Digital Commons Network^™

‘In Texas, Everybody Wants Antibiotics’: Reducing Inappropriate Antibiotic Expectations And Use With A Provider-Patient Communication Tool In Primary Care, Ashley Collazo, Paige Wermuth, Johanan Luna Rodriguez, Kiara Olmeda, Azalia Mancera, Fabrizia Faustinella, Michael K Paasche-Orlow, Roger Zoorob, Barbara Wells Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Background/objective: Patients often expect antibiotics for self-limiting diseases, pressuring providers to prescribe antibiotics unnecessarily. These expectations also contribute to the unsafe practice of taking antibiotics without a prescription (non-prescription use), such as pills retained from prior prescriptions or antibiotics from non-medical sources. Previous work shows that non-prescription use is due to strong, widely held misconceptions regarding the curative power of antibiotics. To reduce unnecessary use of antibiotics, we developed and pilot-tested a patient-focused, bilingual (English and Spanish) educational tool with patient and provider stakeholder input. The tool, a trifold brochure, included information on safe antibiotic use, potential antibiotic harms and …

Influenza Vaccine Effectiveness Against Medically Attended Outpatients Illness, United States, 2023-2024 Season, Jessie R Chung, Stacey L House, Tara Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2023-2024 US influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with cocirculation of A(H3N2) and B/Victoria viruses. We estimated vaccine effectiveness (VE) in the United States against mild-to-moderate medically attended influenza illness in the 2023-2024 season.

METHODS: We enrolled outpatients aged ≥8 months with acute respiratory illness in 7 states. Respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction. Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants. We estimated VE by virus subtype/lineage and A(H1N1)pdm09 genetic subclades.

RESULTS: Among 6629 …

Large-Scale Profiling Of Antibody Reactivity To Glycolipids In Patients With Guillain-Barré Syndrome, Robin C M Thomma, Susan K Halstead, Laura C De Koning, Eveline J A Wiegers, Dawn S Gourlay, Anne P Tio-Gillen, Wouter Van Rijs, Henning Andersen, Giovanni Antonini, Samuel Arends, Shahram Attarian, Fabio A Barroso, Kathleen J Bateman, Luana Benedetti, Peter Van Den Bergh, Jan Bürmann, Mark Busby, Carlos Casasnovas, Efthimios Dardiotis, Amy Davidson, Thomas E Feasby, Janev Fehmi, Giuliana Galassi, Tania Garcia-Sobrino, Volkan Granit, Gerardo Gutiérrez-Gutiérrez, Robert D M Hadden, Thomas Harbo, Hans-Peter Hartung, Imran Hasan, James K L Holt, Zhahirul Islam, Summer Karafiath, Hans D Katzberg, Noah Kolb, Susumu Kusunoki, Satoshi Kuwabara, Motoi Kuwahara, Helmar C Lehmann, Sonja E Leonhard, Lorena Martín-Aguilar, Soledad Monges, Eduardo Nobile-Orazio, Julio Pardo, Yann Pereon, Luis Querol, Ricardo C Reisin, Simon Rinaldi, Paolo Ripellino, Rhys C Roberts, Olivier Scheidegger, Nortina Shahrizaila, Kazim A Sheikh, Nicholas J Silvestri, Soren H Sindrup, Beth Stein, Cheng Y Tan, Hatice Tankisi, Leo H Visser, Waqar Waheed, Ruth Huizinga, Bart C Jacobs, Hugh J Willison

Faculty, Staff and Student Publications

Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside antibody specificities has been performed. Recent research has highlighted glycolipid complexes, glycolipid combinations that may alter antibody binding, as targets. In this study, we investigated antibody reactivity patterns to glycolipids and glycolipid complexes using combinatorial array, in relation to clinical features in Guillain-Barré syndrome. In total, …

