Digital Commons Network^™

Screening For Diabetes After Solid Organ Transplantation: A 10-Year Retrospective Study, Joseph A Spinner, Daniel H Leung, Sridevi Devaraj

Faculty, Staff and Students Publications

Post-transplantation diabetes mellitus (PTDM) is a common and important complication after solid organ transplantation, affecting long-term outcomes. Graft rejection, decreased patient survival, infections and increased cardiovascular risk are associated with PTDM and may arise from both transplant-related and traditional risk factors. Early screening for PTDM is crucial for early detection and management. Despite clinical guidelines recommending regular screening for PTDM, screening rates remain suboptimal. This retrospective study analyzes PTDM screening rates between January 2014-January 2024 among pediatric kidney, liver, heart and lung transplant recipients at a large quaternary academic pediatric transplant center. PTDM screening rates vary by organ type, with …

Adrenomedullin Overexpression Protects Mice From Experimental Bronchopulmonary Dysplasia And Associated Pulmonary Hypertension, Roberto Barrios, Madhulata Chauhan, Chandrasekhar Yallampalli, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) or BPD-PH is a lung disease of infants with significant morbidity. Adrenomedullin (Adm) is an angiogenic peptide that signals through calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2 (RAMP2). Adm deficiency potentiates hyperoxia-induced experimental BPD-PH in mice; however, whether Adm overexpression can mitigate this lung disease is unclear. Thus, we tested the hypothesis that Adm overexpression attenuates hyperoxia (HO)-induced murine experimental BPD-PH by using a novel transgenic mouse that overexpresses Adm globally (Admhi/hi mice). One-day-old Admhi/hi mice or their wild-type littermates (Adm+/+ mice) were exposed to …

Racial And Ethnic Associations With Interstitial Lung Disease And Healthcare Utilization In Patients With Systemic Sclerosis, Paul F Dellaripa, Gary Matthew Hunninghake, David W Bates

Faculty, Staff and Students Publications

Objective: Racial and ethnic differences in presentation and outcomes have been reported in SSc and SSc-interstitial lung disease (ILD). However, prior studies have limited diversity. We aim to evaluate if there are racial/ethnic differences associated with ILD, time intervals between SSc and ILD, and emergency department (ED) visit or hospitalization rates.

Methods: Clinical and sociodemographic variables were extracted for 756 patients with SSc from longitudinal health records in an integrated health-system. Logistic regression models analysed the association of covariates with ILD and age at SSc-ILD. Healthcare outcomes were analysed with complementary log-log regression models.

Results: Overall, 33.7% of patients in …

Frequency, Duration, And Cost Of Pulmonary Exacerbations Among Patients With Bronchiectasis, Reina Rau, John Fastenau, Joseph Feliciano, Sunjay R Devarajan

Faculty, Staff and Students Publications

Background: In administrative claims database studies of bronchiectasis, pulmonary exacerbations are usually defined using a fixed period for their start and end, which prevents assessment of exacerbation duration and thereby limits assessment of exacerbation characteristics. Here, we applied a novel cost-based algorithm to characterize exacerbations.

Methods: This cohort study used the Merative MarketScan Commercial Claims and Encounters database, 1-Jan-2016 to 31-Dec-2022. Patients ≥18 years with bronchiectasis (≥2 outpatient or ≥1 inpatient claim with bronchiectasis; no cystic fibrosis) had 12 months of continuous enrollment before (baseline) and ≥12 months after (follow-up) index (first bronchiectasis claim). Cost-based exacerbations were identified by compound …

Factors Associated With Child Protective Services Referrals In Young Children With Isolated Skull Fractures, Tagrid M Ruiz-Maldonado, Daniel M Lindberg, Angela Bachim, Lori Frasier, Terra N Frazier, Nancy S Harper, Sara E Kruczek, Farah Brink, Jennifer E Wolford, Jan Leonard, M Katherine Henry

Faculty, Staff and Students Publications

Objective: Many young children with isolated skull fractures are referred to child protective services (CPS) despite being assessed to have a low likelihood of abuse. We sought to identify factors associated with CPS referrals in this population and to quantify hospital-level variation.

