Biostatistics Commons^™

Ratio And Difference Of Average Hazard With Survival Weight: New Measures To Quantify Survival Benefit Of New Therapy, Hajime Uno, Miki Horiguchi

Harvard University Biostatistics Working Paper Series

The hazard ratio (HR) has been the most popular measure to quantify the magnitude of treatment effect on time-to-event outcomes in clinical research. However, the HR estimated by Cox's method has several drawbacks. One major issue is that there is no clear interpretation when the proportional hazards (PH) assumption does not hold, because it is affected by study-specific censoring time distribution in non-PH cases. Another major issue is that the lack of a group-specific absolute hazard value in each group obscures the clinical significance of the magnitude of the treatment effect. Given these, we propose average hazard with survival weight …

Maternal Diet In Pregnancy And Child’S Respiratory Outcomes: An Individual Participant Data Meta-Analysis Of 18 000 Children, Sara M. Mensink-Bout, Evelien R. Van Meel, Johan C. De Jongste, Isabella Annesi-Maesano, Adrien M. Aubert, Jonathan Y. Bernard, Ling-Wei Chen, Cyrus Cooper, Sarah R. Crozier, Wojciech Hanke, Nicholas C. Harvey, James R. Hébert Scd, Barbara Heude, Joanna Jerzynska, Cecily C. Kelleher, John Mehegan, Fionnuala M. Mcauliffe, Catherine M. Phillips, Kinga Polanska, Caroline L. Relton, Nitin Shivappa Mbbs, Mph, Ph.D., Matthew Suderman, Vincent W.V. Jaddoe, Liesbeth Duijts

Faculty Publications

Rationale Severe fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health.

Methods We performed an individual participant meta-analysis among 18 326 mother–child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using …

Hiv Infection And The Risk Of World Health Organization-Defined Sudden Cardiac Death, Matthew S. Freiberg, Meredith S. Duncan, Charles Alcorn, Chung-Chou H. Chang, Suman Kundu, Asri Mumpuni, Emily K. Smith, Sarah Loch, Annie Bedigian, Eric Vittinghoff, Kaku So-Armah, Priscilla Y. Hsue, Amy C. Justice, Zian H. Tseng

Biostatistics Faculty Publications

Background

People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear.

Methods and Results

This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral …

Associations Of Circulating Dimethylarginines With The Metabolic Syndrome In The Framingham Offspring Study, Ibrahim Musa Yola, Carlee Moser, Meredith S. Duncan, Edzard Schwedhelm, Dorothee Atzler, Renke Maas, Juliane Hannemann, Rainer H. Böger, Ramachandran S. Vasan, Vanessa Xanthakis

Biostatistics Faculty Publications

BACKGROUND: Circulating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively.

METHODS: We related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study …

A Computational Study Of Genotype-Phenotype Mutation Patterns, Kamaludin Dingle, Omar Tawfik, Ahmed Aldabagh

Undergraduate Research Symposium

Understanding properties of genotype-phenotype maps is important for understanding biology and evolution. In this project we make a computational study of the statistical effects of genetic mutations, in particular computing the probabilities of each phenotype transitioning to any other phenotype. We also investigate the importance of the local phenotypic environment of a single genotype, and its role in determining mutation transition probabilities. We use HP protein folding, RNA structure, and a simplified GRN matrix model to study these questions.

Prevalence, Awareness, And Control Of Hypertension Among Bangladeshi Adults: An Analysis Of Demographic And Health Survey 2017-18, Gulam Muhammed Al Kibria, Rajat Das Gupta Ph.D., Jannatun Nayeem

Faculty Publications

Background

The prevalence of hypertension is increasing in Bangladesh, however, few recent studies investigated the proportion of people and factors associated with prevalence, awareness, and control of this condition in this country. This study investigated these among Bangladeshi adults.

Methods

Using Bangladesh Demographic and Health Survey 2017–18 data, a cross-sectional study was conducted. Multilevel logistic regression analysis was employed after descriptive analysis and prevalence estimation.