A Temperature-Sensitive Crispr-Cas12a System For Sterile Insect Technique, Christina Nguyen, Ahmed Idowu Omotayo, Sara Sanz Juste, Xuechun Feng, Víctor López Del Amo

Faculty, Staff and Student Publications

The sterile insect technique (SIT) reduces population numbers by releasing sterile males that produce non-viable progeny. Specifically, CRISPR/Cas9-based precision-guided SIT (pgSIT) generates sterile males through genetic crosses of two transgenic lines: a Cas9 strain and a guide RNA (gRNA) strain targeting male sterility and female viability or infertility. However, pgSIT requires separate maintenance of the two lines and sorting to obtain sterile males, creating possible challenges for scaling. To overcome this, we propose using Cas12a nuclease, which is inoperative at lower temperatures but active at higher temperatures. Here, we develop a Cas12a-based pgSIT system involving a single strain containing both …

A Multi-National Cross-Sectional Exploration Of Rehabilitation Services For Children And Young People Following Brain Injury In Low And Middle Income Countries, Mark A Linden, Leigh Schrieff-Brown, Linda Ewing-Cobbs, R A Leonard, Rajendra Prasad, Juan Carlos Arango-Lasprilla, Sandra Strazzer, Lucia Braga, Consuelo Reyes Payeras, Kim C Davis, Lisa Kalungwana-Mambwe, Flavia Dorrego, Mathilde Chevignard

Faculty, Staff and Student Publications

Background: Brain injury (BI) is the largest cause of mortality and morbidity among children and can lead to significant cognitive, social, emotional and behavioural deficits. There has been an absence of research examining the availability of rehabilitation services for affected children and young people in low and middle income countries (LMICs). This study therefore investigated current rehabilitation provision in LMICs for children and young people with BI.

Methods: An online survey was developed which collected data on funding support for rehabilitation, causes of BI and access to services. The survey was distributed to healthcare professionals known to members of the …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Physical Activity And Molecular Subtypes Of Colorectal Cancer: A Pooled Observational Analysis And Mendelian Randomization Study, Christos V Chalitsios, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity.

METHODS: Pooled observational (cases: n = 5386; controls: n = 6798; studies n = 5) and genome-wide association data (cases: n = 8178; controls: n = 10 472; studies n = 5) were used. We used multivariable logistic regression models and Mendelian randomization to assess the association between physical activity and the risk of CRC subtypes …

Real-World Data For Tisagenlecleucel In Patients With R/R B-All: Subgroup Analyses From The Cibmtr Registry., Samuel John, Kevin J. Curran, Erin Hall, Amy K. Keating, Susanne H C Baumeister, Sarah Nikiforow, Timothy Driscoll, Amy Moskop, Kevin O. Mcnerney, Christine L. Phillips, Michael A. Pulsipher, Emily M. Hsieh, Rayne H. Rouce, Marcelo C. Pasquini, Ranjan Tiwari, Jennifer Willert, Roberto Ramos, Joerg Krueger, Erin Guest, Stephan A. Grupp

Manuscripts, Articles, Book Chapters and Other Papers

Since the first approval of tisagenlecleucel in 2017, pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) may receive this CD19-directed chimeric antigen receptor T-cell therapy. We report real-world data from the Center for International Blood and Marrow Transplant Research (>2.5 years of follow-up). As of 4 May 2022, 768 patients with B-ALL had received tisagenlecleucel. Patients aged ≥18 and < 18 years of age (including those < 3 years) were treated during first relapse (26.6% and 26.7% [< 3 years, 44.8%], respectively) or primary refractory disease (12.4% and 12.1% [< 3 years, 15.5%], respectively) with 17.6% and 11.6% (< 3 years, 13.8%), respectively, having high disease burden (≥50% bone marrow [BM] blasts) and 20.2% and 20.2% (< 3 years, 13.8%), respectively, having low disease burden (>0 to < 5% BM blasts). Among patients with ≥12 months postinfusion follow-up (n = 578; median follow-up, 32.1 months), the best overall response of complete remission/complete remission with incomplete blood count recovery was 86.0%. The 12-month relapse-free survival (RFS) and overall survival (OS) were 61.8% and 79.4%, respectively, whereas the 24-month RFS and OS were 50.3% and 63.8%, respectively. Age (< 18 years) and disease burden (< 50% BM blasts) were associated with better outcomes. Previous inotuzumab therapy and KMT2A rearrangement were associated with worse outcomes. Older patients (≥18 years) experienced a higher rate of any-grade cytokine release syndrome (CRS) associated with higher disease burden before infusion. Any-grade CRS and neurotoxicity were lower in patients aged < 3 years. Extended follow-up continues to demonstrate high rates of RFS and favorable safety in this population.

