Digital Commons Network^™

Interventions To Improve Timely Cancer Diagnosis: An Integrative Review, Mark L Graber, Bradford D Winters, Roni Matin, Rosann T Cholankeril, Daniel R Murphy, Hardeep Singh, Andrea Bradford

Faculty, Staff and Students Publications

Cancer will affect more than one in three U.S. residents in their lifetime, and although the diagnosis will be made efficiently in most of these cases, roughly one in five patients will experience a delayed or missed diagnosis. In this integrative review, we focus on missed opportunities in the diagnosis of breast, lung, and colorectal cancer in the ambulatory care environment. From a review of 493 publications, we summarize the current evidence regarding the contributing factors to missed or delayed cancer diagnosis in ambulatory care, as well as evidence to support possible strategies for intervention. Cancer diagnoses are made after …

Antibiotic Prophylaxis With Urodynamic Studies In Spinal Cord Injury: Assessing Practice Patterns And Outcomes To Guide Future Practice In A Single Center, Du Pham, Bradley Chi, Felicia Skelton, Donna Huang

Faculty, Staff and Students Publications

Context/objective: Despite urinary tract infections (UTIs) being a common problem in patients with spinal cord injuries (SCIs), and a well-known complication of invasive urologic procedures, little consensus exists regarding the standard of care for peri-procedural antibiotic use for SCI patients undergoing urodynamics studies (UDS). Our research seeks to evaluate local antibiotic prophylaxis pattern in SCI patients undergoing UDS, assess incidence of post-procedural UTI, describe local antibiotic resistance trends, and provide antibiotic stewardship considerations to guide future practice.

Design/setting/participants: Retrospective cohort study of SCI patients undergoing UDS from January 2010 to January 2020 at a Veterans Affairs SCI Center. Data on …

Cortical Structure In Nodes Of The Default Mode Network Estimates General Intelligence, Abhinav Yadav, Archana Purushotham

Faculty, Staff and Students Publications

Introduction: A growing number of studies implicate functional brain networks in intelligence, but it is unclear if network nodal structure relates to intelligence.

Methods: Using MRI, we studied the relationship of the general intelligence factor (g) with cortical thickness (CT), local gyrification index (LGI), and voxel-based morphometry in the nodes of the default mode network (DMN) and task-positive network (TPN) in a cohort of 44 young, healthy adults. Employing a novel strategy, we performed repeated analyses with multiple sets of g estimates to remove false positives.

Results: CT and LGI in medial and temporal nodes of the DMN were reliably …

Otolaryngology-Assisted Approach For Anterior Cervical Discectomy And Fusion, M Benjamin Larkin, Anthony K Allam, Cyrus B King, N Eddie Liou, Alexander E Ropper

Faculty, Staff and Students Publications

First introduced in 1955, anterior cervical discectomy and fusion (ACDF) surgery has seen minimal changes over the years. Its reproducibility, impressive long-term results, and minimal complication rates have established it as one of the most frequently performed cervical spinal fusion surgeries. Yet, postoperative dysphagia remains a concern with a 60% incidence rate. An otolaryngologist's expertise regarding cervical fascial anatomy can inform the spine surgeon's approach to an ACDF to potentially reduce postoperative dysphagia rates. We describe an illustrative case of a 35-year-old woman who presented with 8/10 neck and arm pain along with numbness in her fourth and fifth digits …

Maternal-Fetal Surgery For Myelomeningocele Longitudinal Follow-Up Model: Mitigation Of Care Fragmentation Through Care Coordination And Outcomes Reporting, Jonathan Castillo, Mary M Locastro, Romain Corroenne, Anjali Malhotra, Alexander Van Speybroeck, Grace Lai, Michael A Belfort, Magdalena Sanz Cortes, Heidi Castillo

Faculty, Staff and Students Publications

Purpose

Methods

Results

Bile Acid And Microbiome Interactions In The Developing Child, Mary Elizabeth M Tessier, Benjamin L Shneider, Joseph F Petrosino, Geoffrey A Preidis

