Digital Commons Network^™

Longitudinal Program Evaluation Of An Inter-Institutional Mentorship Network For Pediatric Rheumatology Using A Quality Improvement Framework, Kristen Hayward, Alexi Grom, Eyal Muscal, Peter A Nigrovic, Kelly A Rouster-Stevens, Kaveh Ardalan, Linda Hiraki, L Nandini Moorthy

Faculty, Staff and Students Publications

BACKGROUND: The American College of Rheumatology (ACR)/Childhood Arthritis and Rheumatology Research Alliance (CARRA) Mentoring Interest Group (AMIGO) is an inter-institutional mentorship program launched to target mentorship gaps within pediatric rheumatology. Initial program evaluation indicated increased mentorship access. Given the small size of the pediatric rheumatology workforce, maintaining a consistent supply of mentors was a potential threat to the longevity of the network. Our aims were to: (i) describe the sustainability of AMIGO over the period 2011-2018, (ii) highlight ongoing benefits to participants, and (iii) describe challenges in the maintenance of a mentorship network.

METHODS: A mixed-methods approach centered on a …

The Cns Relapse In T-Cell Lymphoma Index Predicts Cns Relapse In Patients With T- And Nk-Cell Lymphomas, Rahul S Bhansali, Fredrik Ellin, Thomas Relander, Miao Cao, Wenrui Li, Qi Long, Nivetha Ganesan, Robert Stuver, Steven M Horwitz, Kitsada Wudhikarn, Steven R Hwang, N Nora Bennani, Julio Chavez, Lubomir Sokol, Hayder Saeed, Frank Duan, Pierluigi Porcu, Priyanka Pullarkat, Neha Mehta-Shah, Jasmine M Zain, Miguel Ruiz, Jonathan E Brammer, Rishab Prakash, Swaminathan P Iyer, Adam J Olszewski, Ajay Major, Peter A Riedell, Sonali M Smith, Caroline Goldin, Bradley Haverkos, Bei Hu, Tony Z Zhuang, Pamela B Allen, Wael Toama, Murali Janakiram, Taylor R Brooks, Deepa Jagadeesh, Nisha Hariharan, Aaron M Goodman, Gabrielle Hartman, Paola Ghione, Fatima Fayyaz, Joanna M Rhodes, Elise A Chong, James N Gerson, Daniel J Landsburg, Sunita D Nasta, Stephen J Schuster, Jakub Svoboda, Mats Jerkeman, Stefan K Barta

Faculty, Staff and Student Publications

Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. …

Defining Primary Refractory Large B-Cell Lymphoma, Allison M Bock, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Patients with large B-cell lymphoma (LBCL) that fail to achieve a complete response (CR) or who relapse early after anthracycline-containing immunochemotherapy (IC) have a poor prognosis and are commonly considered to have "primary refractory disease." However, different definitions of primary refractory disease are used in the literature and clinical practice. In this study, we examined variation in the time to relapse used to define refractory status and association with survival outcomes in patients with primary refractory LBCL in a single-center prospective cohort with validation in an independent multicenter cohort. Patients with newly diagnosed LBCL were enrolled in the Molecular Epidemiological …

The Cns Relapse In T-Cell Lymphoma Index Predicts Cns Relapse In Patients With T- And Nk-Cell Lymphomas, Rahul S Bhansali, Neha Mehta-Shah, Et Al.

2020-Current year OA Pubs

Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. …

Incidence And Types Of Cardiac Arrhythmias In The Peri-Ictal Period In Patients Having A Generalized Convulsive Seizure, Laura Vilella, Christina Y Miyake, Ganne Chaitanya, Johnson P Hampson, Shirin Jamal Omidi, Manuela Ochoa-Urrea, Blanca Talavera, Oscar Mancera, Norma J Hupp, Jaison S Hampson, M R Sandhya Rani, Nuria Lacuey, Shiqiang Tao, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine A Scott, Brian Gehlbach, Stephan U Schuele, Jennifer A Ogren, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo

Faculty, Staff and Students Publications

Background and objectives: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases.

