Digital Commons Network^™

Evaluation Of Total Body Weight Versus Adjusted Body Weight Liposomal Amphotericin B Dosing In Obese Patients, Michelle H Ting, Andrej Spec, Scott T Micek, David J Ritchie, Tamara Krekel

Open Access Publications

Liposomal amphotericin B (LAmB) is used for various fungal infections, but it is unclear which dosing weight to use in obese patients. The purpose of this study was to compare clinical outcomes of adjusted body weight (adjBW) versus total body weight (TBW) dosing of LAmB. This single-center, retrospective cohort study included patients who received LAmB for definitive therapy and whose TBW exceeded 120% of their ideal body weight (IBW). Analyses were conducted for 3 mg/kg for adjBW versus TBW and 5 mg/kg for adjBW versus TBW. A total of 238 patients were included. For the 68 patients who received LAmB …

Rheumatic Heart Disease In The United States: Forgotten But Not Gone: Results Of A 10 Year Multicenter Review, Sarah R De Loizaga, Lakshmi R Gokanapudy Hahn, Et Al

Open Access Publications

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty-two US pediatric institutions participated in a 10-year review (2008-2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract-based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community …

A Systematic Review And Network Meta-Analyses To Assess The Effectiveness Of Human Immunodeficiency Virus (Hiv) Self-Testing Distribution Strategies, Ingrid Eshun-Wilson, Muhammad S Jamil, T Charles Witzel, David V Glidded, Cheryl Johnson, Noelle Le Trouneau, Nathan Ford, Kathleen Mcgee, Chris Kemp, Stefan Baral, Sheree Schwartz, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: We conducted a systematic review and network meta-analysis to identify which human immunodeficiency virus (HIV) self-testing (HIVST) distribution strategies are most effective.

METHODS: We abstracted data from randomized controlled trials and observational studies published between 4 June 2006 and 4 June 2019.

RESULTS: We included 33 studies, yielding 6 HIVST distribution strategies. All distribution strategies increased testing uptake compared to standard testing: in sub-Saharan Africa, partner HIVST distribution ranked highest (78% probability); in North America, Asia, and the Pacific regions, web-based distribution ranked highest (93% probability), and facility based distribution ranked second in all settings. Across HIVST distribution strategies …

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Michael L Alosco, Daniel S Marcus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …

Das181 Treatment Of Severe Lower Respiratory Tract Parainfluenza Virus Infection In Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study, Roy F Chemaly, Francisco M Marty, Cameron R Wolfe, Steven J Lawrence, Sanjeet Dadwal, Rosemary Soave, Jason Farthing, Stephen Hawley, Paul Montanez, Jimmy Hwang, Jennifer Hui-Chun Ho, Stanley Lewis, George Wang, Michael Boeckh

2020-Current year OA Pubs

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV.

METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least …

Relative Risks Of Covid-19 Fatality Between The First And Second Waves Of The Pandemic In Ontario, Canada, Sylvia H Hsu, Su-Hsin Chang, Cary P Gross, Shi-Yi Wang

Open Access Publications

OBJECTIVES: To examine whether the case fatality rate (CFR) of COVID-19 decreased over time and whether the COVID-19 testing rate is a driving factor for the changes if the CFR decreased.

METHODS: Analyzing COVID-19 cases, deaths and tests in Ontario, Canada, we compared the CFR between the first wave and the second wave across 26 public health units in Ontario. We also explored whether a high testing rate was associated with a large CFR decrease.

RESULTS: The first wave CFR ranged from 0.004 to 0.146, whereas the second wave CFR ranged from 0.003 to 0.034. The pooled RR estimate of …

Modern Acinetobacter Baumannii Clinical Isolates Replicate Inside Spacious Vacuoles And Egress From Macrophages, Gabriela Sycz, Gisela Di Venanzio, Jesus S. Distel, Mariana G. Sartorio, Nguyen-Hung Le, Nichollas E. Scott, Wandy L. Beatty, Mario F. Feldman

Open Access Publications

Multidrug-resistant Acinetobacter baumannii infections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat these A. baumannii infections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium's pathobiology, which remains poorly understood. A. baumannii is regarded as an extracellular opportunistic pathogen. However, research on Acinetobacter has largely focused on common lab strains, such as ATCC 19606, that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that, unlike ATCC 19606, several modern A. baumannii clinical isolates, including …

