4,481 results on '"Division of Pediatric Infectious Diseases"'
Search Results
2. New onset severe right ventricular failure associated with COVID-19 in a young infant without previous heart disease
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María Isabel Sánchez-Códez, Ana Castellano-Martinez, Irene Gutierrez-Rosa, Amado Rodríguez-Benítez, Patricia Rodríguez-Campoy, Moises Rodriguez-Gonzalez, [Rodriguez-González,M] Division of Pediatric Cardiology, Puerta del Mar University Hospital, Cadiz, Spain. [Rodriguez-González,M, Rodríguez-Campoy,P, Castellano-Martinez,A] Institute of Biomedical Research and Innovation of Cadiz (INIBICA), Research Institute, Puerta del Mar University Hospital, Cadiz, Spain. [Rodríguez-Campoy,P] Division of Pediatric Intensive Care Unit, Puerta del Mar University Hospital, Cadiz, Spain. [Sánchez-Códez,M, and Gutiérrez-Rosa,I] Division of Pediatric Infectious Diseases, Puerta del Mar University Hospital, Cadiz, Spain. [Castellano-Martinez,A] Division of Pediatric Nephrology, Puerta del Mar University Hospital, Cadiz, Spain. [Rodríguez-Benítez,A] Division of Radiology, Puerta del Mar University Hospital, Cadiz, Spain.
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Male ,Heart disease ,Computed Tomography Angiography ,Diseases::Respiratory Tract Diseases::Lung Diseases::Hypertension, Pulmonary [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Critical Care [Medical Subject Headings] ,heart failure ,Disease ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Respiratory Therapy::Respiration, Artificial [Medical Subject Headings] ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Shock::Systemic Inflammatory Response Syndrome [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Electrocardiography ,0302 clinical medicine ,pulmonary hypertension ,030212 general & internal medicine ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Cardiac Imaging Techniques::Echocardiography [Medical Subject Headings] ,Persons::Persons::Age Groups::Infant [Medical Subject Headings] ,Cardiogenic shock ,Brief Report ,cardiogenic shock ,Insuficiencia cardíaca ,Diseases::Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial Infarction::Shock, Cardiogenic [Medical Subject Headings] ,General Medicine ,Short bowel syndrome ,Choque cardiogénico ,Systemic Inflammatory Response Syndrome ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Health Status Indicators::Patient Acuity::Severity of Illness Index [Medical Subject Headings] ,Treatment Outcome ,paediatric multisystem inflammatory syndrome ,Echocardiography ,Cardiology ,Radiography, Thoracic ,Cardiology and Cardiovascular Medicine ,Coronavirus Infections ,medicine.medical_specialty ,Critical Care ,Hypertension, Pulmonary ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Tomography, X-Ray::Tomography, X-Ray Computed [Medical Subject Headings] ,Pneumonia, Viral ,Shock, Cardiogenic ,Check Tags::Male [Medical Subject Headings] ,03 medical and health sciences ,Betacoronavirus ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Electrodiagnosis::Electrocardiography [Medical Subject Headings] ,Internal medicine ,medicine ,Humans ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Radiography::Radiography, Thoracic [Medical Subject Headings] ,Pediatrics, Perinatology, and Child Health ,Pandemics ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,business.industry ,SARS-CoV-2 ,Diseases::Cardiovascular Diseases::Heart Diseases::Heart Failure [Medical Subject Headings] ,COVID-19 ,Infant ,medicine.disease ,Pulmonary hypertension ,Respiration, Artificial ,Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings] ,COVID-19 Drug Treatment ,Coronavirus ,Systemic inflammatory response syndrome ,Heart failure ,Pediatrics, Perinatology and Child Health ,Kawasaki disease ,business ,Hipertensión pulmonar - Abstract
We present our recent experience with a 6-month-old infant with a personal history of short bowel syndrome that presented with fever, cyanosis, and cardiogenic shock secondary to severe pulmonary hypertension and right ventricular failure without pulmonary thromboembolism. He did not present signs of toxin-mediated disease or Kawasaki disease. He was finally diagnosed with SARS-CoV-2 infection. If this presentation is confirmed in future research, the severe cardiovascular impairment in children with COVID-19 could be also attributable to the primary pulmonary infection, not only to a multisystem inflammatory syndrome but also in children without heart disease.
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- 2020
3. FimH adhesin of Escherichia coli K1 type 1 fimbriae activates BV-2 microglia
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Kim, Kwang [Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205 (United States)]
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- 2005
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4. Pharmacodynamics of Voriconazole in Children
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William W. Hope, Wim J. E. Tissing, Michael Neely, Jan-Willem C. Alffenaar, Anette Veringa, Virginia Ramos-Martin, Luc J. Huurneman, Fernando Docobo Pérez, [Huurneman,LJ, Veringa,A, Alffenaar,JWC] University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands. [Neely,M] Laboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute, and Division of Pediatric Infectious Diseases, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA. [Docobo Pérez,F] Department of Molecular and Clinical Pharmacology, Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom. Unidad Intercentros de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain. [Ramos-Martin,V] Department of Molecular and Clinical Pharmacology, Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom. [Tissing,WJ] University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatric Oncology, Groningen, the Netherlands. [Hope,W] Department of Molecular and Clinical Pharmacology, Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom., CS/08/08/10, Department of Health, United Kingdom, R01 HD070886, NICHD NIH HHS, United States, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Microbes in Health and Disease (MHD)
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0301 basic medicine ,Oncology ,Male ,INVASIVE ASPERGILLOSIS ,Antifungal Agents ,Pharmacology ,Aspergillosis ,GUIDELINES ,030226 pharmacology & pharmacy ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Mannans ,chemistry.chemical_compound ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical [Medical Subject Headings] ,0302 clinical medicine ,Information Science::Information Science::Computing Methodologies::Software [Medical Subject Headings] ,GALACTOMANNAN ,Pharmacology (medical) ,Precision Medicine ,Child ,skin and connective tissue diseases ,education.field_of_study ,Área bajo la curva ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability [Medical Subject Headings] ,3. Good health ,Infectious Diseases ,INFECTIONS ,Area Under Curve ,Child, Preschool ,DISEASES ,SAFETY ,Female ,Drug Monitoring ,Antifúngicos ,medicine.drug ,Antifungal ,medicine.medical_specialty ,Dose ,medicine.drug_class ,030106 microbiology ,Population ,SOCIETY ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Triazoles::Voriconazole [Medical Subject Headings] ,Microbial Sensitivity Tests ,03 medical and health sciences ,Galactomannan ,Chemicals and Drugs::Carbohydrates::Polysaccharides::Mannans [Medical Subject Headings] ,Pharmacokinetics ,Diseases::Bacterial Infections and Mycoses::Infection::Skin Diseases, Infectious::Dermatomycoses::Hyalohyphomycosis::Aspergillosis [Medical Subject Headings] ,Internal medicine ,medicine ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Bayes Theorem [Medical Subject Headings] ,Humans ,Computer Simulation ,education ,KINETICS ,Voriconazole ,Models, Statistical ,business.industry ,Aspergillus fumigatus ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve [Medical Subject Headings] ,ANTIFUNGAL THERAPY ,Galactose ,Fungal Polysaccharides ,medicine.disease ,EFFICACY ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antifungal Agents [Medical Subject Headings] ,Mananos ,chemistry ,Aspergilosis ,Pharmacodynamics ,business ,Probabilidad ,Biomarkers - Abstract
Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC/EC 50 ) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC/EC 50 )/15.4 predicted terminal galactomannan ( P = 0.003), and a ratio of >6 suggested a lower terminal galactomannan level ( P = 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival.
