Medicine and Health Sciences Commons^™

Phase Ii Trial Of Medi0457 And Durvalumab For Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers, Van K Morris, Amir Jazaeri, Shannon N Westin, Curtis Pettaway, Solly George, Ryan W Huey, Michaela Grinsfelder, Aaron Shafer, Benny Johnson, David Vining, Ming Guo, Bryan Fellman, Michael Frumovitz

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers.

METHODS: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg …

Accuracy Of Baseline Prevalence Estimates For Sample-Size Calculations In Randomized Controlled Trials, Andrew Aultman, Kelly C Ditter, Hector Mendez-Figueroa, Megha Gupta, Michal Fishel Bartal, Suneet P Chauhan, Stephen Wagner

Faculty, Staff and Student Publications

No abstract provided.

A Phase Ib/Ii Study Of Ivosidenib With Venetoclax ± Azacitidine In Idh1-Mutated Myeloid Malignancies, Curtis A Lachowiez, Sanam Loghavi, Zhihong Zeng, Tomoyuki Tanaka, Yi June Kim, Hidetaka Uryu, Sven Turkalj, Niels Asger Jakobsen, Marlise R Luskin, Dzifa Y Duose, Rebecca S S Tidwell, Nicholas J Short, Gautam Borthakur, Tapan M Kadia, Lucia Masarova, George D Tippett, Prithviraj Bose, Elias J Jabbour, Farhad Ravandi, Naval G Daver, Guillermo Garcia-Manero, Hagop Kantarjian, Jacqueline S Garcia, Paresh Vyas, Koichi Takahashi, Marina Konopleva, Courtney D Dinardo

Faculty, Staff and Student Publications

UNLABELLED: The safety and efficacy of combining the isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib (IVO) with the BCL2 inhibitor venetoclax (VEN; IVO + VEN) ± azacitidine (AZA; IVO + VEN + AZA) were evaluated in four cohorts of patients with IDH1-mutated myeloid malignancies (n = 31). Most (91%) adverse events were grade 1 or 2. The maximal tolerated dose was not reached. Composite complete remission with IVO + VEN + AZA versus IVO + VEN was 90% versus 83%. Among measurable residual disease (MRD)-evaluable patients (N = 16), 63% attained MRD--negative remissions; IDH1 mutation clearance occurred in 64% of patients receiving …

Circadian Disruption And Colorectal Cancer Incidence In Black Women, Lauren E Barber, Trang Vopham, Laura F White, Hemant K Roy, Julie R Palmer, Kimberly A Bertrand

Faculty, Staff and Students Publications

BACKGROUND: Animal and experimental studies suggest circadian disruption increases colorectal cancer risk, but evidence in humans is limited. We examined night shift work, chronotype, and residential position within a time zone, proxies for circadian disruption, in relation to colorectal cancer risk.

METHODS: Participants in the Black Women's Health Study, a prospective cohort of 59,000 Black American women established in 1995, reported history of night shift work and chronotype on follow-up questionnaires. Residential position within a time zone was estimated using participant addresses at each questionnaire cycle. Number of colorectal cancer cases and follow-up duration varied by analysis depending on timing …

A Comprehensive Analysis Of Lung Cancer Highlighting Epidemiological Factors And Psychiatric Comorbidities From The All Of Us Research Program, Vikram R Shaw, Jinyoung Byun, Rowland W Pettit, Younghun Han, David A Hsiou, Luke A Nordstrom, Christopher I Amos

Faculty, Staff and Students Publications

Lung cancer is the leading cause of cancer-related mortality in the United States. Investigating epidemiological and clinical parameters can contribute to an improved understanding of disease development and management. In this cross-sectional, case-control study, we used the All of Us database to compare healthcare access, family history, smoking-related behaviors, and psychiatric comorbidities in light smoking controls, matched smoking controls, and primary and secondary lung cancer patients. We found a decreased odds of primary lung cancer patients versus matched smoking controls reporting inability to afford follow-up or specialist care. Additionally, we found a significantly increased odds of secondary lung cancer patients …

Tissue Mass Spectrometry: How Solid Is Our Future?, Daisy Unsihuay, William S Phipps, Amanda G Paulovich, Jessica R Chapman, Axel Ducret, Livia S Eberlin, Jeffrey M Spraggins, Richard J A Goodwin

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Rad51 Foci As A Biomarker Predictive Of Platinum Chemotherapy Response In Ovarian Cancer, Amanda J Compadre, Lillian N Van Biljon, Mark C Valentine, Emily Graham, Bisiayo Fashemi, Emilee N Kotnik, Isaac Cooper, Lindsay M Kuroki, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, David G Mutch, Matthew A Powell, Lulu Sun, Nima Mosammaparast, Peinan Zhao, Elena Lomonosova, Dineo Khabele, Mary M Mullen, Et Al.