Results

Among 12,926 persons (mean age: 40 years, 57% women), the prevalence of hypertension was 27.4% (n = 3551), it was 28.4 and 26.2% among females and males, respectively. Among hypertensive people, about 42.4% …

The Relationship Of Delivery Method, Birth Weight And Race On Infant Mortality, Anjie Adeyemo

Symposium of Student Scholars

Infant mortality is defined as the number of deaths per 1000 births. The U.S. infant mortality rate in 2014 was reported as 5.8 deaths per 1000 births which is very high compared to other countries such as Japan where the rate 2.1 deaths per 1000 births. The leading causes of infant death are congenital malformations, SIDS, low birthweight, pre-term births and maternal complications. For this project, I will analyze birthweight in addition to other factors related to infant death. My research aims to see how the factors of delivery method, birthweight, and race influence infant mortality to see how it …

Anti-Vaxxers: Parents Fighting Science, Katie West

Symposium of Student Scholars

Immunizing children helps protect the health of our community, especially those people who cannot be immunized. Yet, since 1996 after a study was released that linked autism to vaccinations, there has been a trend of parents refusing to vaccinate their children. What are the demographics of the parents who believe their children are better off without vaccines? By knowing where these parents live and what decisions they make for their children’s education, counties and medical professionals can provide education and address their concerns.

My research involves data on 116,141 kindergarten classes from 2000-2015 in California. The two vaccine exemption options …

Determining Malignancy: Can Mammogram Results Help Predict The Diagnosis Of Breast Tumors?, Taylor Behrens

Symposium of Student Scholars

Even with advancements in treatment and preventative care, breast cancer remains an epidemic claiming more than 40,000 American male and female lives each year. The mammogram dataset that I am analyzing was initially complied in the early 1990s by a team from the University of Wisconsin - Madison. Past research diagnoses breast cancer from fine-needle aspirates. My research focuses on predicting whether we can determine breast cancer diagnoses without the use of invasive procedures and, in particular, whether we can predict breast cancer based on mammogram data. Do measures of gray-scale texture, radius, concavity, perimeter, compactness, area, and smoothness of …

Accidental Overdoses: Insights To Aid In Prevention, Annabel Nganga

Symposium of Student Scholars

Having lost a friend six years ago to an accidental cocaine overdose, I am very passionate about spreading awareness of accidental drug overdoses that have affected thousands of families countrywide. According to past research, deaths resulting from opiates specifically have been on the rise, and a significant number of deaths in the United States for those below fifty years are caused by drug overdoses. Data exists indicating which states have more overdoses. The data set I will be using includes variables on race, sex, age, drug with which person overdosed, location of the overdose, ultimate cause of death and year …

Community Level Physiological Profiling Of The Longleaf Pine Savannah Microbiome, Gavin Treadaway

Symposium of Student Scholars

Soil microorganisms secrete chemicals into their surroundings, which the root system will uptake and in return release root exudates, which usually consist of low-molecular-weight organic compounds. These root exudates behave as signaling molecules and substrates for microorganisms to recruit beneficial soil bacteria to the plant root system, which will provide the plants with immunity to foliar diseases and pathogen infection. Studies have shown that bacteria on the root surface can protect aerial sections of the plant by promoting induced systemic resistance, a mechanism of increasing physical or chemical barriers of the plant.

The longleaf pine is an endangered species of …

Accelerating The Provision Of Safe Water Supply In Urban And Rural Areas Of Indonesia, Sumengen Sutomo, Salord Sagala, Bebi Sutomo, Sri Winarti, Gelant Sanjaya

Kesmas

Over the past 100 years, the provision of a safe water supply to drink in Indonesia has been slowly progressed with low coverage. The majority of the population does not have access to safe water. Morbidity and mortality of water-related diseases, including diarrhea, are very high. The provision of safe water is not a technological issue but good water management that comprises content, institutional, and communication layer. This paper provided information for strategic and operational decisions to accelerate the provision of safe water services in urban and rural areas. Benchmarking good water management with the characteristics of the water supply …

Association Between Self-Reported Fatigue And Sarcopenia Measures Among Elderly In Selangor, Malaysia, Maria Justine, Aliff Latir, Nadhirah Noor, Angelbeth Joanny, Izzaty Iskandar, Maisarah Sakinah Amirul Faizi, Dzulhelmi Edinan

