Translational Medical Research Commons^™

Distributing Data And Analysis Software Containers For Better Data Sharing In Clinical Research, William A. Mattingly Phd, Stephen Furmanek, Christopher M. Sinclair, Timothy L. Wiemken Phd

The University of Louisville Journal of Respiratory Infections

Introduction: Data sharing in clinical research is critical for increasing knowledge discovery. Data and software tools should be FAIR: Findable, Accessible, Inter-operable and Re-usable. Many bottlenecks exist in the process of a clinical investigator using shared data including data acquisition and statistical analysis. The objective of this project is to develop a structure for sharing data and providing rapid automated statistical analysis through creation of a pre-packaged, open-source software container.

Methods: We use the open source software container technologies VirtualBox and Vagrant to create a template for sharing clinical data and analysis scripts as a single container. We use …

Streptococcus Pneumoniae Antigen, Missing Opportunities Of A Promising Point Of Care Diagnostic Test, Magdelina Słomka, Ruby Gupta, Baltej Singh, Venkatesh Gondhi, Siddartha Bhandary, Ekezie Francis, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Background: The etiologic diagnosis of community acquired pneumonia (CAP) and community-acquired meningitis (CAM) are still far from optimal accuracy and turnaround time. The most common bacterial pathogen identified in both CAP and CAM is Streptococcus pneumoniae.

Methods: We reviewed the literature on S. pneumoniae antigen to highlight opportunities to optimize its use as a point of care diagnostic test to maximize quality of patient care, antimicrobial stewardship outcomes and cost saving. A PubMed search was performed using key words “S. pneumoniae antigen; rapid diagnostic tests for S. pneumoniae”. We selected articles in English and sorted into randomized …

Most Common Statistical Methodologies In Recent Clinical Studies Of Community-Acquired Pneumonia, Stephen Furmanek, Connor L. English, Thomas Chandler, Timothy L. Wiemken Phd

The University of Louisville Journal of Respiratory Infections

Background: Training new individuals in pneumonia research is imperative to produce a new generation of clinical investigators with the expertise necessary to fill gaps in knowledge. Clinical investigators are often intimidated by their unfamiliarity with statistics. The objective of this study is to define the most common statistical methodologies in recent clinical studies of CAP to inform teaching approaches in the field.

Methods: Articles met inclusion criteria if they were clinical research with an emphasis on incidence, epidemiology, or patient outcomes, searchable via PubMed or Google Scholar, published within the timeframe of January 1st 2012 to August 1st 2017, …

Rationale And Methods Of The Study Protocol: Streptococcus Pneumoniae Serotypes In Adults 18 Years And Older With Radiographically-Confirmed Community-Acquired Pneumonia (Cap), Ronika Alexander, Paula Peyrani, Julio A. Ramirez, Wesley H. Self Md, Mph, Carlos Grijalva, Francis Counselman, Gregory A. Volturo, Heidi Kabler, Luis Ostrosky-Zeichner, Richard Wunderink, Robert L. Sherwin, Senen Pena, Thomas File, Timothy L. Wiemken, Sharon Gray, Michael Pride, Kimbal D. Ford, Qin Jiang, Raul Isturiz

The University of Louisville Journal of Respiratory Infections

This study was an active, prospective surveillance study of adults 18 years and older hospitalized with community-acquired pneumonia (CAP) due to Streptococcus pneumoniae conducted at 21 hospitals in ten cities across the United States. This report describes the surveillance methodology applied between October 7, 2013 and September 30, 2016, including the identification and description of surveillance areas and populations at-risk for CAP hospitalization for estimation of incidence rates for selected study sites.