Faculty, Staff and Students Publications

Interactions between the gut microbiome and bile acids are complex and are linked to outcomes in pediatric liver disease by mechanisms that are incompletely understood. In adults, primary bile acids are synthesized in the liver and secreted into the intestine, where complex communities of gut microbes deconjugate, oxidize, epimerize, and 7α-dehydroxylate bile acids into a diverse array of unconjugated, secondary, allo-, iso-, and oxo-bile acids. In contrast, the infant gut microbiota contains a simple, Bifidobacterium-dominant community that transitions to a more diverse, adult-like community as additional microbes colonize the gut. This microbial succession gradually confers deconjugation, oxidation, epimerization, and 7α-dehydroxylation …

Functional Genomics In Age-Related Macular Degeneration: From Genetic Associations To Understanding Disease Mechanisms, Rinki Ratnapriya, Felix Grassman, Rui Chen, Alex Hewitt, Jianhai Du, Daniel R Saban, Caroline C W Klaver, John Ash, Dwight Stambolian, Santa J Tumminia, Jiang Qian, Deeba Husain, Sudha K Iyengar, Anneke I Den Hollander

Faculty, Staff and Students Publications

Genome-wide association studies have been remarkably successful in identifying genetic variants associated with age-related macular degeneration (AMD), demonstrating a strong genetic component largely driven by common variants. However, progress in translating these genetic findings into a deeper understanding of disease mechanisms and new therapies has been slow. Slow progress in this area can be attributed to limited knowledge of the functional impact of AMD-associated non-coding variants on gene function, the molecular mechanisms and cell types underlying disease. This review offers a comprehensive overview of functional genomics approaches to uncover the genetic, epigenetic, cellular and molecular mechanisms underlying AMD and outlines …

Efficacy And Safety Of Epicutaneous Immunotherapy In Peanut-Allergic Toddlers: Open-Label Extension To Epitope, Matthew Greenhawt, Deborah Albright, Sara Anvari, Nicolette Arends, Peter D Arkwright, Philippe Bégin, Katharina Blümchen, Terri Brown-Whitehorn, Heather Cassell, Edmond S Chan, Christina E Ciaccio, Antoine Deschildre, Amandine Divaret-Chauveau, Stacy Dorris, Morna Dorsey, George Du Toit, Thomas Eiwegger, Michel Erlewyn-Lajeunesse, David M Fleischer, Lara S Ford, Maria Garcia-Lloret, Jonathan O'B Hourihane, Nicola Jay, Stacie M Jones, Edwin H Kim, Kirsten Kloepfer, Stephanie Leonard, Guillaume Lezmi, Jay Lieberman, Jeanne Lomas, Melanie Makhija, Michael O'Sullivan, Christopher Parrish, Jane Peake, Kirsten P Perrett, Daniel Petroni, Jacqueline A Pongracic, Patrick Quinn, Rachel G Robison, Georgiana Sanders, Lynda Schneider, Hemant Sharma, Sayantani B Sindher, Juan Trujillo, Paul J Turner, Katherine Tuttle, Julia Upton, Pooja Varshney, Brian P Vickery, Christian Vogelberg, Brynn Wainstein, Julie Wang, Robert Wood, Katharine J Bee, Dianne E Campbell, Todd D Green, Rihab Rouissi, Henry T Bahnson, Timothée Bois, Hugh A Sampson, A Wesley Burks

Faculty, Staff and Students Publications

Background: The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN patch containing 250 μg of peanut protein (VP250), previously reported significant treatment response versus placebo in peanut-allergic toddlers aged 1 through 3 years.

Objective: To assess the interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study.

Methods: Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFCs) and safety assessments; here we report the first-year OLE (year 2) results.