Everolimus And Low-Dose Tacrolimus After Heart Transplant In Children: A Randomized Clinical Trial, Christopher S Almond, Kevin P Daly, Erin L Albers, Juan C Alejos, Rebecca Ameduri, Scott R Auerbach, Lynsey Barkoff, Aliessa P Barnes, Matthew J Bock, Arene Butto, Waldemar F Carlo, Chesney D Castleberry, Maryanne R Chrisant, Shriprasad R Deshpande, William J Dreyer, Melanie D Everitt, Brian Feingold, Selena Gonzales, Seth A Hollander, Steven J Kindel, Gloria L Klein, Ashwin K Lal, Jacqueline M Lamour, Joanne Lee, Minmin Lu, Irene D Lytrivi, Shelley D Miyamoto, Elfriede Pahl, David M Peng, Thomas D Ryan, Tajinder P Singh, Jennifer A Su, David L Sutcliffe, A Marian Ybarra, Steven Zangwill, Joseph W Rossano, Lynn A Sleeper

Faculty, Staff and Students Publications

Importance: Studies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.

Objective: To evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in …

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Vaccine Effectiveness Against Influenza A(H1n1), A(H3n2), And B-Associated Hospitalizations, United States, 1 September 2023 To 31 May 2024, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2023-2024 influenza season included sustained elevated activity from December 2023 to February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season.

METHODS: During 1 September 2023 to 31 May 2024, a multistate sentinel surveillance network of 24 medical centers in 20 US states enrolled adults aged ≥18 years hospitalized with acute respiratory illness. Consistent with a test-negative design, cases tested positive for influenza viruses by molecular or antigen test, and controls tested negative for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccine effectiveness (VE) against influenza-associated hospitalization …

Changes In Antiviral Prescribing For Children With Influenza In Us Emergency Departments., Tess Stopczynski, Olla Hamdan, Justin Z. Amarin, James W. Antoon, Laura S. Stewart, Haya Hayek, James Chappell, Andrew J. Spieker, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, John V. Williams, Marian G. Michaels, Julie A. Boom, Leila C. Sahni, Mary Allen Staat, Elizabeth P. Schlaudecker, Jennifer E. Schuster, Rangaraj Selvarangan, Ayzsa Tannis, Heidi L. Moline, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite national recommendations, antiviral prescribing in emergency departments (EDs) for children at higher risk of severe influenza, such as those younger than 5 years and those with specific underlying conditions, remains low.

OBJECTIVE: To assess whether there were changes in antiviral prescribing for children at higher risk of severe influenza in academic pediatric EDs before the COVID-19 pandemic (2016-2020) vs the late pandemic period (2021-2023).