Methods: We performed a multicenter retrospective cross-sectional study of children < 2 years with skull fractures with or without a small underlying intracranial hemorrhage (ICH) and no additional injuries undergoing a child abuse pediatrics (CAP) subspecialty evaluation. We explored associations between demographic factors, clinical characteristics, psychosocial risk factors, and hospital site with CPS referral status. We performed multivariable logistic regression, adjusting for transfer status and all significant covariates from unadjusted analyses. We utilized marginal standardization to calculate the estimated probability of CPS referrals at each site, adjusting for all factors in the final model.

Results: Of 528 children, 303 (57.4%) were referred to CPS, with 86.5% referred prior to CAP consultation. In multivariable logistic regression, presence of psychosocial risk factors (OR 4.00; 95% CI 2.25, 7.11), in-person CAP consult (OR 3.93; 1.61, 9.62), inflicted or no trauma history provided (OR 6.15; 3.30, …

Fibroblasts Are The Primary Contributors To A Disrupted Micro-Environment In End-Stage Pediatric Hypertrophic Cardiomyopathy, Chang-Ru Tsai, Iki A Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.

Methods: We performed single-nucleus RNA sequencing (snRNA-seq) on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.

Results: We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes …

Real-World Adherence And Effectiveness Of Inclisiran In Lowering Ldl-C: Results From 1 Year Of Follow-Up, Bruce J Iteld, Harvey Serota, Xiaoli Niu, Sean Mcelligott, Kelly E Hanna, Tyler J Varisco

Faculty, Staff and Students Publications

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is a global health concern. Reducing low-density lipoprotein cholesterol (LDL-C) is critical in ASCVD prevention and treatment. Inclisiran, a novel RNA therapeutic agent, offers a promising solution by lowering LDL-C with twice-yearly dosing after an initial and 3-month dose. The study objective was to evaluate adherence to inclisiran and its lipid-lowering effectiveness over a year of treatment.

Methods: This retrospective cohort study involved patients over 18 years old with ASCVD or hyperlipidemia who initiated inclisiran between January 1, 2022, and May 17, 2023, in US outpatient clinics. LDL-C reduction was evaluated in patients with ≥ …

A Deep Generative Model For Deciphering Cellular Dynamics And In Silico Drug Discovery In Complex Diseases, Geremy Clair, Aurelien Justet, Farida Ahangari, Xiting Yan, Paul Hansen, Marianne Carlon, Emanuela Cortesi, Marie Vermant, Robin Vos, Laurens J De Sadeleer, Ivan O Rosas, Ricardo Pineda, John Sembrat, Melanie Königshoff, John E Mcdonough, Bart M Vanaudenaerde, Wim A Wuyts, Naftali Kaminski, Jun Ding

Faculty, Staff and Students Publications

Human diseases are characterized by intricate cellular dynamics. Single-cell transcriptomics provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in silico drug interventions. Here we introduce UNAGI, a deep generative neural network tailored to analyse time-series single-cell transcriptomic data. This tool captures the complex cellular dynamics underlying disease progression, enhancing drug perturbation modelling and screening. When applied to a dataset from patients with idiopathic pulmonary fibrosis, UNAGI learns disease-informed cell embeddings that sharpen our understanding of disease progression, leading to the identification of potential therapeutic drug candidates. Validation using proteomics reveals …

The Neonatal Gut Microbiome In Health And Disease

Faculty, Staff and Students Publications

No abstract provided.

A Review Of The Efficacy Of Complementary And Alternative Medicines In Managing Dermatologic Infectious Diseases, Ida Orengo, Theodore Rosen

Faculty, Staff and Students Publications

Dermatologic infections, particularly fungal and viral, are globally prevalent and often lead patients to seek complementary and alternative medicines (CAMs). This review critically evaluates 17 studies investigating CAM efficacy in treating dermatologic infectious diseases, focusing on those evaluated in randomized controlled trials (RCTs). Tea tree oil shows modest benefit for fungal infections such as tinea pedis and onychomycosis, though studies are limited by poor blinding and dropout rates. For herpes simplex virus (HSV), propolis and Melissa officinalis demonstrate potential antiviral effects, but findings are limited by subjective outcomes and industry sponsorship. Green tea extract (polyphenon E) shows efficacy in treating …

Healthy Aging And Aging-Related Kidney Diseases: Lessons From Centenarians, Minami Matsumoto, Ryo Yamada, Takahisa Yoshikawa, Motoko Yanagita

