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Bach P.B.,Sloan Kettering Cancer Center | Mirkin J.N.,SUNY Downstate Medical Center | Oliver T.K.,American Society of Clinical Oncology | Azzoli C.G.,Sloan Kettering Cancer Center | And 10 more authors.
JAMA - Journal of the American Medical Association | Year: 2012

Context: Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer. Objective: To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline. Data Sources: MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012). Study Selection: Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation. Data Extraction: Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus. Results: Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53 454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer-specific mortality, 274 vs 309 events per 100000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P=.004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare. Conclusion: Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results. ©2012 American Medical Association. All rights reserved.


Chung L.,Stanford University | Chung L.,VA Palo Alto Health Care System | Domsic R.T.,University of Pittsburgh | Lingala B.,Stanford University | And 22 more authors.
Arthritis Care and Research | Year: 2014

Objective To assess cumulative survival rates and identify independent predictors of mortality in patients with incident systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) who had undergone routine screening for PAH at SSc centers in the US. Methods The Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma registry is a prospective registry of SSc patients at high risk for PAH or with definite pulmonary hypertension diagnosed by right-sided heart catheterization within 6 months of enrollment. Only patients with World Health Organization group I PAH (mean pulmonary artery pressure ≥25 mm Hg and pulmonary capillary wedge pressure ≤15 mm Hg without significant interstitial lung disease) were included in these analyses. Results In total, 131 SSc patients with incident PAH were followed for a mean ± SD of 2.0 ± 1.4 years. The 1-, 2-, and 3-year cumulative survival rates were 93%, 88%, and 75%, respectively. On multivariate analysis, age >60 years (hazard ratio [HR] 3.0, 95% confidence interval [95% CI] 1.1-8.4), male sex (HR 3.9, 95% CI 1.1-13.9), functional class (FC) IV status (HR 6.5, 95% CI 1.8-22.8), and diffusing capacity for carbon monoxide (DLco) <39% predicted (HR 4.2, 95% CI 1.3-13.8) were significant predictors of mortality. Conclusion This is the largest study describing survival in patients with incident SSc-associated PAH followed up at multiple SSc centers in the US who had undergone routine screening for PAH. The survival rates were better than those reported in other recently described SSc-associated PAH cohorts. Severely reduced DLco and FC IV status at the time of PAH diagnosis portended a poor prognosis in these patients. © Published 2014. This article is a U.S. Government work and is in the public domain in the USA.


Bhatt N.M.,M. S. University of Baroda | Bhatt N.M.,Johns Hopkins University | Chauhan K.,M. S. University of Baroda | Gupta S.,Gupta Pathology Laboratory | And 4 more authors.
American Journal of Infectious Diseases | Year: 2011

Problem statement: The Amino glycoside antibiotics cause drug induced nephrotoxicity at therapeutic doses and thus limits the use clinically. Oxidative stress is one of the main reasons for the development of nephrotoxicity. Approach: In light of this the aim of the present study was to investigate the role of mitochondrial as well as post-mitochondrial oxidative stress in the development of Gentamicin (GM) induced nephrotoxicity and to elucidate the role of Enicostemma Littoral blame (EL) extract, as a promising antioxidant therapy. Rats were divided into four groups, 1) (Control 2) GM (i.p., 80 mg kg -1 day -1 for 8 days) (treated 3) GM+EL treated (i.g, 2.5 gm kg -1 day -1) and (4) GM+ Vitamin C (VC) treated (i.g, 600 mg kg -1 day -1). GM treated animals showed high oxidative stress in mitochondrial as well as post-mitochondrial fractions of renal tissues as evidenced by increased lipid per oxidation levels, decrease in GSH content and activities of antioxidant enzymes, SOD and GPx. Results: Oxidative stress was more pronounced in mitochondrial fraction as compared to post-mitochondrial fraction. GM-induced nephrotoxicity was further corroborated by an increase in serum cretonne and Blood Urea Nitrogen (BUN) levels and altered kidney histopathological observations. Treatment with EL ameliorates antioxidant defense system of mitochondrial as well as post-mitochondrial fraction, with better improvement seen in mitochondrial fraction. Conclusion: The present study explored beneficial effect of EL extract as an antioxidant therapy to counteract mitochondrial and post-mitochondrial oxidative stress generated in kidney upon GM-treatment, thus prevented nephrotoxicity. © 2011 Science Publications.