Results: A total …

Testing For Bleeding Disorders In Child Abuse: Aap Recommendation Adherence And Testing Results, Lyndsey Hultman, Angela Doswell, Henry T Puls, Shannon L Carpenter, Angela Bachim, Caitlin R Mcnamara, Farah W Brink, Lori D Frasier, Nancy S Harper, Natalie Laub, Kristine A Campbell, Daniel M Lindberg, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Objectives: Using a multicenter child abuse pediatrics research network (CAPNET), the study objectives were to characterize the adherence to American Academy of Pediatrics (AAP) recommendations for bleeding disorder testing and the frequency of bleeding disorder identification.

Methods: We performed a descriptive study of bleeding disorder evaluations among children younger than 10 years of age who presented with bruising and/or intracranial hemorrhage (ICH) concerning for abuse from February 2021-May 2022 utilizing CAPNET. Cases were classified as bruising without ICH or ICH with or without bruising. Based on AAP guidance, testing was not recommended in cases with concomitant suspicious injuries, inflicted injury …

Prevalence Of And Risk Factors For Osteoporosis And Fragility Fracture In Adults With Cerebral Palsy: A Systematic Review, Anne Trinh, Ellen Fremion, Shayan Bhathena, Craig F Munns, Prue Morgan, Daniel G Whitney, Bernadette Gillick, Margaret Zacharin, Darcy Fehlings, Amanda J Vincent, Frances Milat

Faculty, Staff and Students Publications

Aim: To systematically review the prevalence and incidence of osteoporosis, osteopenia, low bone mass, and fragility fracture in adults with cerebral palsy (CP), and identify the risk factors for osteoporosis and fracture.

Method: A systematic literature search was performed in the MEDLINE, PubMed, CINAHL, AMED, Cochrane Reviews, EMBASE, and EBM database reviews from inception until May 2024. Search terms covered a combination of keywords for CP, fracture, osteoporosis, incidence and prevalence, and risk factors. Participants were adults with CP aged 18 years and older. JBI critical appraisal instruments were used to assess quality and risk of bias.

Results: Seventeen of …

Normative Variability In Retinal Nerve Fiber Layer Thickness: Does It Matter Where The Peaks Are?, Sowjanya Gowrisankaran, Ashkan Abbasi, Xubo Song, Joel Schuman, Gadi Wollstein, Bhavna Antony, Hiroshi Ishikawa

Wills Eye Hospital Papers

PURPOSE: Retinal nerve fiber layer thickness (RNFLT), a glaucoma biomarker, has a wide normative range affecting its sensitivity and specificity for abnormality detection. The interindividual RNFLT peak location variability contribution to this wide normative range has not been directly evaluated. The purpose of this study is to assess the effect of RNFLT peak normalization (PN) on normative variability.

METHODS: Circumpapillary RNFLT profiles at 1.7 mm radius from the optic nerve head (ONH) were re-sampled from optical coherence tomography (OCT) volumes (Cirrus HD-OCT, 200 × 200) obtained from one eye of 83 healthy individuals. Fovea-ONH axis (FOA) was calculated from corresponding …

Insights Into The Role Of The Glymphatic System In The Pathogenesis Of Post-Hemorrhagic Hydrocephalus, Ahmed T Massoud, Dillon A Noltensmeyer, Jenifer Juranek, Charles S Cox, Fred Christian Velasquez, Banghe Zhu, Eva M Sevick-Muraca, Manish N Shah

The Brown Foundation: Institute of Molecular Medicine

Recently, it has been well-established that the glymphatic or glial-lymphatic system plays a vital role in the pathophysiology of various neurological compromise, especially hydrocephalus (HCP). Till now, the complete pathway is not yet fully understood, and little evidence is available from the literature that links hydrocephalus to disorders of the glymphatic system. Most published molecular studies and animal research have shown that, in models with hydrocephalus, the drainage of cerebrospinal fluid (CSF) via the glymphatic system is disrupted. This is strongly observed in normal pressure and post-hemorrhagic hydrocephalus cases. A thorough search of the literature to date yields scarce evidence …

