Biostatistics Commons^™

Dietary Inflammatory Index And Cardiovascular Risk And Mortality—A Meta-Analysis, Nitin Shivappa, Justyna Godos, James R. Hébert, Michael Wirth, Gabriele Piuri, Attilio Speciani, Giuseppe Grosso

Faculty Publications

Diet and chronic inflammation have been suggested to be risk factors in the development of cardiovascular disease (CVD) and related mortality. The possible link between the inflammatory potential of diet measured through the Dietary Inflammatory Index (DII^®) and CVD has been investigated in several populations across the world. The aim of this study was to conduct a meta-analysis on studies exploring this association. Data from 14 studies were eligible, of which two were case-control, eleven were cohort, and one was cross-sectional. Results from the random-effects meta-analysis showed a positive association between increasing DII, indicating a pro-inflammatory diet, and …

Lower Dietary Inflammatory Index Scores Are Associated With Lower Glycemic Index Scores Among College Students, Yeonsoo Kim, Jie Chen, Michael Wirth, Nitin Shivappa, James R. Hébert

Faculty Publications

The association between the Dietary Inflammatory Index (DII^®), the glycemic index (GI), and the glycemic load (GL) is not known, although it is known that carbohydrates are pro-inflammatory. We aimed to measure the association between the DII and both GI and GL among college students. In this cross-sectional study, 110 college students completed a 3-day food diary, which was used to calculate the DII, the GI, the GL, and the healthy eating index (HEI)-2010. Least square means and 95% confidence intervals of the GI, the GL, and the HEI-2010 were presented per DII tertile using generalized linear mixed …

Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels …

Optimized Adaptive Enrichment Designs For Multi-Arm Trials: Learning Which Subpopulations Benefit From Different Treatments, Jon Arni Steingrimsson, Joshua Betz, Tiachen Qian, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

We consider the problem of designing a randomized trial for comparing two treatments versus a common control in two disjoint subpopulations. The subpopulations could be defined in terms of a biomarker or disease severity measured at baseline. The goal is to determine which treatments benefit which subpopulations. We develop a new class of adaptive enrichment designs tailored to solving this problem. Adaptive enrichment designs involve a preplanned rule for modifying enrollment based on accruing data in an ongoing trial. The proposed designs have preplanned rules for stopping accrual of treatment by subpopulation combinations, either for efficacy or futility. The motivation …

Phase Ii Adaptive Enrichment Design To Determine The Population To Enroll In Phase Iii Trials, By Selecting Thresholds For Baseline Disease Severity, Yu Du, Gary L. Rosner, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

We propose and evaluate a two-stage, phase 2, adaptive clinical trial design. Its goal is to determine whether future phase 3 (confirmatory) trials should be conducted, and if so, which population should be enrolled. The population selected for phase 3 enrollment is defined in terms of a disease severity score measured at baseline. We optimize the phase 2 trial design and analysis in a decision theory framework. Our utility function represents a combination of the cost of conducting phase 3 trials and, if the phase 3 trials are successful, the improved health of the future population minus the cost of …

Treatment And Outcomes Of Non-Small-Cell Lung Cancer Patients With High Comorbidity, Jorge Rios, Rahul Gosain, Bernardo H. L. Goulart, Bin Huang, Margaret N. Oechsli, Jaclyn K. Mcdowell, Quan Chen, Thomas Tucker, Goetz H. Kloecker

Biostatistics Faculty Publications

Background: The life expectancy of untreated non-small-cell lung cancer (NSCLC) is dismal, while treatment for NSCLC improves survival. The presence of comorbidities is thought to play a significant role in the decision to treat or not treat a given patient. We aim to evaluate the association of comorbidities with the survival of patients treated for NSCLC.