The Alternative Serotonin Transporter Promoter P2 Impacts Gene Function In Females With Irritable Bowel Syndrome, Sandra Mohr, Gregory Sayuk, Et Al

Open Access Publications

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from …

Decreased Antiviral Immune Response Within The Central Nervous System Of Aged Mice Is Associated With Increased Lethality Of West Nile Virus Encephalitis, Kristen E Funk, Artem D Arutyunov, Pritesh Desai, James P White, Allison L Soung, Sarah F Rosen, Michael S Diamond, Robyn S Klein

Open Access Publications

West Nile virus (WNV) is an emerging pathogen that causes disease syndromes ranging from a mild flu-like illness to encephalitis. While the incidence of WNV infection is fairly uniform across age groups, the risk of lethal encephalitis increases with advanced age. Prior studies have demonstrated age-related, functional immune deficits that limit systemic antiviral immunity and increase mortality; however, the effect of age on antiviral immune responses specifically within the central nervous system (CNS) is unknown. Here, we show that aged mice exhibit increased peripheral organ and CNS tissue viral burden, the latter of which is associated with alterations in activation …

Use Of Convalescent Plasma In Covid-19 Patients With Immunosuppression, Jonathon W Senefeld, Jeffrey P Henderson, Et Al.

2020-Current year OA Pubs

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after …

Progress Towards Antibiotic Use Targets In Eight High-Income Countries, Bryony Simmons, Koya Ariyoshi, Norio Ohmagari, Celine Pulcini, Benedikt Huttner, Sumanth Gandra, Giovanni Satta, Lorenzo Moja, Michael Sharland, Nicola Magrini, Marisa Miraldo, Graham Cooke

2020-Current year OA Pubs

OBJECTIVE: To compare antibiotic sales in eight high-income countries using the 2019 World Health Organization (WHO) Access, Watch and Reserve (AWaRe) classification and the target of 60% consumption of Access category antibiotics.

METHODS: We analysed data from a commercial database of sales of systemic antibiotics in France, Germany, Italy, Japan, Spain, Switzerland, United Kingdom of Great Britain and Northern Ireland, and United States of America over the years 2013-2018. We classified antibiotics according to the 2019 AWaRe categories: Access, Watch, Reserve and Not Recommended. We measured antibiotic sales per capita in standard units (SU) per capita and calculated Access group …

The Clinical Sustainability Assessment Tool: Measuring Organizational Capacity To Promote Sustainability In Healthcare, Sara Malone, Kim Prewitt, Rachel Hackett, John C Lin, Virginia Mckay, Callie Walsh-Bailey, Douglas A Luke

2020-Current year OA Pubs

BACKGROUND: Few validated assessment tools are available to increase understanding and measure factors associated with sustainment of clinical practices, an increasingly recognized need among clinicians. We describe the development of the Clinical Sustainability Assessment Tool (CSAT), designed to assess factors that contribute to sustainable practices in clinical settings.

METHODS: Sixty-four participants from clinical and research fields participated in concept mapping and were recruited to brainstorm factors that lead to sustained clinical practices. Once repeated factors were removed, participants sorted items based on similarity and rated them by importance and feasibility. Using concept mapping analyses, items were grouped into meaningful domains …

Bioavailability Of Single-Dose Suba-Itraconazole Compared To Conventional Itraconazole Under Fasted And Fed Conditions, Adriana M Rauseo, Patrick Mazi, Phoebe Lewis, Bruce Burnett, Stuart Mudge, Andrej Spec

Open Access Publications

Conventional itraconazole (C-ITZ) suffers from absorption variability. SUBA-itraconazole (S-ITZ) is more bioavailable than C-ITZ at steady state in a fed condition, but there are no data comparing the two under a fasted state. An open-label, single-dose, randomized, bioequivalence study was performed comparing S-ITZ to C-ITZ capsules under fasted and fed conditions in healthy adults measuring itraconazole and hydroxyitraconazole plasma levels. This study demonstrated less variability of S-ITZ compared to C-ITZ capsules under fasted conditions.