Survival In Patients With Rheumatoid Arthritis And Recently Diagnosed Early-Stage Colorectal, Lung, Or Prostate Cancer Receiving Tumour Necrosis Factor Inhibitors: A Retrospective Cohort Study, Juan I Ruiz, Xiudong Lei, Sharon H Giordano, Hui Zhao, Suja S Rajan, Heather Lin, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Background: Tumor necrosis factor (TNF) inhibitors could impair tumoural immunity in patients with rheumatoid arthritis and cancer. We aimed to investigate the association between survival and TNF inhibitor treatment during the first 3 years after a diagnosis of colorectal, lung, or prostate cancer in patients with rheumatoid arthritis.

Methods: In this cohort study, we conducted a secondary data analysis of the Surveillance, Epidemiology, and End Results Medicare-linked dataset. We included patients aged 66 years and older with rheumatoid arthritis diagnosed with colorectal, lung, or prostate cancer between Jan 1, 2008, and Dec 31, 2019, using ICD-O-3 site and histology codes. …

An Updated Systematic Review And Consensus Definitions For Standardised Endpoints In Perioperative Medicine: Patient Comfort And Pain Relief, Paul S Myles, Sophie Wallace, Oliver Boney, Mari Botti, Frances Chung, Allan M Cyna, Tong J Gan, Michael P W Grocott, Mark P Jensen, Henrik Kehlet, Andrea Kurz, Maxime Leger, Ulrica Nilsson, Phillip Peyton, Daniel I Sessler, Martin R Tramèr, Christopher L Wu, Alfred Health Patient Experience And Consumer Engagement Group

Faculty, Staff and Student Publications

Background: Improving comfort during and after surgery is a key concern for anaesthetists and other clinicians. With the inclusion of patient and public involvement, we undertook a Delphi consensus process to update previously recommended endpoints to be used in clinical trials evaluating treatments aiming to improve patient comfort after surgery.

Methods: We undertook a systematic review to identify domains and outcome measures of patient comfort used in perioperative studies. Focus groups, workshops, and a multi-round Delphi consensus process that included clinician-researchers and a patient experience and consumer group updated a recommended list of standardised endpoints focused on patient comfort. Consensus …

Associations Between The Timing Of 24 H Physical Activity And Diabetes Mellitus: Results From A Nationally Representative Sample Of The Us Population, Qian Xiao, Qiuyu Feng, Martin K Rutter, Gali Albalak, Heming Wang, Raymond Noordam

Faculty, Staff and Student Publications

Aims/hypothesis: Growing evidence suggests that timing may be an important aspect of physical activity that influences cardiometabolic health. However, the current literature is inconclusive regarding the time of day that physical activity offers the greatest metabolic advantages. We investigated associations between hourly physical activity levels and diabetes mellitus and glycaemic biomarkers in a cross-sectional and nationally representative sample of US adults.

Methods: We studied 7074 adults (mean age 48 years; 52% women) from the National Health and Nutrition Examination Survey (2011-2014). Physical activity was measured by actigraphy. A monitor-independent movement summary (MIMS) unit was used to derive the total activity …

Comparison Of Risk Assessment Tools' Prediction Of Outcomes For Penetrating Trauma, Jeffrey Santos, Catherine M Kuza, Xi Luo, Tiffany Moon, Thomas Shoultz, Anne Feeler, Roman Dudaryk, Jose Navas, Georgia Vasileiou, Kazuhide Matsushima, Matthew Forestiere, Tiffany Lian, Areg Grigorian, Joni Ricks-Oddie, Jeffry Nahmias

Faculty, Staff and Student Publications

Introduction: The Trauma and Injury Severity Score (TRISS) uses anatomic and/or physiologic variables to predict mortality; however, Injury Severity Score is less reliable for penetrating trauma. National Surgical Quality Improvement Program Surgical Risk Calculator (NSQIP-SRC) and American Society of Anesthesiologists Physical Status (ASA-PS) include functional status and comorbidities. This study evaluates the accuracy of these tools in predicting mortality, length of stay (LOS), and complications for operative penetrating trauma.