Faculty, Staff and Students Publications

The world's population is aging, and age-related diseases such as neurodegenerative, cardiovascular, and metabolic disorders are rapidly increasing. The field of nephrology is expected to be profoundly influenced by the demographic trend toward increased life expectancy. Consequently, promoting healthy aging has emerged as a critical priority for both individuals and society. Centenarians (those who have reached the age of 100) exemplify exceptional longevity and are regarded as a model of healthy aging. They are distinguished by a notable resistance to risk factors commonly associated with cardiovascular diseases, such as diabetes and dyslipidemia. Remarkably, although centenarians exhibit a high prevalence of …

Assessing The Impact Of Maternal Oral Health On The Risk Of Adverse Birth Outcomes, May Amr Salama

Health Services Research Dissertations

Preterm birth (PTB) and low birth weight (LBW) are leading causes of neonatal morbidity and mortality. Maternal periodontal disease (PD) has been increasingly linked to these adverse birth outcomes (ABOs), yet questions about causality and treatment effectiveness persist due to study design heterogeneity and potential unmeasured confounding. These gaps hinder the development of clear clinical and public health guidelines. This dissertation addresses these gaps through three interconnected studies assessing the relationship between maternal oral health and ABOs.

The first study employed a meta-epidemiological analysis of 62 original studies from nine systematic reviews to evaluate the impact of unmeasured confounding on …

Challenges And Opportunities In Multidisciplinary Supportive Care During Radiotherapy For Head And Neck Cancer, Jeffrey C Shogan, Anna Lee, Yvonne M Mowery

Faculty, Staff and Student Publications

No abstract provided.

Individualizing Nsaid Therapy In Axial Spondyloarthritis: N-Of-1 Trials With Bayesian Analysis, Mark C Hwang, Seokhun Kim, Shervin Assassi, Reyna Chavez, Joyce Samuel, Charles Green, Jon Tyson, John Reveille

Faculty, Staff and Student Publications

Objective: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the spine and sacroiliac joints. NSAIDs are first-line therapy, but individual responses vary widely. We evaluated the efficacy and patient preference of three NSAIDs (celecoxib, meloxicam and naproxen) through Bayesian N-of-1 clinical trials to optimize axSpA management.

Methods: We conducted N-of-1 trials with 42 patients meeting ASAS criteria for axSpA. Each patient was asked to complete two cycles of randomized double-blind crossover comparisons of the three NSAIDs, each for 4 weeks. The primary end point was the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS). Bayesian analysis assessed …

The Pneumonia Challenge: Time To End The Global Neglect, Catia Cillóniz, Markus Fally, Scott Evans, Guinevere Dy-Agra, Pneumo-Strategy Group

Faculty, Staff and Student Publications

No abstract provided.

Activity-Dependent Transit Dose Assessment In 192ir High-Dose-Rate Brachytherapy Surface Applicator Using Gafchromictm Ebt4 Film, Daniel Liu, Emily Draeger, Christopher J Tien, Fada Guan

Faculty, Staff and Student Publications

Purpose: To characterize the newly released GafChromicTM EBT4 film for transit dose measurement in high-dose rate brachytherapy (HDR-BT) surface applicators and to systematically investigate the relationship between transit dose and 192Ir source activity.

Methods: EBT4 film was used to measure dose at 3 mm depth from a horizontally oriented Leipzig-style surface applicator connected to a 192Ir HDR-BT remote afterloading unit. Transit dose was systematically characterized across eight different source activities ranging from 3.372 to 9.716 Ci (13,724 U to 39,544 U) using measurements with seven nominal dwell times (5-100 seconds, scaled to 10 Ci (40,700 U)). Transit dose was derived …

Normalization Of Temperature Effects For Quality Assurance Of Quantitative Prostate Apparent Diffusion Coefficient Imaging Across Multiple Sites, Ken-Pin Hwang, Joshua Yung, R Jason Stafford, Caroline Chung, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Background: Apparent Diffusion Coefficient (ADC) as measured by diffusion weighted imaging is known to negatively correlate with prostate tumor aggressiveness. Heterogeneity in system and protocol performance causes potential variability in ADC acquired across a large scanner network, prompting a need to evaluate quantitative ADC from a prostate-specific MR diffusion protocol as part of quality assurance (QA). Due to the temperature dependence of ADC, repeatability and reproducibility assessments typically require phantoms to maintain a temperature of 0°C, imposing a considerable burden when assessing large numbers of scanners.