2020-Current year OA Pubs

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.

EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.

RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell …

Unexpected Sound Omissions Are Signaled In Human Posterior Superior Temporal Gyrus: An Intracranial Study, Hohyun Cho, Yvonne M Fonken, Markus Adamek, Richard Jimenez, Jack J Lin, Gerwin Schalk, Robert T Knight, Peter Brunner

2020-Current year OA Pubs

Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent of any auditory evoked activity by assessing the response to omitted expected sounds. Electrocorticographic signals were recorded directly from subdural electrode grids placed over the superior temporal gyrus (STG). Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found high-frequency band activity (HFA, 70-170 Hz) in response to omissions, which overlapped with a posterior subset of auditory-active electrodes …

Comparison Of Patient Exit Interviews With Unannounced Standardised Patients For Assessing Hiv Service Delivery In Zambia: A Study Nested Within A Cluster Randomised Trial, Kombatende Sikombe, Aaloke Mody, Ingrid Eshun-Wilson, Elvin Geng, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To compare unannounced standardised patient approach (eg, mystery clients) with typical exit interviews for assessing patient experiences in HIV care (eg, unfriendly providers, long waiting times). We hypothesise standardised patients would report more negative experiences than typical exit interviews affected by social desirability bias.

SETTING: Cross-sectional surveys in 16 government-operated HIV primary care clinics in Lusaka, Zambia providing antiretroviral therapy (ART).

PARTICIPANTS: 3526 participants aged ≥18 years receiving ART participated in the exit surveys between August 2019 and November 2021.

INTERVENTION: Systematic sample (every n

OUTCOME MEASURES: We compared patient experience among patients who received brief training prior to …

Early Antiretroviral Therapy Not Associated With Higher Cryptococcal Meningitis Mortality In People With Human Immunodeficiency Virus In High-Income Countries: An International Collaborative Cohort Study, Suzanne M Ingle, Elvin Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings.

METHODS: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 …

Evaluating The Generalizability Of Predictive Classifiers Built From Desi Imaging Lipid Data Across Mass Spectrometry Platformsjournal Of The American Society For Mass Spectrometry, Rachel J Dehoog, Monica Lin, Gregory Roman, Roy Martin, James Suliburk, Livia S Eberlin

Faculty, Staff and Students Publications

In this study, we evaluate the generalizability of predictive classifiers built from DESI lipid data for thyroid fine needle aspiration (FNA) biopsy analysis and classification using two high-performance mass spectrometers (time-of-flight and orbitrap) suited with different DESI imaging sources operated by different users. The molecular profiles obtained from thyroid samples with the different platforms presented similar trends, although specific differences in ion abundances were observed. When using a previously published statistical model built to discriminate thyroid cancer from benign thyroid tissues to predict on a new independent data set obtained, agreement for 24 of the 30 samples across the imaging …

A Bayesian Network Approach To Social And Nonsocial Cognition In Schizophrenia: Are Some Domains More Fundamental Than Others?, Samuel J Abplanalp, Junghee Lee, William P Horan, Robert S Kern, David L Penn, Michael F Green

Faculty, Staff and Student Publications

OBJECTIVES: Social and nonsocial cognition are defined as distinct yet related constructs. However, the relative independence of individual variables-and whether specific tasks directly depend on performance in other tasks-is still unclear. The current study aimed to answer this question by using a Bayesian network approach to explore directional dependencies among social and nonsocial cognitive domains.

STUDY DESIGN: The study sample comprised 173 participants with schizophrenia (71.7% male; 28.3% female). Participants completed 5 social cognitive tasks and the MATRICS Consensus Cognitive Battery. We estimated Bayesian networks using directed acyclic graph structures to examine directional dependencies among the variables.