Methods: We performed a retrospective study of patients aged ≥66 years with invasive NSCLC between the years 2007 and 2011 in the Surveillance, Epidemiology, and End Results Kentucky Cancer Registry. Comorbidity was measured using the Klabunde Comorbidity Index (KCI), and univariate and multivariate logistic …

Power Calculation For Cross-Sectional Stepped Wedge Cluster-Randomized Trials With Variable Cluster Sizes, Linda J. Harrison, Tom Chen, Rui Wang

Harvard University Biostatistics Working Paper Series

Standard sample size calculation formulas for Stepped Wedge Cluster Randomized Trials (SW-CRTs) assume that cluster sizes are equal. When cluster sizes vary substantially, ignoring this variation may lead to an under-powered study. We investigate the relative efficiency of a SW-CRT with varying cluster sizes to equal cluster sizes, and derive variance estimators for the intervention effect that account for this variation under the assumption of a mixed effects model; a commonly-used approach for analyzing data from cluster randomized trials. When cluster sizes vary, the power of a SW-CRT depends on the order in which clusters receive the intervention, which is …

Zero-Inflated Models For Rna-Seq Count Data, Morshed Alam, Naim Al Mahi, Munni Begum

Journal Articles: Biostatistics

One of the main objectives of many biological studies is to explore differential gene expression profiles between samples. Genes are referred to as differentially expressed (DE) if the read counts change across treatments or conditions systematically. Poisson and negative binomial (NB) regressions are widely used methods for non-over-dispersed (NOD) and over-dispersed (OD) count data respectively. However, in the presence of excessive number of zeros, these methods need adjustments. In this paper, we consider a zero-inflated Poisson mixed effects model (ZIPMM) and zero-inflated negative binomial mixed effects model (ZINBMM) to address excessive zero counts in the NOD and OD RNA-seq data …

Crosstalk Among Lncrnas, Micrornas And Mrnas In The Muscle ‘Degradome’ Of Rainbow Trout, Bam Paneru, Ali Ali, Rafet Al-Tobasei, Brett Kenney, Mohamed Salem

Faculty & Staff Scholarship

In fish, protein-coding and noncoding genes involved in muscle atrophy are not fully characterized. In this study, we characterized coding and noncoding genes involved in gonadogenesis-associated muscle atrophy, and investigated the potential functional interplay between these genes. Using RNA- Seq, we compared expression pattern of mRNAs, long noncoding RNAs (lncRNAs) and microRNAs of atrophying skeletal muscle from gravid females and control skeletal muscle from age-matched sterile individuals. A total of 852 mRNAs, 1,160 lncRNAs and 28 microRNAs were differentially expressed (DE) between the two groups. Muscle atrophy appears to be mediated by many genes encoding ubiquitin- proteasome system, autophagy related …

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects On Neuroinflammation And Synaptic Function Markers In A Mouse Model Of Doxorubicin-Based Chemotherapy, Tonya S. Orchard, Monica M. Gaudier-Diaz, Panchita Phuwamongkolwiwat-Chu, Rebecca Andridge, Maryam B. Lustberg, Joshua Bomser, Rachel M. Cole, Martha A. Belury, Courtney A. Devries

Faculty & Staff Scholarship

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six …

Waking Up Every Day In A Body That Is Not Yours: A Qualitative Research Inquiry Into The Intersection Between Eating Disorders And Pregnancy, Elizabeth A. Claydon, Danielle M. Davidov, Keith J. Zullig, Christa L. Lilly, Lesley Cattrell, Stephanie C. Zerwas

Faculty & Staff Scholarship

Background: Women with eating disorders are more likely to negatively react to finding out they are pregnant, although this difference in attitudes between women with eating disorders and controls disappears at 18-weeks’ gestation. Those with anorexia also are twice as likely to have an unplanned pregnancy and those with bulimia have a 30-fold increased chance compared with healthy controls. Therefore, due to these considerations, pregnancy and the transition to motherhood can be an extremely challenging time for these women both psychologically and physically. The purpose of this qualitative descriptive study was to understand the intersection between eating disorders and pregnancy …

Rubella Immunity And Serum Perfluoroalkyl Substances: Sex And Analytic Strategy, Courtney S. Pilkerton, Gerald R. Hobbs, Christa Lilly, Sarah S. Knox

Faculty & Staff Scholarship

Background

Perfluoroalkyl substances (PFASs) have been associated with decreased immunity to child- hood tetanus and diphtheria immunizations. If these vaccinations are vulnerable to influence from PFASs, questions arise about associations with other common inoculations.