Methods: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during …

Ai-Assisted Segmentation Tool For Brain Tumor Mr Image Analysis, Myungeun Lee, Jong Hyo Kim, Wookjin Choi, Ki Hong Lee

Department of Radiation Oncology Faculty Papers

TumorPrism3D software was developed to segment brain tumors with a straightforward and user-friendly graphical interface applied to two- and three-dimensional brain magnetic resonance (MR) images. The MR images of 185 patients (103 males, 82 females) with glioblastoma multiforme were downloaded from The Cancer Imaging Archive (TCIA) to test the tumor segmentation performance of this software. Regions of interest (ROIs) corresponding to contrast-enhancing lesions, necrotic portions, and non-enhancing T2 high signal intensity components were segmented for each tumor. TumorPrism3D demonstrated high accuracy in segmenting all three tumor components in cases of glioblastoma multiforme. They achieved a better Dice similarity coefficient (DSC) …

Daratumumab In Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma: Final Analysis Of Clinically Relevant Subgroups In Griffin, Ajai Chari, Jonathan L Kaufman, Jacob Laubach, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Rebecca Silbermann, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a …

Contributions Of Brain Microstructures And Metabolism To Visual Field Loss Patterns In Glaucoma Using Archetypal And Information Gain Analyses, Yueyin Pang, Ji Won Bang, Anisha Kasi, Jeremy Li, Carlos Parra, Els Fieremans, Gadi Wollstein, Joel S. Schuman, Mengyu Wang, Kevin C Chan

Wills Eye Hospital Papers

PURPOSE: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures.

METHODS: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with …

Efficacy, Safety, And Tolerability Of Tivozanib In Heavily Pretreated Patients With Advanced Clear Cell Renal Cell Carcinoma, Andrew C Johns, Matthew T Campbell, Mamie Gao, Andrew W Hahn, Zita Lim, Emily Wang, Jianjun Gao, Amishi Y Shah, Pavlos Msaouel, Nizar M Tannir

Faculty, Staff and Student Publications

BACKGROUND: Tivozanib has been approved as a third-line or later therapy for advanced renal cell carcinoma based on the TIVO-3 trial, which was conducted before immune checkpoint therapies (ICT), cabozantinib, and lenvatinib/everolimus became incorporated in the current sequential treatment paradigm for advanced clear cell RCC (ccRCC).

METHODS: We performed a retrospective study of patients with advanced ccRCC treated with tivozanib at MD Anderson Cancer Center during 6/2021-7/2023. A blinded radiologist assessed tumor response by RECIST v1.1. We assessed overall response rate (ORR), clinical benefit rate (CBR) [percentage of all treated patients who achieved radiologic response or stable disease (SD) for …

Dissociation Of Reading And Naming In Ventral Occipitotemporal Cortex, Oscar Woolnough, Nitin Tandon

Faculty, Staff and Student Publications

Lesions in the language-dominant ventral occipitotemporal cortex (vOTC) can result in selective impairment of either reading or naming, resulting in alexia or anomia. Yet, functional imaging studies that show differential activation for naming and reading do not reveal activity exclusively tuned to one of these inputs. To resolve this dissonance in the functional architecture of the vOTC, we used focused stimulation to the vOTC in 49 adult patients during reading and naming, and generated a population-level, probabilistic map to evaluate if reading and naming are clearly dissociable within individuals. Language mapping (50 Hz, 2829 stimulations) was performed during passage reading …

Reverse Phase Proteomic Array Profiling Of Asparagine Synthetase Expression In Newly Diagnosed Acute Myeloid Leukemia, Nisha Narayanan, Jennifer Marvin-Peek, Mohamad K Abouelnaaj, Dhabya Majid, Bofei Wang, Brandon D Brown, Yihua Qiu, Steven M Kornblau, Hussein A Abbas

Faculty, Staff and Student Publications

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower …

Rate Of Abnormalities In Quantitative Mr Neuroimaging Of Persons With Chronic Traumatic Brain Injury, Farzaneh Rahmani, Richard D Batson, Alexandra Zimmerman, Samir Reddigari, Erin D Bigler, Shawn C Lanning, Eveline Ilasa, Jordan H Grafman, Hanzhang Lu, Alexander P Lin, Cyrus A Raji

2020-Current year OA Pubs

BACKGROUND: Mild traumatic brain injury (mTBI) can result in lasting brain damage that is often too subtle to detect by qualitative visual inspection on conventional MR imaging. Although a number of FDA-cleared MR neuroimaging tools have demonstrated changes associated with mTBI, they are still under-utilized in clinical practice.