STUDY RESULTS: After …

Caudal Dmn Neurons Innervate The Spleen And Release Cart Peptide To Regulate Neuroimmune Function, Nobuhide Kobori, Anthony N Moore, John B Redell, Pramod K Dash

Faculty, Staff and Student Publications

BACKGROUND: Inflammation is a fundamental biological response to injury and infection, which if unregulated can contribute to the pathophysiology of many diseases. The vagus nerve, which primarily originates from the dorsal motor nucleus (DMN), plays an important role in rapidly dampening inflammation by regulating splenic function. However, direct vagal innervation of the spleen, which houses the majority of immune and inflammatory cells, has not been established. As an alternative to direct innervation, an anti-inflammatory reflex pathway has been proposed which involves the vagus nerve, the sympathetic celiac ganglion, and the neurotransmitter norepinephrine. Although sympathetic regulation of inflammation has been shown, …

Human Gut Bacteria Tailor Extracellular Vesicle Cargo For The Breakdown Of Diet- And Host-Derived Glycans, Mariana G Sartorio, Evan J Pardue, Nichollas E Scott, Mario F Feldman

2020-Current year OA Pubs

Extracellular vesicles are produced in all three domains of life, and their biogenesis has common ancient origins in eukaryotes and archaea. Although bacterial vesicles were discovered several decades ago and multiple roles have been attributed to them, no mechanism has been established for vesicles biogenesis in bacteria. For this reason, there is a significant level of skepticism about the biological relevance of bacterial vesicles.

Two Neuroanatomical Signatures In Schizophrenia: Expression Strengths Over The First 2 Years Of Treatment And Their Relationships To Neurodevelopmental Compromise And Antipsychotic Treatment, Stefan Du Plessis, Ganesh B Chand, Guray Erus, Lebogang Phahladira, Hilmar K Luckhoff, Retha Smit, Laila Asmal, Daniel H Wolf, Christos Davatzikos, Robin Emsley

2020-Current year OA Pubs

BACKGROUND AND HYPOTHESIS: Two machine learning derived neuroanatomical signatures were recently described. Signature 1 is associated with widespread grey matter volume reductions and signature 2 with larger basal ganglia and internal capsule volumes. We hypothesized that they represent the neurodevelopmental and treatment-responsive components of schizophrenia respectively.

STUDY DESIGN: We assessed the expression strength trajectories of these signatures and evaluated their relationships with indicators of neurodevelopmental compromise and with antipsychotic treatment effects in 83 previously minimally treated individuals with a first episode of a schizophrenia spectrum disorder who received standardized treatment and underwent comprehensive clinical, cognitive and neuroimaging assessments over 24 …

Metabolic Signatures Of Cardiac Dysfunction, Multimorbidity, And Post-Transcatheter Aortic Valve Implantation Death, Andrew S Perry, Nishath Quader, Alan Zajarias, Et Al.

2020-Current year OA Pubs

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort …

Social And Environmental Determinants Influencing Injection Drug Use And Hiv Risk Among Two Sister Cities On The Us-Mexico Border: A Comparative Cross-Sectional Study, 2016–2018, Julia Lechuga, Rebeca Ramos, Natasha Ludwig-Barron, Gilberto Perez, Maria Elena Ramos, João B Ferreira-Pinto, Jacquelin I Cordero, John Sauceda, Jorge Salazar

Faculty, Staff and Student Publications

The economic, social, cultural and political milieus that influence injection drug-related HIV risk behaviors along the US-Mexico border in the previous decade have been studied comparing cities on an East-West axis. In an effort to inform interventions targeting factors beyond the individual level, we used a cross-sectional study design comparing people who inject drugs during 2016-2018, living on a North-South axis, in two cities-Ciudad Juárez, Chihuahua, Mexico and El Paso, Texas, USA-situated at the midpoint of the 2000 US-Mexico borderland stretch. We conceptualize injection drug use and its antecedents and consequences as influenced by factors operating at various levels of …

A Rapid Cell-Free Expression And Screening Platform For Antibody Discovery, Andrew C Hunt, Bastian Vögeli, Ahmed O Hassan, Laura Guerrero, Weston Kightlinger, Danielle J Yoesep, Antje Krüger, Madison Dewinter, Michael S Diamond, Ashty S Karim, Michael C Jewett

