Medicine and Health Sciences Commons^™

The Β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis In Obese Humans, Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.

METHODS. Before and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and …

Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza

Internal Medicine Faculty Publications

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (< 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky < 90, stage III, > 1 line of induction and lack of maintenance. Post-AHCT early relapse remains …

Delayed Sternal Closure Does Not Reduce Complications Associated With Coagulopathy And Right Ventricular Failure After Left Ventricular Assist Device Implantation, Roh Yanagida, Navin Rajagopalan, Daniel L. Davenport, Thomas A. Tribble, Mark A. Bradley, Charles W. Hoopes

Internal Medicine Faculty Publications

Delayed sternal closure (DSC) is occasionally adopted after implantation of left ventricular assist device (LVAD). Recent studies suggest that DSC be used for high risk group of patients with coagulopathy, hemodynamic instability or right ventricular failure. However, whether DSC is efficacious for bleeding complication or right ventricular failure is not known. This study is single center analysis of 52 patients, who underwent LVAD implantation. Of those 52 patients, 40 consecutive patients underwent DSC routinely. The sternum was left open with vacuum assist device after implantation of LVAD. Perioperative outcome of the patients who underwent routine DSC were compared with 12 …

Central Nervous System Histoplasmosis: Multicenter Retrospective Study On Clinical Features, Diagnostic Approach And Outcome Of Treatment, Joseph Wheat, Thein Myint, Ying Guo, Phebe Kemmer, Chadi A. Hage, Colin Terry, Marwan M. Azar, James Riddell, Peter Ender, Sharon Chen, Kareem Shehab, Kerry Cleveland, Eden Esguerra, James Johnson, Patty Wright, Vanja Douglas, Pascalis Vergidis, Winnie Ooi, John Baddley, David Bamberger, Raed N. Khairy, Holenarasipur R. Vikram, Elizabeth Jenny-Avital, Geetha Sivasubramanian, Karen Bowlware, Barbara Pahud, Juan Sarria, Townson Tsai, Maha Assi, Satish Mocherla

Internal Medicine Faculty Publications

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.

A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.

Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the …

Common Tdp1 Polymorphisms In Relation To Survival Among Small Cell Lung Cancer Patients: A Multicenter Study From The International Lung Cancer Consortium, Pawadee Lohavanichbutr, Lori C. Sakoda, Christopher I. Amos, Susanne M. Arnold, David C. Christiani, Michael P. A. Davies, John K. Field, Eric B. Haura, Rayjean J Hung, Takashi Kohno, Maria Teresa Landi, Geoffrey Liu, Yi Liu, Michael W. Marcus, Grainne M. O'Kane, Matthew B. Schabath, Kouya Shiraishi, Stacey A. Slone, Adonina Tardón, Ping Yang, Kazushi Yoshida, Ruyang Zhang, Xuchen Zong, Gary E. Goodman, Noel S. Weiss, Chu Chen

Internal Medicine Faculty Publications

Background—DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.

Methods—Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan–Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …

Pleiotropy Of Genetic Variants On Obesity And Smoking Phenotypes: Results From The Oncoarray Project Of The International Lung Cancer Consortium, Tao Wang, Jee-Young Moon, Yiqun Wu, Christopher I. Amos, Rayjean J. Hung, Adonina Tardon, Angeline Andrew, Chu Chen, David C. Christiani, Demetrios Albanes, Erik H. F. M. Van Der Heijden, Eric Duell, Gadi Rennert, Gary Goodman, Geoffrey Liu, James D. Mckay, Jian-Min Yuan, John K. Field, Jonas Manjer, Kjell Grankvist, Lambertus A. Kiemeney, Loic Le Marchand, M. Dawn Teare, Matthew B. Schabath, Mattias Johansson, Melinda C. Aldrich, Michael Davies, Mikael Johansson, Ming-Sound Tsao, Neil Caporaso, Susanne Arnold

Internal Medicine Faculty Publications

Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively correlated with pack-years of smoking (p < 0.001) in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p < 0.05), respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF) …

Causes, Timing, And Impact Of Dual Antiplatelet Therapy Interruption For Surgery (From The Paris Registry), Mikkel Schoos, Jaya Chandrasekhar, Usman Baber, Aarti Bhasin, Samantha Sartori, Melissa Aquino, Birgit Vogel, Serdar Farhan, Sabato Sorrentino, Annapoorna Kini, Mitchell Kruckoff, David J. Moliterno, Timothy D. Henry, Giora Weisz, C. Michael Gibson, Ioannis Iakovou, Antonio Colombo, P. Gabriel Steg, Bernhard Witzenbichler, Alaide Chieffo, David Cohen, Thomas Stuckey, Cono Ariti, George Dangas, Stuart Pocock, Roxana Mehran