Significant Regional Differences In Antibiotic Use Across 576 Us Hospitals And 11 701 326 Adult Admissions, 2016-2017, Katherine E Goodman, Sara E Cosgrove, Lisa Pineles, Laurence S Magder, Deverick J Anderson, Elizabeth Dodds Ashley, Ronald E Polk, Hude Quan, William E Trick, Keith F Woeltje, Surbhi Leekha, Anthony D Harris

2020-Current year OA Pubs

BACKGROUND: Quantifying the amount and diversity of antibiotic use in United States hospitals assists antibiotic stewardship efforts but is hampered by limited national surveillance. Our study aimed to address this knowledge gap by examining adult antibiotic use across 576 hospitals and nearly 12 million encounters in 2016-2017.

METHODS: We conducted a retrospective study of patients aged ≥ 18 years discharged from hospitals in the Premier Healthcare Database between 1 January 2016 and 31 December 2017. Using daily antibiotic charge data, we mapped antibiotics to mutually exclusive classes and to spectrum of activity categories. We evaluated relationships between facility and case-mix …

Predicting The Environmental Suitability For Onchocerciasis In Africa As An Aid To Elimination Planning, Elizabeth A. Cromwell, Ziyad Al-Aly, Et Al

Open Access Publications

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where …

Comparison Of Total Body Irradiation Versus Non-Total Body Irradiation Containing Regimens For De Novo Acute Myeloid Leukemia In Children, Christopher E. Dandoy, Robert Hayashi, Et Al.

Open Access Publications

With limited data comparing hematopoietic cell transplant outcomes between myeloablative total body irradiation (TBI) containing and non-TBI regimens in children with de novo acute myeloid leukemia, the aim of this study was to compare transplant-outcomes between these regimens. Cox regression models were used to compare transplant-outcomes after TBI and non-TBI regimens in 624 children transplanted between 2008 and 2016. Thirty two percent (n=199) received TBI regimens whereas 68% (n=425) received non-TBI regimens. Five-year non-relapse mortality was higher with TBI regimens (22% vs. 11%, p<0.0001) but relapse was lower (23% vs. 37%, p<0.0001) compared to non-TBI regimens. Consequently, overall (62% vs. 60%, p=1.00) and leukemia-free survival (55% vs. 52%, p=0.42) did not differ between treatment groups. Grade II-IV acute GVHD was higher with TBI regimens (56% vs. 27%, p<0.0001) but not chronic GVHD. The 3-year incidence of gonadal or growth hormone deficiency was higher with TBI regimens (24% vs. 8%, p<0.001) but there were no differences in late pulmonary, cardiac or renal impairment. In the absence of a survival advantage, the choice of TBI or non-TBI regimen merits careful consideration with the data favoring non-TBI regimens to limit the burden of morbidity associated with endocrine dysfunction.

Cystic Fibrosis Foundation Consensus Statements For The Care Of Cystic Fibrosis Lung Transplant Recipients, Pali Shah, Marina Litvin, Ramsey R Hachem, Et Al.

2020-Current year OA Pubs

Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed …

Comparison Of Early Warning Scores For Sepsis Early Identification And Prediction In The General Ward Setting, Sean C Yu, Nirmala Shivakumar, Kevin Betthauser, Aditi Gupta, Albert M Lai, Marin H Kollef, Philip R O Payne, Andrew P Michelson

2020-Current year OA Pubs

The objective of this study was to directly compare the ability of commonly used early warning scores (EWS) for early identification and prediction of sepsis in the general ward setting. For general ward patients at a large, academic medical center between early-2012 and mid-2018, common EWS and patient acuity scoring systems were calculated from electronic health records (EHR) data for patients that both met and did not meet Sepsis-3 criteria. For identification of sepsis at index time, National Early Warning Score 2 (NEWS 2) had the highest performance (area under the receiver operating characteristic curve: 0.803 [95% confidence interval [CI]: …

Results From 2 Cohort Studies In Central Africa Show That Clearance Of Wuchereria Bancrofti Infection After Repeated Rounds Of Mass Drug Administration With Albendazole Alone Is Closely Linked To Individual Adherence, Jérémy T Campillo, Naomi P Awaca-Uvon, Francois Missamou, Jean-Paul Tambwe, Godefroy Kuyangisa-Simuna, Gary J Weil, Frédéric Louya, Michel Boussinesq, Sébastien D S Pion, Cédric B Chesnais

2020-Current year OA Pubs

BACKGROUND: Two community trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of the Congo demonstrated the efficacy of semiannual mass drug administration (MDA) with albendazole (ALB) alone on lymphatic filariasis (LF). However, a high interindividual heterogeneity in the clearance of infection was observed.

