Digital Commons Network^™

"It's Way More Than Just Writing A Prescription": A Qualitative Study Of Preferences For Integrated Versus Non-Integrated Treatment Models Among Individuals With Opioid Use Disorder, Elizabeth C Saunders, Sarah K Moore, Olivia Walsh, Stephen A Metcalf, Alan J Budney, Patricia Cavazos-Rehg, Emily Scherer, Lisa A Marsch

Open Access Publications

BACKGROUND: Increasingly, treatment for opioid use disorder (OUD) is offered in integrated treatment models addressing both substance use and other health conditions within the same system. This often includes offering medications for OUD in general medical settings. It remains uncertain whether integrated OUD treatment models are preferred to non-integrated models, where treatment is provided within a distinct treatment system. This study aimed to explore preferences for integrated versus non-integrated treatment models among people with OUD and examine what factors may influence preferences.

METHODS: This qualitative study recruited participants (n = 40) through Craigslist advertisements and flyers posted in treatment programs …

Genomic Characterization Of Emerging Bacterial Uropathogen Neisseria Meningitidis, Which Was Misidentified As Neisseria Gonorrhoeae By Nucleic Acid Amplification Testing, Kimberley V Sukhum, Sophonie Jean, Meghan Wallace, Neil Anderson, C A Burnham, Gautam Dantas

Open Access Publications

No abstract provided.

Short-Term Effects Of Appropriate Empirical Antimicrobial Treatment With Ceftolozane/Tazobactam In A Swine Model Of Nosocomial Pneumonia, Ana Motos, Marin Kollef, Et Al

Open Access Publications

The rising frequency of multidrug-resistant and extensively drug-resistant (MDR/XDR) pathogens is making more frequent the inappropriate empirical antimicrobial therapy (IEAT) in nosocomial pneumonia, which is associated with increased mortality. We aim to determine the short-term benefits of appropriate empirical antimicrobial treatment (AEAT) with ceftolozane/tazobactam (C/T) compared with IEAT with piperacillin/tazobactam (TZP) in MDR

Sars-Cov-2 Infection Severity Is Linked To Superior Humoral Immunity Against The Spike, Jenna J Guthmiller, Ya-Nan Dai, Christopher A Nelson, Paige D Hall, Daved H Fremont, Et Al

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable …

Zika Virus Oncolytic Activity Requires Cd8+ T Cells And Is Boosted By Immune Checkpoint Blockade, Sharmila Nair, Luciano Mazzoccoli, Arijita Jash, Jennifer Govero, Sachendra S Bais, Tong Hu, Camila R Fontes-Garfias, Chao Shan, Hideho Okada, Sujan Shresta, Jeremy N Rich, Pei-Yong Shi, Michael S Diamond, Milan G Chheda

Open Access Publications

Glioblastoma multiforme (GBM) is a fatal human cancer in part because GBM stem cells are resistant to therapy and recurrence is inevitable. Previously, we demonstrated Zika virus (ZIKV) targets GBM stem cells and prevents death of mice with gliomas. Here, we evaluated the immunological basis of ZIKV-mediated protection against GBM. Introduction of ZIKV into the brain tumor increased recruitment of CD8+ T and myeloid cells to the tumor microenvironment. CD8+ T cells were required for ZIKV-dependent tumor clearance because survival benefits were lost with CD8+ T cell depletion. Moreover, while anti-PD-1 antibody monotherapy moderately improved tumor survival, when coadministered with …

The Dark Kinase Knowledgebase: An Online Compendium Of Knowledge And Experimental Results Of Understudied Kinases, Matthew E. Berginski, Nienke Moret, Changchang Liu, Dennis Goldfarb, Peter K. Sorger, Shawn M. Gomez

Open Access Publications

Kinases form the backbone of numerous cell signaling pathways, with their dysfunction similarly implicated in multiple pathologies. Further facilitated by their druggability, kinases are a major focus of therapeutic development efforts in diseases such as cancer, infectious disease and autoimmune disorders. While their importance is clear, the role or biological function of nearly one-third of kinases is largely unknown. Here, we describe a data resource, the Dark Kinase Knowledgebase (DKK; https://darkkinome.org), that is specifically focused on providing data and reagents for these understudied kinases to the broader research community. Supported through NIH's Illuminating the Druggable Genome (IDG) Program, the DKK …

The Risks Of Stone Diagnosis And Stone Removal Procedure After Different Bariatric Surgeries, Steven M. Monda, Joel M. Vetter, Margaret A. Olsen, Matthew R. Keller, J. Christopher Eagon, Michael S. Chevinsky, Vasian Markollari, Ramakrishna Venkatesh, Alana C. Desai

Open Access Publications

No abstract provided.

