Anatomy Commons^™

Association Of Altered Collagen Content And Lysyl Oxidase Expression In Degenerative Mitral Valve Disease, K-Raman Purushothaman, Meerarani Purushothaman, Irene C. Turnbull, David H. Adams, Anelechi Anyanwu, Prakash Krishnan, Annapoorna Kini, Samin K. Sharma, William N. O'Connor, Pedro R. Moreno

Pathology and Laboratory Medicine Faculty Publications

Background—Collagen cross-linking is mediated by lysyl oxidase (LOX) enzyme in the extracellular matrix (ECM) of mitral valve leaflets. Alterations in collagen content and LOX protein expression in the ECM of degenerative mitral valve may enhance leaflet expansion and disease severity.

Methods—Twenty posterior degenerative mitral valve leaflets from patients with severe mitral regurgitation were obtained at surgery. Five normal posterior mitral valve leaflets procured during autopsy served as controls. Valvular interstitial cells (VICs) density was quantified by immunohistochemistry, collagen types I and III by picro-sirius red staining and immunohistochemistry, and proteoglycans by alcian blue staining. Protein expression of LOX …

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …

Rectal Colonic Mural Hematoma Following Enema For Constipation While On Therapeutic Anticoagulation., Rebecca M. Rentea, Charles H. Fehring

Manuscripts, Articles, Book Chapters and Other Papers

Causes of colonic and recto-sigmoid hematomas are multifactorial. Patients can present with a combination of dropping hemoglobin, bowel obstruction and perforation. Computed tomography imaging can provide clues to a diagnosis of intramural hematoma. We present a case of rectal hematoma and a review of current management literature. A 72-year-old male on therapeutic anticoagulation for a pulmonary embolism, was administered an enema resulting in severe abdominal pain unresponsive to blood transfusion. A sigmoid colectomy with end colostomy was performed. Although rare, colonic and recto-sigmoid hematomas should be considered as a possible diagnosis for adults with abdominal pain on anticoagulant therapy.

Variability In Objective And Subjective Measures Affects Baseline Values In Studies Of Patients With Copd, Wayne H. Anderson, Jae Wook Ha, David J. Couper, Wanda K. O'Neal, R. Graham Barr, Eugene R. Bleecker, Elizabeth E. Carretta, Christopher B. Cooper, Claire M. Doerschuk, M. Bradley Drummond, Meilan K. Han, Nadia N. Hansel, Victor Kim, Eric C. Kleerup, Fernando J. Martinez, Stephen I. Rennard, Donald Tashkin, Prescott G. Woodruff, Robert Paine, Jeffrey L. Curtis, Richard W. Kanner, Spiromics Research Group

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety.

OBJECTIVES: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes.

METHODS: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same …

Body Mass Index Change In Gastrointestinal Cancer And Chronic Obstructive Pulmonary Disease Is Associated With Dedicator Of Cytokinesis 1, Merry-Lynn Noelle Mcdonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.

METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years …

Network-Based Analysis Reveals Novel Gene Signatures In Peripheral Blood Of Patients With Chronic Obstructive Pulmonary Disease, Ma'en Obeidat, Yunlong Nie, Virginia Chen, Casey P. Shannon, Anand Kumar Andiappan, Bernett Lee, Olaf Rotzschke, Peter J. Castaldi, Craig P. Hersh, Nick Fishbane, Raymond T. Ng, Bruce Mcmanus, Bruce E. Miller, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death and there is a huge unmet clinical need to identify disease biomarkers in peripheral blood. Compared to gene level differential expression approaches to identify gene signatures, network analyses provide a biologically intuitive approach which leverages the co-expression patterns in the transcriptome to identify modules of co-expressed genes.