Methods: Adult penetrating trauma patients (≥18 y) who underwent surgery within 24 h of admission were included in this subgroup analysis of a prospective observational study at four trauma centers. The …

Digital Twins, Synthetic Patient Data, And In-Silico Trials: Can They Empower Paediatric Clinical Trials?, Mohan Pammi, Prakesh S Shah, Liu K Yang, Joseph Hagan, Nima Aghaeepour, Josef Neu

Faculty, Staff and Students Publications

Randomised controlled trials are the gold standard to assess the effectiveness and safety of clinical interventions; however, many paediatric trials are discontinued early due to challenges in patient enrolment. Hence, most paediatric clinical trials suffer from lack of adequate power. Additionally, trials are expensive and might expose patients to unproven therapies. Alternatives to overcome these issues using virtual patient data—namely, digital twins, synthetic patient data, and in-silico trials—are now possible due to rapid advances in digital health-care tools and interventions. However, such digital innovations have been rarely used in paediatric trials. In this Viewpoint, we propose using virtual patient data …

Metastatic Medulloblastoma Remodels The Local Leptomeningeal Microenvironment To Promote Further Metastatic Colonization And Growth, Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino De Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G Lucas, Charles G Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N Rich, Xiaochong Wu, Xi Huang, Michael D Taylor

Faculty, Staff and Students Publications

Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges …

Functional Vision Assessment Over 4 Years In Ush2a Using The Veteran Affairs Low-Vision Visual Functioning Questionnaire, Bela Parekh, Nicholas Peck-Dimit, Jacque L Duncan, Lassana Samarakoon, Maria Fernanda Abalem, Chris A Andrews, Isabelle Audo, Allison R Ayala, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Rachel M Huckfeldt, Gabrielle D Lacy, Brett Malbin, Michel Michaelides, David C Musch, Katarina Stingl, Christina Y Weng, Alex Z Zmejkoski, Michele Melia, K Thiran Jayasundera, Foundation Fighting Blindness Clinical Consortium Investigator Group

Faculty, Staff and Students Publications

Purpose: The purpose of this study was to evaluate the validity of the Veterans Affairs Low Vision Visual Functioning Questionnaire (VALVVFQ-48) functional vision scores (FVS) in patients with USH2A-associated retinal degeneration. In addition, to correlate the change in the VALVVFQ-48 FVS with the change in visual function (VF) measurements.

Methods: The VALVVFQ-48 was administered verbally to participants ≥18 years of age at baseline, and after 2 and 4 years. Associations among changes in FVS and changes in VF measures were assessed using the Spearman correlation coefficients. Mixed effects regression models with a random intercept were used to estimate annual rates …

Glands Of Moll: History, Current Knowledge And Their Role In Ocular Surface Homeostasis And Disease, Michael Stopfer, Ingrid Zahn, Katharina Jüngert, Gerhard Aumüller, Frans L Moll, Martin Schicht, Helen P Makarenkova, Cintia S De Paiva, Friedrich P Paulsen

Faculty, Staff and Students Publications

Over the last 20 years, research into the Meibomian glands of the eyelids has increased exponentially and is now widely recognized as a field of research. It is all the more astonishing that knowledge about another type of gland in the eyelids, the Moll glands or ciliary glands, has almost stagnated and there has been little to almost no progress, even though this type of gland as a whole takes up a relatively large volume in the upper and lower eyelids. There is not much information about the namesake Moll or the function of the glands although these are listed …

Clerkship Students' Use Of Clinical Reasoning Concepts After A Pre-Clinical Reasoning Course, Shradha A Kulkarni, Gurpreet Dhaliwal, Arianne Teherani, Denise M Connor

Faculty, Staff and Students Publications

Background: Many medical schools have incorporated clinical reasoning (CR) courses into their pre-clinical curricula to address the quality and safety issue of diagnostic error. It is unknown how students use concepts and practices from pre-clinical CR courses once in clerkships.