Unexpected Role Of Sterol Synthesis In Rna Stability And Translation In Leishmania, Zemfira N Karamysheva, Samrat Moitra, Andrea Perez, Sumit Mukherjee, Elena B Tikhonova, Andrey L Karamyshev, Kai Zhang

Open Access Publications

No abstract provided.

Engaging Caregivers And Providers Of Children With Sickle Cell Anemia In Shared Decision Making For Hydroxyurea: Protocol For A Multicenter Randomized Controlled Trial, Anna M Hood, Allison A King, Cecelia Calhoun, Et Al

Open Access Publications

BACKGROUND: Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months. However, the uptake remains suboptimal, likely because caregivers lack information about hydroxyurea and have concerns about its safety and potential long-term …

Development And Validation Of A Multivariable Prediction Model For Missed Hiv Health Care Provider Visits In A Large Us Clinical Cohort, April C. Pettit, Aihua Bian, Cassandra O. Schember, Peter F. Rebeiro, Jeanne C. Keruly, Kenneth H. Mayer, W. Christopher Mathews, Richard D. Moore, Heidi M. Crane, Elvin Geng, Sonia Napravnik, Bryan E. Shepherd, Michael J. Mugavero

Open Access Publications

Background: Identifying individuals at high risk of missing HIV care provider visits could support proactive intervention. Previous prediction models for missed visits have not incorporated data beyond the individual level.

Methods: We developed prediction models for missed visits among people with HIV (PWH) with ≥1 follow-up visit in the Center for AIDS Research Network of Integrated Clinical Systems from 2010 to 2016. Individual-level (medical record data and patient-reported outcomes), community-level (American Community Survey), HIV care site-level (standardized clinic leadership survey), and structural-level (HIV criminalization laws, Medicaid expansion, and state AIDS Drug Assistance Program budget) predictors were included. Models were developed …

Evaluation Of A Clinical Decision Support Strategy To Increase Seasonal Influenza Vaccination Among Hospitalized Children Before Inpatient Discharge, Evan W. Orenstein, Omar Elsayed-Ali, Swaminathan Kandaswamy, Erin Masterson, Reena Blanco, Pareen Shah, Patricia Lantis, Amy Kolwaite, Thomas E. Dawson, Edwin Ray, Christy Bryant, Srikant Iyer, Andi L. Shane, Stephanie Jernigan

Open Access Publications

Importance: Hospitalized children are at increased risk of influenza-related complications, yet influenza vaccine coverage remains low among this group. Evidence-based strategies about vaccination of vulnerable children during all health care visits are especially important during the COVID-19 pandemic.

Objective: To design and evaluate a clinical decision support (CDS) strategy to increase the proportion of eligible hospitalized children who receive a seasonal influenza vaccine prior to inpatient discharge.

Design, Setting, and Participants: This quality improvement study was conducted among children eligible for the seasonal influenza vaccine who were hospitalized in a tertiary pediatric health system providing care to more than half …

Cd16+Cd163+ Monocytes Traffic To Sites Of Inflammation During Necrotizing Enterocolitis In Premature Infants, Oluwabunmi O. Olaloye, Misty Good, Et Al

Open Access Publications

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes …

Extracorporeal Support Prognostication-Time To Move The Goal Posts?, Neel Shah, Ahmed S Said

Open Access Publications

Advances in extracorporeal membrane oxygenation (ECMO) technology are associated with expanded indications, increased utilization and improved outcome. There is growing interest in developing ECMO prognostication scores to aid in bedside decision making. To date, the majority of available scores have been limited to mostly registry-based data and with mortality as the main outcome of interest. There continues to be a gap in clinically applicable decision support tools to aid in the timing of ECMO cannulation to improve patients' long-term outcomes. We present a brief review of the commonly available adult and pediatric ECMO prognostication tools, their limitations, and future directions.

An Open Label, Block Randomized, Community Study Of The Safety And Efficacy Of Co-Administered Ivermectin, Diethylcarbamazine Plus Albendazole Vs. Diethylcarbamazine Plus Albendazole For Lymphatic Filariasis In India, Purushothaman Jambulingam, Vijesh Sreedhar Kuttiatt, Kaliannagounder Krishnamoorthy, Swaminathan Subramanian, Adinarayanan Srividya, Hari Kishan K. Raju, Manju Rahi, Roopali K. Somani, Mallanna K. Suryaprakash, Gangeshwar P. Dwivedi, Gary J Weil

Open Access Publications

No abstract provided.