METHODS: A weighted gene co-expression network analysis (WGCNA) was applied to peripheral blood transcriptome from 238 COPD subjects to discover co-expressed gene modules. We then determined the relationship between these modules and forced expiratory volume in 1 s (FEV …

Walking Performance Is Positively Correlated To Calf Muscle Fiber Size In Peripheral Artery Disease Subjects, But Fibers Show Aberrant Mitophagy: An Observational Study, Sarah H. White, Mary M. Mcdermott, Robert L. Sufit, Kate Kosmac, Alex W. Bugg, Marta Gonzalez-Freire, Luigi Ferrucci, Lu Tian, Lihui Zhao, Ying Gao, Melina R. Kibbe, Michael H. Criqui, Christiaan Leeuwenburgh, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background: Patients with lower extremity peripheral artery disease (PAD) have decreased mobility, which is not fully explained by impaired blood supply to the lower limb. Additionally, reports are conflicted regarding fiber type distribution patterns in PAD, but agree that skeletal muscle mitochondrial respiration is impaired.

Methods: To test the hypothesis that reduced muscle fiber oxidative activity and type I distribution are negatively associated with walking performance in PAD, calf muscle biopsies from non-PAD (n = 7) and PAD participants (n = 26) were analyzed immunohistochemically for fiber type and size, oxidative activity, markers of autophagy, and capillary density. Data were …

The Relationship Between Foot Arch Measurements And Walking Parameters In Children, Simone V. Gill, Sara Keimig, Damian Kelty-Stephen, Ya-Ching Hung, Jeremy M. Desilva

Dartmouth Scholarship

Walking mechanics are influenced by body morphology. Foot arch height is one aspect of body morphology central to walking. However, generalizations about the relationship between arch height and walking are limited due to previous methodologies used for measuring the arch and the populations that have been studied. To gain the knowledge needed to support healthy gait in children and adults, we need to understand this relationship in unimpaired, typically developing children and adults using dynamic measures. The purpose of the current study was to examine the relationship between arch height and gait in a sample of healthy children and adults …

Effects Of Roflumilast In Copd Patients Receiving Inhaled Corticosteroid/Long-Acting Β2-Agonist Fixed-Dose Combination: Re(2)Spond Rationale And Study Design, Stephen I. Rennard, Fernando J. Martinez, Klaus F. Rabe, Sanjay Sethi, Emilio Pizzichini, Andrew Mcivor, Shahid Siddiqui, Antonio Anzueto, Haiyuan Zhu

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE(2)SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combination (FDC), further reduces exacerbations. The methodology is described herein.

METHODS: In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use) to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate-severe exacerbations within …

Effect Of Tiotropium On Night-Time Awakening And Daily Rescue Medication Use In Patients With Copd, Peter M.A. Calverley, Stephen I. Rennard, Emmanuelle Clerisme-Beaty, Norbert Metzdorf, Valentina Bayer Zubek, Richard Zuwallack

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Several small studies found night-time awakenings due to COPD symptoms were associated with decreased health status. In this study, night-time awakenings in patients with COPD were examined and effects of tiotropium therapy evaluated.

METHODS: This study was a post hoc, exploratory, pooled analysis of twin, multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. Patients with stable moderate-to-severe COPD were randomized to tiotropium HandiHaler® (n = 550) or placebo (n = 371) and followed for 13 weeks. During a 2-week, pre-treatment baseline period and for 13 weeks on treatment, self-reported night-time awakenings due to COPD symptoms, rescue medication (albuterol) use, and morning …

Copd Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry, Janice M. Leung, Virginia Chen, Zsuzsanna Hollander, Darlene Dai, Scott J. Tebbutt, Shawn D. Aaron, Kathy L. Vandemheen, Stephen I. Rennard, J. Mark Fitzgerald, Prescott G. Woodruff, Stephen C. Lazarus, John E. Connett, Harvey O. Coxson, Bruce Miller, Christoph Borchers, Bruce M. Mcmanus, Raymond T. Ng, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD.