METHODS: We analyzed trial data to assess the effect of individual adherence to ALB MDA on clearance of circulating filarial antigenemia (CFA) and microfilaremia. Community residents were offered a single dose of ALB every 6 months and tested for LF with a rapid test for CFA at baseline and then …

Protein Prenylation And Hsp40 In Thermotolerance Of Plasmodium Falciparum Malaria Parasites, Emily S Mathews, Andrew J Jezewski, Audrey R Odom John

Open Access Publications

During its complex life cycle, the malaria parasite survives dramatic environmental stresses, including large temperature shifts. Protein prenylation is required during asexual replication of Plasmodium falciparum, and the canonical heat shock protein 40 protein (HSP40; PF3D7_1437900) is posttranslationally modified with a 15-carbon farnesyl isoprenyl group. In other organisms, farnesylation of Hsp40 orthologs controls their localization and function in resisting environmental stress. In this work, we find that plastidial isopentenyl pyrophosphate (IPP) synthesis and protein farnesylation are required for malaria parasite survival after cold and heat shock. Furthermore, loss of HSP40 farnesylation alters its membrane attachment and interaction with proteins in …

Sars-Cov-2 E Gene Variant Alters Analytical Sensitivity Characteristics Of Viral Detection Using A Commercial Reverse Transcription-Pcr Assay, Stephen Tahan, Bijal A Parikh, Lindsay Droit, Meghan A. Wallace, Carey-Ann D Burnham, David Wang

Open Access Publications

Diagnostic assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for patient management, infection prevention, and the public health response for coronavirus disease 2019 (COVID-19). The efficacy and reliability of these assays are of paramount importance in both tracking and controlling the spread of the virus. Real-time reverse transcription-PCR (RT-PCR) assays rely on a fixed genetic sequence for primer and probe binding. Mutations can potentially alter the accuracy of these assays and lead to unpredictable analytical performance characteristics and false-negative results. Here, we identify a G-to-U transversion (nucleotide 26372) in the SARS-CoV-2 E gene in three specimens …

A Pragmatic Machine Learning Model To Predict Carbapenem Resistance, Ryan J Mcguire, Sean C Yu, Philip R O Payne, Albert M Lai, M Cristina Vazquez-Guillamet, Marin H Kollef, Andrew P Michelson

Open Access Publications

Infection caused by carbapenem-resistant (CR) organisms is a rising problem in the United States. While the risk factors for antibiotic resistance are well known, there remains a large need for the early identification of antibiotic-resistant infections. Using machine learning (ML), we sought to develop a prediction model for carbapenem resistance. All patients >18 years of age admitted to a tertiary-care academic medical center between 1 January 2012 and 10 October 2017 with ≥1 bacterial culture were eligible for inclusion. All demographic, medication, vital sign, procedure, laboratory, and culture/sensitivity data were extracted from the electronic health record. Organisms were considered CR …

Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

METHODS: In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of …

New Perspectives On Antimicrobial Agents: Ceftolozane-Tazobactam, Bryan D Lizza, Kevin D Betthauser, David J Ritchie, Scott T Micek, Marin H Kollef

Open Access Publications

Ceftolozane-tazobactam (C/T) is a new fifth-generation cephalosporin/beta-lactamase inhibitor combination approved by the Food and Drug Administration and the European Medicines Agency for treatment of complicated intraabdominal infections, complicated urinary tract infections, and hospital-acquired pneumonia in adult patients. This review will briefly describe the pharmacology of C/T and focus on the emerging clinical trial and real-world data supporting its current utilization. Additionally, our synthesis of these data over time has set our current usage of C/T at Barnes-Jewish Hospital (BJH). C/T is primarily employed as directed monotherapy at BJH when Pseudomonas aeruginosa isolates are identified with resistance to other beta-lactams. C/T …