Il-7 Immunotherapy In A Nonimmunocompromised Patient With Intractable Fungal Wound Sepsis, Isaiah R. Turnbull, Monty B. Mazer, Mark H. Hoofnagle, John P. Kirby, Jennifer M. Leonard, Carlos Mejia-Chew, Andrej Spec, Jane Blood, Sydney M. Miles, Eric M. Ransom, Robert F. Potter, Joseph P. Gaut, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

A nonimmunocompromised patient developed life-threatening soft tissue infection with

Evaluation Of Commercial Rapid Lateral Flow Tests, Alone Or In Combination, For Sars-Cov-2 Antibody Testing, Peter U Fischer, Kerstin Fischer, Kurt C Curtis, Yuefang Huang, Nicole Fetcho, Charles W Goss, Gary J Weil

Open Access Publications

Antibody tests can be tools for detecting current or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 [coronavirus disease 2019 (COVID-19)]) infections. Independent test evaluations are needed to document the performance with different sample sets. We evaluated six lateral flow assays (LFAs) and two laboratory-based tests (EUROIMMUN-SARS-CoV-2 ELISA and Abbott-Architect-SARS-CoV-2-IgG). We tested 210 plasma samples from 89 patients diagnosed with acute COVID-19. These samples were collected at different time points after the onset of symptoms. In addition, 80 convalescent plasma samples, and 168 pre-pandemic samples collected from adults in the United States and in Africa were tested. LFA performance varied …

Tlr3 Controls Constitutive Ifn-Β Antiviral Immunity In Human Fibroblasts And Cortical Neurons, Daxing Gao, Michael S Diamond, Et Al

Open Access Publications

Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes …

Use Of Machine Learning To Develop And Evaluate Models Using Preoperative And Intraoperative Data To Identify Risks Of Postoperative Complications, Bing Xue, Dingwen Li, Chenyang Lu, Christopher R. King, Troy Wildes, Michael S. Avidan, Thomas Kannampallil, Joanna Abraham

Open Access Publications

Importance: Postoperative complications can significantly impact perioperative care management and planning.

Objectives: To assess machine learning (ML) models for predicting postoperative complications using independent and combined preoperative and intraoperative data and their clinically meaningful model-agnostic interpretations.

Design, Setting, and Participants: This retrospective cohort study assessed 111 888 operations performed on adults at a single academic medical center from June 1, 2012, to August 31, 2016, with a mean duration of follow-up based on the length of postoperative hospital stay less than 7 days. Data analysis was performed from February 1 to September 31, 2020.

Main Outcomes and Measures: Outcomes included …

Taking Account Of Asymptomatic Infections: A Modeling Study Of The Covid-19 Outbreak On The Diamond Princess Cruise Ship, Li-Shan Huang, Li Li, Lucia Dunn, Mai He

Open Access Publications

The COVID-19 outbreak on the Diamond Princess (DP) cruise ship has provided empirical data to study the transmission potential of COVID-19 with the presence of pre/asymptomatic cases. We studied the changes in R0 on DP from January 21 to February 19, 2020 based on chain binomial models under two scenarios: no quarantine assuming a random mixing condition, and quarantine of passengers in cabins-passengers may get infected either by an infectious case in a shared cabin or by pre/asymptomatic crew who continued to work. Estimates of R0 at the beginning of the epidemic were 3.27 (95% CI, 3.02-3.54) and 3.78 (95% …

Broadly Neutralizing Monoclonal Antibodies Protect Against Multiple Tick-Borne Flaviviruses, Laura A. Vanblargan, John M. Errico, Natasha M. Kafai, Prashant N. Jethva, Christopher A. Nelson, David Wang, Scott A. Handley, Michael L. Gross, Daved H. Fremont, Michael S. Diamond, Et Al

Open Access Publications

Although Powassan virus (POWV) is an emerging tick-transmitted flavivirus that causes severe or fatal neuroinvasive disease in humans, medical countermeasures have not yet been developed. Here, we developed a panel of neutralizing anti-POWV mAbs recognizing six distinct antigenic sites. The most potent of these mAbs bind sites within domain II or III of the envelope (E) protein and inhibit postattachment viral entry steps. A subset of these mAbs cross-react with other flaviviruses. Both POWV type-specific and cross-reactive neutralizing mAbs confer protection in mice against POWV infection when given as prophylaxis or postexposure therapy. Several cross-reactive mAbs mapping to either domain …

Variables Associated With Intravenous Rehydration And Hospitalization In Children With Acute Gastroenteritis: A Secondary Analysis Of 2 Randomized Clinical Trials, Naveen Poonai, Philip Tarr, Et Al

Open Access Publications

Importance: Despite guidelines endorsing oral rehydration therapy, intravenous fluids are commonly administered to children with acute gastroenteritis in high-income countries.

Objective: To identify factors associated with intravenous fluid administration and hospitalization in children with acute gastroenteritis.