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- 2016
5. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa
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Ben Amos, Roxanne Alter, Samuel Kariuki, Elizabeth de Pinna, Robert F. Breiman, Anthony M. Smith, Calman A. MacLennan, Nicholas A. Feasey, Peter J. Hart, Stephen K. Obaro, Gordon Dougan, Chinyere K. Okoro, Huda Munir, Melita A. Gordon, Andrew J. Page, Vanessa K. Wong, Octavie Lunguya, Paul D. Fey, Simon Le Hello, Robert S. Heyderman, Chisomo L. Msefula, Robert S. Onsare, Kathryn E. Holt, Florian Marks, Derek Pickard, Karen H. Keddy, Stephen Baker, François-Xavier Weill, Satheesh Nair, Grace Olanipekun, Jan Jacobs, The Wellcome Trust Sanger Institute [Cambridge], Addenbrooke's Hospital, Cambridge University NHS Trust, Bio21 Molecular Science & Biotechnology Institute [Melbourne] (School of Chemistry), Faculty of Science [Melbourne], University of Melbourne-University of Melbourne, University of Melbourne, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], London School of Hygiene and Tropical Medicine (LSHTM), Department of Epidemiology, International Vaccine Institute (IVI), International Foundation Against Infectious Diseases in Nigeria (IFAIN), Department of Medical Microbiology, Aminu Kano Teaching Hospital, University of Nebraska Medical Center, University of Nebraska System, Liverpool School of Tropical Medicine (LSTM), Centre National de Référence - National Reference Center Escherichia coli, Shigella et Salmonella (CNR-ESS), Institut Pasteur [Paris], Institut National de Recherche Biomédicale [Kinshasa] (INRB), St. George’s, University of London, Kenya Medical Research Institute (KEMRI), Global Disease Detection Division, Centers for Disease Control and Prevention, Emory Global Health Institute [Atlanta] (EGHI), Emory University [Atlanta, GA], University of Liverpool, University College of London [London] (UCL), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Malawi, National Institute for Communicable Diseases [Johannesburg] (NICD), St Augustine’s Hospital, Division of Pediatric Infectious Diseases, University of Nebraska System-University of Nebraska System, University of Abuja, Bingham University, This work was supported by a number of organizations. The Wellcome Trust Sanger Institute authors were funded by Wellcome Trust Award 098051, NAF was supported by the Wellcome Trust Research Fellowship WT092152MA. NAF, RSH and this work were supported by a strategic award from the Wellcome Trust for the MLW Clinical Research Programme (101113/Z/13/Z). KEH was supported by the NHMRC of Australia (fellowship #1061409) and the Victorian Life Sciences Computation Initiative (VLSCI) (grant #VR0082). CAM was supported by a Clinical Research Fellowship from GlaxoSmithKline and PJH by a UK Medical Research Council PhD studentship. This work forms part of an EU FP7 Marie Curie Actions Industry Academia Partnerships and Pathways (IAPP) Consortium Programme, entitled GENDRIVAX (Genome-driven vaccine development for bacterial infections), involving the Wellcome Trust Sanger Institute, KEMRI Nairobi and Novartis Vaccines Institute for Global Health. The Institut Pasteur (IP) authors were funded by the IP, the Institut de Veille Sanitaire, and by the French Government 'Investissement d'Avenir' program(Integrative Biology of Emerging Infectious Diseases' Laboratory of Excellence, grant no. ANR-10-LABX-62-IBEID). CO was supported by Society in Science, The Branco Weiss Fellowship, administered by the ETH Zurich. JJ was supported by the antibioticresistance surveillance project in DR Congo, funded by Project 2.01 of the Third Framework Agreement between the Belgian Directorate General of Development Cooperation and the Institute of Tropical Medicine, Antwerp, Belgium. FM was supported by a research grant from the Bill & Melinda Gates Foundation. The findings and conclusions contained within this publication are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. SK was supported by the NIH Grant Number R01 AI099525-02. SB is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society(100087/Z/12/Z). SO was supported by the National Institute Of Allergy And Infectious Diseases (NIAID) of the National Institutes of Health (#R01AI097493). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis,decision to publish, or preparation of the manuscript., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Baker, Stephen [0000-0003-1308-5755], Marks, Florian [0000-0002-6043-7170], Dougan, Gordon [0000-0003-0022-965X], Apollo - University of Cambridge Repository, University of Oxford, Institut Pasteur [Paris] (IP), and Ryan, E
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0301 basic medicine ,Bacterial Diseases ,Veterinary medicine ,Salmonella typhi ,Pathology and Laboratory Medicine ,Global Health ,Salmonella Typhi ,Geographical Locations ,0302 clinical medicine ,Salmonella ,Epidemiology ,Global health ,Medicine and Health Sciences ,Typhoid ,Medicine ,Public and Occupational Health ,Clade ,Mammals ,lcsh:Public aspects of medicine ,International Typhoid Consortium ,3. Good health ,Bacterial Pathogens ,Europe ,Infectious Diseases ,Medical Microbiology ,Vertebrates ,Pathogens ,Research Article ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,030231 tropical medicine ,Nigeria ,Microbiology ,complex mixtures ,Typhoid fever ,wa_110 ,03 medical and health sciences ,Antibiotic resistance ,Enterobacteriaceae ,Environmental health ,Microbial Control ,Animals ,Microbial Pathogens ,QR355 ,Pharmacology ,Bacteria ,business.industry ,qw_138 ,wc_270 ,Public Health, Environmental and Occupational Health ,Organisms ,Biology and Life Sciences ,lcsh:RA1-1270 ,medicine.disease ,bacterial infections and mycoses ,R1 ,United Kingdom ,030104 developmental biology ,Carriage ,Parasitology ,Amniotes ,People and Places ,Africa ,Cats ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Antimicrobial Resistance ,business - Abstract