METHODS: We investigated a group of 65 individuals with predominantly mTBI (60 mTBI, 48 due to motor-vehicle collision, mean age 47 ± 13 years, 27 men and 38 women) with MR neuroimaging performed in a median of 37 months post-injury. We evaluated abnormalities in brain volumetry including analysis of left-right asymmetry by …

Ai Driven Analysis Of Mri To Measure Health And Disease Progression In Fshd, Lara Riem, Olivia Ducharme, Matthew Cousins, Xue Feng, Allison Kenney, Jacob Morris, Stephen J Tapscott, Rabi Tawil, Jeff Statland, Dennis Shaw, Leo Wang, Michaela Walker, Leann Lewis, Michael A Jacobs, Doris G Leung, Seth D Friedman, Silvia S Blemker

Faculty, Staff and Student Publications

Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image …

Olaparib For Childhood Tumors Harboring Defects In Dna Damage Repair Genes: Arm H Of The Nci-Cog Pediatric Match Trial, Julia L Glade Bender, Kerice Pinkney, Paul M Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent D Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Nilsa C Ramirez, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, Donald W Parsons

Center for Medical Ethics and Health Policy Staff Publications

Background: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib.

Methods: Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response.

Results: Eighteen patients matched …

Genomic Determinants Of Response And Resistance To Inotuzumab Ozogamicin In B-Cell All, Yaqi Zhao, Nicholas J Short, Hagop M Kantarjian, Ti-Cheng Chang, Pankaj S Ghate, Chunxu Qu, Walid Macaron, Nitin Jain, Beenu Thakral, Aaron H Phillips, Joseph Khoury, Guillermo Garcia-Manero, Wenchao Zhang, Yiping Fan, Hui Yang, Rebecca S Garris, Lewis F Nasr, Richard W Kriwacki, Kathryn G Roberts, Marina Konopleva, Elias J Jabbour, Charles G Mullighan

Faculty, Staff and Student Publications

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO-treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of the response and resistance to InO. Pre- and post-InO-treated patient samples were analyzed by whole genome, exome, and/or transcriptome sequencing. Acquired CD22 mutations were observed in 11% (3/27) of post-InO-relapsed tumor samples, but not in refractory samples (0/16). There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included epitope loss (protein truncation and destabilization) and epitope alteration. Two CD22 mutant cases were post-InO …

Oral Sebetralstat For On-Demand Treatment Of Hereditary Angioedema Attacks, Marc A Riedl, H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Approved on-demand treatments for hereditary angioedema attacks need to be administered parenterally, a route of administration that is associated with delays in treatment or withholding of therapy.

METHODS: In this phase 3, double-blind, three-way crossover trial, we randomly assigned participants at least 12 years of age with type 1 or type 2 hereditary angioedema to take up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack. The primary end point, assessed in a time-to-event analysis, was the beginning of symptom relief, defined as a rating of "a little better" on the …

Ledoxy-Sl: A Placebo-Controlled, Double-Blind, Randomized, 24-Month Trial Of Six Weeks Of Daily Doxycycline Plus Hygiene-Based Essential Care For Reducing Progression Of Filarial Lymphedema In Sri Lanka, Thishan Channa Yahathugoda, Nirmitha Lalindi De Silva, Janaka Ruben, Sharmini Gunawardena, Mirani Vasanthamala Weerasooriya, John Horton, Philip Budge, Eric Ottesen, Sarah Mary Sullivan, Mariana Stephens, John Shen, Ute Klarmann-Schulz, Achim Hoerauf, Joseph Patrick Shott, Charles Mackenzie