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, cross-sectional study included influenza-positive children younger than 18 years presenting to the ED at 1 of 7 US pediatric academic hospitals participating in the Centers for Disease Control …

Cervical And Tumor-Associated Microbiomes In Botswana Women With And Without Hiv With Carcinoma Of The Cervix Before And After Definitive Chemoradiation, Travis T Sims, Kyoko Yoshida-Court, Molly B El Alam, Pleasure Ramatlho, Rebecca Ketlametswe, Matthew S Ning, Erle S Robertson, Kathleen M Schmeler, Lauren E Colbert, Ann H Klopp, Surbhi Grover

Faculty, Staff and Student Publications

Purpose: Cervical cancer remains a significant public health concern globally and particularly in sub-Saharan Africa, where high rates of HIV infection exacerbate cervical cancer incidence. Understanding the cervical microbiome and its role in cancer progression is essential, especially in regions where both cervical cancer incidence and HIV prevalence are high. This study aimed to characterize the cervical microbiome in women living with HIV (WLWH) and HIV-negative women with squamous cell carcinoma of the cervix in Botswana, compare the microbiome between before and after chemoradiation therapy (CRT) in WLWH, and assess the prognostic value of specific microbial taxa for overall survival …

Motivations, Facilitators, And Barriers Of Donation-Based Interventions In Hiv And Sexually Transmitted Infection Research: A Systematic Review, Dorian Ho, Ye Liu, Jamie Conklin, Thomas Fitzpatrick, Jiayu Wang, Suzanne Day, Takhona G Hlatshwako, Rohit Ramaswamy, Ruby Congjiang Wang, Eneyi E Kpokiri, Weiming Tang, Elvin Geng, Joseph D Tucker

2020-Current year OA Pubs

IMPORTANCE: Donation-based prosocial interventions involve someone receiving a free health service and then distributing or donating to support health services for others; examples within the HIV and sexually transmitted infection (STI) literature include secondary distribution of HIV self-tests, secondary syringe exchange, and pay it forward for STI testing. These interventions answer research and policy recommendations to incorporate prosocial behaviors into HIV/STI services.

OBJECTIVE: To describe motivations, facilitators, and barriers of donation-based interventions in HIV and STI research using data from qualitative studies.

EVIDENCE REVIEW: In this systematic review, 5 databases (PubMed, CINAHL, Embase, PsycInfo, and Scopus) and references were searched …

Covid-19 Booster Vaccine Messaging In Emergency Departments: A Cluster Randomized Clinical Trial, Melanie F Molina, Stephanie A Eucker, Kristin L Rising, Efrat R Kean, Zubaid Rafique, Heba Mesbah, David V Glidden, Mireya I Arreguin, Christopher Alvarez, Robert M Rodriguez

Faculty, Staff and Students Publications

Importance: Patient uptake of updated COVID-19 vaccines is crucial for reducing severe outcomes, yet national uptake remains low.

Objective: To determine if tailored messaging or simple inquiry about vaccine acceptance increases 30-day uptake of updated COVID-19 vaccines among emergency department (ED) patients.

Design, setting, and participants: This 3-arm, cluster randomized clinical trial conducted from January 29 to June 18, 2024, enrolled adult ED patients who had not received a COVID-19 vaccine in the prior 6 months across 6 EDs in San Francisco, California; Philadelphia, Pennsylvania; Houston, Texas; and Durham, North Carolina.

Interventions: Intervention M involved tailored messaging about updated COVID-19 …

Molecular Dynamics Of The Host Response To Streptococcus Pneumoniae Pneumonia In Baboons, Bryan D Kraft, Et Al.

2020-Current year OA Pubs

BACKGROUND: Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics. Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy. Using an established baboon model of S. pneumoniae pneumonia, we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.

METHODS: We performed whole blood transcriptomics, unbiased proteomics, and peripheral cytokine measurements serially in baboons inoculated with S. pneumoniae (n = 23) or saline (n = 10) and modeled the peripheral blood host response using principal components analysis …

Exposure To Household Air Pollution From Biomass Cooking And Severe Pneumonia In Infants, John P Mccracken, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Household air pollution from biomass cooking is considered an important risk factor for child pneumonia.