Purpose: To develop a QA procedure at room temperature for assessing the reproducibility of …

Loss Of The Lysosomal Protein Cln3 Triggers C-Abl-Dependent Yap1 Pro-Apoptotic Signaling, Neuza Domingues, Alessia Calcagni', Sofia Freire, Joana Pires, Ricardo Casqueiro, Ivan L Salazar, Niculin Joachim Herz, Tuong Huynh, Katarzyna Wieciorek, Tiago Fleming Outeiro, Henrique Girão, Ira Milosevic, Andrea Ballabio, Nuno Raimundo

Duncan NRI Faculty and Staff Publications

Batten disease is characterized by early-onset blindness, juvenile dementia and death within the second decade of life. The most common genetic cause are mutations in CLN3, encoding a lysosomal protein. Currently, no therapies targeting disease progression are available, largely because its molecular mechanisms remain poorly understood. To understand how CLN3 loss affects cellular signaling, we generated human CLN3 knock-out cells (CLN3-KO) and performed RNA-seq analysis. Our multi-dimensional analysis reveals the transcriptional regulator YAP1 as a key factor in remodeling the transcriptome in CLN3-KO cells. YAP1-mediated pro-apoptotic signaling is also increased as a consequence of CLN3 functional loss in retinal pigment …

From Bladder To Brain: How You Know When It’S Time To Go, Anne M J Verstegen, Kara L Marshall

Duncan NRI Faculty and Staff Publications

The decision to urinate relies on assessing bladder fullness and context to determine an appropriate time and place to go. Any disruption in this interoceptive process results in frequent and sometimes debilitating consequences in daily life. Recent work has uncovered key pathways and brain regions that contribute to the sense of bladder stretch and the control of urinary reflexes, but many open questions remain. Here, we review the known mechanisms that convey sensory information from the bladder to the brain and back down again, and we highlight the knowledge gaps and opportunities for better understanding this system, which will be …

Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly

Center on Aging Staff Publications

Objective: We sought to evaluate the relationship between neighborhood-level deprivation and perinatal outcomes, particularly preterm birth, as well as COVID-19 outcomes among pregnant patients during the early pandemic.

Methods: We performed a secondary analysis of a prospective longitudinal cohort study that investigated the impact of prenatal COVID-19 exposure on perinatal outcomes. Pregnant patients were recruited 12/23/20-7/18/22 and serially assessed for COVID-19 exposure during pregnancy, with serum antibody testing, electronic medical record review, and patient report. For this secondary analysis, address at the time of delivery was used to categorize patients into low ADI (≤50th percentile Area Deprivation Index, indicating low …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Profiling The Preclinical Pharmacokinetics And Biodistribution Of A Platinum(Iv)-Based Oxaliplatin Prodrug Oxalitex And Their Significance To Antitumor Response, Guangan He, Gregory D Thiabaud, Kathryn A Shelton, Luke J Segura, Jonathan F Arambula, Rick A Finch

Faculty, Staff and Student Publications

OxaliTEX (NOVO-111) is a novel gadolinium(III) texaphyrin-platinum(IV) complex that is under development for clinical trials. It was designed as a prodrug of oxaliplatin (1,2-diaminocyclohexane-platinum(II) oxalate) tethered to a tumor-affinic texaphyrin moiety to improve drug delivery to the tumor. However, oxaliTEX was not only more effective as an antitumor agent but also better tolerated in mice. To appreciate this higher therapeutic index and advance its preclinical development, studies were undertaken to profile its plasma pharmacokinetics, distribution to tumor and normal tissues, and pharmacodynamics of the p53/p21 molecular pathway. Nude mice, with or without a subcutaneous colorectal HCT-116 xenograft harboring a phenotypically …

Standardized Research Electronic Cigarette Acceptability Among Adult Men And Women Who Smoke Combustible Cigarettes, Jason D Robinson, Yong Cui, Maher Karam-Hage, Janice A Blalock, Sanjay Shete, Peiying Yang

Faculty, Staff and Student Publications

Objective: The U.S. electronic cigarette marketplace is diverse and has evolved rapidly. To provide a standardized research model, the U.S. National Institute on Drug Abuse developed the Standard Research E-Cigarette (SREC). This study characterized potential gender differences in product use, acceptability, reinforcement, and nicotine dependence symptoms when switching from combustible cigarettes (CCs) to nicotine and placebo SRECs.

