Medicine and Health Sciences Commons^™

Onecut2 Acts As A Lineage Plasticity Driver In Adenocarcinoma As Well As Neuroendocrine Variants Of Prostate Cancer, Chen Qian, Qian Yang, Mirja Rotinen, Rongrong Huang, Hyoyoung Kim, Brad Gallent, Yiwu Yan, Radu M Cadaneanu, Baohui Zhang, Salma Kaochar, Stephen J Freedland, Edwin M Posadas, Leigh Ellis, Dolores Di Vizio, Colm Morrissey, Peter S Nelson, Lauren Brady, Ramachandran Murali, Moray J Campbell, Wei Yang, Beatrice S Knudsen, Elahe A Mostaghel, Huihui Ye, Isla P Garraway, Sungyong You, Michael R Freeman

Faculty, Staff and Students Publications

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic …

Senescent Cancer-Associated Fibroblasts In Pancreatic Adenocarcinoma Restrict Cd8+ T Cell Activation And Limit Responsiveness To Immunotherapy In Mice, Benjamin Assouline, Sheila A Stewart, Et Al.

2020-Current year OA Pubs

Senescent cells within tumors and their stroma exert complex pro- and anti-tumorigenic functions. However, the identities and traits of these cells, and the potential for improving cancer therapy through their targeting, remain poorly characterized. Here, we identify a senescent subset within previously-defined cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinomas (PDAC) and in premalignant lesions in mice and humans. Senescent CAFs isolated from mouse and humans expressed elevated levels of immune-regulatory genes. Depletion of senescent CAFs, either genetically or using the Bcl-2 inhibitor ABT-199 (venetoclax), increased the proportion of activated CD8

Leukemia Cutis And Anterior Uveitis Associated With Chronic Myelomonocytic Leukemia, Kamran K. Harper, Vanessa Mutch, Jordan Philip Safran, Daisy Wu, Nidhi Aggarwal, Ekta Maheshwari, Allison K. Weinstock, Kevin F. Gibson, Marie-Helene Errera, Jing-Zhou Hou, Arivarasan D. Karunamurthy, Yuri L. Bunimovich

Student Papers, Posters & Projects

Chronic myelomonocytic leukemia (CMML) is an uncommon myeloid neoplasm with myeloproliferative and myelodysplastic features characterized by peripheral monocytosis and cytopenia. CMML may have cutaneous manifestations known as leukemia cutis (LC). LC in the setting of CMML may portend malignant transformation to acute myeloid leukemia (AML). The distribution and morphologic features of LC in CMML are highly variable and often nonspecific. CMML may coexist with numerous secondary autoimmune and inflammatory processes; this phenomenon presents a clinical challenge which can delay correct diagnosis and appropriate therapeutic management. Thus, careful consideration of extramedullary manifestations of CMML and associated autoimmune conditions in the skin …

A Rapid Review Of The Barriers And Facilitators Of Mental Health Service Access Among Veterans And Their Families, Natalie Ein, Julia Gervasio, Kate St. Cyr, Jenny J.W. Liu, Clara Baker, Anthony Nazarov, J. Don Richardson

MacDonald Franklin OSI Research Centre

Introduction: Transitioning to civilian life after military service can be challenging for both Veterans and their families. Accessible mental health services are crucial during this period to provide support. The objective of this review was to conduct a rapid review to capture the barriers and identify facilitators that influence access to mental health services for Veterans and their families during the post-service transition period.

Methods: This review was conducted using the Cochrane Handbook for Systematic Reviews of Interventions as a methodological framework and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Rapid Review (PRISMA-RR).

Results: A total …

Connecting With Your Teen, Maggie Mckay, Brian Burghardt

Parent-ish Podcast

As your child grows up, it can become harder to find ways to connect with them. Dr. Brian Burghardt discusses how you can connect with your teen in a genuine way while respecting their boundaries in our newest podcast.

Click here to stream the podcast episode.

Quality Improvement Project: Incivility In Nursing Education: Utilizing An Educational Module And Professionalism Guide To Address Incivility In A Nursing Students, Jennifer Schadler

Doctor of Nursing Practice Projects

Incivility is a well-documented issue in the nursing profession that begins in nursing education and follows graduates into nursing practice. Nursing academia has a responsibility to address incivility to prevent inappropriate behaviors from becoming embedded into the culture. The problem addressed in this quality improvement project is incivility among nursing students at a private college. The purpose of this project was to apply evidence-based incivility interventions to address uncivil behaviors of nursing students. The hypothesis was that the implementation of a civility mentor module and professionalism guide would impact perceived incivility among nursing students. The project was conducted using the …