Pneumonia Pathogenesis And The Lung Microbiome: Back To The Drawing Board, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Level Of Recall Bias Regarding Pneumococcal Vaccination History Among Adults Hospitalized With Community-Acquired Pneumonia: Results From The University Of Louisville Pneumonia Study, Sarah Van Heiden, Ruth Carrico, Timothy L. Wiemken, Ronika Alexander, John M. Mclaughlin, Qin Jiang, Paula Peyrani, William A. Mattingly, Stephen P. Furmanek, Connor L. English, Senen Pena, Raul Isturiz, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Recall bias is likely to occur in vaccine effectiveness studies using self-reported vaccination history. The validity of patient-reported vaccination status for adults is not well defined. The objective of this study was to evaluate the validity of self-reported pneumococcal vaccination history among patients hospitalized with community-acquired pneumonia (CAP).

Methods: Prospective ancillary study of a population-based observational study of hospitalized patients with CAP in the city of Louisville. To be included in the analysis, patients had to (i) be reached by phone 30-days after discharge from the hospital and (ii) report that they remembered whether or not they received a …

Preliminary Evaluation Of An Lyta Pcr Assay For Detection Of Streptococcus Pneumoniae In Urine Specimens From Hospitalized Patients With Community-Acquired Pneumonia, Subathra Marimuthu, James T. Summersgill, Kuldeep Ghosh, Leslie A Wolf

The University of Louisville Journal of Respiratory Infections

Community acquired pneumonia (CAP) due to Streptococcus pneumoniae still occurs in at risk populations, despite the availability of effective vaccines. Laboratory confirmation of S. pneumoniae remains challenging in cases of CAP despite advances in blood culture techniques and the availability of nucleic acid amplification tests such as PCR-based methods. Urine specimens are an attractive sample type because they are non-invasive compared to bronchial washes or whole blood specimens for patients with CAP. While urine specimens have been used successfully in antigen detection assays, they have not been extensively evaluated for PCR-based assays. In this preliminary study, we evaluated the potential …

Antimicrobial Stewardship In Hospitalized Patients With Respiratory Infections: Ten-Year Experience From The Robley Rex Louisville Va Medical Center, Leslie A. Beavin, Forest W. Arnold, Paula Peyrani, Anupama Raghuram, David Newman, Ronald Smith, Carmen Sciortino, Stephen P. Furmanek, Ruth M. Carrico, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Rationale: Antibiotic stewardship has been defined as coordinated interventions designed to improve and measure the appropriate use of antibiotic agents. Respiratory infections are the most common infectious reason for hospitalization in the United States. Therefore, one could extrapolate that respiratory infections are then also the most common reason for hospital antibiotic use and possess the highest potential for hospital antibiotic misuse. The primary objective of this article was to evaluate the role of antimicrobial stewardship on improving antibiotic use for respiratory infections in hospitalized patients on intravenous (IV) antibiotics at the Robley Rex Louisville VAMC over a 10-year period.

Methods: …

One-Year Mortality In Patients With Community-Acquired Pneumonia, Paula Peyrani, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Pneumonia remains a common cause of morbidity and mortality in the US. Although, communityacquired pneumonia (CAP) has traditionally been considered an acute process, more recently, data have emerged showing that patients surviving an episode of CAP are at increased risk of death long after hospital discharged. In this descriptive review, we examine the current knowledge of long-term mortality and propose a hypothesis explaining the pathogenesis of long-term mortality in patients with CAP.

Using Steroids In Patients With Community-Acquired Pneumonia At The University Of Louisville Hospital: Who, What, And When, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Lung Cytokines And Systemic Inflammation In Patients With Copd, Alessandra Morello Gearhart, Rodrigo Cavallazzi, Paula Peyrani, Timothy L. Wiemken, Stephen P. Furmanek, Andrea Reyes-Vega, Umair Gauhar, Hiram Rivas-Perez, Jesse Roman, Julio A. Ramirez, Rafael Fernandez-Botran

The University of Louisville Journal of Respiratory Infections

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by lung and systemic inflammation. The role of cytokines in local and systemic inflammation in COPD is not well understood. This study aimed to compare plasma and bronchoalveolar lavage (BAL) fluid cytokine levels in COPD and non-COPD subjects with the intent of better understand their potential roles in driving local and systemic inflammation.