Background The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid., Author Summary Typhoid fever, a serious bloodstream infection caused by the bacterium Salmonella Typhi, is a major cause of disease and death around the world. There have been limited data on the epidemiology of typhoid in many countries in sub-Saharan African, including Nigeria. Recent evidence, however, showed that typhoid was an important cause of bacteraemia in children residing in two regions of Nigeria. Here, we analyzed the whole genome sequences of 128 S. Typhi isolates from two studies in order to elucidate the population structure and characterize the genetic components of antimicrobial resistance. We found that the multiple S. Typhi genotypes identified were closely related to other S. Typhi from neighboring regions of Africa and that multidrug resistance (MDR) was common among these isolates, and in many cases was associated with the IncHI1 plasmid known to cause MDR typhoid. These results provide evidence that typhoid was established in Nigeria as a result of several independent introductions into the country and that there has been extensive exchange of S. Typhi in and around the region of West Africa. This study emphasizes the importance of surveillance to improve our understanding of the epidemiology of typhoid, which is needed to underpin public health measures to reduce the spread of disease and facilitate patient management.
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- 2016
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6. Characterizing the pathotype of neonatal meningitis causing Escherichia coli (NMEC)
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Ignacio-Andres Romero, Kwang Sik Kim, Pierre Olivier Couraud, Sudharsan Gongati, Chitrita DebRoy, Subhashinie Kariyawasam, Dona Saumya S. Wijetunge, Babette B. Weksler, Department of Veterinary and Biomedical Sciences, Pennsylvania State University (Penn State), Penn State System-Penn State System, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine [Baltimore], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Biological Sciences, The Open University [Milton Keynes] (OU), Department of Medicine, Weill Medical College of Cornell University [New York], Center for Molecular Immunology and Infectious Disease, This research was supported by start-up funds to S.K. from the Departmentof Veterinary and Biomedical Sciences at the Pennsylvania State University., Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bos, Mireille, PennState University [Pennsylvania] (PSU), Johns Hopkins University School of Medicine, Institut Cochin (UM3 (UMR 8104 / U1016)), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
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Serotype ,Microbiology (medical) ,Blood Bactericidal Activity ,Genotyping ,Genotype ,Virulence Factors ,Neonatal meningitis ,Virulence ,Microbial Sensitivity Tests ,Biology ,medicine.disease_cause ,Serogroup ,Microbiology ,Meningitis, Bacterial ,03 medical and health sciences ,Gentamicin protection assay ,medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Escherichia coli ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Serotyping ,Pathogen ,Escherichia coli Infections ,030304 developmental biology ,0303 health sciences ,030306 microbiology ,Infant, Newborn ,Invasion assay ,medicine.disease ,Endocytosis ,3. Good health ,Molecular Typing ,Phenotype ,Biofilms ,Research Article - Abstract
Background Neonatal meningitis-causing Escherichia coli (NMEC) is the predominant Gram-negative bacterial pathogen associated with meningitis in newborn infants. High levels of heterogeneity and diversity have been observed in the repertoire of virulence traits and other characteristics among strains of NMEC making it difficult to define the NMEC pathotype. The objective of the present study was to identify genotypic and phenotypic characteristics of NMEC that can be used to distinguish them from commensal E. coli. Methods A total of 53 isolates of NMEC obtained from neonates with meningitis and 48 isolates of fecal E. coli obtained from healthy individuals (HFEC) were comparatively evaluated using five phenotypic (serotyping, serum bactericidal assay, biofilm assay, antimicorbial susceptibility testing, and in vitro cell invasion assay) and three genotypic (phylogrouping, virulence genotyping, and pulsed-field gel electrophoresis) methods. Results A majority (67.92 %) of NMEC belonged to B2 phylogenetic group whereas 59 % of HFEC belonged to groups A and D. Serotyping revealed that the most common O and H types present in NMEC tested were O1 (15 %), O8 (11.3 %), O18 (13.2 %), and H7 (25.3 %). In contrast, none of the HFEC tested belonged to O1 or O18 serogroups. The most common serogroup identified in HFEC was O8 (6.25 %). The virulence genotyping reflected that more than 70 % of NMEC carried kpsII, K1, neuC, iucC, sitA, and vat genes with only less than 27 % of HFEC possessing these genes. All NMEC and 79 % of HFEC tested were able to invade human cerebral microvascular endothelial cells. No statistically significant difference was observed in the serum resistance phenotype between NMEC and HFEC. The NMEC strains demonstrated a greater ability to form biofilms in Luria Bertani broth medium than did HFEC (79.2 % vs 39.9 %). Conclusion The results of our study demonstrated that virulence genotyping and phylogrouping may assist in defining the potential NMEC pathotype. Electronic supplementary material The online version of this article (doi:10.1186/s12866-015-0547-9) contains supplementary material, which is available to authorized users.
