Epidemiology Commons^™

Oxidative Stress And Cardiovascular Risk In Type 1 Diabetes Mellitus: Insights From The Dcct/Edic Study, W. Wilson Tang, P. Mcgee, John M. Lachin, D. Li, B. Hoogwerf, S. Hazen, +Several Additional Authors

Epidemiology Faculty Publications

Background--Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results--A random subcohort of 349 participants was selected from the DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT, and 1 to 2 years post-DCCT (EDIC years 1 and …

Association Of C-Reactive Protein With Bacterial And Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years In The Perch Study., Melissa M Higdon, Tham Le, Katherine L O'Brien, David R Murdoch, Christine Prosperi, Henry C Baggett, Daniel E Park, +Several Additional Authors

Epidemiology Faculty Publications

Background.

Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods.

We measured serum CRP levels in cases with World Health Organization–defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for “confirmed” bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid …

Is Higher Viral Load In The Upper Respiratory Tract Associated With Severe Pneumonia? Findings From The Perch Study., Daniel R Feikin, Wei Fu, Daniel E Park, Qiyuan Shi, Melissa M Higdon, Henry C Baggett, +Several Additional Authors

Epidemiology Faculty Publications

Background.

The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls.

Methods.

In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed …

Standardization Of Clinical Assessment And Sample Collection Across All Perch Study Sites., Jane Crawley, Christine Prosperi, Henry C Baggett, W Abdullah Brooks, Maria Deloria Knoll, Daniel E Park, +Several Additional Authors

Epidemiology Faculty Publications

Background.: Variable adherence to standardized case definitions, clinical procedures, specimen collection techniques, and laboratory methods has complicated the interpretation of previous multicenter pneumonia etiology studies. To circumvent these problems, a program of clinical standardization was embedded in the Pneumonia Etiology Research for Child Health (PERCH) study.

Methods.: Between March 2011 and August 2013, standardized training on the PERCH case definition, clinical procedures, and collection of laboratory specimens was delivered to 331 clinical staff at 9 study sites in 7 countries (The Gambia, Kenya, Mali, South Africa, Zambia, Thailand, and Bangladesh), through 32 on-site courses and a training website. Staff competency …

Data Management And Data Quality In Perch, A Large International Case-Control Study Of Severe Childhood Pneumonia., Nora L Watson, Christine Prosperi, Amanda J Driscoll, Melissa M Higdon, Daniel E Park, Megan Sanza, Andrea N Deluca, Juliet O Awori, Doli Goswami, Emily Hammond, Lokman Hossain, Catherine Johnson, Alice Kamau, Locadiah Kuwanda, David P Moore, Omid Neyzari, Uma Onwuchekwa, David Parker, Patranuch Sapchookul

Epidemiology Faculty Publications

The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study. To ensure high-quality data, the project developed …

Safety Of Induced Sputum Collection In Children Hospitalized With Severe Or Very Severe Pneumonia., Andrea N Deluca, Laura L Hammitt, Julia Kim, Melissa M Higdon, Henry C Baggett, Daniel E Park, +Several Additional Authors

Epidemiology Faculty Publications

Background.: Induced sputum (IS) may provide diagnostic information about the etiology of pneumonia. The safety of this procedure across a heterogeneous population with severe pneumonia in low- and middle-income countries has not been described.

Methods.: IS specimens were obtained as part a 7-country study of the etiology of severe and very severe pneumonia in hospitalized childrenbefore, during, and after the procedure to record oxygen requirement, oxygen saturation, respiratory rate, consciousness level, and other evidence of clinical deterioration. Criteria for IS contraindications were predefined and serious adverse events (SAEs) were reported to ethics committees and a central safety monitor.

Results.: A …

Microscopic Analysis And Quality Assessment Of Induced Sputum From Children With Pneumonia In The Perch Study., David R Murdoch, Susan C Morpeth, Laura L Hammitt, Amanda J Driscoll, Daniel E Park, +Several Additional Authors

Epidemiology Faculty Publications

Background.

It is standard practice for laboratories to assess the cellular quality of expectorated sputum specimens to check that they originated from the lower respiratory tract. The presence of low numbers of squamous epithelial cells (SECs) and high numbers of polymorphonuclear (PMN) cells are regarded as indicative of a lower respiratory tract specimen. However, these quality ratings have never been evaluated for induced sputum specimens from children with suspected pneumonia. Methods.

We evaluated induced sputum Gram stain smears and cultures from hospitalized children aged 1–59 months enrolled in a large study of community-acquired pneumonia. We hypothesized that a specimen representative …

The Diagnostic Utility Of Induced Sputum Microscopy And Culture In Childhood Pneumonia., David R Murdoch, Susan C Morpeth, Laura L Hammitt, Amanda J Driscoll, Nora L Watson, Daniel E Park, +Several Additional Authors

Epidemiology Faculty Publications

Background.