Methods: This cross-sectional study analyzed data from 65 subjects: 31 with COPD confirmed by spirometry and 34 non-COPD controls. All subjects underwent spirometry, plasma sample collection, and bronchoscopy/BAL. Levels of 21 inflammatory cytokines were measured in the plasma (systemic …

Lung Cytokines And Systemic Inflammation In Patients With Copd., Alessandra Morello Gearhart, Rodrigo Cavallazzi, Paula Peyrani, Timothy L. Wiemken, Stephen P. Furmanek, Andrea Reyes-Vega, Umair Gauhar, Hiram Rivas-Perez, Jesse Roman, Julio A. Ramirez, Rafael Fernandez-Botran

Faculty Scholarship

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by lung and systemic inflammation. The role of cytokines in local and systemic inflammation in COPD is not well understood. This study aimed to compare plasma and bronchoalveolar lavage (BAL) fluid cytokine levels in COPD and non-COPD subjects with the intent of better understand their potential roles in driving local and systemic inflammation.

Methods: This cross-sectional study analyzed data from 65 subjects: 31 with COPD confirmed by spirometry and 34 non-COPD controls. All subjects underwent spirometry, plasma sample collection, and bronchoscopy/BAL. Levels of 21 inflammatory cytokines were measured in the plasma (systemic …

Gender Differences In Virologic Response After Antiretroviral Therapy In Treatment-Naïve Hiv-Infected Individuals: Results From The 550 Clinic Hiv Cohort Study., Andrea Reyes-Vega, Alejandra Loban, Kavitha Srinivasan, Stephen P. Furmanek, Conner English, Mary Bishop, Cathy Spencer, Daniel Truelove, Julio A. Ramirez, Anupama Raghuram, Paula Peyrani

Faculty Scholarship

Background

Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals. Methods

This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as < 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value <0.05 was considered statistically significant. R version 3.3.2 was used for the statistical analysis. Results

A total of 70 women and 90 men were included …

Pneumonia Research And The Omics Revolution: It Is Time For Pneumomics, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Short Duration Of Antibiotic Therapy In Hospitalized Patients With Community-Acquired Pneumonia: Results From The Capo International Cohort Study, Alejandro Chirino Navarta, Paula Peyrani, Timothy L. Wiemken, Marcos I. Restrepo, James D. Chalmers, Carlos M. Luna, Francesco Blasi, Julio A. Ramirez, Stefano Aliberti

The University of Louisville Journal of Respiratory Infections

Introduction: Experts suggest a short duration of antibiotic therapy (DOT) in responding patients with community-acquired pneumonia (CAP). The aim of this study was to evaluate clinical outcomes after hospital discharge among patients treated with short-course antibiotic therapy (SCT) vs. long-course antibiotic therapy (LCT) for CAP.

Methods: A secondary analysis of the Community-Acquired Pneumonia Organization (CAPO) database from January 2007 to June 2013 was performed, including hospitalized CAP patients who reached clinical stability within 5 days. Two groups were identified: patients who were treated with antibiotic therapy for a total duration of 5 days or less (SCT Group) vs. …

Clinical Research: Educational Videos - The Process Of Clinical Research: Step-By-Step From Idea To Publication, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Clinical research can be defined as the creation and dissemination of new knowledge with the goal to improve outcomes in patients with a particular health problem. In this short video, Dr. Julio Ramirez, from the University of Louisville, offers an overview of the process of clinical research and describe how an investigator moves from the generation of an idea to the publication of study findings.

Predicting 30-Day Mortality In Hospitalized Patients With Community-Acquired Pneumonia Using Statistical And Machine Learning Approaches, Timothy L. Wiemken, Stephen P. Furmanek, William A. Mattingly, Brian E. Guinn, Rodrigo Cavallazzi, Rafael Fernandez-Botran, Leslie A Wolf, Connor L. English, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Predicting if a hospitalized patient with community-acquired pneumonia (CAP) will or will not survive after admission to the hospital is important for research purposes as well as for institution of early patient management interventions. Although population-level mortality prediction scores for these patients have been around for many years, novel patient-level algorithms are needed. The objective of this study was to assess several statistical and machine learning models for their ability to predict 30-day mortality in hospitalized patients with CAP.