Objective

To examine whether serum PFASs were associated with reduced immunity to rubella immu- nization, and whether interactions with sex or ethnicity warranted analytic stratification. Usually, toxicology analyses are calculated controlling for race and sex. However, sex differ- ences in immune function have been reported and a reduction of immunity to rubella in women could pose risks such miscarriage.

Methods

We analyzed a nationally representative sample …

Genome-Wide Association Analysis With A 50k Transcribed Gene Snp-Chip Identifies Qtl Affecting Muscle Yield In Rainbow Trout, Mohamed Salem, Rafet Al-Tobasei, Ali Ali, Daniela Lourenco, Guangtu Gao, Yniv Palti, Brett Kenney, Timothy D. Leeds

Faculty & Staff Scholarship

Detection of coding/functional SNPs that change the biological function of a gene may lead to identification of putative causative alleles within QTL regions and discovery of genetic markers with large effects on phenotypes. This study has two-fold objectives, first to develop, and validate a 50K transcribed gene SNP-chip using RNA-Seq data. To achieve this objective, two bioinformatics pipelines, GATK and SAMtools, were used to identify ∼21K transcribed SNPs with allelic imbalances associated with important aquaculture production traits including body weight, muscle yield, muscle fat content, shear force, and whiteness in addition to resistance/susceptibility to bacterial cold-water disease (BCWD). SNPs ere …

Integrated Analysis Of Lncrna And Mrna Expression In Rainbow Trout Families Showing Variation In Muscle Growth And Fillet Quality Traits, Ali Ali, Rafet Al-Tobasei, Brett Kenney, Timothy D. Leeds, Mohamed Salem

Faculty & Staff Scholarship

Muscle yield and quality traits are important for the aquaculture industry and consumers. Genetic selection for these traits is difficult because they are polygenic and result from multifactorial interactions. To study the genetic architecture of these traits, phenotypic characterization of whole body weight (WBW), muscle yield, fat content, shear force and whiteness were measured in ~500 fish representing 98 families from a growth-selected line. RNA-Seq was used to sequence the muscle transcriptome of different families exhibiting divergent phenotypes for each trait. We have identified 240 and 1,280 differentially expressed (DE) protein-coding genes and long noncoding RNAs (lncRNAs), respectively, in fish …

Adverse Event Detection By Integrating Twitter Data And Vaers, Junxiang Wang, Liang Zhao, Yanfang Ye, Yuji Zhang

Faculty & Staff Scholarship

Background: Vaccinehasbeenoneofthemostsuccessfulpublichealthinterventionstodate.However,vaccines are pharmaceutical products that carry risks so that many adverse events (AEs) are reported after receiving vaccines. Traditional adverse event reporting systems suffer from several crucial challenges including poor timeliness. This motivates increasing social media-based detection systems, which demonstrate successful capability to capture timely and prevalent disease information. Despite these advantages, social media-based AE detection suffers from serious challenges such as labor-intensive labeling and class imbalance of the training data.

Results: Totacklebothchallengesfromtraditionalreportingsystemsandsocialmedia,weexploittheircomplementary strength and develop a combinatorial classification approach by integrating Twitter data and the Vaccine Adverse Event Reporting System (VAERS) information aiming to identify potential AEs after …

Method Overtness, Forensic Autopsy, And The Evidentiary Suicide Note: A Multilevel National Violent Death Reporting System Analysis, Ian R. H. Rockett, Eric D. Caine, Steven Stack, Hilary S. Connery, Kurt B. Nolte, Christa L. Lilly, Ted R. Miller, Lewis S. Nelson, Sandra L. Putnam, Paul S. Nestadt, Haomiao Jia

Faculty & Staff Scholarship

Objective

Higher prevalence of suicide notes could signify more conservatism in accounting and greater proneness to undercounting of suicide by method. We tested two hypotheses: (1) an evidentiary suicide note is more likely to accompany suicides by drug-intoxication and by other poisoning, as less violent and less forensically overt methods, than suicides by firearm and hanging/suffocation; and (2) performance of a forensic autopsy attenuates any observed association between overtness of method and the reported presence of a note.