OBJECTIVE: To evaluate the longitudinal association between exposure to particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5) or carbon monoxide (CO) and severe pneumonia in infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included infants (aged ≤12 months) whose mothers participated in a 4-country randomized clinical trial. Conducted from May 2018 to September 2021, the trial tested whether an 18-month liquefied petroleum gas stove and fuel distribution intervention reduced the incidence of severe pneumonia in offspring during infancy …

Gata2 Mutation Is Associated With Immune Dysfunction And Increased Mycobacterium Haemophilum Susceptibility In Immunocompromised Individuals, Ananya Gupta, Shail B. Mehta, Abhimanyu, Bruce A. Rosa, John Martin, Mushtaq Ahmed, Shyamala Thirunavukkarasu, Farheen Fatma, Gaya K. Amarasinghe, Makedonka Mitreva, Thomas C. Bailey, David B. Clifford, Shabaana A. Khader

2020-Current year OA Pubs

Infections with nontuberculous mycobacterium (NTM) are on the rise. Here, we investigated an uncommon NTM infection, by M. haemophilum (Mh, n = 4), from a shared geographic location in the United States. All patients had underlying immunosuppressive conditions or treatments. We identified that all these individuals had a nonsynonymous mutation in GATA2 gene, which was absent in healthy controls (HCs, n = 4) from the same geographic area (Missouri, USA). Whole blood from these individuals had attenuated cytokine responses to Mh stimulation for IL-1β, IL-6, IL-8, MIP-1α and MIP-1β, but not to phytohemagglutinin (PHA) or another NTM, M. abscessus. Impaired …

Antiviral Use Among Children Hospitalized With Laboratory-Confirmed Influenza Illness: A Prospective, Multicenter Surveillance Study., James W. Antoon, Justin Z. Amarin, Olla Hamdan, Tess Stopczynski, Laura S. Stewart, Marian G. Michaels, John V. Williams, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, Jennifer E. Schuster, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Flor M. Muñoz, Mary Allen Staat, Elizabeth P. Schlaudecker, James D. Chappell, Benjamin R. Clopper, Heidi L. Moline, Angela P. Campbell, Andrew J. Spieker, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children.

METHODS: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network. The cohort consisted of children hospitalized with influenza A or B confirmed by clinical or research testing. The primary outcome was frequency of antiviral receipt during hospitalization. We used logistic regression to obtain adjusted …

Rural Providers' Attitudes Toward Integrating Harm Reduction Strategies And Prep Prescribing Into Rural Primary Care Settings In The Us. Southeast And Midwest, Phillip L Marotta, Miryam Biaid, Virginia Mckay, Hilary Reno, Lindsey Filiatreau, Kaileigh Backes, Patricia Cavazos-Rehg, Et Al.

2020-Current year OA Pubs

BACKGROUND: People with opioid use disorders (OUD) living in the South and Midwest are under-prescribed pre-exposure prophylaxis (PrEP) despite an increasing number of providers writing PrEP prescriptions in other regions of the United States. Greater research is needed into attitudes toward integrating harm reduction strategies into primary care and PrEP prescribing among prescribers working in rural primary care settings. The objective of this paper was to examine relationships between providers' attitudes toward buprenorphine and methadone, comprehensive harm reduction (e.g., fentanyl test strips) and self-reported PrEP prescribing in the past year.

METHODS: Relationships were examined between attitudes toward buprenorphine and harm …

Innate And Adaptive Immune Features Associated With Immune-Related Adverse Events, Shaheen Khan, Venkat S Malladi, Mitchell S Von Itzstein, Hong Mu-Mosley, Farjana J Fattah, Yang Liu, Mary E Gwin, Jason Y Park, Suzanne M Cole, Sheena Bhalla, Jay Lohrey, David Hsiehchen, Angela Moses, Tao Wang, Yaming Xue, Angela B Mobley, J David Farrar, Marjaan Imam, Michelle Wu, Quan-Zhen Li, Edward K Wakeland, Yang Xie, Jeffrey A Sorelle, David E Gerber

Faculty, Staff and Student Publications

Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.

Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.

Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57+ T and natural killer (NK) T cells, plasmablasts, proliferating and …

Community Mobilisation For Adoption Of Clean Cookstoves And Clean Fuel To Reduce Household Air Pollution And Blood Pressure In Lagos, Nigeria: Protocol For A Cluster-Randomised Trial, Ololade Wright, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

INTRODUCTION: In Africa, 75% of households are exposed to household air pollution (HAP), a key contributor to cardiovascular disease (CVD). In Nigeria, 90 million households rely on solid fuels for cooking, and 40% of adults have hypertension. Though clean fuel and clean stove (CF-CS) technologies can reduce HAP and CVD risk, their adoption in Africa remains limited.

METHODS AND ANALYSIS: Using the Exploration, Preparation, Implementation and Sustainment framework, this cluster-randomised controlled trial evaluates the implementation and effectiveness of a community mobilisation (CM) strategy versus a self-directed condition (i.e., receipt of information on CF-CS use without CM) on adoption of CF-CS …

Clinical Testing For Covid-19, Influenza, And Rsv In Hospitalized Youths, 2016-2024., Ariana P. Toepfer, Rachel E. Rutkowski, Leila C. Sahni, Geoffrey A. Weinberg, Marian G. Michaels, Rangaraj Selvarangan, Mary Allen Staat, Natasha Halasa, Janet A. Englund, Julie A. Boom, Peter G. Szilagyi, Jennifer E. Schuster, Elizabeth P P. Schlaudecker, Laura S. Stewart, Eileen J. Klein, Samantha M. Olson, Sascha Ellington, Meredith L. Mcmorrow, Heidi L. Moline, Fatimah S. Dawood, New Vaccine Surveillance Network Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Studies of COVID-19, influenza, and respiratory syncytial virus (RSV) disease clinical epidemiology, disease burden, and vaccine effectiveness often rely on clinical testing to identify cases, particularly with increasing use of electronic health record data. However, few data are available describing clinical testing practices to inform interpretation of these studies.

OBJECTIVE: To characterize clinical testing frequency for SARS-CoV-2, influenza, and RSV among children and adolescents hospitalized with acute respiratory illness during the 2016 to 2024 respiratory illness seasons by age, intensive care unit admission, and time period (2016-2020 and each season in 2020-2024); estimate the case fraction missed by clinical …

Scenario Projections Of Covid-19 Burden In The Us, 2024-2025, Sara L Loo, Sung-Mok Jung, Lucie Contamin, Emily Howerton, Samantha J Bents, Harry Hochheiser, Michael C Runge, Claire P Smith, Erica C Carcelén, Katie Yan, Joseph C Lemaitre, Emily Przykucki, Clifton D Mckee, Koji Sato, Allison L Hill, Matteo Chinazzi, Jessica T Davis, Clara Bay, Alessandro Vespignani, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Sean M Moore, T Alex Perkins, Ajitesh Srivastava, Majd Al Aawar, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Spencer J Fox, Lauren Ancel Meyers, Przemyslaw Porebski, Srinivasan Venkatramanan, Bryan Lewis, Jiangzhuo Chen, Madhav Marathe, Michal Ben-Nun, James Turtle, Pete Riley, Katriona Shea, Cécile Viboud, Justin Lessler, Shaun Truelove

Faculty, Staff and Student Publications

Importance: COVID-19 remains a disease with high burden in the US, prompting continued debate about optimal targets for annual vaccination.

Objective: To project COVID-19 burden in the US for April 2024 to April 2025 under 6 scenarios of immune escape (20% and 50% per year) and levels of vaccine recommendation (no recommendation, vaccination for individuals at high risk only, vaccination for all eligible groups) and to assess the potential benefit of vaccine recommendations in reducing disease burden.