Methods: This was a secondary analysis of the University of Louisville (UofL) Pneumonia Study database. Six different statistical and/or machine …

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, …

A 49-Year-Old Woman With Chronic Skin Lesions, Acute Mental Status Changes And New Pulmonary Infiltrate: Case Discussion From The University Of Louisville Hospital, Bhavani Puskur, Youssef Khafateh, Srikant Ramachandruni, Veronica Corcino, Mark Burns, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Impact Of Obesity On Mortality In Hospitalized Patients With Pneumonia Due To 2009 H1n1 Influenza A Virus Versus Other Etiologies, Martin A. Espinosa-Ginic, Ryan T. Hurt, Stephen P. Furmanek, Paula Peyrani, Julio A. Ramirez, Timothy Lee Wiemken, The Capo Investigators

The University of Louisville Journal of Respiratory Infections

Background: Reports from the 2009 H1N1 influenza A virus (2009 H1N1) pandemic indicate increased mortality in obese patients hospitalized with pneumonia. However, articles published prior to the pandemic have suggested that obesity may be a protective factor for mortality in these patients. The objective of this study was to compare the impact of obesity on mortality in hospitalized patients with pneumonia due to the 2009 H1N1 versus pneumonia due to other etiologies.

Methods: This was a secondary analysis of the CAPO international cohort study. Study groups were defined as follows: Group One, pneumonia due to 2009 H1N1: Patients hospitalized with …

A New Journal Section: Patient Management, Forest W. Arnold, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Impact Of Temperature Relative Humidity And Absolute Humidity On The Incidence Of Hospitalizations For Lower Respiratory Tract Infections Due To Influenza, Rhinovirus, And Respiratory Syncytial Virus: Results From Community-Acquired Pneumonia Organization (Capo) International Cohort Study, Timothy L. Wiemken, William A. Mattingly, Stephen P. Furmanek, Brian E. Guinn, Connor L. English, Ruth Carrico, Paula Peyrani, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Abstract

Background: Transmissibility of several etiologies of lower respiratory tract infections (LRTI) may vary based on outdoor climate factors. The objective of this study was to evaluate the impact of outdoor temperature, relative humidity, and absolute humidity on the incidence of hospitalizations for lower respiratory tract infections due to influenza, rhinovirus, and respiratory syncytial virus (RSV).

Methods: This was a secondary analysis of an ancillary study of the Community Acquired Pneumonia Organization (CAPO) database. Respiratory viruses were detected using the Luminex xTAG respiratory viral panel. Climate factors were obtained from the National Weather Service. Adjusted Poisson regression models with robust …

The Community-Acquired Pneumonia Organization (Capo) Cloud-Based Research Platform (The Capo-Cloud): Facilitating Data Sharing In Clinical Research, William A. Mattingly, Timothy L. Wiemken, Stephen P. Furmanek, Paula Peyrani, Robert R. Kelley, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Pneumonia is a costly and deadly respiratory disease that afflicts millions every year. Advances in pneumonia care require significant research investment and collaboration among pneumonia investigators. Despite the importance of data sharing for clinical research it remains difficult to share datasets with old and new investigators. We present CAPOCloud, a web-based pneumonia research platform intended to facilitate data sharing and make data more accessible to new investigators.