Methods

This multilevel (individual/county), multivariable analysis employed a generalized linear mixed model (GLMM). Representing the 17 states participating in the United States …

The Complementary Health Approaches For Pain Survey (Chaps): Validity Testing And Characteristics Of A Rural Population With Pain, Termeh Feinberg, Dina L. Jones, Christa Lilly, Amna Umer, Kim Innes

Faculty & Staff Scholarship

Objectives

Little is known about patterns and correlates of Complementary Health Approaches (CHAs) in chronic pain populations, particularly in rural, underserved communities. This article details the development and implementation of a new survey instrument designed to address this gap, the Complementary Health Approaches for Pain Survey (CHAPS).

Design

Following pilot-testing using pre-specified criteria to assess quality and comprehension in our target population, and after feedback regarding face-validity from content experts and stakeholders, the final cross-sectional self-report survey required 10–12 minutes to com- plete. It contained 69 demographic, lifestyle and health-related factors, and utilized a Trans- theoretical Model (TTM) underpinning to …

Subclinical Atherosclerosis, Cardiovascular Health, And Disease Risk: Is There A Case For The Cardiovascular Health Index In The Primary Prevention Population?, Sarah S. Singh, Courtney S. Pilkerton, Carl D. Shrader Jr, Stephanie J. Frisbee

Faculty & Staff Scholarship

Background: Current primary prevention guidelines for cardiovascular disease (CVD) prioritize risk identification, risk stratification using clinical and risk scores, and risk reduction with lifestyle interventions and pharmacotherapy. Subclinical atherosclerosis is an early indicator of atherosclerotic burden and its timely recognition can slow or prevent progression to CVD. Thus, individuals with subclinical atherosclerosis are a priority for primary prevention. This study takes a practical approach to answering a challenge commonly faced by primary care practitioners: in patients with no known CVD, how can individuals likely to have subclinical atherosclerosis be easily identified using existing clinical data and/or information provided by the …

Brief Report: Exercise And Blood Pressure In Older Adults—An Updated Look, George A. Kelley, Kristi S. Kelley

Faculty & Staff Scholarship

Background/Objectives. Raised blood pressure is a major problem in older adults. Using a random-effects model, a recent meta- analysis reported statistically significant reductions in both resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) as a result of aerobic, resistance, and combined aerobic and resistance exercise in adults ≥65 years. To provide more objective information regarding this nonpharmacologic approach, this study applied more robust methods to this data. Design. Meta-analysis of 41 randomized controlled trials representing 96 groups (52 exercise; 44 control). Setting. Any location where a randomized controlled trial could be conducted. Participants. Adults ≥65 years. Intervention. Trials …

Brief Report: Exercise And Anxiety In Adults With Arthritis And Other Rheumatic Diseases: Support For Evidential Value, George A. Kelley, Kristi S. Kelley, Leigh F. Callahan

Faculty & Staff Scholarship

Objective. Given the high prevalence of anxiety in adults with arthritis and other rheumatic diseases (AORD) and the subsequent need for interventions to reduce anxiety, this brief report sought to determine if evidential value exists to support the role of exercise for reducing anxiety in adults with AORD. Methods. Utilizing data from a prior meta-analysis, a recently developed approach, P- curve, was used to determine evidential value by assessing for publication bias and p-hacking. Binomial tests as well as the more robust Stouffer’s test were used to examine for evidential value. To examine the influence of selected studies on p-curve …