Design, Setting, and Participants: This study is a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) probiotic trials. Participants include children aged 3 to 48 months with 3 or more watery stools in 24 hours between November 5, 2013, and April 7, 2017, for the PERC study and July 8, 2014, and June 23, …

Guidelines For Conducting Virtual Cognitive Interviews During A Pandemic, James A Shepperd, Gabrielle Pogge, Jean M Hunleth, Sienna Ruiz, Erika A Waters

Open Access Publications

The COVID-19 pandemic has challenged researchers working in physical contact with research participants. Cognitive interviews examine whether study components (most often questionnaire items) are worded or structured in a manner that allows study participants to interpret the items in a way intended by the researcher. We developed guidelines to conduct cognitive interviews virtually to accommodate interviewees who have limited access to the internet. The guidelines describe the essential communication and safety equipment requirements and outline a procedure for collecting responses while maintaining the safety of the participants and researchers. Furthermore, the guidelines provide suggestions regarding training of participants to use …

Cxcl17 Is A Specific Diagnostic Biomarker For Severe Pandemic Influenza A(H1n1) That Predicts Poor Clinical Outcome, Jose Alberto Choreño-Parra, Shabaana A Khader, Et Al

Open Access Publications

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The …

Gestational Age-Specific Complete Blood Count Signatures In Necrotizing Enterocolitis, Julia M Pantalone, Silvia Liu, Oluwabunmi O Olaloye, Erica C Prochaska, Toby Yanowitz, Melissa M Riley, Justin R Buland, Beverly S Brozanski, Misty Good, Liza Konnikova

Open Access Publications

No abstract provided.

Single-Cell Analyses Of Crohn’S Disease Tissues Reveal Intestinal Intraepithelial T Cells Heterogeneity And Altered Subset Distributions, Natalia Jaeger, Ramya Gamini, Marina Cella, Jorge L. Schettini, Mattia Bugatti, Shanrong Zhao, Charles V. Rosadini, Ekaterina Esaulova, Blanda Di Luccia, Baylee Kinnett, William Vermi, Maxim N. Artyomov, Thomas A. Wynn, Ramnik J. Xavier, Scott A. Jelinsky, Marco Colonna

Open Access Publications

No abstract provided.

Diagnostic Accuracy Of Health Care Administrative Diagnosis Codes To Identify Nontuberculous Mycobacteria Disease: A Systematic Review, Carlos Mejia-Chew, Lauren Yaeger, Kevin Montes, Thomas C. Bailey, Margaret A. Olsen

Open Access Publications

Background: Health care administrative database research frequently uses standard medical codes to identify diagnoses or procedures. The aim of this review was to establish the diagnostic accuracy of codes used in administrative data research to identify nontuberculous mycobacterial (NTM) disease, including lung disease (NTMLD).

Methods: We searched Ovid Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to April 2019. We included studies assessing the diagnostic accuracy of

Results: We identified 5549 unique citations. Of the 96 full-text articles reviewed, 7 eligible studies of moderate quality (3730 participants) were included in …

Surgical Infection Society 2020 Updated Guidelines On The Management Of Complicated Skin And Soft Tissue Infections, Therese M. Duane, Jared M. Huston, Morgan Collom, Adam Beyer, Sara Parli, Sara Buckman, Mark Shapiro, Amy Mcdonald, Jose Diaz, Jeffrey M. Tessier, James Sanders

Open Access Publications

No abstract provided.

Trem2 Is A Receptor For Non-Glycosylated Mycolic Acids Of Mycobacteria That Limits Antimycobacterial Macrophage Activation, Ei'ichi Iizasa, Yasushi Chuma, Takayuki Uematsu, Mio Kubota, Hiroaki Kawaguchi, Masayuki Umemura, Kenji Toyonaga, Hideyasu Kiyohara, Ikuya Yano, Marco Colonna, Masahiko Sugita, Goro Matsuzaki, Sho Yamasaki, Hiroki Yoshida, Hiromitsu Hara

Open Access Publications

No abstract provided.

Substance Use Disorders And Behavioral Addictions During The Covid-19 Pandemic And Covid-19-Related Restrictions, Nicole M Avena, Julia Simkus, Anne Lewandowski, Mark S Gold, Marc N Potenza

Open Access Publications

COVID-19 was first identified in Wuhan, China in December of 2019 and appeared in the United States 1 month later. Between the onset of the pandemic and January 13, 2021, over 92 million people have tested positive for the virus and over 1.9 million people have died globally. Virtually every country in the world has been impacted by this virus. Beginning in March 2020, many U.S. state governments enforced a "quarantine" to respond to the growing health crisis. Citizens were required to remain at home; schools, restaurants, and non-essential businesses were forced to close, and large gatherings were prohibited. Americans' …

Antigen Presenting Cells Link The Female Genital Tract Microbiome To Mucosal Inflammation, With Hormonal Contraception As An Additional Modulator Of Inflammatory Signatures, Elizabeth H Byrne, Barry L Hykes, Scott A Handley, Et Al

Open Access Publications

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low