Sputum microscopy and culture are commonly used for diagnosing the cause of pneumonia in adults but are rarely performed in children due to difficulties in obtaining specimens. Induced sputum is occasionally used to investigate lower respiratory infections in children but has not been widely used in pneumonia etiology studies. Methods.

We evaluated the diagnostic utility of induced sputum microscopy and culture in patients enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study, a large study of community-acquired pneumonia in children aged 1–59 months. Comparisons were made between induced sputum samples from hospitalized children with radiographically confirmed pneumonia …

Biomarkers Of Tubulointerstitial Damage And Function In Type 1 Diabetes, Ian De Boer, Xiaoyu Gao, Ionut Bebu, Andrew Hoofnagle, John Lachin, Diabetes Control And Complications Trial/Epidemiology Of Diabetes Interventions And Complications (Dcct/Edic) Research Group.

Epidemiology Faculty Publications

Objective To evaluate biomarkers of renal tubulointerstitial damage and function in type 1 diabetes with and without diabetic kidney disease.

Research design and methods Cross-sectional case-control study of Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants. Cases (N=43) had incident persistent estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with urinary albumin excretion >300 mg/24 hour. Controls (N=43) had persistent eGFR >90 mL/min/1.73 m2 and urinary albumin excretion <30 mg/24 hour. Urinary and plasma biomarkers reflecting tubular injury, inflammation, fibrosis, secretion, and synthetic function were measured from stored specimens collected at the first study visit with reduced eGFR (for case participants) or the corresponding study year (for control participants).

Results Mean (SD) age was 51 (9) and 50 (8) years for case and control participants, and mean (SD) duration of diabetes was 30 (6) and 30 (5) years, respectively. Mean (SD) eGFR was 39 …

Heart Failure Outcomes With Empagliflozin In Patients With Type 2 Diabetes At High Cardiovascular Risk: Results Of The Empa-Reg Outcome® Trial., David Fitchett, Bernard Zinman, Christoph Wanner, John M. Lachin, Stefan Hantel, Afshin Salsali, Odd Erik Johansen, Hans J Woerle, Uli C Broedl, Silvio E Inzucchi

Epidemiology Faculty Publications

AIMS: We previously reported that in the EMPA-REG OUTCOME(®) trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure.

METHODS AND RESULTS: Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Seven thousand and twenty patients were treated; 706 (10.1%) had heart failure at baseline. Heart failure hospitalization or …

Importance Of Hereditary And Selected Environmental Risk Factors In The Etiology Of Inflammatory Breast Cancer: A Case-Comparison Study., Roxana Moslehi, Elizabeth Freedman, Nur Zeinomar, Carmela Veneroso, Paul H. Levine

Epidemiology Faculty Publications

BACKGROUND: To assess the importance of heredity in the etiology of inflammatory breast cancer (IBC), we compared IBC patients to several carefully chosen comparison groups with respect to the prevalence of first-degree family history of breast cancer.

METHODS: IBC cases (n = 141) were compared to non-inflammatory breast cancer cases (n = 178) ascertained through George Washington University (GWU) with respect to the prevalence of first-degree family history of breast cancer and selected environmental/lifestyle risk factors for breast cancer. Similar comparisons were conducted with subjects from three case-control studies: breast cancer cases (n = 1145) and unaffected controls (n = …

Nitrate And Nitrite Ingestion And Risk Of Ovarian Cancer Among Postmenopausal Women In Iowa, Maki Inoue-Choi, Rena R. Jones, Kristin E. Anderson, Kenneth P. Cantor, James R. Cerhan, Stuart Krasner, Kimberly Robien, Peter J. Weyer, Mary H. Ward

Epidemiology Faculty Publications

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO₃-N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were …

Association Between Respiratory Syncytial Virus Activity And Pneumococcal Disease In Infants: A Time Series Analysis Of Us Hospitalization Data., Daniel M. Weinberger, Keith P. Klugman, Claudia A. Steiner, Lone Simonsen, Cécile Viboud

Epidemiology Faculty Publications

BACKGROUND:

The importance of bacterial infections following respiratory syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were associated with changes in the rate of hospitalizations coded as RSV.

METHODS AND FINDINGS:

We used data from the State Inpatient Databases (Agency for Healthcare Research and Quality), including >700,000 RSV hospitalizations and >16,000 pneumococcal pneumonia hospitalizations in 36 states (1992/1993-2008/2009). Harmonic regression was used to estimate the timing of the average seasonal …