2020-Current year OA Pubs

Morbidity management of filarial lymphedema remains a challenge even during the post-lymphatic filariasis elimination era in Sri Lanka despite provision of the predominantly hygiene-based WHO Essential Package of Care. Because prior studies have suggested that 6 weeks of doxycycline may reduce progression of limb lymphedema, we conducted a randomized, placebo-controlled, superiority study to evaluate this possibility in Sri Lanka. Patients aged 14 to 65 years with lymphedema in one or both legs received either 200 mg of doxycycline daily for 6 weeks or matching placebo. The primary efficacy endpoint was improvement or lack of progression in lymphedema stage at 24 …

Task And Stimulus Coding In The Multiple-Demand Network, Sneha Shashidhara, Moataz Assem, Matthew F Glasser, John Duncan

2020-Current year OA Pubs

In the human brain, a multiple-demand (MD) network plays a key role in cognitive control, with core components in lateral frontal, dorsomedial frontal and lateral parietal cortex, and multivariate activity patterns that discriminate the contents of many cognitive activities. In prefrontal cortex of the behaving monkey, different cognitive operations are associated with very different patterns of neural activity, while details of a particular stimulus are encoded as small variations on these basic patterns (Sigala et al, 2008). Here, using the advanced fMRI methods of the Human Connectome Project and their 360-region cortical parcellation, we searched for a similar result in …

Celecoxib-Tramadol Co-Crystal In Patients With Moderate-To-Severe Pain Following Bunionectomy With Osteotomy: Secondary Analyses By Baseline Pain Intensity And Use Of Rescue Medication Of A Phase 3, Randomized, Double-Blind, Factorial, Active- And Placebo-Controlled Trial, Eugene R. Viscusi, Oscar De Leon-Casasola, Jesús Cebrecos, Adam Jacobs, Adelaida Morte, Esther Ortiz, Mariano Sust, Anna Vaqué, Ira Gottlieb, Stephen Daniels, Derek Muse, Michael E. Kuss, Sebastián Videla, Neus Gascón, Carlos Plata-Salamán

Department of Anesthesiology Faculty Papers

BACKGROUND: In the randomized, phase 3, SUSA-301 trial, celecoxib-tramadol co-crystal (CTC) provided significantly greater analgesia compared with celecoxib, tramadol, or placebo in adults with acute, moderate-to-severe, postoperative pain. This post hoc, secondary analysis further evaluated the use of rescue medication and the incidence of treatment-emergent adverse events (TEAEs).

METHODS: Patients (N = 637) were randomized 2:2:2:1 to receive oral CTC 200 mg twice daily (BID; n = 184), tramadol 50 mg four times daily (QID; n = 183), celecoxib 100 mg BID (n = 181), or placebo QID (n = 89). Post hoc analyses were conducted on the use of …

Experiences From Patients In Mental Healthcare Accessing Their Electronic Health Records: Results From A Cross-National Survey In Estonia, Finland, Norway, And Sweden, A. J. Fagerlund, Annika Bärkås, A. Kharko, C. R. Blease, J. Hagström, I. Huvila, I. Hörhammer, B. Kane, E. Kristiansen, S. Kujala, J. Moll, H. Rexhepi, I. Scandurra, S. Simola, H. Soone, B. Wang, R. M. Åhlfeldt, M. Hägglund, M. A. Johansen

School of Psychology

Background: Patients’ online record access (ORA) enables patients to read and use their health data through online digital solutions. One such solution, patient-accessible electronic health records (PAEHRs) have been implemented in Estonia, Finland, Norway, and Sweden. While accumulated research has pointed to many potential benefits of ORA, its application in mental healthcare (MHC) continues to be contested. The present study aimed to describe MHC users’ overall experiences with national PAEHR services. Methods: The study analysed the MHC-part of the NORDeHEALTH 2022 Patient Survey, a large-scale multi-country survey. The survey consisted of 45 questions, including demographic variables and questions related to …

Validating A Curvature-Based Marker Of Cervical Carotid Tortuosity For Risk Assessment In Heritable Aortopathies, Jin Vivian Lee, Anna L Huguenard, Ralph G Dacey, Alan C Braverman, Joshua W Osbun

2020-Current year OA Pubs

BACKGROUND: Cervical arterial tortuosity is associated with adverse outcomes in Loeys-Dietz syndrome and other heritable aortopathies.