Method: In total, 169 adults (82 women) who smoke were enrolled in this all-remote randomized double-blind crossover trial. During Weeks 1-2, participants used their usual brand cigarettes (UBCs). During Weeks 3-4 and 5-6, they were instructed to use the tobacco-flavored SREC (either nicotine …

Inhibiting Monocyte Migration Reduces Arterial Thrombosis And Facilitates Thrombolysis, Hee Jeong Jang, Jiwon Kim, Ha Kim, Taesu Kim, Jinyong Chung, Marvin Krohn-Grimberghe, Dawid Schellingerhout, Matthias Nahrendorf, Dong-Eog Kim

Faculty, Staff and Student Publications

Background: Monocytes contribute to the initiation and propagation of venous thrombosis. Little is known about the roles monocytes play in arterial thrombosis, the cause of stroke and myocardial infarction.

Methods: We investigated how CCR2 (CC chemokine receptor 2) knockout (-/-)-mediated monocyte deficiency affects platelet function, blood coagulation, thrombus volume, and thrombolytic susceptibility in 666 male mice with FeCl3-mediated carotid arterial thrombosis, including 365 C57BL/6 wild type (WT) mice, 295 CCR2-/- mice, and 6 CX3CR1-GFP (CX3C chemokine receptor 1-green fluorescent protein) mice.

Results: Intravital microscopy and flow cytometry showed that both neutrophils and monocytes were recruited to the acute arterial thrombus, …

Molecular And Immunological Features Associated With Long-Term Benefits In Metastatic Nsclc Patients Undergoing Immune Checkpoint Blockade, Pedro Rocha, Rafael Bach, Laura Masfarré, Sharia Hernandez, Nil Navarro-Gorro, Xavier Villanueva, Ignacio Sanchéz, Miguel Galindo, Raúl Del Rey-Vergara, Albert Iñañez, Beatriz Sanchéz-Espiridion, Wei Lu, Ariadna Acedo-Terrades, Pau Berenguer-Molins, Albert Sánchez-Font, Roberto Chalela, Victor Curull, Álvaro Taus, Max Hardy-Werbin, Mark Sausen, Andrew Georgiadis, James White, Jennifer B Jackson, Laura Moliner, Sergi Clavé, Beatriz Bellosillo, Ana Rovira, Ignacio Wistuba, Luisa M Solis Soto, Júlia Perera-Bel, Edurne Arriola

Faculty, Staff and Student Publications

Introduction: Immunotherapy is firmly established as a treatment regimen in various solid tumors, driven by its exceptional benefits in a selected group of patients. Despite widespread adoption of immune checkpoint blockade (ICB) across diverse solid tumors, the quest for a clinically informative biomarker for long-term benefit remains unmet.

Methods: A total of 49 patients with metastatic NSCLC treated with ICB were included. Long-term (LTR) and short-term responders (STR) were defined as those with a response to ICB lasting more than 24 months or less than 6 months, respectively. Longitudinal blood specimens were collected before ICB treatment initiation and early-on treatment. …

Lymphodepletion, Tumor-Infiltrating Lymphocytes, And High Versus Low Dose Il-2 Followed By Pembrolizumab In Patients With Metastatic Melanoma, Merve Hasanov, Simin Kiany, Marie-Andrée Forget, Roland Bassett, Michael A Davies, Jeffrey E Gershenwald, Jeffrey E Lee, Anthony Lucci, Jennifer L Mcquade, Sapna P Patel, Merrick I Ross, Hussein A Tawbi, Jennifer A Wargo, Michael K Wong, Chantale Bernatchez, Patrick Hwu, Cara Haymaker, Rodabe N Amaria

