These are molecular targets for new cancer therapeutics such as receptor tyrosine kinase inhibitors. This information could advance risk assessment, early detection, prognosis, and therapy for lung cancer.