Objective: We sought to understand how students utilize CR concepts from a pre-clinical course during clerkships and to identify facilitators and barriers to the use of reasoning concepts.

Design: We used structured interviews to gain insight into medical students' experiences with CR concepts in clerkships.

Participants: We interviewed 16 students who had completed a pre-clinical CR course and subsequently completed …

Repeat Ascaris Challenge Reduces Worm Intensity Through Gastric Cellular Reprograming, Yifan Wu, Charlie Suarez-Reyes, Nina L Tang, Alexander R Kneubehl, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most prevalent parasitic nematode infection worldwide, impacting approximately 500 million people predominantly in low- and middle-income countries (LMICs). While people of all ages are infected with Ascaris, infection intensity (defined by worm burden) paradoxically peaks in pre-school and school-aged children but then declines with age. The cause of age-dependent Ascaris worm intensity is not well understood but may be dependent on cellular changes in mucosal barrier sites. We have previously found that the gastric mucosa is a critical barrier site for Ascaris infection as ingested Ascaris larvae use acidic mammalian chitinase (AMCase) secreted by gastric chief …

Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) share overlapping features for which similar cognitive behavioral treatment (CBT) strategies can be employed. However, the comorbid presence of these conditions poses unique clinical considerations, and a nuanced approach to assessment, conceptualization, and treatment is needed when working with individuals with co-occurring OCD and PTSD. Treatment providers may not be aware of these nuances and may hold misconceptions about co-occurring OCD and PTSD, impacting their approach to assessment, conceptualization, and treatment. The current study sought to examine possible misconceptions among mental health treatment providers of differing specializations. Among 146 primarily CBT-oriented treatment …

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

Spaceflight Associated Neuro-Ocular Syndrome (Sans) And Its Countermeasures, Tuan Nguyen, Joshua Ong, Tyson Brunstetter, C Robert Gibson, Brandon R Macias, Steven Laurie, Thomas Mader, Alan Hargens, Jay C Buckey, Mimi Lan, Peter Wostyn, Cihan Kadipasaoglu, Scott M Smith, Sara R Zwart, Benjamin J Frankfort, Sarah Aman, Jessica M Scott, Ethan Waisberg, Mouayad Masalkhi, Andrew G Lee

Faculty, Staff and Students Publications

Astronauts can develop a distinct collection of neuro-ophthalmic findings during long duration spaceflight, collectively known as Spaceflight Associated Neuro-ocular Syndrome (SANS). These clinical characteristics include optic disc edema, hyperopic refractive shifts, globe flattening, and chorioretinal folds, which may pose a health risk for future space exploration. Obtaining knowledge of SANS and countermeasures for its prevention is crucial for upcoming crewed space missions and warrants a multidisciplinary approach. This review examines the potential causes and countermeasures of SANS, including space anticipation glasses, lower body negative pressure, venoconstrictive thigh cuffs, impedance threshold devices, translaminar pressure gradient modulation, centrifugation, artificial gravity, pharmaceuticals, and …

Long-Term Safety Of Epicutaneous Immunotherapy In Peanut-Allergic Children: An Open-Label Active Treatment (Realise Study), Jacqueline A Pongracic, Rémi Gagnon, Gordon Sussman, Dareen Siri, Roxanne C Oriel, Terri F Brown-Whitehorn, Sara Anvari, William E Berger, J Andrew Bird, Edmond S Chan, R Sharon Chinthrajah, Hey J Chong, Stanley M Fineman, David M Fleischer, Erika Gonzalez-Reyes, Edwin H Kim, Bruce J Lanser, Andrew Macginnitie, Hemalini Mehta, Daniel Petroni, Ned Rupp, Lynda C Schneider, Amy M Scurlock, Lawrence D Sher, Wayne G Shreffler, Sayantani B Sindher, Robert Wood, William H Yang, Hugh A Sampson, Timothée Bois, Todd D Green, Dianne E Campbell, Katharine J Bee, Philippe Bégin

Faculty, Staff and Students Publications

Background: Owing to limited treatment options for peanut allergy, patients remain at risk for allergic reactions due to accidental exposure. Epicutaneous immunotherapy (EPIT) is a novel treatment being investigated for peanut allergy.