METHODS: We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate < 0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel …

Identifying Cases Of Undiagnosed, Clinically Significant Copd In Primary Care: Qualitative Insight From Patients In The Target Population, Nancy K. Leidy, Katherine Kim, Elizabeth D. Bacci, Barbara P. Yawn, David M. Mannino, Byron M. Thomashow, R. Graham Barr, Stephen I. Rennard, Julia F. Houfek, Meilan K. Han, Catherine A. Meldrum, Barry J. Make, Russ P. Bowler, Anna W. Steenrod, Lindsey T. Murray, John W. Walsh, Fernando Martinez, High-Risk-Copd Screening Study Group

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations.

AIMS: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care.

METHODS: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the …

The Effect Of Statins On Blood Gene Expression In Copd, Ma'en Obeidat, Nick Fishbane, Yunlong Nie, Virginia Chen, Zsuzsanna Hollander, Scottj Tebbutt, Yohan Bossé, Raymond T. Ng, Bruce E. Miller, Bruce Mcmanus, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: COPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.

OBJECTIVE: Identify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.

METHODS: Whole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. …

Identifying A Gene Expression Signature Of Frequent Copd Exacerbations In Peripheral Blood Using Network Methods, Jarrett D. Morrow, Weiliang Qiu, Divya Chhabra, Stephen I. Rennard, Paula Belloni, Anton Belousov, Sreekumar G. Pillai, Craig P. Hersh

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors. Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility. Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.

METHODS: Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) …

Non-Emphysematous Chronic Obstructive Pulmonary Disease Is Associated With Diabetes Mellitus, Craig P. Hersh, Barry J. Make, David A. Lynch, R. Graham Barr, Russell P. Bowler, Peter M.A. Calverley, Peter J. Castaldi, Michael H. Cho, Harvey O. Coxson, Dawn L. Demeo, Marilyn G. Foreman, Meilan K. Han, Benjamin J. Harshfield, John E. Hokanson, Sharon Lutz, Joe W. Ramsdell, Elizabeth A. Regan, Stephen I. Rennard, Joyce D. Schroeder, Frank C. Sciurba, Robert M. Steiner, Ruth Tal-Singer, Edwin Van Beek, Edwin K. Silverman, James D. Crapo, Copdgene And Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.

METHODS: Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 …

The Association Of Plasma Biomarkers With Computed Tomography-Assessed Emphysema Phenotypes, Brendan J. Carolan, Grant Hughes, Jarrett Morrow, Craig P. Hersh, Wanda K. O'Neal, Stephen I. Rennard, Sreekumar G. Pillai, Paula Belloni, Debra A. Cockayne, Alejandro P. Comellas, Meilan Han, Rachel L. Zemans, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema.

METHODS: 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ …

Randomized Study Of The Safety, Pharmacokinetics, And Bronchodilatory Efficacy Of A Proprietary Glycopyrronium Metered-Dose Inhaler In Study Patients With Chronic Obstructive Pulmonary Disease, Stephen I. Rennard, Charles Fogarty, Colin Reisner, Carlos Fernandez, Tracy Fischer, Michael Golden, Earl St Rose, Patrick Darken, Gregory Tardie, Chadwick Orevillo

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Bronchodilator medications are central to the symptomatic management of chronic obstructive pulmonary disease (COPD). Metered-dose inhalers (MDIs) are the most commonly used devices to deliver treatment to patients with COPD and asthma, comprising approximately 70% of bronchodilator prescriptions. Proprietary porous-particle technology permits the formulation of long-acting muscarinic antagonists, long-acting β2-agonists, and a combination of both in hydrofluoroalkane (HFA) MDIs, providing a solution to formulation challenges inherent to the development of HFA MDIs, which have contributed to the development of dry-powder inhalers.