Evaluation Of Total Body Weight Versus Adjusted Body Weight Voriconazole Dosing In Obese Patients, Elizabeth Diller, Tamara Krekel, Andrej Spec, Jeff Klaus

Open Access Publications

This retrospective single-center study of a cohort of adult patients who received voriconazole with a steady-state trough concentration measured during therapy evaluated the rate of therapeutic trough attainment using adjusted body weight (AdjBW)-based and total body weight (TBW)-based dosing in overweight and obese patients. Of the 130 patients included, 45 patients received TBW-based dosing and 85 patients received AdjBW-based dosing. Therapeutic trough attainment was significantly improved with AdjBW-based dosing compared to TBW-based dosing (64.7% versus 46.7%;

Destination Shapes Antibiotic Resistance Gene Acquisitions, Abundance Increases, And Diversity Changes In Dutch Travelers, Alaric W D'Souza, Manish Boolchandani, Sanket Patel, Gianluca Galazzo, Jarne M Van Hattem, Maris S Arcilla, Damian C Melles, Menno D De Jong, Constance Schultsz, Combat Consortium, Gautam Dantas, John Penders

2020-Current year OA Pubs

BACKGROUND: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel's effects on the gut resistome remain largely unknown.

METHODS: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of …

Cervical Cancer Screening Outcomes In Zambia, 2010-19: A Cohort Study, Jake M Pry, Albert Manasyan, Sharon Kapambwe, Katayoun Taghavi, Miquel Duran-Frigola, Mulindi Mwanahamuntu, Izukanji Sikazwe, Jane Matambo, Jack Mubita, Kennedy Lishimpi, Kennedy Malama, Carolyn Bolton Moore

Open Access Publications

BACKGROUND: Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort.

METHODS: We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a …

Epidemic Preparedness: Prenatal Zika Virus Screening During The Next Epidemic, Luxi Qiao, Celina M Turchi Martelli, Amber I Raja, Nuria Sanchez Clemente, Thalia Velho Barreto De Araùjo, Ricardo Arraes De Alencar Ximenes, Demócrito De Barros Miranda-Filho, Anna Ramond, Elizabeth B Brickley

Open Access Publications

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of …

Longitudinal Data Reveal Strong Genetic And Weak Non-Genetic Components Of Ethnicity-Dependent Blood Dna Methylation Levels, Chris Mckennan, Katherine Naughton, Catherine Stanhope, Meyer Kattan, George T O'Connor, Megan T Sandel, Cynthia M Visness, Robert A Wood, Leonard B Bacharier, Avraham Beigelman, Stephanie Lovinsky-Desir, Alkis Togias, James E Gern, Dan Nicolae, Carole Ober

Open Access Publications

Epigenetic architecture is influenced by genetic and environmental factors, but little is known about their relative contributions or longitudinal dynamics. Here, we studied DNA methylation (DNAm) at over 750,000 CpG sites in mononuclear blood cells collected at birth and age 7 from 196 children of primarily self-reported Black and Hispanic ethnicities to study race-associated DNAm patterns. We developed a novel Bayesian method for high-dimensional longitudinal data and showed that race-associated DNAm patterns at birth and age 7 are nearly identical. Additionally, we estimated that up to 51% of all self-reported race-associated CpGs had race-dependent DNAm levels that were mediated through …

The Azithromycin To Prevent Wheezing Following Severe Rsv Bronchiolitis-Ii Clinical Trial: Rationale, Study Design, Methods, And Characteristics Of Study Population, Mythili Srinivasan, Leonard B Bacharier, Charles W Goss, Yanjiao Zhou, Jonathan Boomer, Sarah Bram, Dana Burgdorf, Carey-Ann Burnham, Timothy Casper, Mario Castro, Andrea Coverstone, Matthew Haslam, Watcharoot Kanchongkittiphon, Cadence Kuklinski, Qinghua Lian, Kenneth Schechtman, Gregory A Storch, Kelly True, Meghan A Wallace, Huiqing Yin-Declue, Elizabeth Ahrens, Jinli Wang, Avraham Beigelman

2020-Current year OA Pubs

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 …