Internal Medicine Faculty Publications

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation forcohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT …

Multimodality Therapy Improves Survival In Intramedullary Spinal Cord Metastasis Of Lung Primary, Hayder Saeed, Reema Patel, Jigisha Thakkar, Lames Hamoodi, Li Chen, John L. Villano

Internal Medicine Faculty Publications

Background: Most metastatic spinal cord lesions are located either in the intradural, extramedullary, or in the epidural compartments. Intramedullary spinal cord metastasis (ISCM) is a rare central nervous system spread of cancer. The aim of this report was to evaluate ISCM in the published literature.

Methods: A literature review of PubMed from 1960 to 2016 was undertaken for the publications having demographic, clinical, histological, and outcome data.

Results: A total of 59 relevant papers were identified, showing 128 cases of intramedullary metastasis from lung cancer. The incidence of lung cancer as the primary malignancy with intramedullary metastasis was 56%. The …

Higher Mineralized Bone Volume Is Associated With A Lower Plain X-Ray Vascular Calcification Score In Hemodialysis Patients, Teresa Adragao, Anibal Ferreira, Joao M. Frazao, Ana Luisa Papoila, Iola Pinto, Marie-Claude Monier-Faugere, Hartmut H. Malluche

Internal Medicine Faculty Publications

Background and objectives

In dialysis patients, there is an increasing evidence that altered bone metabolism is associated with cardiovascular calcifications. The main objective of this study was to analyse, in hemodialysis patients, the relationships between bone turnover, mineralization and volume, evaluated in bone biopsies, with a plain X-ray vascular calcification score.

Design, setting, participants and measurements

In a cross-sectional study, bone biopsies and evaluation of vascular calcifications were performed in fifty hemodialysis patients. Cancellous bone volume, mineralized bone volume, osteoid volume, activation frequency, bone formation rate/bone surface, osteoid thickness and mineralization lag time were determined by histomorphometry. Vascular calcifications were …

Lisinopril Or Coreg Cr In Reducing Cardiotoxicity In Women With Breast Cancer Receiving Trastuzumab: A Rationale And Design Of A Randomized Clinical Trial, Maya Guglin, Pamela Munster, Angelina Fink, Jeffrey Krischer

Internal Medicine Faculty Publications

Background—Trastuzumab (TZB) is an established therapy for HER2 positive breast cancer. The use of TZB is commonly associated with cardiotoxicity manifesting as asymptomatic decrease in left ventricular ejection fraction (LVEF) or overt heart failure. Several studies demonstrated favorable effects of angiotensin converting enzyme (ACE) inhibitors and beta blockers (BB) in the prevention of chemotherapy-induced cardiotoxicity. We hypothesize that patients, randomized to receive an ACE inhibitor or a beta-blocker during trastuzumab therapy for breast cancer, will maintain a higher LVEF than patients randomized to placebo.

Methods and Results—We designed a prospective, multicenter, randomized, phase II placebo-controlled clinical trial to …

Acute Effects Of Implantable Cardioverter-Defibrillator Shocks On Biomarkers Of Myocardial Injury, Apoptosis, Heart Failure, And Systemic Inflammation, Jordan Brewster, Travis Sexton, Gary Dhaliwal, Richard Charnigo, Gustavo Morales, Kevin Parrott, Yousef Darrat, John C. Gurley, Susan S. Smyth, Claude S. Elayi

Internal Medicine Faculty Publications

Background: Implantable cardioverter‐defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT.

Methods: We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT−).

Results: Sixty‐three patients were enrolled, 40 in the DFT+ group and 23 in the DFT− group. Average levels of troponin I, hsCRP, …

Retention In Continuous Care And Sustained Viral Suppression: Examining The Association Among Individuals Living With Hiv, Timothy N. Crawford, Alice C. Thornton

Internal Medicine Faculty Publications

Objectives: To examine the relationship between retention in continuous care and sustained viral suppression.

Methods: The authors retrospectively followed 653 persons who were virally suppressed and seeking care at an infectious disease clinic in Kentucky for an average of 6 years to determine the rates of retention in medical care (≥2 visits separated by ≥3 months within a 12-month period) and sustained viral suppression (<400 copies/mL). A generalized linear mixed model was used to determine an association between retention and suppression over time.