Refining The Optimal Caf Cluster Marker For Predicting Tme-Dependent Survival Expectancy And Treatment Benefits In Nsclc Patients, Kai Li, Rui Wang, Guo-Wei Liu, Zi-Yang Peng, Ji-Chang Wang, Guo-Dong Xiao, Shou-Ching Tang, Ning Du, Jia Zhang, Jing Zhang, Hong Ren, Xin Sun, Yi-Ping Yang, Da-Peng Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we …

Refining The Optimal Caf Cluster Marker For Predicting Tme-Dependent Survival Expectancy And Treatment Benefits In Nsclc Patients, Kai Li, Rui Wang, Guo Wei Liu, Zi Yang Peng, Ji Chang Wang, Guo Dong Xiao, Shou Ching Tang, Ning Du, Jia Zhang, Jing Zhang, Hong Ren, Xin Sun, Yi Ping Yang, Da Peng Liu

School of Medicine Faculty Publications

The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we …

Reducing Rates Of Blood Culture Contamination In The Emergency Room, Erika Goldberg

Student Scholarly Projects

Practice Problem: In one emergency room (ER) blood cultures (BC) drawn by nurses had a high contamination rate due to lack of collection standards, which lead to poor patient outcomes.

PICOT: The PICOT question that guided this project was; In adult emergency room patients where blood cultures are drawn (P), how does implementation of an evidence-based practice method (I), compared to the standard method of obtaining blood cultures (C), affect blood culture contamination rates (O), within ten weeks. (T)?

Evidence: Based on multiple sources within the literature; best evidence for lowering blood culture contamination rates (BCC) is done using EBP …

Radium-223 Treatment Produces Prolonged Suppression Of Resident Osteoblasts And Decreased Bone Mineral Density In Trabecular Bone In Osteoblast Reporter Mice, Song-Chang Lin, Guoyu Yu, Paul G Corn, Jossana Damasco, Yu-Chen Lee, Jian H Song, Nora M Navone, Christopher J Logothetis, Marites P Melancon, Theocharis Panaretakis, Sue-Hwa Lin

Faculty, Staff and Student Publications

Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as …

Transcatheter Heart Valve Explant With Infective Endocarditis-Associated Prosthesis Failure And Outcomes: The Explant-Tavr International Registry, Mateo Marin-Cuartas, Gilbert H L Tang, Philipp Kiefer, Shinichi Fukuhara, Rudiger Lange, Katherine B Harrington, Shekhar Saha, Christian Hagl, Neal S Kleiman, Sachin S Goel, Joerg Kempfert, Paul Werner, George A Petrossian, Arnar Geirsson, Nimesh D Desai, Michael W A Chu, Oliver D Bhadra, Christian Shults, Andrea Garatti, Flavien Vincent, Kendra J Grubb, Joshua B Goldberg, Michael J Mack, Thomas Modine, Paolo Denti, Tsuyoshi Kaneko, Vinayak N Bapat, Michael J Reardon, Michael A Borger, Syed Zaid

Faculty, Staff and Students Publications

Background and aims: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE.

Methods: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD).

Results: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant …

Implantable And Semi-Implantable Biosensors For Minimally Invasive Disease Diagnosis, Yameng Xu, Jingyuan Zhang, Wilson Z. Ray, Matthew R. Macewan

2020-Current year OA Pubs

No abstract provided.

Low Skeletal Muscle Mass Is Associated With Inferior Preoperative And Postoperative Shoulder Function In Elderly Rotator Cuff Tear Patients, Yang Yang, Binbin Zheng, Xiaofang Lin, Mengqin Zhang, Yongzhi Ye, Haixiao Chen, Xiaobo Zhou

Faculty, Staff and Student Publications

BACKGROUND: The age-related loss of skeletal muscle mass is an important characteristic of sarcopenia, an increasingly recognized condition with systemic implications. However, its association with shoulder function in elderly patients with rotator cuff tears (RCT) remains unknown. This study aimed to investigate the relationship between low skeletal muscle mass and shoulder function in elderly RCT patients.