2020-Current year OA Pubs

Antibody discovery is bottlenecked by the individual expression and evaluation of antigen-specific hits. Here, we address this bottleneck by developing a workflow combining cell-free DNA template generation, cell-free protein synthesis, and binding measurements of antibody fragments in a process that takes hours rather than weeks. We apply this workflow to evaluate 135 previously published antibodies targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including all 8 antibodies previously granted emergency use authorization for coronavirus disease 2019 (COVID-19), and demonstrate identification of the most potent antibodies. We also evaluate 119 anti-SARS-CoV-2 antibodies from a mouse immunized with the SARS-CoV-2 spike …

Clinical And Demographic Factors Associated With Covid-19, Severe Covid-19, And Sars-Cov-2 Infection In Adults: A Secondary Cross-Protocol Analysis Of 4 Randomized Clinical Trials, Deborah A Theodore, Angela R Branche, Lily Zhang, Daniel S Graciaa, Madhu Choudhary, Timothy J Hatlen, Raadhiya Osman, Tara M Babu, Samuel T Robinson, Peter B Gilbert, Dean Follmann, Holly Janes, James G Kublin, Lindsey R Baden, Paul Goepfert, Glenda E Gray, Beatriz Grinsztejn, Karen L Kotloff, Cynthia L Gay, Brett Leav, Jacqueline Miller, Ian Hirsch, Jerald Sadoff, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Ann R Falsey, Hana M El Sahly, Magdalena E Sobieszczyk, Yunda Huang

Faculty, Staff and Student Publications

IMPORTANCE: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders.

OBJECTIVE: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network. Individual-level data from participants randomized to receive placebo within each trial were combined and analyzed. Enrollment began July 2020 and the last data cutoff was in July 2021. Participants included adults in stable health, at risk for SARS-CoV-2, and assigned to the placebo group …

Conditional Metastasis Of Uveal Melanoma In 8091 Patients Over Half-Century (51 Years) By Age Group: Assessing The Entire Population And The Extremes Of Age, Carol L. Shields, Annika Samuelson, Glenn Oh, Joseph D. Desimone, Zaynab Sajjadi, Zeynep Bas, Nicholas E Kalafatis, Sara E. Lally, Jerry A. Shields, Philip W. Dockery

Wills Eye Hospital Papers

PURPOSE: To evaluate cumulative incidence of metastasis at specific timepoints after treatment of uveal melanoma in a large cohort of patients and to provide comparison of conditional outcomes in the youngest and oldest cohorts (extremes of age).

METHODS: Retrospective analysis of 8091 consecutive patients with uveal melanoma at a single center over a 51-year period. The patients were categorized by age at presentation (0-29 years [n = 348, 4%], 30-59 years [n = 3859, 48%], 60-79 years [n = 3425, 42%], 80 to 99 years [n = 459, 6%]) and evaluated for nonconditional (from presentation date) and conditional (from specific …

Trends And Seasonality Of Emergency Department Visits And Hospitalizations For Suicidality Among Children And Adolescents In The Us From 2016 To 2021, Youngran Kim, Trudy Millard Krause, Scott D Lane

Faculty, Staff and Student Publications

IMPORTANCE: The detection of seasonal patterns in suicidality should be of interest to clinicians and US public health officials, as intervention efforts can benefit by targeting periods of heightened risk.

OBJECTIVES: to examine recent trends in suicidality rates, quantify the seasonality in suicidality, and demonstrate the disrupted seasonality patterns during the spring 2020 COVID-19-related school closures among US children and adolescents.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, descriptive cross-sectional study used administrative claims data from Optum's deidentifed Clinformatics Data Mart Database. Participants included children aged 10 to 12 years and adolescents aged 13 to 18 years who were commercially insured …

Reasons Patients Cite To Their Health-Care Professional For Not Initiating Or Completing Human Papillomavirus Vaccination, Onyema Greg Chido-Amajuoyi, Ikponmwosa Osaghae, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: Vaccination against human papillomavirus (HPV) is critical to the prevention of HPV-associated cancers. This study aimed to describe the reasons patients cited for not initiating or completing the HPV vaccination series, as reported by health-care professionals.

METHODS: Study data were obtained from a University of Texas MD Anderson Cancer Center population-based cross-sectional survey of health-care professionals practicing in Texas. Prevalence estimates of reasons cited for not initiating or completing HPV vaccination were estimated by patient population (parents of children and adult patients).