Faculty, Staff and Student Publications

This study evaluated the efficacy and safety of unengineered tumor-infiltrating lymphocytes (TILs) combined with pembrolizumab and either high (HD, Arm-1) or low (LD, Arm-2) doses of IL-2 in patients with metastatic melanoma (MM). Patients were lymphodepleted with cyclophosphamide and fludarabine, followed by TIL infusion and IL-2 (Arm-1: 720,000 IU/kg IV q 8 hrs up to 15 doses; Arm-2: 2 million IU SC for 14 days). Patients received pembrolizumab 200 mg IV starting 21 days post-TIL infusion, and every 3 weeks for up to 2 years. The primary endpoint was overall response rate (ORR) per RECIST 1.1. Blood samples were collected …

Smart Spatial Omics (S2-Omics) Optimizes Region Of Interest Selection To Capture Molecular Heterogeneity In Diverse Tissues, Musu Yuan, Kaitian Jin, Hanying Yan, Amelia Schroeder, Chunyu Luo, Bernhard Dumoulin, Tianhao Luo, Jean R Clemenceau, Inyeop Jang, Minji Kim, Yunhe Liu, Minghua Deng, Emma E Furth, Parker Wilson, Anupma Nayak, Idania Lubo, Luisa Maren Solis Soto, Linghua Wang, Jeong Hwan Park, Katalin Susztak, Tae Hyun Hwang, Mingyao Li

Faculty, Staff and Student Publications

Spatial omics technologies have transformed biomedical research by enabling high-resolution molecular profiling while preserving the native tissue architecture. These advances provide unprecedented insights into tissue structure and function. However, the high cost and time-intensive nature of spatial omics experiments necessitate careful experimental design, particularly in selecting regions of interest (ROIs) from large tissue sections. Currently, ROI selection is performed manually, which introduces subjectivity, inconsistency and a lack of reproducibility. Previous studies have shown strong correlations between spatial molecular patterns and histological features, suggesting that readily available and cost-effective histology images can be leveraged to guide spatial omics experiments. Here we …

Bayesian Prediction Of Event Times Using Mixture Model For Blinded Randomized Controlled Trials, Jingyan Fu, Dan Zhao, Donia Skanji, Hua Liu, Rui Sammi Tang

Faculty, Staff and Student Publications

Accurate prediction of key milestone dates, such as the timing of interim and final analyses, is crucial in event-driven clinical trials with time-to-event endpoints. These predictions facilitate timely decision-making, enhance strategic planning and optimize resource allocation while minimizing patient exposure to potentially ineffective or harmful therapies. Existing methods for predicting event timing in blinded randomized clinical trials (RCTs) typically assume identical time-to-event distributions for the treatment and control arms, implying no treatment effect. This assumption fails when the treatment is more effective than the control, which is often the very outcome the trial seeks to detect, leading to biased predictions. …

Study Protocol For Project Shine (Sleep Health Initiative For Equity): A Community-Based Pilot Rct To Promote Sleep And Physical Activity Among Black/African American Adults, Ivan Hc Wu, Lorna Mcneill, Kristen Knutson, Yisheng Li, Diwakar Balachandran, Pamela L Lutsey, Shikha Bista, Rachel Price, Vanessa Anyanso, Taylor Smith, Rev Melvin Miller

Faculty, Staff and Student Publications

Background: Black/African American (AA) adults experience shorter sleep duration and poorer sleep quality compared to White counterparts, contributing to higher risks of chronic diseases. Project SHINE (Sleep Health INitiative for Equity) aims to address these sleep disparities by evaluating the feasibility, satisfaction, and plausibility (i.e., preliminary efficacy) of a culturally tailored sleep intervention designed to improve sleep duration and physical activity among AA adults with body mass index (BMI) ≥ 25 not meeting physical activity and sleep guideline recommendations.

Methods: This pilot community-based randomized controlled trial (RCT) includes two phases. Phase 1 involves qualitative interviews with AA adults to explore …

Statistical Innovations In Clinical Trial Design With A Focus On Drug Combinations, Factorials, And Other Multiple Therapy Issues, Donald A Berry

Faculty, Staff and Student Publications

Statistical methods in clinical research tend to become entrenched. Innovations threaten the status quo. The "right way" becomes frozen in lore. This is so even when the "right way" is not best. "Statistical significance" and the associated requirement of "high power" is an example. This attitude is an impediment to efficient design. Willingness to address some design issues with moderate power enables building highly informative and highly efficient clinical trials. This article considers several types of clinical trials, including dose-finding, combinations, and factorial designs. Bayesian adaptive methods are used to show that trials can be made more efficient and more …