METHODS: A retrospective analysis was conducted on RCT patients who underwent chest computed tomography (CT) scans for clinical evaluation. Preoperative CT scan images of the chest were used to calculate the cross-sectional area (CSA) of thoracic muscle at the T4 level. The medical records …

The Influence Of Active, Passive, And Manual Therapy Interventions On Escalation Of Health Care Events After Physical Therapist Care In Veterans With Low Back Pain, John M. Mayer, M. Jason Highsmith, Jason Maikos, Charity G. Patterson, Joseph Kakyomya, Bridget Smith, Nigel Shenoy, Christopher L. Dearth, Shawn Farrokhi

Physical Therapy Faculty Articles and Research

Objective The objective of this study was to examine the associations between active, passive, and manual therapy interventions with the escalation-of-care events following physical therapist care for veterans with low back pain (LBP). Methods A retrospective cohort study was conducted in 3618 veterans who received physical therapist care for LBP between January 1, 2015 and January 1, 2018. The VA Corporate Data Warehouse was utilized to identify LBP-related physical therapist visits and procedures, as well as opioid prescription and non-physical therapy clinic encounters. The association between physical therapist interventions with 1-year escalation-of-care events were assessed using adjusted odds ratios from …

Predicting Choroidal Nevus Transformation To Melanoma Using Machine Learning, Prashant D. Tailor, Piotr K. Kopinski, Haley S. D'Souza, David A. Leske, Timothy W. Olsen, Carol L. Shields, Jerry A. Shields, Lauren A. Dalvin

Wills Eye Hospital Papers

PURPOSE: To develop and validate machine learning (ML) models to predict choroidal nevus transformation to melanoma based on multimodal imaging at initial presentation.

DESIGN: Retrospective multicenter study.

PARTICIPANTS: Patients diagnosed with choroidal nevus on the Ocular Oncology Service at Wills Eye Hospital (2007-2017) or Mayo Clinic Rochester (2015-2023).

METHODS: Multimodal imaging was obtained, including fundus photography, fundus autofluorescence, spectral domain OCT, and B-scan ultrasonography. Machine learning models were created (XGBoost, LGBM, Random Forest, Extra Tree) and optimized for area under receiver operating characteristic curve (AUROC). The Wills Eye Hospital cohort was used for training and testing (80% training-20% testing) with …

Efficient Matrix Profile Computation With Euclidean Distance Using Eigen Transformation: Performance Evaluation Based On Beat-To-Beat Interval (Bbi) Data, James J Yang, Anne Buu

Faculty, Staff and Student Publications

The matrix profile serves as a fundamental tool to provide insights into similar patterns within time series. Existing matrix profile algorithms have been primarily developed for the normalized Euclidean distance, which may not be a proper distance measure in many settings. The methodology work of this paper was motivated by statistical analysis of beat-to-beat interval (BBI) data collected from smartwatches to monitor e-cigarette users’ heart rate change patterns for which the original Euclidean distance (L2-norm) would be a more suitable choice. Yet, incorporating the Euclidean distance into existing matrix profile algorithms turned out to be computationally challenging, especially …

Histopathological  Spectrum Of Glomerular Diseases Over Two Years In A Single Center, Ali Al Saedi, Saad Hamza, Dalia Ali

Iraqi National Journal of Medicine

Background: Glomerular diseases are the leading causes of end-stage renal disease globally. Recognizing the glomerular disease pattern in a specific geographical area is crucial for understanding the region's pathobiology as well as the incidence and progression of the disorder. Aim: To determine the overall spectrum of glomerular diseases based on renal biopsy and compare the results with studies from other countries. Methods: This study was conducted at the Nephrology and Renal Transplant Center, Medical City, Baghdad, Iraq from January 2016 to December 2017. The cohort comprised 849 patients aged 3–65 years who were referred to the center for management. Parameters …

Nasal Microbiome And The Effect Of Nasal Decolonization With A Novel Povidone-Iodine Antiseptic Solution: A Prospective And Randomized Clinical Trial, Diana Fernández-Rodríguez, Jeongeun Cho, Emanuele Chisari, Martin J Citardi, Javad Parvizi

Faculty, Staff and Student Publications

The aim of this study was to assess the profile of nasal microbiome and evaluate the effect of a specific nasal decolonization solution on the microbiome. We conducted a randomized, placebo-controlled, and parallel-group clinical study of 50 volunteers aged 18 years and older. The subjects were randomly assigned to receive a nasal antiseptic solution, containing povidone-iodine as the main ingredient, (n = 25) or a control solution (n = 25). Nasal swabs were obtained before application (baseline) and at 3 timepoints after application (5 min, 2 h, 24 h). Nasal swabs were subjected to next generation sequencing analysis and cultured …

Development And Implementation Of A Digital Quality Measure Of Emergency Cancer Diagnosis, Paarth Kapadia, Andrew J Zimolzak, Divvy K Upadhyay, Saritha Korukonda, Riyaa Murugaesh Rekha, Umair Mushtaq, Usman Mir, Daniel R Murphy, Alexis Offner, Gary A Abel, Georgios Lyratzopoulos, Luke T A Mounce, Hardeep Singh

Faculty, Staff and Students Publications

PURPOSE: Missed and delayed cancer diagnoses are common, harmful, and often preventable. Automated measures of quality of cancer diagnosis are lacking but could identify gaps and guide interventions. We developed and implemented a digital quality measure (dQM) of cancer emergency presentation (EP) using electronic health record databases of two health systems and characterized the measure's association with missed opportunities for diagnosis (MODs) and mortality.