RESULTS: The study included 973 primary care clinicians, of whom 45.53% were physicians and 54.47% were midlevel …

Risks Of Alcohol And Drug Use Disorders In Prostate Cancer Survivors: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Alexis C Edwards, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

BACKGROUND: Prostate cancer (PC) survivors may potentially use substances to cope with psychological distress or poorly controlled physical symptoms. Little is known, however, about the long-term risks of alcohol use disorder (AUD) or drug use disorders in men with PC.

METHODS: A national cohort study was conducted in Sweden of 180 189 men diagnosed with PC between 1998 and 2017 and 1 801 890 age-matched population-based control men. AUD and drug use disorders were ascertained from nationwide records through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors and prior psychiatric disorders. Subanalyses examined …

Association Of Circulating Tumor Dna Testing Before Tissue Diagnosis With Time To Treatment Among Patients With Suspected Advanced Lung Cancer: The Accelerate Nonrandomized Clinical Trial, Miguel García-Pardo, Kasia Czarnecka-Kujawa, Jennifer H Law, Alexandra M Salvarrey, Roxanne Fernandes, Zhen J Fan, Thomas K Waddell, Kazuhiro Yasufuku, Geoffrey Liu, Laura L Donahoe, Andrew Pierre, Lisa W Le, Tharsiga Gunasegaran, Noor Ghumman, Frances A Shepherd, Penelope A Bradbury, Adrian G Sacher, Sabine Schmid, Lucy Corke, Jamie Feng, Tracy Stockley, Prodipto Pal, Patrik Rogalla, Christodoulos Pipinikas, Karen Howarth, Bana Ambasager, Laura Mezquita, Ming S Tsao, Natasha B Leighl

Faculty, Staff and Student Publications

IMPORTANCE: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear.

OBJECTIVE: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment.

DESIGN, SETTING, AND PARTICIPANTS: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients …

Prognostic And Predictive Value Of Endothelial Dysfunction Biomarkers In Sepsis-Associated Acute Kidney Injury: Risk-Stratified Analysis From A Prospective Observational Cohort Of Pediatric Septic Shock., Mihir R. Atreya, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Scott L. Weiss, Michael T. Bigham, Parag N. Jain, Adam J. Schwarz, Riad Lutfi, Jeffrey Nowak, Geoffrey L. Allen, Neal J. Thomas, Jocelyn R. Grunwell, Torrey Baines, Michael Quasney, Bereketeab Haileselassie, Matthew N. Alder, Stuart L. Goldstein, Natalja L. Stanski

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is associated with high morbidity, with no current therapies available beyond continuous renal replacement therapy (CRRT). Systemic inflammation and endothelial dysfunction are key drivers of SA-AKI. We sought to measure differences between endothelial dysfunction markers among children with and without SA-AKI, test whether this association varied across inflammatory biomarker-based risk strata, and develop prediction models to identify those at highest risk of SA-AKI.

METHODS: Secondary analyses of prospective observational cohort of pediatric septic shock. Primary outcome of interest was the presence of ≥ Stage II KDIGO SA-AKI on day 3 based on serum creatinine …

Physician-Investigator, Research Coordinator, And Patient Perspectives On Dual-Role Consent In Oncology: A Qualitative Study, Stephanie R Morain, Dorit Barlevy, Steven Joffe, Emily A Largent

Center for Medical Ethics and Health Policy Staff Publications

Importance: Classic statements of research ethics generally advise against dual-role consent in which physician-investigators seek consent for research participation from patients with whom they have preexisting treatment relationships. Yet dual-role consent is common in clinical oncology research, as studies are often conducted in close relationship with clinical care.

Objective: To explore key stakeholders' perspectives on dual-role consent in clinical oncology trials.

Design, setting, and participants: This qualitative study with 43 participants was conducted at a National Cancer Institute-designated comprehensive cancer center from 2018 to 2022. Semistructured qualitative interviews of physician-investigators, research coordinators, and patients were performed. Respondents were recruited from …

Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jason A Dominitz, Alexander Beed, Kathy D Boardman, Barbara J Del Curto, Peter D Guarino, Thomas F Imperiale, Andrew Lacasse, Meaghan F Larson, Samir Gupta, David Lieberman, Beata Planeta, Aasma Shaukat, Shanaz Sultan, Stacy B Menees, Sameer D Saini, Philip Schoenfeld, Stephan Goebel, Erik C Von Rosenvinge, Gyorgy Baffy, Ildiko Halasz, Marcos C Pedrosa, Lyn Sue Kahng, Riaz Cassim, Katarina B Greer, Margaret F Kinnard, Divya B Bhatt, Kerry B Dunbar, William V Harford, John A Mengshol, Jed E Olson, Swati G Patel, Fadi Antaki, Deborah A Fisher, Brian A Sullivan, Christopher Lenza, Devang N Prajapati, Helen Wong, Rebecca Beyth, John G Lieb, Joseph Manlolo, Fernando V Ona, Rhonda A Cole, Natalia Khalaf, Charles J Kahi, Divyanshoo Rai Kohli, Tarun Rai, Prateek Sharma, Jiannis Anastasiou, Curt Hagedorn, Ronald S Fernando, Christian S Jackson, M Mazen Jamal, Robert H Lee, Farrukh Merchant, Folasade P May, Joseph R Pisegna, Endashaw Omer, Dipendra Parajuli, Adnan Said, Toan D Nguyen, Claudio Ruben Tombazzi, Paul A Feldman, Leslie Jacob, Rachel N Koppelman, Kyle P Lehenbauer, Deepak S Desai, Mohammad F Madhoun, William M Tierney, Minh Q Ho, Heather J Hockman, Christopher Lopez, Emily Carter Paulson, Martin Tobi, Hugo L Pinillos, Michele Young, Nancy C Ho, Ranjan Mascarenhas, Kirrichai Promrat, Pritesh R Mutha, William M Pandak, Tilak Shah, Mitchell Schubert, Frank S Pancotto, Andrew J Gawron, Amelia E Underwood, Samuel B Ho, Priscilla Magno-Pagatzaurtundua, Doris H Toro, Charles H Beymer, Andrew M Kaz, Jill Elwing, Jeffrey A Gill, Susan F Goldsmith, Michael D Yao, Petr Protiva, Heiko Pohl, Tassos Kyriakides

Faculty, Staff and Student Publications

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy.

OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs …

Loss Of The Batten Disease Protein Cln3 Leads To Mis-Trafficking Of M6pr And Defective Autophagic-Lysosomal Reformation, Alessia Calcagni', Leopoldo Staiano, Nicolina Zampelli, Nadia Minopoli, Niculin J Herz, Giuseppe Di Tullio, Tuong Huynh, Jlenia Monfregola, Alessandra Esposito, Carmine Cirillo, Aleksandar Bajic, Mahla Zahabiyon, Rachel Curnock, Elena Polishchuk, Luke Parkitny, Diego Luis Medina, Nunzia Pastore, Peter J Cullen, Giancarlo Parenti, Maria Antonietta De Matteis, Paolo Grumati, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Batten disease, one of the most devastating types of neurodegenerative lysosomal storage disorders, is caused by mutations in CLN3. Here, we show that CLN3 is a vesicular trafficking hub connecting the Golgi and lysosome compartments. Proteomic analysis reveals that CLN3 interacts with several endo-lysosomal trafficking proteins, including the cation-independent mannose 6 phosphate receptor (CI-M6PR), which coordinates the targeting of lysosomal enzymes to lysosomes. CLN3 depletion results in mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation. Conversely, CLN3 overexpression promotes the formation of multiple lysosomal tubules, which are autophagy and CI-M6PR-dependent, generating newly formed proto-lysosomes. Together, our …

Baseline Features And Reasons For Nonparticipation In The Colonoscopy Versus Fecal Immunochemical Test In Reducing Mortality From Colorectal Cancer (Confirm) Study, A Colorectal Cancer Screening Trial, Douglas J Robertson, Jill Elwing, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy.

OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs …

Assessment Of Gastroesophageal Reflux Symptoms And Sleep Quality Among Women In The Nurses' Health Study Ii, Jane Ha, Raaj S Mehta, Yin Cao, Tianyi Huang, Kyle Staller, Andrew T Chan

2020-Current year OA Pubs

IMPORTANCE: Limited data exist on the association of gastroesophageal reflux (GER) symptoms with sleep quality.

OBJECTIVE: To prospectively investigate the association between GER symptoms and sleep quality.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included data from the Nurses' Health Study II of female nurses in the US. Participants self-reported the frequency and duration of GER symptoms beginning June 2005, with updates every 4 years through June 2015. Follow-up was completed June 2019, and data were analyzed from November 15, 2022, to June 4, 2023.

EXPOSURES: Frequency and duration of GER symptoms.

MAIN OUTCOMES AND MEASURES: Poor sleep quality …