Objective: This study assessed long-term safety of EPIT with VIASKIN peanut patch 250 μg (VP250) via an open-label extension of the REAL Life Use and Safety of EPIT (REALISE) trial.

Methods: REALISE was a phase 3 trial in peanut-allergic children aged 4 through 11 years that included a 6-month, randomized, double-blind, placebo-controlled treatment phase, followed by an open-label, single-arm, active treatment period for up to 36 months.

Results: …

Evaluating The Test-Negative Design For Covid-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis Of 5 Randomized Clinical Trials, Leah I B Andrews, M Elizabeth Halloran, Kathleen M Neuzil, Lars Van Der Laan, Yunda Huang, Jessica Andriesen, Mayur Patel, Leigh H Fisher, Holly Janes, Nadine Rouphael, Stephen R Walsh, Deborah A Theodore, Hong-Van Tieu, Magdalena Sobieszczyk, Hana M El Sahly, Lindsey R Baden, Ann R Falsey, Thomas B Campbell, Colleen F Kelley, Catherine Mary Healy, Lilly Immergluck, Benjamin Luft, Ian Hirsch, Guy De Bruyn, Carla Truyers, Frances Priddy, Kelsey M Sumner, Brendan Flannery, Dean Follmann, Peter B Gilbert, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

Design, setting, and participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults …

The Central Role Of Cytochrome P450 Reductase (Cpr) In Hyperoxic Lung Injury, Deven Narke, Bhagavatula Moorthy

Faculty, Staff and Students Publications

Introduction: Hyperoxic lung injury results from excessive supplemental oxygen therapy in conditions such as bronchopulmonary dysplasia (BPD) in preterm infants and acute respiratory distress syndrome (ARDS) in adults. This review explores the role of cytochrome P450 reductase (CPR) in hyperoxic lung injury.

Areas covered: Hyperoxia induces the production of reactive oxygen species in excessive amounts, overwhelming the body's antioxidant defenses and exacerbating lung injury in ARDS/BPD. This review examines the differential roles of CPR-dependent enzymes in the context of hyperoxic lung injury. Additionally, we highlight the potential of targeting CPR to study mechanisms of lung injury and leverage gene-editing technologies …

Comparative Risk Of Mortality In New Users Of Prescription Opioids For Noncancer Pain: Results From The International Pharmacosurveillance Study, Meghna Jani, Nadyne Girard, David W Bates, David L Buckeridge, William G Dixon, Robyn Tamblyn

Faculty, Staff and Students Publications

Although opioids continue to be used internationally for noncancer pain, evidence to date on the comparative safety of different opioids is sparse and conflicting. The aim of this study was to examine the comparative risk of all-cause mortality in patients newly initiated on opioids for noncancer pain, across 3 jurisdictions in the United Kingdom (UK), United States, and Canada. A multicentre retrospective, population-based cohort study was conducted. Data sources included UK national primary care electronic health records (Clinical Practice Research Datalink), The Partners HealthCare Research Patient Data in Boston (US), and The Montreal Population Health Record data (Canada). New users …

Clinical, Immunologic, And Genetic Characteristics Of 148 Patients With Natural Killer Cell Deficiency, Manar Abdalgani, Evelyn R Hernandez, Luis A Pedroza, Ivan K Chinn, Lisa R Forbes Satter, Nicholas L Rider, Pinaki P Banerjee, M Cecilia Poli, Sanjana Mahapatra, Debra Canter, Tram Cao, Linda M Shawver, Sarada L Nandiwada, James R Lupski, Jennifer E Posey, Rajasekhar Ramakrishnan, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Background: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.

Objective: We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice.

Methods: During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.

Results: NK cell abnormalities consistent with …