METHODS: In this randomized, double-blind, 4-period, 6-treatment, placebo- and active-controlled, multicenter, crossover study, 4 ascending single doses of …

Clinical And Computed Tomographic Predictors Of Chronic Bronchitis In Copd: A Cross Sectional Analysis Of The Copdgene Study, Victor Kim, Adam Davey, Alejandro P. Comellas, Meilan K. Han, George Washko, Carlos H. Martinez, David Lynch, Jin Hwa Lee, Edwin K. Silverman, James D. Crapo, Barry J. Make, Gerard J. Criner, The Copdgene® Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways …

Dnah5 Is Associated With Total Lung Capacity In Chronic Obstructive Pulmonary Disease, Jin Hwa Lee, Merry-Lynn N Mcdonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, David A. Lynch, James D. Crapo, David A. Lomas, Harvey O. Coxson, Per S. Bakke, Edwin K. Silverman, Craig P. Hersh, The Copdgene And Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

METHODS: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers …

Roflumilast And Dyspnea In Patients With Moderate To Very Severe Chronic Obstructive Pulmonary Disease: A Pooled Analysis Of Four Clinical Trials, Stephen I. Rennard, Shawn X. Sun, Stavros Tourkodimitris, Paul Rowe, Udo M. Goehring, Dirk Bredenbröker, Peter M.A. Calverley

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Breathlessness is a predominant symptom of chronic obstructive pulmonary disease (COPD), making it a valuable outcome in addition to lung function to assess treatment benefit. The phosphodiesterase-4 inhibitor roflumilast has been shown to provide small but significant improvements in dyspnea, as measured by the transition dyspnea index (TDI), in two 1-year studies in patients with severe to very severe COPD.

PATIENTS AND METHODS: To provide a more comprehensive assessment of the impact of roflumilast on dyspnea, post hoc analyses of four 1-year roflumilast studies (M2-111, M2-112, M2-124, and M2-125) in patients with moderate to very severe COPD were conducted. …

Efficacy And Safety Of Fixed-Dose Combinations Of Aclidinium Bromide/Formoterol Fumarate: The 24-Week, Randomized, Placebo-Controlled Augment Copd Study, Anthony D. D'Urzo, Stephen I. Rennard, Edward M. Kerwin, Victor Mergel, Anne R. Leselbaum, Cynthia F. Caracta, Augment Copd Study Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.

METHODS: In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, …

A Divisive Shuffling Approach (Vista) For Gene Expression Analysis To Identify Subtypes In Chronic Obstructive Pulmonary Disease, Jörg Menche, Amitabh Sharma, Michael H. Cho, Ruth J. Mayer, Stephen I. Rennard, Bartolome Celli, Bruce E. Miller, Nick Locantore, Ruth Tal-Singer, Soumitra Ghosh, Chris Larminie, Glyn Bradley, John H. Riley, Alvar Agusti, Edwin K. Silverman, Albert-László Barabási

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: An important step toward understanding the biological mechanisms underlying a complex disease is a refined understanding of its clinical heterogeneity. Relating clinical and molecular differences may allow us to define more specific subtypes of patients that respond differently to therapeutic interventions.

RESULTS: We developed a novel unbiased method called diVIsive Shuffling Approach (VIStA) that identifies subgroups of patients by maximizing the difference in their gene expression patterns. We tested our algorithm on 140 subjects with Chronic Obstructive Pulmonary Disease (COPD) and found four distinct, biologically and clinically meaningful combinations of clinical characteristics that are associated with large gene expression …

Navigating Veterans With An Abnormal Prostate Cancer Screening Test: A Quasi-Experimental Study, Melissa A. Simon, Narissa J. Nonzee, June M. Mckoy, Dachao Liu, Thanh Ha Luu, Peter Byer, Elizabeth A. Eklund, Elizabeth A. Richey

Dartmouth Scholarship

Prostate cancer disproportionately affects low-income and minority men. This study evaluates the impact of a patient navigation intervention on timeliness of diagnostic resolution and treatment initiation among veterans with an abnormal prostate cancer screen.MethodsParticipants were enrolled between 2006 and 2010. The intervention involved a social worker and lay health worker navigation team that assisted patients in overcoming barriers to care. For navigated (n = 245) versus control (n = 245) participants, we evaluated rates of diagnostic resolution and treatment and adjusted for race, age, and Gleason score.