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- 2015
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7. Comment on Mugisha et al. J Med Primatol 2010; 39: 71-76
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Gessain, Antoine, Rose, Timothy M, Lavergne, Anne, Lacoste, Vincent, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Division of Pediatric Infectious Diseases, University of Washington [Seattle], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
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MESH: Humans ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,MESH: Pan troglodytes/virology ,MESH: Gammaherpesvirinae/genetics ,MESH: Gammaherpesvirinae/isolation & purification ,MESH: Animals - Abstract
Comment on : A novel herpesvirus in the sanctuary chimpanzees on Ngamba Island in Uganda. [J Med Primatol. 2010]; International audience; Letter to the Editor
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- 2010
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8. International Consensus (ICON): allergic reactions to vaccines
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Antonella Muraro, James T. Li, Mario Sánchez-Borges, Pascal Demoly, Kathryn M. Edwards, Michael Gold, Neal A. Halsey, Jean-Christoph Roger J-P Caubet, Renata J.M. Engler, Robert A. Wood, John M. Kelso, Stephen C. Dreskin, Menachem Rottem, Claude Ponvert, Lanny J. Rosenwasser, Donna S. Hummell, Division of Allergy and Clinical Immunology [Aurora, CO, USA], University of Colorado Anschutz [Aurora], Department of International Health [Baltimore, MD, USA], Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Division of Allergy, Asthma, and Immunology [San Diego, CA, USA], Scripps Clinic [San Diego, CA, USA], The Division of Pediatric Allergy and Immunology [Baltimore, USA], Johns Hopkins University School of Medicine [Baltimore], Division of Pediatric Allergy, Immunology, and Pulmonary Medicine [Nashville, TN, USA], Vanderbilt University School of Medicine [Nashville], Division of Pediatric Infectious Diseases [Nashville, TN, USA], Department of Pediatrics [Geneva, Switzerland], Hôpitaux Universitaires de Genève (HUG), Department of Medicine and Pediatrics [Bethesda, MD, USA] (Allergy-Immunology-Immunization), Uniformed Services University of the Health Sciences (USUHS)-Walter Reed Army Institute of Research, Disipline of Paediatrics [Adelaide SA, Australia], University of Adelaide, Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Department of Allergy and Clinical Immunology [Caracas, Venezuela], Centro Medico-Docente La Trinidad, Food Allergy Referral Centre Veneto Region [Padua, Italy], Universita degli Studi di Padova, Division of Allergic Diseases [Rochester, MN, USA], Mayo Clinic [Rochester], Allergy Asthma and Immunology [Haifa, Israel], Ha'Emek Medical Center, Afula-Rappaport Faculty of Medicine, Allergy-Immunology Division [Kansas City, MO, USA], Children's Mercy Hospital [Kansas City]-University of Missouri [Kansas City] (UMKC), University of Missouri System-University of Missouri System, Walter Reed Army Institute of Research-Uniformed Services University of the Health Sciences (USUHS), Centro Médico Docente La Trinidad, Università degli Studi di Padova = University of Padua (Unipd), University of Colorado Denver School of Medicine [Aurora, CO, USA], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University ( JHU ) -Johns Hopkins University ( JHU ) -Institute for Vaccine Safety [Baltimore, MD, USA], Vanderbilt University School of Medicine [[Nashville, TN, USA]], Hôpitaux Universitaires de Genève ( HUG ), Department of Medicine and Pediatrics [Bethesda, MD, USA] ( Allergy-Immunology-Immunization ), Uniformed Services University of the Health Sciences [Bethesda, MD, USA]-Walter Reed Army Medical Center [Bethesda, MD, USA], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Sorbonne Universités, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, University Hospital of Padua, Mayo Clinic Rochester [USA], Children's Mercy Hospital [Kansas City, MO, USA]-University of Missouri–Kansas City School of Medicine [USA], and BMC, BMC
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lcsh:Immunologic diseases. Allergy ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Allergy ,Consensus ,[SDV]Life Sciences [q-bio] ,Immunology ,Alternative medicine ,Vaccines Administered ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,medicine ,Immunology and Allergy ,030212 general & internal medicine ,Consensus Document ,Anaphylaxis ,Components ,computer.programming_language ,Asthma ,ddc:618 ,[ SDV ] Life Sciences [q-bio] ,business.industry ,Routine immunization ,medicine.disease ,3. Good health ,[SDV] Life Sciences [q-bio] ,Causality ,Immunization ,International ,Family medicine ,Allergic reactions ,Icon ,lcsh:RC581-607 ,business ,Vaccine ,computer - Abstract
Background Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines.Methods Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists.Results Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines.Conclusions This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines. Keywords: Allergy, Allergic reactions, Anaphylaxis, Causality, Components, International, Consensus, Vaccine
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- 2016
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9. COVID-19 vaccine effectiveness against severe omicron-related outcomes in children aged 5 to 11 years in Ontario: A Canadian immunization research network (CIRN) study.
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Piché-Renaud PP, Drover SSM, Austin PC, Morris SK, Buchan SA, Nasreen S, Schwartz KL, Tadrous M, Thampi N, Wilson SE, Wilson K, Guttmann A, and Kwong JC
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- Humans, Child, Preschool, Male, Female, Ontario epidemiology, Child, Retrospective Studies, Vaccination, Proportional Hazards Models, Systemic Inflammatory Response Syndrome, COVID-19 prevention & control, COVID-19 epidemiology, COVID-19 immunology, COVID-19 complications, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Vaccine Efficacy, SARS-CoV-2 immunology, Hospitalization statistics & numerical data
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Background: Understanding how the efficacy of COVID-19 vaccines translates from clinical trials to real-world settings is critical to inform evolving vaccination policies. The objective of this study was to assess COVID-19 vaccine effectiveness (VE) against severe COVID-19-related outcomes in children aged 5-11 years, including COVID-19-related hospital admissions and multisystem inflammatory syndrome in children (MIS-C)., Methods: We conducted a retrospective, population-based cohort study using linked health administrative data in the first year following the emergence of the Omicron variant (January 2 to December 31, 2022) in Ontario, Canada. Baseline differences between subgroups of interest were compared using standardized differences. We used multivariable Cox proportional hazard regression models to estimate VE by time since last vaccine dose by treating vaccination as a time-varying exposure, compared to unvaccinated children., Results: We included a total of 1,058,740 children, of which 583,867 (55.1 %) had received at least one vaccine dose by the end of the study period. In total, there were 185 COVID-19-related hospital admissions and 39 cases of MIS-C. The rate of COVID-19-related admission was substantially higher in children with an underlying comorbid condition compared to children who were previously healthy (adjusted hazard ratio [aHR] = 4.77, 95 %CI, 3.56-6.38). VE against COVID-19-related admission ranged from 93 % (95 %CI, 52-99 %) 7-29 days after a second dose to 63 % (95 %CI; 41-77 %) ≥120 days after a second dose. There was no statistically significant difference in the rate of MIS-C in children who received at least one dose of the vaccine compared to unvaccinated children (aHR = 0.71; 95 %CI, 0.38-1.34)., Conclusions: We found that, for children aged 5-11 years, VE against COVID-19-related hospitalization was high in the first four months after a second dose. Children with comorbid conditions were found to be at much higher risk of COVID-19-related severe outcomes and thus may benefit most from COVID-19 vaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeffrey C. Kwong reports financial support was provided by Canadian Institutes of Health Research. Jeffrey C. Kwong reports financial support was provided by Public Health Agency of Canada. Kumanan Wilson reports a relationship with CANImmunize that includes: board membership. Shaun K. Morris reports a relationship with GlaxoSmithKline that includes: consulting or advisory and speaking and lecture fees. Shaun K. Morris reports a relationship with Sanofi Pasteur that includes: consulting or advisory and speaking and lecture fees. Shaun K. Morris reports a relationship with Pfizer that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2025
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10. Efficacy and safety of posaconazole and liposomal amphotericin B use for prophylaxis of invasive fungal infections in a paediatric and young adult haemato-oncological population.