Design, setting, and participants: For this decision analytical model, the US Scenario Modeling Hub, a collaborative modeling effort, convened 9 teams to provide …

Risk Of Cardiovascular Events During Delivery Hospitalization Among Pregnant Patients With Mental Health Conditions, Kavya Parekh, R J Waken, Khavya Avula, Katelin B Nickel, Kathryn J Lindley, Cynthia Rogers, Karen E Joynt Maddox

2020-Current year OA Pubs

BACKGROUND: Cardiovascular disease remains the leading cause of maternal mortality. Mental health disorders are risk factors for cardiovascular disease in nonpregnant populations, but their association with delivery outcomes is unknown.

METHODS: This cross-sectional study used delivery hospitalizations from the 2021 National Inpatient Sample. We used generalized estimating equations to fit quasi-Poisson regression models for cardiovascular severe maternal morbidity and mortality (SMM) events as defined by the Centers for Disease Control and Prevention, and non-SMM cardiovascular conditions or complications as defined by the Alliance for Innovation on Maternal Health. Incidence rate ratios were calculated for depression, anxiety, psychosis, bipolar, obsessive-compulsive disorder, …

Optimal Head-Of-Bed Positioning Before Thrombectomy In Large Vessel Occlusion Stroke: A Randomized Clinical Trial, Anne W Alexandrov, Anne J Shearin, Pitchaiah Mandava, Gabriel Torrealba-Acosta, Cheran Elangovan, Balaji Krishnaiah, Katherine Nearing, Elizabeth Robinson, Cara Guthrie-Chu, Matthew Holzmann, Bryan Fill, Dharti R Trivedi, Alicia Richardson, Sandy Middleton, Barbara B Brewer, David S Liebeskind, Nitin Goyal, James C Grotta, Andrei V Alexandrov

Faculty, Staff and Students Publications

Importance: Small studies show that 0° head positioning of patients with large vessel occlusion (LVO) stroke improves penumbral blood flow and clinical stability. Understanding whether 0° head position maintains clinical stability would allow for optimal patient positioning before thrombectomy.

Objective: To determine superiority of 0° over 30° head positioning at maintaining clinical stability in patients with LVO before thrombectomy.

Design, setting, and participants: This was a prospective randomized clinical trial with blinding to study enrollment/end points conducted from May 2018 to November 2023. There were 3 planned interim analyses, and the study was conducted at certified thrombectomy hospitals in the …

Identifying Care Gaps Along The Hiv Treatment Failure Cascade: A Multistate Analysis Of Viral Load Monitoring, Re-Suppression, And Regimen Switches In Zambia, Kombatende Sikombe, Noelle Le Tourneau, Brian Rice, Jake M. Pry, Sandra Simbeza, Laura K. Beres, Anjali Sharma, Njekwa Mukamba, Alison Wringe, James R. Hargreaves, Jacob Mutale, Carolyn Bolton Moore, Izukanji Sikazwe, Elvin Geng, Aaloke Mody

2020-Current year OA Pubs

BACKGROUND: Timely response to treatment failure is critical for improved outcomes and viral re-suppression among people living with HIV, but care gaps along the treatment failure cascade can occur due to delays by both clients (e.g., retention and adherence) and health systems (e.g., fidelity to viral load [VL] monitoring guidelines). We used multistate analysis to identify drivers of implementation gaps in the treatment failure cascade, including time to HIV VL monitoring, re-suppression, and regimen switches, in Zambia.

METHODS AND FINDINGS: We used national electronic HIV health records to identify adults on antiretroviral therapy (ART) for more than 6 months who …

Hiv-1 Controllers Possess A Unique Cd8+ T Cell Activation Phenotype And Loss Of Control Is Associated With Increased Expression Of Exhaustion Markers, Amber D. Jones, Zachary Capriotti, Erin Santos, Angel Lin, Rachel Van Duyne, Stephen Smith, Zachary Klase

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

BACKGROUND: HIV-1 controllers are a rare population of individuals that exhibit spontaneous control of HIV-1 infection without antiretroviral therapy. Understanding the mechanisms by which HIV-1 controllers maintain and eventually lose this ability would be highly valuable in HIV-1 cure or vaccine research. Previous work revealed the ability of CD8+ T cells isolated from HIV-1 controllers to suppress HIV-1 replication in matched CD4+ T cells and PBMCs ex vivo and suggested the loss of control may be tied to CD8+ T cell exhaustion.