METHODS AND RESULTS: A method to assess tortuosity based on curvature of the vessel centerline in 3-dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys-Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow-up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow-up). …

Individual And Joint Associations Of High-Sensitivity Troponin I And High-Sensitivity Troponin T With Cardiac Phenotypes And Outcomes In The General Population: An Analysis From The Dallas Heart Study, Rebecca Vigen, Colby Ayers, Jarett Berry, Anand Rohatgi, Vijay Nambi, Christie M Ballantyne, Torbjorn Omland, Christopher R De Filippi, James De Lemos

Faculty, Staff and Students Publications

Background: High-sensitivity troponin I (hs-cTnI) and T (hs-cTnT) provide complementary information regarding cardiovascular disease risk. The explanation for their distinct risk profiles is incompletely understood.

Methods and results: hs-cTnI and hs-cTnT were measured in Dallas Heart Study participants. Associations of hs-cTnI and hs-cTnT with demographics and phenotypes were assessed using linear regression. Associations with incident heart failure, atherosclerotic cardiovascular disease, global cardiovascular disease, and cardiovascular and all-cause mortality were assessed using Cox models. Among 3276 participants (56% women, 50% Black persons, median age 43 years), the correlation between hs-cTnI and hs-cTnT was modest (Spearman rho=0.35). Variables associated with hs-cTnI but …

A Prognostic Model For Use Before Elective Surgery To Estimate The Risk Of Postoperative Pulmonary Complications (Gsu-Pulmonary Score), Nihr Global Health Research Unit On Global Surgery, Starsurg Collaborative

Department of Surgery Faculty Publications

Background: Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used before elective surgery to estimate the risk of postoperative pulmonary complications and to support resource allocation and prioritisation during pandemic recovery. Methods: Data from an international, prospective cohort study were used to develop a novel prognostic risk model for pulmonary complications after elective surgery in adult patients (aged ≥18 years) across all operation and disease types. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery, which was a …

Predicting Nutrition And Environmental Factors Associated With Female Reproductive Disorders Using A Knowledge Graph And Random Forests., Lauren E Chan, Elena Casiraghi, Justin Reese, Quaker E Harmon, Kevin Schaper, Harshad Hegde, Giorgio Valentini, Charles Schmitt, Alison Motsinger-Reif, Janet E Hall, Christopher J Mungall, Peter N Robinson, Melissa A Haendel

Faculty Research 2024

OBJECTIVE: Female reproductive disorders (FRDs) are common health conditions that may present with significant symptoms. Diet and environment are potential areas for FRD interventions. We utilized a knowledge graph (KG) method to predict factors associated with common FRDs (for example, endometriosis, ovarian cyst, and uterine fibroids).

MATERIALS AND METHODS: We harmonized survey data from the Personalized Environment and Genes Study (PEGS) on internal and external environmental exposures and health conditions with biomedical ontology content. We merged the harmonized data and ontologies with supplemental nutrient and agricultural chemical data to create a KG. We analyzed the KG by embedding edges and …

Efficacy Of Tezepelumab In Patients With Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups In The Navigator Study, Tara F Carr, Wendy C Moore, Monica Kraft, Guy Brusselle, Mario Castro, Geoffrey L Chupp, Michael E Wechsler, Gillian Hunter, Andrew W Lindsley, Jean-Pierre Llanos, Luke K Burke, Shradha Chandarana, Christopher S Ambrose

Faculty, Staff and Student Publications

INTRODUCTION: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR.

METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses …

Extended-Release 7-Day Injectable Buprenorphine For Patients With Minimal To Mild Opioid Withdrawal., Gail D'Onofrio, Andrew A. Herring, Jeanmarie Perrone, Kathryn Hawk, Elizabeth A. Samuels, Ethan Cowan, Erik Anderson, Ryan Mccormack, Kristen Huntley, Patricia Owens, Shara Martel, Mark Schactman, Michelle R. Lofwall, Sharon L. Walsh, James Dziura, David A. Fiellin

Behavioral Science Faculty Publications

IMPORTANCE: Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD).

OBJECTIVE: To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal.

DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive …

Efficacy And Safety Of Odevixibat In Patients With Alagille Syndrome (Assert): A Phase 3, Double-Blind, Randomised, Placebo-Controlled Trial., Nadia Ovchinsky, Madeleine Aumar, Alastair Baker, Ulrich Baumann, Philip Bufler, Mara Cananzi, Piotr Czubkowski, Özlem Durmaz, Ryan T. Fischer, Giuseppe Indolfi, Wikrom W. Karnsakul, Florence Lacaille, Way S. Lee, Giuseppe Maggiore, Philip Rosenthal, Mathias Ruiz, Etienne Sokal, Ekkehard Sturm, Wendy Van Der Woerd, Henkjan J. Verkade, Andrew Wehrman, Christine Clemson, Qifeng Yu, Quanhong Ni, Jessica Ruvido, Susan Manganaro, Jan P. Mattsson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In patients with Alagille syndrome, cholestasis-associated clinical features can include high serum bile acids and severe pruritus that can necessitate liver transplantation. We aimed to evaluate the efficacy and safety of the ileal bile acid transporter inhibitor odevixibat versus placebo in patients with Alagille syndrome.

METHODS: The ASSERT study was a phase 3, double-blind, randomised, placebo-controlled trial that enrolled patients at 21 medical centres or hospitals in ten countries (Belgium, France, Germany, Italy, Malaysia, the Netherlands, Poland, Türkiye, the UK, and the USA). Eligible patients had a genetically confirmed diagnosis of Alagille syndrome, a history of significant pruritus, and …

Risk Factors For Postpartum Depression And Severe Distress Among Mothers Of Very Preterm Infants At Nicu Discharge., Julie A. Hofheimer, Elisabeth C. Mcgowan, Lynne M. Smith, Samantha Meltzer-Brody, Brian S. Carter, Lynne M. Dansereau, Steven Pastyrnak, Jennifer B. Helderman, Charles R. Neal, Sheri A. Dellagrotta, Thomas Michael D O'Shea, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE:  To identify psychological, medical, and socioenvironmental risk factors for maternal postpartum depression (PPD) and severe psychological distress (SPD) at intensive care nursery discharge among mothers of very preterm infants.

STUDY DESIGN:  We studied 562 self-identified mothers of 641 infants born(NOVI) conducted in nine university-affiliated intensive care nurseries. Enrollment interviews collected socioenvironmental data, depression, and anxiety diagnoses prior to and during the study pregnancy. Standardized medical record reviews ascertained prenatal substance use, maternal and neonatal medical complications. The Edinburgh Postnatal Depression Scale and Brief Symptom Inventory were administered at nursery discharge to screen for PPD and SPD symptoms, respectively.

RESULTS: …

Preeclampsia, Fetal Growth Restriction, And 24-Month Neurodevelopment In Very Preterm Infants., Jennifer Check, Coral Shuster, Julie Hofheimer, Marie Camerota, Lynne M. Dansereau, Lynne M. Smith, Brian S. Carter, Sheri A. Dellagrotta, Jennifer Helderman, Howard Kilbride, Cynthia M. Loncar, Elisabeth Mcgowan, Charles R. Neal, T Michael O'Shea, Steven L. Pastyrnak, Stephen J. Sheinkopf, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized.

OBJECTIVE: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care …

Financial Incentives For Smoking Cessation Among Socioeconomically Disadvantaged Adults: A Randomized Clinical Trial, Darla Kendzor, Michael Businelle, Summer Frank-Pearce, Joseph Waring, Sixia Chen, Emily Hébert, Michael Swartz, Adam Alexander, Munjireen Sifat, Laili Kharazi Boozary, David Wetter

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Socioeconomically disadvantaged individuals (ie, those with low socioeconomic status [SES]) have difficulty quitting smoking and may benefit from incentive-based cessation interventions.

OBJECTIVES: To evaluate the impact of incentivizing smoking abstinence on smoking cessation among adults with low SES.

DESIGN, SETTING, AND PARTICIPANTS: This study used a 2-group randomized clinical trial design. Data collection occurred between January 30, 2017, and February 7, 2022. Participants included adults with low SES who were willing to undergo smoking cessation treatment. Data were analyzed from April 18, 2023, to April 19, 2024.

INTERVENTIONS: Participants were randomized to usual care (UC) for smoking cessation (counseling …