State-By-State Variation In Emergency Versus Elective Colon Resections: Room For Improvement., Augustine C. Obirieze, Mehreen Kisat, Caitlin W. Hicks, Tolulope A. Oyetunji, Eric B. Schneider, Darrell J. Gaskin, Elliott R. Haut, David T. Efron, Edward E. Cornwell, Adil H. Haider

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Compared with elective surgical procedures, emergency procedures are associated with higher cost, morbidity, and mortality. This study seeks to investigate potential state-by-state variations in the incidence of emergent versus elective colon resections.

METHODS: A retrospective analysis of all adult patients (aged ≥18 years) included in the Nationwide Inpatient Sample from 2005 to 2009 who underwent hemicolectomy (right or left) or sigmoidectomy was conducted. Discharge-level weights were applied, and generalized linear models were used to assess the odds of a patient undergoing emergent versus elective colon surgery nationally and for each state after adjusting for patient and hospital factors. Odds …

Incomplete Polyp Resection During Colonoscopy—Results Of The Complete Adenoma Resection (Care) Study, Heiko Pohl, Amitabh Srivastava, Steve P. Bensen, Peter Anderson, Richard I. Rothstein, Stuart R. Gordon, L Campbell Levy, Arifa Toor, Todd A. Mackenzie, Thomas Rosch, Douglas J. Robertson

Dartmouth Scholarship

Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice.We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. …

Design Of A Prostate Cancer Patient Navigation Intervention For A Veterans Affairs Hospital, Narissa J. Nonzee, June M. Mckoy, Alfred W. Rademaker, Peter Byer, Thanh H. Luu, Dachao Liu, Elizabeth A. Richey

Dartmouth Scholarship

Patient navigation programs have been launched nationwide in an attempt to reduce racial/ethnic and socio-demographic disparities in cancer care, but few have evaluated outcomes in the prostate cancer setting. The National Cancer Institute-funded Chicago Patient Navigation Research Program (C-PNRP) aims to implement and evaluate the efficacy of a patient navigation intervention for predominantly low-income minority patients with an abnormal prostate cancer screening test at a Veterans Affairs (VA) hospital in Chicago.

Examining Fatigue In Copd: Development, Validity And Reliability Of A Modified Version Of Facit-F Scale, Khaled Al-Shair, Hana Muellerova, Janelle Yorke, Stephen I. Rennard, Emiel F.M. Wouters, Nicola A. Hanania, Amir Sharafkhaneh, Jørgen Vestbo, Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Fatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities. The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD.

METHODS: At baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale. We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F.

RESULTS: Four items were less able to capture fatigue characteristics in COPD and were deleted. PCA was applied to the remaining …

Effects Of Inhaled Corticosteroids On Airway Inflammation In Chronic Obstructive Pulmonary Disease: A Systematic Review And Meta-Analysis, Rachel Jen, Stephen I. Rennard, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.

METHODS: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment …

Efficacy And Safety Of Once-Daily Aclidinium In Chronic Obstructive Pulmonary Disease, Paul W. Jones, Stephen I. Rennard, Alvar Agusti, Pascal Chanez, Helgo Magnussen, Leonardo Fabbri, James F. Donohue, Eric D. Bateman, Nicholas J. Gross, Rosa Lamarca, Cynthia Caracta, Esther Garcia Gil

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

METHODS: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1< 80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.

RESULTS: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p< 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p< 0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies.

CONCLUSION: Aclidinium is effective and well tolerated …

Reduction Of Exacerbations By The Pde4 Inhibitor Roflumilast--The Importance Of Defining Different Subsets Of Patients With Copd, Stephen I. Rennard, Peter M.A. Calverley, Udo M. Goehring, Dirk Bredenbröker, Fernando J. Martinez

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive. This led to the question of whether a responsive subset existed that could be investigated further.

METHODS: The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in …