RESULTS: We explored whether CD8+ T cell exhaustion plays a role in the maintenance and loss of control …

Heterozygous Variants In Plcg1 Affect Hearing, Vision, Cardiac, And Immune Function, Mengqi Ma, Yiming Zheng, Mingxi Deng, Shenzhao Lu, Xueyang Pan, Xi Luo, Michelle Etoundi, David Li-Kroeger, Kim C Worley, Lindsay C Burrage, Lauren S Blieden, Aimee Allworth, Wei-Liang Chen, Giuseppe Merla, Barbara Mandriani, Catherine E Otten, Pierre Blanc, Jill A Rosenfeld, Debdeep Dutta, Shinya Yamamoto, Michael F Wangler, Ian A Glass, Jingheng Chen, Elizabeth Blue, Paolo Prontera, Jeremie Rosain, Sandrine Marlin, Seema R Lalani, Hugo J Bellen, Undiagnosed Diseases Network

Duncan NRI Faculty and Staff Publications

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca²⁺ release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven individuals with heterozygous missense variants in PLCG1 [p.(Asp1019Gly), p.(His380Arg), p.(Asp1165Gly), and p.(Leu597Phe)] who present with hearing impairment (5/7), ocular pathology (4/7), cardiac septal defects (3/6), and various immunological issues (5/7). To model these …

Influenza-Associated Acute Necrotizing Encephalopathy In Us Children, Andrew Silverman, Rachel Walsh, Jonathan D Santoro, Katherine Thomas, Elizabeth Ballinger, Kristen S Fisher, Ajay X Thomas, Brian Appavu, Michael C Kruer, Derek Neilson, Jasmine Knoll, April N Sharp, Hannah E Edelman, Scott Otallah, Alexandra Morgan, Aniela Grzezulkowska, John Nguyen, Lekha M Rao, Shaina M Hecht, Laura Catalano, Hunter Daigle, Catherine Kronfol, Jessica Wharton, David Adams, Adam Z Kalawi, Michael Kung, Janetta L Arellano, Lauren Smith, Devorah Segal, Kristina Feja, Eileen Broomall, Anuj Jayakar, Sandra R Arnold, Hanna Retallack, Craig A Press, Grace Gombolay, Madeleine H Mclaughlin, Varun Kannan, Kavita Thakkar, Tasmia Rezwan, Erin Hulfish, Dalia Eid, Jennifer Meylor, Diane Peng, Ryan Hurtado, Taylor Nickerson, Iris Mandell, Abigail U Carbonell, Mallory Kerner-Rossi, Divya Jayaraman, Mallory Davis, Rosemary Olivero, Neel Shah, Christina M Osborne, Bo Zhang, Christopher Cortina, Adrienne G Randolph, Suchitra Rao, Thomas Larocca, Keith P Van Haren, Molly Wilson-Murphy

Faculty, Staff and Students Publications

Importance: Acute necrotizing encephalopathy (ANE) is a rare, but severe, neurologic condition for which epidemiologic and management data remain limited. During the 2024-2025 US influenza season, clinicians at large pediatric centers anecdotally reported an increased number of children with influenza-associated ANE, prompting this national investigation.

Objective: To understand the clinical presentation, interventions, and outcomes among US children diagnosed with influenza-associated ANE.

Design, setting, and participants: This study was a multicenter case series of children diagnosed with ANE with longitudinal follow-up. A call for cases was issued via academic societies, public health agencies, and by directly contacting pediatric specialists at 76 …