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Chiusaroli L, Barbieri E, Dell'Anna L, Petris MG, Liberati C, Reggiani G, De Pieri M, Mengato D, Marzollo A, Gabelli M, Giaquinto C, Biffi A, and Donà D
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Background: The prevention of invasive fungal infections (IFIs) is crucial for paediatric haemato-oncological patients. This study evaluates the clinical efficacy and side-effects of posaconazole and liposomal amphotericin B (L-AmB) as primary prophylaxis., Materials and Methods: This cohort study included patients aged 3 months to 21 years who received posaconazole or L-AmB (5 mg/kg twice weekly) as prophylaxis from January 2017 to March 2022 at the Hemato-oncological Pediatric Unit, University Hospital of Padua, Italy. Outcomes included adverse events and IFI diagnoses after the start of prophylaxis. Separate analyses were performed for patients with ALL and non-ALL diagnoses, and high-risk and low-risk groups. Cumulative incidence was calculated using the Kaplan-Meier estimator, with significant differences assessed using the log-rank test. Hazard ratios (HR) were estimated using Cox regression., Results: Fifty-one patients received posaconazole, and 37 received L-AmB. Adverse events occurred in 26% of L-AmB patients and 5.6% of posaconazole patients. IFI breakthrough events were similar in both groups (four events each). In ALL patients, 41% experienced adverse events with L-AmB, compared to 5% with posaconazole. After 1 year, the probability of adverse events was lower in the posaconazole group (54% versus 65%, P < 0.001). Overall, posaconazole was associated with a 91% lower risk of adverse events (HR: 0.07, P < 0.001). Among high-risk patients, IFI breakthrough rates were similar between groups (P = 0.964)., Conclusions: Posaconazole was associated with fewer adverse events than L-AmB, and both drugs showed similar efficacy in preventing IFI breakthroughs, making posaconazole a viable alternative for primary prophylaxis., (© The Author(s) 2025. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2025
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11. Outbreak of Rotavirus Diarrheal Infection among Adults in King County, Washington, January-June 2023.
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Ma J, Kumbhakar RG, Casto A, Chow EJ, Englund JA, Gautam R, Jaimes J, Tate JE, Smart S, Mani NS, Cohen SA, Hussein A, Rietberg K, Bryson-Cahn C, and Fang FC
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Rotavirus is a leading cause of diarrhea among children but less known as a cause among adults. We describe clinical, epidemiologic, and genotype characteristics of a rotavirus outbreak among adults in King County, Washington occurring January-June 2023. Adult rotavirus incidence in 2023 was ten times higher than the same period in 2022 (5% versus 0.5% samples). Disease severity was mild. G9P[4], an uncommon, non-vaccine strain in USA, was the predominant genotype. Genotyping suggested spillover from children with subsequent spread among adults. Our study highlights benefits of routine testing and genotyping during outbreaks for surveillance, tracking, and understanding implications on vaccination., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2025
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12. Efficacy and safety of three antiseptics for neonatal skin disinfection: further evidence for chlorhexidine gluconate.
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Prochaska EC and Milstone AM
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Competing Interests: Competing interests: The authors declare no competing interests.
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- 2025
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13. Reducing antibiotic duration for acute otitis media: clinician, administrator, and parental insights to inform implementation of system-level interventions.
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Rinehart DJ, Gilbert A, O'Leary S, Katz SE, and Frost HM
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Objective: This qualitative study aimed to understand facilitators and barriers to implementation of interventions to improve guideline-concordant antibiotic duration prescribing for pediatric acute otitis media (AOM)., Design: Clinicians and clinic administrators participated in semi-structured qualitative interviews, and parents of children 2 years of age or older with a recent diagnosis of AOM participated in focus groups. The Practical Robust Implementation and Sustainability Model (PRISM) guided the study. Interviews were analyzed using the Rapid Assessment Process., Setting: Denver Health and Hospital Authority (Denver, CO) led the study. Recruitment occurred at Vanderbilt University Medical Center (Nashville, TN) and Washington University in St. Louis Medical Center (St. Louis, MO)., Participants: Purposeful sampling was used to recruit clinicians and administrators for qualitative interviews. Convenience sampling was used to recruit parents for focus groups., Results: Thirty-one participants (15 clinicians, 4 administrators, and 12 parents) engaged in interviews and focus groups. Factors influencing antibiotic prescribing included patient history, years of practice, familiarity with the patient, concerns with patient medication adherence, and practice type. Clinicians endorsed electronic health record modifications and clinician prescribing feedback as methods to improve patient care and reduce the durations of prescribed antibiotics. Suggestions for intervention optimization and education needs were also obtained., Conclusions: Findings suggest that clinicians and administrators support reducing prescribed antibiotic durations for AOM and are receptive to the proposed interventions. More education is needed to increase parent awareness about antibiotic stewardship and AOM treatment options., Clinical Trials Identifier: RELAX: Reducing Length of Antibiotics for Children with Ear Infections (RELAX), NCT05608993, https://clinicaltrials.gov/study/NCT05608993., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2025.)
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- 2025
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14. Going commando as part of a multifaceted intervention to reduce CAUTIs in critically ill children.