Results: Approximately 61% of the study population were retained in continuous care and 75% had sustained viral suppression for all patient-years. Persons retained in care were 3 times the odds of sustaining viral suppression over …

A Randomized, Double-Blind, Placebo-Controlled Phase Ii Trial Investigating The Safety And Immunogenicity Of Modified Vaccinia Ankara Smallpox Vaccine (Mva-Bn®) In 56-80-Year-Old Subjects, Richard N. Greenberg, Christine M. Hay, Jack T. Stapleton, Thomas C. Marbury, Eva Wagner, Eva Kreitmeir, Siegfried Röesch, Alfred Von Krempelhuber, Philip Young, Richard Nichols, Thomas P. Meyer, Darja Schmidt, Josef Weigl, Garth Virgin, Nathaly Arndtz-Wiedemann, Paul Chaplin

Internal Medicine Faculty Publications

Background Modified Vaccinia Ankara MVA-BN^® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN^® (MVA) was assessed in a 56–80 years old population.

Methods MVA with a virus titer of 1 x 10⁸ TCID₅₀/dose was administered via subcutaneous injection to 56–80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated …

Project Achieve – Using Implementation Research To Guide The Evaluation Of Transitional Care Effectiveness, Jing Li, Jane Brock, Brian Jack, Brian Mittman, Mary Naylor, Joann Sorra, Glen P. Mays, Mark V. Williams, Arnold J. Stromberg, Heather M. Bush, Allison Scott, Robert Duff, Emily R. Clear, Hannah Keeler, Project Achieve

Internal Medicine Faculty Publications

Background: Poorly managed hospital discharges and care transitions between health care facilities can cause poor outcomes for both patients and their caregivers. Unfortunately, the usual approach to health care delivery does not support continuity and coordination across the settings of hospital, doctors’ offices, home or nursing homes. Though complex efforts with multiple components can improve patient outcomes and reduce 30-day readmissions, research has not identified which components are necessary. Also we do not know how delivery of core components may need to be adjusted based on patient, caregiver, setting or characteristics of the community, or how system redesign can be …

Differences In Rhodococcus Equi Infections Based On Immune Status And Antibiotic Susceptibility Of Clinical Isolates In A Case Series Of 12 Patients And Cases In The Literature, Praveen Gundelly, Yasuhiro Suzuki, Julie A. Ribes, Alice C. Thornton

Internal Medicine Faculty Publications

Rhodococcus equi is an unusual zoonotic pathogen that can cause life-threatening diseases in susceptible hosts. Twelve patients with R. equi infection in Kentucky were compared to 137 cases reported in the literature. Although lungs were the primary sites of infection in immunocompromised patients, extrapulmonary involvement only was more common in immunocompetent patients (P > 0.0001). Mortality in R. equi-infected HIV patients was lower in the HAART era (8%) than in pre-HAART era (56%) (P > 0.0001), suggesting that HAART improves prognosis in these patients. Most (85–100%) of clinical isolates were susceptible to vancomycin, clarithromycin, rifampin, aminoglycosides, ciprofloxacin, and imipenem. …

Reduction In Overall Occurrences Of Ischemic Events With Vorapaxar: Results From Tracer, Harvey D. White, Zhen Huang, Pierluigi Tricoci, Frans Van De Werf, Lars Wallentin, Yuliya Lokhnygina, David J. Moliterno, Philip E. Aylward, Kenneth W. Mahaffey, Paul W. Armstrong

Internal Medicine Faculty Publications

BACKGROUND: Clinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER.

METHODS AND RESULTS: TRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar …

New Oral Anticoagulants Are Not Superior To Warfarin In Secondary Prevention Of Stroke Or Transient Ischemic Attacks, But Lower The Risk Of Intracranial Bleeding: Insights From A Meta-Analysis And Indirect Treatment Comparisons, Partha Sardar, Saurav Chatterjee, Wen-Chih Wu, Edgar Lichstein, Joydeep Ghosh, Shamik Aikat, Debabrata Mukherjee

Internal Medicine Faculty Publications

PURPOSE: Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).

METHODS: Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan …

An Acacb Variant Implicated In Diabetic Nephropathy Associates With Body Mass Index And Gene Expression In Obese Subjects, Lijun Ma, Mariana Murea, James A. Snipes, Alejandra Marinelarena, Jacqueline Krüger, Pamela J. Hicks, Kurt A. Langberg, Meredith A. Bostrom, Jessica N. Cooke, Daisuke Suzuki, Tetsuya Babazono, Takashi Uzu, Sydney C. W. Tang, Ashis K. Mondal, Neeraj K. Sharma, Sayuko Kobes, Peter A. Antinozzi, Matthew Davis, Swapan K. Das, Neda Rasouli, Philip A. Kern, Nathan J. Shores, Lawrence L. Rudel, Matthias Blüher, Michael Stumvoll, Donald W. Bowden, Shiro Maeda, John S. Parks, Peter Kovacs, Robert L. Hanson, Leslie J. Baier, Steven C. Elbein, Barry I. Freedman