Kesmas

The association between fatigue and sarcopenia is not well understood, therefore, this study aimed to compare the sarcopenia measures among elderly with mild and severe fatigue and to determine whether fatigue severity is associated with sarcopenia measures. This was a cross-sectional study conducted on201 elderly (age = 68.45±6.30 years). The elderly was classified into either mild or severe fatigue based on the Fatigue Severity Scale (FSS), meanwhile, sarcopenia measures include SARC-F score, muscle mass (ASM/height2), calf circumference (CC), upper (handgrip) and lower limb muscle strength, as well as physical performance (gait speed). Data were analyzed using independent t-tests and logistic …

A Randomized Controlled Trial To Determine Whether Beta-Hydroxy-Beta-Methylbutyrate And/Or Eicosapentaenoic Acid Improves Diaphragm And Quadriceps Strength In Critically Ill Mechanically Ventilated Patients, Gerald S. Supinski, Paul F. Netzel, Philip M. Westgate, Elizabeth A. Schroder, Lin Wang, Leigh Ann Callahan

Internal Medicine Faculty Publications

BACKGROUND: Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients.

METHODS: Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski, Zhuwei Zhang, J. Robert Mccorkle, Jodi M. Dejohn, Chi Wang, Rachel W. Miller, Holly H. Gallion, Charles S. Dietrich Iii, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC₅₀ values …

Chagas Disease In Hiv-Infected Patients: It’S Time To Consider The Diagnosis, Melissa Nolan Ph.D., Mph, Natasha S. Hochberg

Faculty Publications

No abstract provided.

Effect Of An Antenatal Lifestyle Intervention On Dietary Inflammatory Index And Its Associations With Maternal And Fetal Outcomes: A Secondary Analysis Of The Pears Trial, Sarah Louise Killen, Catherine M. Phillips, Anna Delahunt, Cara A. Yelverton, Nitin Shivappa Mbbs, Mph, Ph.D., James Hébert Scd, Maria A. Kennelly, Martina Cronin, John Mehegan, Fionnuala M. Mcauliffe

Faculty Publications

We investigated the effect of an antenatal lifestyle intervention of a low-glycaemic index (GI) diet and physical activity on energy-adjusted dietary inflammatory index (E-DIITM) and explored its relationship with maternal and child health in women with overweight and obesity. This was a secondary analysis of 434 mother−child pairs from the Pregnancy Exercise and Nutrition Study (PEARS) trial in Dublin, Ireland. E-DII^TM scores were calculated for early (10–16 weeks) and late (28 weeks) pregnancy. Outcomes included lipids, inflammation markers, insulin resistance, mode of delivery, infant size, pre-eclampsia, and gestational diabetes. T-tests were used to assess changes in E-DII^TM. …

Urinary Bile Acid Indices As Prognostic Biomarkers For The Complications Of Liver Diseases, Wenkuan Li

Theses & Dissertations

Hepatobilary diseases cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may lead to an unfavorable prognosis. In this study, we compared the urinary BA profile in 257 patients with hepatobilary diseases during a 7-year follow-up period. We investigated the use of the urinary BA profile to develop logistic regression models to predict the prognosis of hepatobiliary diseases in terms of developing disease-related complications, especially for ascites. The urinary BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. All patients had high …

Effect Sizes And Intra-Cluster Correlation Coefficients Measured From The Green Dot High School Study For Guiding Sample Size Calculations When Designing Future Violence Prevention Cluster Randomized Trials In School Settings, Md. Tofial Azam, Heather M. Bush, Ann L. Coker, Philip M. Westgate

Biostatistics Faculty Publications

Purpose: Cluster randomized controlled trials (cRCTs) are popular in school-based research designs where schools are randomized to different trial arms. To help guide future study planning, we provide information on anticipated effect sizes and intra-cluster correlation coefficients (ICCs), as well as school sizes, for dating violence (DV) and interpersonal violence outcomes based on data from a cRCT which evaluated the bystander-based violence intervention ‘Green Dot’.