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Linam M, Wannemacher L, Powell K, Calamaro C, and Walson K
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This project was initiated in a large pediatric intensive care unit to reduce catheter-associated urinary tract infections (CAUTIs). Implementing removal of diapers and a urine collection device that prevented urine backflow in March 2021 decreased the rate from 3.3 to 0.9 CAUTIs/1000 catheter-days. These interventions could augment CAUTI prevention strategies., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2025.)
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- 2025
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15. Recommendation for the use of respiratory syncytial virus vaccines.
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Lee PI, Huang YC, Liu CC, Chen SU, Hsueh PR, Ku SC, Chen PY, Chen CJ, Lin YT, Lu CY, Chiu NC, Chi H, Chen YC, Chang FY, Yen MY, Lu CT, Yang KY, Chiu CH, Hwang KP, Lee WS, Yen TY, Hsu JF, Lin YC, Hu YL, and Lin TY
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Respiratory syncytial virus (RSV) is the most common pathogen for young children hospitalized with bronchiolitis and pneumonia. Most infections occur below 1 year of age. RSV is also a significant viral pathogen for adults with respiratory tract infection. Vaccines targeting the pre-fusion protein of RSV, including recombinant and mRNA vaccines, are now available. A committee of experts from related fields was convened by the Taiwan Immunization Vision and Strategy to develop recommendations for RSV vaccination in the elderly and pregnant women. The recommendation is not intended as a sole source of guidance in the prevention of RSV infection in children. The provisions listed in this recommendation are comprehensive suggestions made by experts in Taiwan based on existing medical evidence. This recommendation should be subject to modification in light of additional medical research findings in the future, and these provisions should not be cited as a basis for dispute resolution., (Copyright © 2025. Published by Elsevier B.V.)
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- 2025
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16. The Masked Bandit of Milestones: A Case of Baylisascaris procyonis.
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Witkowski MJ, Sharma H, Adams N, Meara JM, Batwa A, Hecht SM, and Kamath A
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Competing Interests: The authors have no funding or conflicts of interest to disclose.
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- 2025
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17. Building a growing genomic repository for maternal and fetal health through the PING Consortium.
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Abdelmalek CM, Singh S, Fasil B, Horvath AR, Mulkey SB, Curé C, Campos M, Cavalcanti DP, Tong VT, Mercado M, Daza M, Benavides MM, Acosta J, Gilboa S, Valencia D, Sancken CL, Newton S, Scalabrin DMF, Mussi-Pinhata MM, Vasconcelos Z, Chakhtoura N, Moye J, Leslie EJ, Bulas D, Vezina G, Marques FJP, Leyser M, Del Campo M, Vilain E, DeBiasi RL, Wang T, Nath A, Haydar T, Muenke M, Mansour TA, du Plessis AJ, Murray JC, Cordero JF, and Kousa YA
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Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome. Currently, there is no preventative treatment or cure. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium aims to identify modulators of brain injury and adverse neurodevelopmental outcomes for Zika and other prenatal viral infections., Methods: The Consortium pools information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic repository, which is being mined for modifiers of virally induced brain injury. Partners include Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), Zika Instituto Fernandes Figueira (Brazil), the Centers for Disease Control and Prevention, and the National Institutes of Health., Results: We have enrolled 4102 mothers and 3877 infants with 3063 biological samples and clinical data covering over 80 phenotypic fields and 5000 variables. Thus far, we have performed whole exome sequencing on 1226 participants., Conclusion: Here, we present the Consortium's formation and overarching study design., Impact: The PING Consortium brings together investigators and institutions to determine the causes of virally induced brain injury and neurological deficits. The clinical and genomic repository, with data from over 8000 patients, will serve as a foundation for a variety of basic and clinical studies., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent statement: Samples and associated data collected through the Prenatal Infection and Neurodevelopmental Genetics Consortium were IRB approved by participating institutions and by Children’s National Hospital (IRB reference number 8259). Any changes to the protocol or materials are submitted for approval by the IRB/CEP before being implemented, through amendments to the project. The research team notifies the IRB/CEP of deviations from the protocol or any adverse events that might be related to the present study. Brazilian studies were also approved by CONEP (approval numbers of the original related projects: CAAEs: 61936216.9.0000.5404; 56673616.3.2002.5440; 61936216.9.0000.5404). The researchers ensured that this study was conducted in full compliance with the principles set out in the Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects in Research by the US National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research (18 April 1979) and encoded in 45 CFR Section 46 or the ICH E6; 62 Federal Regulations 25691 (1997). The Investigators’ institution must maintain an up-to-date, federal-level policy (FWA) issued by the Office of Human Protection in Research for US government-funded research. Both multi-center and site-specific IRB approvals were obtained in one of in two ways. A majority of the studies obtained informed consent for genetic testing prospectively. In some cases, informed consent was obtained retrospectively., (© 2025. The Author(s).)
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- 2025
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18. Antibiotic prescribing patterns at outpatient clinics in Western and Coastal Kenya.
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Kiener M, Ichura C, Ndenga BA, Mutuku FM, Winter CA, Okuta V, Mwambingu L, Ogamba K, Shaita KN, Ronga C, Chebii P, Amugongo J, Malumbo S, Godana O, Jembe Z, Ng'ang'a C, Mazera M, and LaBeaud AD
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Antimicrobial resistant pathogens are a leading cause of morbidity and mortality worldwide, with overuse and misuse of antimicrobials being key contributors. We aimed to identify factors associated with antibiotic prescriptions among patients presenting to clinics in Kenya. We performed a retrospective, descriptive cohort study of persons presenting to outpatient clinics in Western and Coastal Kenya, including symptoms, physical exams, clinician assessments, laboratory results and prescriptions. We reviewed 1,526 visits among 1,059 people who sought care from December 2019-February 2022. Median age was 16 (IQR 6-35) and 22% were under 5. 30% of malaria RDTs were positive and 3% of dengue RT-qPCRs were positive. Antibiotics were prescribed in 73% of encounters overall and in 84% among children under 5. In 48% of visits antibiotics were prescribed without a provisional bacterial diagnosis. In the multivariable model, factors associated with increased odds of an antibiotic prescription were the clinic in Western Kenya (OR 5.1, 95% CI 3.0-8.8), age less than or equal to 18 (OR 2.1, 95% CI 1.4-3.2), endorsement of cardiorespiratory symptoms (OR 5.2, 95% CI 3.2-8.3), a negative malaria RDT (OR 4.0, 95% CI 2.5-6.8), and a provisional diagnosis that could be bacterial in etiology (OR 5.9, 95% CI 3.5-10.3). High rates of antibiotic prescriptions are common even when associated diagnoses are not bacterial. Compared to our 2014-2017 cohort, we found higher rates of antibiotic prescriptions among children. Improved diagnostics to rule in alternative diagnoses as well as stewardship programs are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Kiener et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2025
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19. Comparison of two interferon-gamma release assays for pediatric tuberculosis infection.