METHODS: On the basis of literature and expert input, we defined EP as a new cancer diagnosis within 30 days after emergency department or inpatient visit. We identified EPs for lung cancer and colorectal cancer (CRC) …

Overcoming Challenges For Non-Us International Medical Graduates In Pediatric Infectious Diseases, Zheyi Teoh, Guliz Erdem, Cristina Tomatis-Souverbielle, Diego A Cruz-Vidal, Maria S Rueda, Roberto P Santos, Liset Olarte

Faculty, Staff and Students Publications

No abstract provided.

Gestational Diabetes As A Risk Factor For Gbs Maternal Rectovaginal Colonization: A Systematic Review And Meta-Analysis, Vicki Mercado-Evans, Jacob J Zulk, Zainab A Hameed, Kathryn A Patras

Faculty, Staff and Students Publications

BACKGROUND: Maternal rectovaginal colonization by group B Streptococcus (GBS) increases the risk of perinatal GBS disease that can lead to death or long-term neurological impairment. Factors that increase the risk of rectovaginal GBS carriage are incompletely understood resulting in missed opportunities for detecting GBS in risk-based clinical approaches. There is a lacking consensus on whether gestational diabetes mellitus (GDM) is a risk factor for rectovaginal GBS. This systematic review and meta-analysis aims to address current conflicting findings and determine whether GDM should be clinically considered as a risk factor for maternal GBS colonization.

METHODS: Peer-reviewed studies that provided GDM prevalence …

Innovation Path At Institute For Protein Design Of Washington University And Its Enlightenment For Construction Of New Life Sciences R&D Institutions, Runzhou Zhao, Ming Ni, Yunzhi Fa, Xiaochen Bo, Jian Jiao

Bulletin of Chinese Academy of Sciences (Chinese Version)

The Institute for Protein Design (IPD) at the University of Washington is a pioneering local and state-supported non-profit scientific research institution. Since its establishment in 2012, IPD has seized the opportunity of AI for Science and open science, and continuously enhanced its capabilities of fundamental innovations, breakthrough technologies, and industrial impact. We summarized five factors contributing to IPD’s development, including focusing on the cutting-edge issues of basic scientific research to gain a first-mover advantage and then further expand, integrating AI-enhanced digital tools and solid experimental validations, facilitating the integrated development of innovation and industrial chains, giving full play to the …

The Impact Of Hourly Safety Rounding On Pediatric Fall Rates, Natalie Doskal-Poe

Dissertations

The Impact of Hourly Safety Rounding on Pediatric Fall Rates

Abstract

Problem: Falls are a common adverse event in the inpatient pediatric setting and are a significant risk to patient safety. Environmental factors, such as unclear pathways, bed rails down, beds in high position, and call lights out of reach, are considered avoidable causes of patient falls. The site’s fall data in a 12-month period from January 2023 to January 2024 showed (n=9) patient falls occurred with (n=5, 55.6%) due to environmental factors. The purpose of this Quality Improvement (QI) pilot project was to assess the …

Self-Harm In Female Youth With Undiagnosed Adhd: Implementing American Academy Of Pediatrics Screening Guidelines, Roselie M. Woodard

Dissertations

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. If undiagnosed or untreated, ADHD can lead to severe psychosocial issues such as academic failure, substance abuse, unplanned pregnancy, and incarceration. The financial burden in the U.S. from diagnostic errors creates an immense, rising fiscal impact. Early diagnosis and management are crucial to prevent these complications.

Females with ADHD, particularly those with the inattentive subtype, often face diagnostic challenges due to symptom masking and over-compensation. This results in poorer cognitive functioning and self-esteem compared to males with ADHD. ADHD is linked to autonomic nervous …

Trackins (Trk-Targeting Drugs): A Novel Therapy For Different Diseases, George N Chaldakov, Luigi Aloe, Stanislav G Yanev, Marco Fiore, Anton B Tonchev, Manlio Vinciguerra, Nikolai T Evtimov, Peter Ghenev, Krikor Dikranian