Nelson H.,National Jewish Health Center | Lehmann L.,ALK | Blaiss M.S.,University of Tennessee Health Science Center
Current Medical Research and Opinion | Year: 2012

Objectives: Specific immunotherapy with the grass allergy immunotherapy tablet (AIT) has been developed as an effective, well tolerated, and convenient treatment for grass pollen induced seasonal allergic rhinoconjunctivitis (ARC). Six phase II/III randomized, placebo-controlled trials with the duration of a single grass pollen season of treatment using the SQ-standardized grass AIT, Grazax (Phleum pratense, 75,000 SQ-T/2,800 BAU, ALK, Denmark), have been published previously. This review compares results from these trials. Methods: As outcome measures and methods of assessing them were similar across the trials, we have summarized the main efficacy findings (Total Combined Score [TCS], average daily rhinoconjunctivitis symptom and medication scores, percentage of well days, quality of life scores) during a single season of treatment with grass AIT in adults and children with seasonal ARC. Results: The results of the European and North American trials were similar. Compared with the placebo group, who received symptomatic medications only, treatment with grass AIT resulted in fewer rhinoconjunctivitis symptoms, a lower intake of symptomatic medication, better patient self-rated quality of life and a greater percentage of well days during the entire grass pollen season. The data indicate that grass AIT treatment is equally effective in adults and children; the measured effect varies with pollen exposure, but is comparable across regions and continents, with a consistent difference compared with placebo in TCS that was above 20 for all trials. Local adverse events were experienced by the majority of patients. These reactions were generally mild to moderate in severity and transient in duration. Systemic adverse events were rare. Conclusions: This review confirms SQ-standardized grass AIT as a suitable therapeutic option for seasonal use in patients aged 5 years or older with grass pollen induced ARC. © 2012 Informa UK Ltd. All rights reserved.


Hoffman E.A.,University of Iowa | Lynch D.A.,National Jewish Health Center | Barr R.G.,Columbia University | Van Beek E.J.R.,Queens Medical Research Institute | Parraga G.,University of Western Ontario
Journal of Magnetic Resonance Imaging | Year: 2016

Pulmonary x-ray computed tomographic (CT) and magnetic resonance imaging (MRI) research and development has been motivated, in part, by the quest to subphenotype common chronic lung diseases such as chronic obstructive pulmonary disease (COPD). For thoracic CT and MRI, the main COPD research tools, disease biomarkers are being validated that go beyond anatomy and structure to include pulmonary functional measurements such as regional ventilation, perfusion, and inflammation. In addition, there has also been a drive to improve spatial and contrast resolution while at the same time reducing or eliminating radiation exposure. Therefore, this review focuses on our evolving understanding of patient-relevant and clinically important COPD endpoints and how current and emerging MRI and CT tools and measurements may be exploited for their identification, quantification, and utilization. Since reviews of the imaging physics of pulmonary CT and MRI and reviews of other COPD imaging methods were previously published and well-summarized, we focus on the current clinical challenges in COPD and the potential of newly emerging MR and CT imaging measurements to address them. Here we summarize MRI and CT imaging methods and their clinical translation for generating reproducible and sensitive measurements of COPD related to pulmonary ventilation and perfusion as well as parenchyma morphology. The key clinical problems in COPD provide an important framework in which pulmonary imaging needs to rapidly move in order to address the staggering burden, costs, as well as the mortality and morbidity associated with COPD. J. MAGN. RESON. IMAGING 2016;43:544-557. © 2015 Wiley Periodicals, Inc.


Sieren J.P.,University of Iowa | Newell Jr. J.D.,University of Iowa | Judy P.F.,Brigham and Women's Hospital | Lynch D.A.,National Jewish Health Center | And 3 more authors.
Medical Physics | Year: 2012

Purpose: The purpose of this study was to detect and analyze anomalies between a large number of computed tomography (CT) scanners, tracked over time, utilized to collect human pulmonary CT data for a national multicenter study: chronic obstructive pulmonary disease genetic epidemiology study (COPDGene). Methods: A custom designed CT reference standard Test Object has been developed to evaluate the relevant differences in CT attenuation between CT scanners in COPDGene. The materials used in the Test Object to assess CT scanner accuracy and precision included lung equivalent foam (-856 HU), internal air (-1000 HU), water (0 HU), and acrylic (120 HU). Nineteen examples of the Test Object were manufactured. Initially, all Test Objects were scanned on the same CT scanner before the Test Objects were sent to the 20 specific sites and 42 individual CT scanners that were used in the study. The Test Objects were scanned over 17 months while the COPDGene study continued to recruit subjects. A mixed linear effect statistical analysis of the CT scans on the 19 Test Objects was performed. The statistical model reflected influence of reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency on CT attenuation. Results: Depending on the Test Object material, there were significant differences between reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency. The two Test Object materials of most interest were lung equivalent foam and internal air. With lung equivalent foam, there were significant (p 0.05) differences between the Siemens B31 (-856.6, ±0.82; mean ± SE) and the GE Standard (-856.6 ± 0.83) reconstruction kernel relative to the Siemens B35 reference standard (-852.5 ± 1.4). Comparing lung equivalent foam attenuation there were also significant differences between CT scanner models (p 0.01), tube current (p 0.005), and in temporal consistency (p 0.005) at individual sites. However, there were no significant effects measurable using different examples of the Test Objects at the various sites compared to the reference scans of the 19 Test Objects. For internal air, significant (p 0.005) differences were found between all reconstruction kernels (Siemens B31, GE Standard, and Phillips B) compared to the reference standard. There were significant differences between CT models (p 0.005), and tube current (p 0.005). There were no significant effects measurable using different examples of the Test Objects at the various sites compared to the reference scans of the 19 Test Objects. Differences, across scanners, between external air and internal air measures in this simple (relative to the in vivo lung) test object varied by as much as 15 HU. Conclusions: The authors conclude that the Test Object designed for this study was able to detect significant effects regarding individual CT scanners that altered the CT attenuation measurements relevant to the study that are used to determine lung density. Through an understanding of individual scanners, the Test Object analysis can be used to detect anomalies in an individual CT scanner and to statistically model out scanner differences and individual scanner changes over time in a large multicenter trial. © 2012 American Association of Physicists in Medicine.