Methods: We utilized data from 25 schools from the Green Dot High School study. Effect size and ICC values corresponding to dating and interpersonal violence outcomes are obtained from linear mixed effect models. We …

Lapatinib And Poziotinib Overcome Abcb1-Mediated Paclitaxel Resistance In Ovarian Cancer, J. Robert Mccorkle, Justin W. Gorski, Jinpeng Liu, Mckayla J. Riggs, Anthony B. Mcdowell Jr., Nan Lin, Chi Wang, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Conventional frontline treatment for ovarian cancer consists of successive chemotherapy cycles of paclitaxel and platinum. Despite the initial favorable responses for most patients, chemotherapy resistance frequently leads to recurrent or refractory disease. New treatment strategies that circumvent or prevent mechanisms of resistance are needed to improve ovarian cancer therapy. We established in vitro paclitaxel-resistant ovarian cancer cell line and organoid models. Gene expression differences in resistant and sensitive lines were analyzed by RNA sequencing. We manipulated candidate genes associated with paclitaxel resistance using siRNA or small molecule inhibitors, and then screened the cells for paclitaxel sensitivity using cell viability assays. …

Associations Between Fasting Duration, Timing Of First And Last Meal, And Cardiometabolic Endpoints In The National Health And Nutrition Examination Survey, Michael David Wirth, Longgang Zhao, Gabrielle Turner-Mcgrievy, Andrew Ortaglia

Faculty Publications

Background: Research indicates potential cardiometabolic benefits of energy consumption earlier in the day. This study examined the association between fasting duration, timing of first and last meals, and cardiometabolic endpoints using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Cross-sectional data from NHANES (2005–2016) were utilized. Diet was obtained from one to two 24-h dietary recalls to characterize nighttime fasting duration and timing of first and last meal. Blood samples were obtained for characterization of C-reactive protein (CRP); glycosylated hemoglobin (HbA1c %); insulin; glucose; and high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol. Survey design procedures …

Conditional And Marginal Imputation Models For Multilevel Data, Gang Liu

Legacy Theses & Dissertations (2009 - 2024)

This dissertation study extends sequential hierarchical regression imputation (SHRIMP) methods to multilevel datasets with three levels of nesting and proposes a marginal method based on marginalized multilevel model (MMM) framework. Specifically, the proposed model consists of two levels such that the first level relates the marginal mean of responses with covariates through a generalized regression model and the second level includes subject specific random effects within the same generalized regression model. To draw the inference on the population-averaged or subject-specified coefficients, the hierarchical regression and/or MMM is applied as the imputation and estimation models. We employ Markov Chain Monte Carlo …

Impact Of Inconsistent Imputation Models In Mediation Analysis, Bo Ye

Legacy Theses & Dissertations (2009 - 2024)

In this dissertation, we study the impact of inconsistent imputation methods in mediation analysis and its application. We present the study in three papers.

Predictive Modeling Of Clinical Outcomes For Hospitalized Covid-19 Patients Utilizing Cytof And Clinical Data., Onajia Stubblefield

Electronic Theses and Dissertations

In December 2019, an outbreak of a novel coronavirus initiated a global pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes the disease coronavirus disease 2019 (COVID-19). Symptoms of infection with COVID-19 vary widely between individuals. While some infected individuals are asymptomatic, others need more extensive care and require hospitalization. Indeed, the COVID-19 pandemic was characterized by a shortage of hospital beds which presented additional complications in providing adequate care for patients. In this study, we used a combination of T cell population data collected from mass cytometry analysis and clinical markers to form a predictive …

Bayesian Variable Selection Strategies In Longitudinal Mixture Models And Categorical Regression Problems., Md Nazir Uddin

Electronic Theses and Dissertations

In this work, we seek to develop a variable screening and selection method for Bayesian mixture models with longitudinal data. To develop this method, we consider data from the Health and Retirement Survey (HRS) conducted by University of Michigan. Considering yearly out-of-pocket expenditures as the longitudinal response variable, we consider a Bayesian mixture model with $K$ components. The data consist of a large collection of demographic, financial, and health-related baseline characteristics, and we wish to find a subset of these that impact cluster membership. An initial mixture model without any cluster-level predictors is fit to the data through an MCMC …