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Gaensbauer JT, Reves RR, Katz D, Ahmed A, and Venkatappa T
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Introduction: Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis. Pediatric data comparing the two IGRAs in the United States are very limited. We compared the performance of the two IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cut-off values., Methods: Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON TB-Gold In-Tube (QFT-GIT) tests were identified from a U.S. multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar's Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results., Results: Among 3,793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, p < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cut-off of 0.35 IU/mL., Conclusions: In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cut-offs., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2025. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
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- 2025
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20. Clinical outcomes and the impact of treatment modalities in children with carbapenem-resistant Enterobacteriaceae bloodstream infections: a retrospective cohort study from a tertiary university hospital.
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Avcu G, Erci E, Bilen NM, Ersayoglu I, Ozek G, Celtik U, Terek D, Cilli F, and Bal ZS
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- Humans, Infant, Male, Female, Retrospective Studies, Child, Preschool, Child, Adolescent, Treatment Outcome, Risk Factors, Infant, Newborn, Carbapenems pharmacology, Carbapenems therapeutic use, Carbapenem-Resistant Enterobacteriaceae drug effects, Carbapenem-Resistant Enterobacteriaceae isolation & purification, Enterobacteriaceae Infections drug therapy, Enterobacteriaceae Infections mortality, Enterobacteriaceae Infections microbiology, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents pharmacology, Tertiary Care Centers statistics & numerical data, Bacteremia drug therapy, Bacteremia microbiology, Bacteremia mortality, Hospitals, University
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Background: The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections among children represents a significant global concern, leading to elevated mortality rates. The aim of this study was to evaluate the risk factors, outcomes, 30-day mortality rates and contributing factors in children with CRE bloodstream infections (CRE-BSIs)., Methods: Data regarding demographic characteristics, treatment approaches and outcomes of hospitalized children aged 0-18 years diagnosed with CRE-BSIs between January 2018 and December 2022 were extracted from medical records. Mortality within 30 days of diagnosis and the predictive factors were analysed., Results: A total of 114 children, with a median age of 11 months (range: 6-69.5), were included. All cases of CRE-BSIs were either healthcare associated or hospital acquired and presented with at least one underlying comorbidity. A previous history of CRE colonization or infection rate was 48.2% (55/114). Klebsiella pneumoniae 87.7% (100/114) was the most frequently isolated microorganism, with a 30-day mortality rate of 14% (16/114). Multivariate analysis identified paediatric intensive care unit admission, invasive mechanical ventilation, inotropic support and thrombocytopenia due to CRE-BSIs as the most discriminative predictors for 30-day mortality (P < 0.001). Central venous catheter (CVC) removal was associated with a reduced mortality rate (P = 0.012). High-dose prolonged infusion of MEM-based or polymyxin-based antibiotic combinations did not impact survival. Lower MEM MIC values were associated with improved survival., Conclusions: The mortality rate of CRE-BSI is notably high in childhood. The use of antibiotic combination strategies did not demonstrate a significant impact on 30-day survival; however, the removal of CVCs was found to lower mortality rates., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
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- 2025
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21. A vaccine against cytomegalovirus: how close are we?
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Permar SR, Schleiss MR, and Plotkin SA
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- Humans, Clinical Trials as Topic, Hematopoietic Stem Cell Transplantation, Organ Transplantation adverse effects, Cytomegalovirus immunology, Cytomegalovirus Infections prevention & control, Cytomegalovirus Infections immunology, Cytomegalovirus Vaccines immunology
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The pursuit of a vaccine against the human cytomegalovirus (HCMV) has been ongoing for more than 50 years. HCMV is the leading infectious cause of birth defects, including damage to the brain, and is a common cause of complications in organ transplantation. The complex biology of HCMV has made vaccine development difficult, but a recent meeting sponsored by the National Institute of Allergy and Infectious Diseases in September of 2023 brought together experts from academia, industry, and federal agencies to discuss progress in the field. The meeting reviewed the status of candidate HCMV vaccines under study and the challenges in clinical trial design in demonstrating efficacy against congenital CMV infection or the reduction of HCMV disease following solid organ transplantation or hematopoietic stem cell transplantation. Discussion in the meeting revealed that, with the numerous candidate vaccines that are under study, it is clear that a safe and effective HCMV vaccine is within reach. Meeting attendees achieved a consensus opinion that even a partially effective vaccine would have a major effect on the global health consequences of HCMV infection.
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- 2025
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22. Global burden of tuberculous meningitis in children aged 0-14 years in 2019: a mathematical modelling study.