Internal Medicine Faculty Publications

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Davis Gates, Heribert Staudinger

Internal Medicine Faculty Publications

Background:

The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Methods:

Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged =40 years), and pooled study results are presented herein. Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. After the 26-week treatment period, placebo subjects completed the trial and 75% …

Effects Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination Formulation On Chronic Obstructive Pulmonary Disease (Copd): Results From A 52-Week Phase Iii Trial In Subjects With Moderate-To-Very Severe Copd, Dennis E. Doherty, Donald P. Tashkin, Edward Kerwin, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

RATIONALE: The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).

METHODS: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo. The trial's co-primary endpoints were mean changes from baseline, as area under the curve (AUC), …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

Background: A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F.

Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 …

Predictors Of Survival In A Cohort Of Patients With Polymyositis And Dermatomyositis: Effect Of Corticosteroids, Methotrexate And Azathioprine, Elena Schiopu, Kristine Phillips, Paul M. Macdonald, Leslie J. Crofford, Emily C. Somers

Internal Medicine Faculty Publications

INTRODUCTION: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients.

METHODS: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. …

Academic Detailing To Increase Colorectal Cancer Screening By Primary Care Practices In Appalachian Pennsylvania, William J. Curry, Eugene J. Lengerich, Brenda C. Kluhsman, Marie A. Graybill, Jason Z. Liao, Eric W. Schaefer, Angela M. Spleen, Mark B. Dignan

Internal Medicine Faculty Publications

BACKGROUND: In the United States, colorectal cancer (CRC) is the third most frequently diagnosed cancer and second leading cause of cancer death. Screening is a primary method to prevent CRC, yet screening remains low in the U.S. and particularly in Appalachian Pennsylvania, a largely rural area with high rates of poverty, limited health care access, and increased CRC incidence and mortality rates. Receiving a physician recommendation for CRC screening is a primary predictor for patient adherence with screening guidelines. One strategy to disseminate practice-oriented interventions is academic detailing (AD), a method that transfers knowledge or methods to physicians, nurses or …

Documentation Of Body Mass Index And Control Of Associated Risk Factors In A Large Primary Care Network, Stephanie A. Rose, Alexander Turchin, Richard W. Grant, James B. Meigs

Internal Medicine Faculty Publications

BACKGROUND: Body mass index (BMI) will be a reportable health measure in the United States (US) through implementation of Healthcare Effectiveness Data and Information Set (HEDIS) guidelines. We evaluated current documentation of BMI, and documentation and control of associated risk factors by BMI category, based on electronic health records from a 12-clinic primary care network.

METHODS: We conducted a cross-sectional analysis of 79,947 active network patients greater than 18 years of age seen between 7/05 - 12/06. We defined BMI category as normal weight (NW, 18-24.9 kg/m²), overweight (OW, 25-29.9), and obese (OB, ≥ 30). We measured documentation …

Life Expectancy And Years Of Life Lost In Chronic Obstructive Pulmonary Disease: Findings From The Nhanes Iii Follow-Up Study, Robert M. Shavelle, David R. Paculdo, Scott J. Kush, David M. Mannino, David J. Strauss

Internal Medicine Faculty Publications

RATIONALE: Previous studies have demonstrated that chronic obstructive pulmonary disease (COPD) causes increased mortality in the general population. But life expectancy and the years of life lost have not been reported.

OBJECTIVES: To quantify mortality, examine how it varies with age, sex, and other risk factors, and determine how life expectancy is affected.

METHODS: We constructed mortality models using the Third National Health and Nutrition Examination Survey, adjusting for age, sex, race, and major medical conditions. We used these to compute life expectancy and the years of life lost.

MEASUREMENTS AND MAIN RESULTS: Pulmonary function testing classified patients as having …

Adrb2 Arg16gly Polymorphism, Lung Function, And Mortality: Results From The Atherosclerosis Risk In Communities Study, Jill M. Ferdinands, David M. Mannino, Marta L. Gwinn, Molly S. Bray

Internal Medicine Faculty Publications

BACKGROUND: Growing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy. We sought to examine the association of beta-agonist use and the Arg16Gly polymorphism with lung function and mortality among participants in the Atherosclerosis Risk in Communities study.

METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped study participants and analyzed the association of the Arg16Gly polymorphism and beta-agonist use with lung function at baseline and clinical examination three years later and with all-cause mortality during 10 years of follow-up. Lung function was characterized by percent-predicted forced expiratory volume in 1 …