Identification And Characterization Of De Novo Germline Tp53 Mutation Carriers In Families With Li-Fraumeni Syndrome, Carlos C. Vera Recio

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is an inherited cancer syndrome caused by a deleterious mutation in TP53. An estimated 48% of LFS patients present due to a de novo mutation (DNM) in TP53. The knowledge of DNM status, DNM or familial mutation (FM), of an LFS patient requires genetic testing of both parents which is often inaccessible, making de novo LFS patients difficult to study. Famdenovo.TP53 is a Mendelian Risk prediction model used to predict DNM status of TP53 mutation carriers based on the cancer-family history and several input genetic parameters, including disease-gene penetrance. The good predictive performance of Famdenovo.TP53 was demonstrated …

Predictors Of Chronic Opioid Therapy In Medicaid Beneficiaries With Hiv Who Initiated Antiretroviral Therapy, Gyeon Oh, Emily S. Brouwer, Erin L. Abner, David W. Fardo, Patricia R. Freeman, Chris Delcher, Daniela C. Moga

Epidemiology and Environmental Health Faculty Publications

The factors associated with chronic opioid therapy (COT) in patients with HIV is understudied. Using Medicaid data (2002-2009), this retrospective cohort study examines COT in beneficiaries with HIV who initiated standard combination anti-retroviral therapy (cART). We used generalized estimating equations on logistic regression models with backward selection to identify significant predictors of COT initiation. COT was initiated among 1014 out of 9615 beneficiaries with HIV (male: 10.4%; female: 10.7%). Those with older age, any malignancy, Hepatitis C infection, back pain, arthritis, neuropathy pain, substance use disorder, polypharmacy, (use of) benzodiazepines, gabapentinoids, antidepressants, and prior opioid therapies were positively associated with …

Treatment Patterns And Outcomes In Elderly Patients With Newly Diagnosed Multiple Myeloma: Results From The Connect® Mm Registry, Hans C. Lee, Sikander Ailawadhi, Cristina J. Gasparetto, Sundar Jagannath, Robert M. Rifkin, Brian G.M. Durie, Mohit Narang, Howard R. Terebelo, Kathleen Toomey, James W. Hardin Ph.D., Lynne Wagner, James L. Omel, Mazaher Dhalla, Liang Liu, Prashant Joshi, Rafat Abonour

Faculty Publications

No abstract provided.

Causal Mediation Analysis With Multiple Time-Varying Mediators, An-Shun Tai, Sheng-Hsuan Lin, Yu-Cheng Chu, Tsung Yu, Milo A. Puhan, Tyler Vanderweele

Harvard University Biostatistics Working Paper Series

In longitudinal studies with time-varying exposures and mediators, the mediational g-formula is an important method for the assessment of direct and indirect effects. However, current methodologies based on the mediational g-formula can deal with only one mediator. This limitation makes these methodologies inapplicable to many scenarios. Hence, we develop a novel methodology by extending the mediational g-formula to cover cases with multiple time-varying mediators. We formulate two variants of our approach that are each suited to a distinct set of assumptions and effect definitions and present nonparametric identification results of each variant. We further show how complex causal mechanisms (whose …

Clinical Outcomes Of Molecular Tumor Boards: A Systematic Review, Kara L. Larson, Bin Huang, Heidi L. Weiss, Pamela C. Hull, Philip M. Westgate, Rachel W. Miller, Susanne M. Arnold, Jill M. Kolesar

Markey Cancer Center Faculty Publications

PURPOSE: We conducted this systematic review to evaluate the clinical outcomes associated with molecular tumor board (MTB) review in patients with cancer.

METHODS: A systematic search of PubMed was performed to identify studies reporting clinical outcomes in patients with cancer who were reviewed by an MTB. To be included, studies had to report clinical outcomes, including clinical benefit, response, progression-free survival, or overall survival. Two reviewers independently selected studies and assessed quality with the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group or the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies depending on the type …