2020-Current year OA Pubs

Many routes may lead to the transition from a healthy to a diseased phenotype. However, there are not so many routes to travel in the opposite direction; that is, therapy for different diseases. The following pressing question thus remains: what are the pathogenic routes and how can be they counteracted for therapeutic purposes? Human cells contain >500 protein kinases and nearly 200 protein phosphatases, acting on thousands of proteins, including cell growth factors. We herein discuss neurotrophins with pathogenic or metabotrophic abilities, particularly brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), pro-NGF, neurotrophin-3 (NT-3), and their receptor Trk (tyrosine receptor …

Safety And Effectiveness Of Using Disposable Ultrasonic Shears To Coagulate 5–7 Mm Blood Vessels: Protocol For A Prospective, Multicenter, Randomized, Parallel Controlled, Non-Inferiority Clinical Trial, Xipeng Wang, Chengqiang Li, Junqiang Fan, Jian Hu, Mingsong Wang, Hecheng Li

Faculty, Staff and Student Publications

BACKGROUND: The ultrasonic scalpel is widely used during surgery. It is safe and effective to close the pulmonary artery branch vessels of 7 mm or below with an ultrasonic energy device as reported. However, there have been no multicenter randomized clinical trial to assess the safety and effectiveness of using ultrasonic scalpel to coagulate 5-7 mm blood vessels in thoracic surgery.

METHODS: This is a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial. A total of 144 eligible patients planning to undergo lung or esophageal surgery will be randomly allocated to the experimental group and the control group. The investigational …

Association Of High Fibrinogen To Albumin Ratio With Long-Term Mortality In Patients With Spontaneous Intracerebral Hemorrhage, Shiping Chen, Yu Zhang, Yangchun Xiao, Xin Cheng, Liyuan Peng, Yixin Tian, Tiangui Li, Jialing He, Pengfei Hao, Weelic Chong, Yang Hai, Chao You, Fang Fang

Department of Medical Oncology Faculty Papers

BACKGROUND: The association between fibrinogen-to-albumin ratio (FAR) and in-hospital mortality in patients with spontaneous intracerebral hemorrhage (ICH) has been established. However, the association with long-term mortality in spontaneous ICH remains unclear. This study aims to investigate the association between FAR and long-term mortality in these patients.

METHODS: Our retrospective study involved 3,538 patients who were diagnosed with ICH at West China Hospital, Sichuan University. All serum fibrinogen and serum albumin samples were collected within 24 h of admission and participants were divided into two groups according to the FAR. We conducted a Cox proportional hazard analysis to evaluate the association …

Relationship Between Geographic Location, Race, And Socioeconomic Status On Adolescent Male Hpv Vaccination In The United States, Stacy Herb

Walden Dissertations and Doctoral Studies

Human papillomavirus (HPV) represents the most prevalent sexually transmitted infection in the United States. Despite readily available safe and effective vaccines and established knowledge of influencing factors, HPV vaccination rates in the United States remain suboptimal, particularly among adolescent males. This quantitative study addressed this gap by investigating the association between geographic location, race, and socioeconomic status with HPV vaccination uptake in adolescent males. A secondary data analysis was conducted using the 2022 National Immunization Survey (NIS)—Teen, comprised of 22,667 adolescent males. The fundamental cause theory served as the theoretical framework, guiding the exploration of why a safe and effective …

Bayesian Sequential Monitoring Strategies For Trials Of Digestive Cancer Therapeutics, Guillaume Mulier, Ruitao Lin, Thomas Aparicio, Lucie Biard

Faculty, Staff and Student Publications

Background: New therapeutics in oncology have presented challenges to existing paradigms and trial designs in all phases of drug development. As a motivating example, we considered an ongoing phase II trial planned to evaluate the combination of a MET inhibitor and an anti-PD-L1 immunotherapy to treat advanced oesogastric carcinoma. The objective of the paper was to exemplify the planning of an adaptive phase II trial with novel anti-cancer agents, including prolonged observation windows and joint sequential evaluation of efficacy and toxicity.

Methods: We considered various candidate designs and computed decision rules assuming correlations between efficacy and toxicity. Simulations were conducted …

Exploration Of A Potential Door Endpoint For Hospital-Acquired Bacterial Pneumonia And Ventilator-Associated Bacterial Pneumonia Using Six Registrational Trials For Antibacterial Drugs, Tori Kinamon, Ursula Waack, Mark Needles, Daniel Rubin, Deborah Collyar, Sarah B Doernberg, Scott R Evans, Toshimitsu Hamasaki, Thomas L Holland, Jessica Howard-Anderson, Henry Chambers, Vance G Fowler, Sumati Nambiar, Peter Kim, Helen W Boucher, Ramya Gopinath

Faculty, Staff and Student Publications

BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

METHODS: Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that …