PubMed | National Jewish Health Center, Queens Medical Research Institute, Columbia University, University of Western Ontario and University of Iowa
Type: Journal Article | Journal: Journal of magnetic resonance imaging : JMRI | Year: 2016

Pulmonary x-ray computed tomographic (CT) and magnetic resonance imaging (MRI) research and development has been motivated, in part, by the quest to subphenotype common chronic lung diseases such as chronic obstructive pulmonary disease (COPD). For thoracic CT and MRI, the main COPD research tools, disease biomarkers are being validated that go beyond anatomy and structure to include pulmonary functional measurements such as regional ventilation, perfusion, and inflammation. In addition, there has also been a drive to improve spatial and contrast resolution while at the same time reducing or eliminating radiation exposure. Therefore, this review focuses on our evolving understanding of patient-relevant and clinically important COPD endpoints and how current and emerging MRI and CT tools and measurements may be exploited for their identification, quantification, and utilization. Since reviews of the imaging physics of pulmonary CT and MRI and reviews of other COPD imaging methods were previously published and well-summarized, we focus on the current clinical challenges in COPD and the potential of newly emerging MR and CT imaging measurements to address them. Here we summarize MRI and CT imaging methods and their clinical translation for generating reproducible and sensitive measurements of COPD related to pulmonary ventilation and perfusion as well as parenchyma morphology. The key clinical problems in COPD provide an important framework in which pulmonary imaging needs to rapidly move in order to address the staggering burden, costs, as well as the mortality and morbidity associated with COPD.


Hughes G.,Aurora University | Cruickshank-Quinn C.,National Jewish Health Center | Reisdorph R.,National Jewish Health Center | Lutz S.,Aurora University | And 4 more authors.
Bioinformatics | Year: 2014

Motivation: Although R packages exist for the pre-processing of metabolomic data, they currently do not incorporate additional analysis steps of summarization, filtering and normalization of aligned data. We developed the MSPrep R package to complement other packages by providing these additional steps, implementing a selection of popular normalization algorithms and generating diagnostics to help guide investigators in their analyses. Availability: http://www.sourceforge.net/projects/msprepContact: Supplementary Information: Supplementary materials are available at Bioinformatics online. © 2013 The Author .


Rojas C.A.,University of South Florida | Jawad H.,National Jewish Health Center | Chung J.H.,National Jewish Health Center
American Journal of Roentgenology | Year: 2012

OBJECTIVE. In this article, we describe how we constructed a radiology teaching file that simulates real-life scenarios and discuss some of the advantages it affords. CONCLUSION. Using OsiriX imaging software and iWork Pages, we have created a HIPAA-compliant interstitial lung disease radiology teaching resource that allows the user to navigate through the complete dataset of images for each patient. Integrated within the file is a navigation tool that allows the user to access the patient's clinical report, imaging reports, pulmonary function tests, and pathology report simultaneously. To our knowledge, this is the first teaching file of its kind. © American Roentgen Ray Society.


PubMed | National Jewish Health Center
Type: Comparative Study | Journal: Current medical research and opinion | Year: 2012

Specific immunotherapy with the grass allergy immunotherapy tablet (AIT) has been developed as an effective, well tolerated, and convenient treatment for grass pollen induced seasonal allergic rhinoconjunctivitis (ARC). Six phase II/III randomized, placebo-controlled trials with the duration of a single grass pollen season of treatment using the SQ-standardized grass AIT, Grazax (Phleum pratense, 75,000 SQ-T/2,800 BAU, ALK, Denmark), have been published previously. This review compares results from these trials.As outcome measures and methods of assessing them were similar across the trials, we have summarized the main efficacy findings (Total Combined Score [TCS], average daily rhinoconjunctivitis symptom and medication scores, percentage of well days, quality of life scores) during a single season of treatment with grass AIT in adults and children with seasonal ARC.The results of the European and North American trials were similar. Compared with the placebo group, who received symptomatic medications only, treatment with grass AIT resulted in fewer rhinoconjunctivitis symptoms, a lower intake of symptomatic medication, better patient self-rated quality of life and a greater percentage of well days during the entire grass pollen season. The data indicate that grass AIT treatment is equally effective in adults and children; the measured effect varies with pollen exposure, but is comparable across regions and continents, with a consistent difference compared with placebo in TCS that was above 20% for all trials. Local adverse events were experienced by the majority of patients. These reactions were generally mild to moderate in severity and transient in duration. Systemic adverse events were rare.This review confirms SQ-standardized grass AIT as a suitable therapeutic option for seasonal use in patients aged 5 years or older with grass pollen induced ARC.

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