Methods: We establish the first two use cases for CAPOCloud to be the automatic subsetting and constraining of the CAPO database and the automatic summarization of the database in aggregate. We use …

Clinical & Translational Research In Pneumonia: Defining A Research Agenda For Today And Tomorrow, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

From the Editor in Chief

The reason for this special supplement of the Journal is to inform readers of a scientific research conference supported by the National Institutes of Health (NHI). The NIH Research Conference Grant (R13) supports high quality scientific conferences in areas that are important to the NIH's mission and to the public health. We just received notification that the National Heart, Lung, and Blood Institute (NHLBI) has approved the application for an international research conference entitled: DzClinical & Translational Research in Pneumonia: Defining a Research Agenda for Today and Tomorrowdz. The conference will be held on Wednesday, …

Why A New Journal?, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

-

Clinical Outcomes Of Community-Acquired Pneumonia In Patients With Diabetes Mellitus, Siddartha Bandhary, Bolivar Y. Contreras-Mora, Ruby Gupta, Patricia Fernandez, Patricio Jimenez, Paula Peyrani, Timothy L. Wiemken, Steven Burdette, Julio A. Ramirez, Hadi Harati, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Background: Studies have found admission hyperglycemia as a predictor of poor outcomes in Community acquired Pneumonia (CAP), whereas others have not. The objective of this study was to evaluate the impact of diabetes mellitus (DM) on mortality as well as Length of stay (LOS) and Time to clinical stability (TCS) of hospitalized patients with CAP.

Materials and Methods: Adult patients hospitalized with CAP enrolled at Community-Acquired Pneumonia Organization (CAPO) database with DM were categorized as admission blood glucose ≥ 250 mg/dL (diabetes mellitus blood sugar (BG) > 250) and admission blood glucose ≤ 250 mg/dL (DM BG ≤ 250). CAP outcomes …

Neutrophil Function In Elderly Patients Hospitalized With Community- Acquired Pneumonia, Jorge Perez San Juan, Lisandra Rodriguez Hernandez, Timothy L. Wiemken, Robert R. Kelley, Rafael Fernandez-Botran, Martin Gnoni, Paula Peyrani, Madhavi J. Rane, Forest W. Arnold, Julio A. Ramirez, Silvia Uriarte, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Background: Advanced age is associated with immunosenescence as well as increased risk for poor outcomes during episodes of community-acquired pneumonia (CAP). Data on neutrophil function in hospitalized elderly patients with CAP is lacking. In this study we compared neutrophil function in elderly and non-elderly hospitalized patients with CAP.

Methods: Prospective study of healthy controls (HC) and patients hospitalized with CAP nonelderly (NE-CAP) and elderly (E-CAP). Blood samples were obtained on the day of hospitalization. The following neutrophil functional assays were performed: degranulation of secretory vesicles (CD35), degranulation of specific granules (CD66b), phagocytosis, and hydrogen peroxide (H₂O₂) …

Time To Clinical Stability In Patients With Ventilator-Associated Pneumonia Due To Methicillin-Resistant Staphylococcus Aureus Treated With Linezolid Versus Vancomycin: Results From The Impact-Hap Study, Paula Peyrani, Timothy L. Wiemken, Marcus J. Zervos, Daniel H. Kett, Thomas M. File Jr., Gary E. Stein, Kimbal D. Ford, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Time to clinical stability is a well-defined early clinical outcome in hospitalized patients with community-acquired pneumonia, but it has not been evaluated in patients with ventilator-associated pneumonia (VAP). The objective of this study was to compare time to clinical stability in patients with MRSA VAP treated with linezolid versus vancomycin.

Methods: This was a secondary analysis of the IMPACT-HAP study database. VAP was defined according to CDC criteria. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. A patient was considered to reach clinical stability the day that the following four criteria were …

A Review Of Macrolide Based Regimens For Community-Acquired Pneumonia, Forest W. Arnold, Leslie A. Beavin

The University of Louisville Journal of Respiratory Infections

Community-acquired pneumonia (CAP) has significant morbidity and mortality. The Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines recommend two antimicrobial regimens for hospitalized patients with CAP, one of which includes a macrolide, and one of which does not. Both regimens have antimicrobial properties, but macrolides also possess immunomodulatory properties. Macrolides, however, may also have potential arrhythmia adverse effects. The purpose of this review is to provide an update of studies evaluating outcomes for patients with CAP treated with or without a macrolide-based regimen. Two recent randomized controlled trials conflict with each other regarding the benefit versus noninferiority of including …