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du Preez K, Jenkins HE, Martinez L, Chiang SS, Dlamini SS, Dolynska M, Aleksandrin A, Kobe J, Graham SM, Hesseling AC, Starke JR, Seddon JA, and Dodd PJ
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- Humans, Infant, Child, Adolescent, Child, Preschool, Infant, Newborn, Global Burden of Disease, Bayes Theorem, Female, Male, HIV Infections epidemiology, HIV Infections complications, Tuberculosis, Meningeal epidemiology, Tuberculosis, Meningeal mortality, Global Health statistics & numerical data, Models, Theoretical
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Background: Tuberculous meningitis is fatal if untreated and can lead to lifelong neurological sequelae. However, to our knowledge, there are no data on the number of children affected by this disease. We aimed to estimate the global disease burden and attributable mortality of childhood tuberculous meningitis by WHO regions, age groups, treatment status, and HIV status in 2019., Methods: We developed a Bayesian mathematical model to estimate the number of children aged 0-14 years who developed tuberculous meningitis, died from tuberculous meningitis, and did not die from tuberculous meningitis but had neurological sequelae in 2019. We reviewed the literature and used meta-analyses to quantify key parameters used as model inputs: risk of tuberculous meningitis after Mycobacterium tuberculosis infection, tuberculous meningitis as a proportion of tuberculosis notification data (ie, routine surveillance data that countries report to WHO), and risk ratios for tuberculous-meningitis mortality by age group. We identified routine tuberculosis surveillance data from countries and literature that reported the proportion of notified childhood tuberculosis that was due to tuberculous meningitis. Country-level data were from Brazil; the USA; Ukraine; South Africa; and the European Centre for Disease Prevention and Control, which included 29 countries but was aggregated and considered as one site. We assumed tuberculosis notification was synonymous with detection and treatment, combined age-disaggregated risk ratios and published meta-analytic estimates of the case-fatality rate in children who received treatment to produce estimates of tuberculous-meningitis mortality by age group and HIV status, and assumed that untreated tuberculous meningitis was always fatal. We assumed similar age-disaggregated risk ratios for neurological sequelae among children who had treatment for tuberculous meningitis and lived as for children who died., Findings: An estimated 24 000 (95% credible interval 22 300-25 700) children younger than 15 years developed tuberculous meningitis in 2019. Of these children, 13 000 (12 100-13 900) were estimated to have been diagnosed and treated for tuberculous meningitis. Most untreated children were younger than 5 years. Among the 24 000 children with tuberculous meningitis, 16 100 (14 900-17 300) were estimated to have died in 2019, of whom 1101 (6·8%) had HIV. 13 380 (83·1%) of 16 100 deaths were estimated to be in children younger than 5 years and 11 000 (68·3%) were estimated to be in children who did not receive tuberculous-meningitis treatment. Of the 7900 (5800-10 000) children who did not die, 5550 (5110-5980) were estimated to have neurological sequelae., Interpretation: Our estimates of tuberculous meningitis in children younger than 15 years showed substantial mortality and morbidity. Improved diagnostics and strong health-care systems to facilitate early diagnosis are crucial to improve outcomes, and tuberculosis prevention should be a public health priority., Funding: Fogarty International Center of the US National Institutes of Health., Competing Interests: Declaration of interests KdP received a career development award (K43) from the US National Institutes of Health. ACH is supported by a South African National Research Foundation chair in paediatric tuberculosis. PJD was supported by the UK Medical Research Council (MR/W029227/1). JK was supported by the US National Institutes of Health (award number R03AI164123). All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2025
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23. Prompt Initiation of Maternal Antiretroviral Therapy After HIV Seroconversion in Pregnancy Effectively Prevents Vertical Transmission and Other Adverse Infant Outcomes.
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Sundar KG, Yang LZ, Cambou MC, Varella IRS, Melo MG, Segura ER, Ziegler ÂP, Santos BR, and Nielsen-Saines K
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- Humans, Pregnancy, Female, Infant, Newborn, Brazil epidemiology, Adult, Infant, HIV Seropositivity drug therapy, Anti-Retroviral Agents therapeutic use, Anti-Retroviral Agents adverse effects, Anti-HIV Agents therapeutic use, Anti-HIV Agents adverse effects, Young Adult, Risk Factors, Male, Retrospective Studies, Infectious Disease Transmission, Vertical prevention & control, Pregnancy Complications, Infectious drug therapy, HIV Infections drug therapy, HIV Infections transmission
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From January 2008 to December 2018, 1348 HIV-exposed infants were born in Porto Alegre, Brazil; 18.8% had adverse infant outcomes (AIO) including vertical transmission (1.9%), stillbirth/neonatal death (4.0%) and loss to follow-up before HIV diagnosis (12.9%). Timing of maternal HIV diagnosis was not associated with AIO but absent antiretroviral therapy use was. Lack of maternal antiretroviral therapy use is a significant risk factor for AIO., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2025
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24. Stenotrophomonas maltophilia Associated Factors and Outcomes in a Neonatal Intensive Care Unit: A Retrospective Matched Case-control Study.
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Franco S, Abdelhemid A, Fordjour L, Kohlhoff S, and Hammerschlag MR
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- Humans, Retrospective Studies, Case-Control Studies, Infant, Newborn, Risk Factors, Female, Male, Cross Infection microbiology, Cross Infection epidemiology, Treatment Outcome, Stenotrophomonas maltophilia isolation & purification, Stenotrophomonas maltophilia drug effects, Intensive Care Units, Neonatal statistics & numerical data, Gram-Negative Bacterial Infections epidemiology, Gram-Negative Bacterial Infections microbiology, Gram-Negative Bacterial Infections drug therapy, Anti-Bacterial Agents therapeutic use
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Background: Stenotrophomonas maltophilia is a multi-drug-resistant, hospital-acquired Gram-negative bacillus associated with significant morbidity and mortality. The objective of this study is to identify risk factors and outcomes associated with S. maltophilia isolation in a high-risk neonatal population., Methods: This was a retrospective matched case-control study. Cases were matched 1:2 for years of neonatal intensive care unit admission, completed weeks' gestational age and birth weight in 250-gram incremental categories., Results: A total of 15 cases and 35 controls were included in the analyses. Risk factors for S. maltophilia isolation included days of antibiotics (24 vs. 18, P = 0.036), days of broad-spectrum antibiotics (19 vs. 12 days, P = 0.027), days of meropenem (9 vs. 6 days, P = 0.018) and any meropenem exposure (100% vs. 22%, P = 0.005). Other risk factors were any corticosteroid exposure (66.7% vs. 20%, P = 0.001), days of total parenteral nutrition (55 vs. 31 days, P = 0.017) and days of invasive mechanical ventilation (28 vs. 7, P = 0.015). S. maltophilia isolation was associated with increased length of neonatal intensive care unit stay (134 vs. 69 days, P < 0.001) and mortality (33.3% vs. 0%, P = 0.001)., Conclusions: Antibiotic stewardship efforts should be made to decrease the risk of S. maltophilia isolation and associated mortality. Carbapenem over-use should be specifically addressed with institutional policies and unit-based guidelines. Additional neonatal studies are needed to confirm these findings and explore other possible risk factors., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2025
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25. Universal newborn screening for congenital cytomegalovirus infection.
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Schleiss MR and Blázquez-Gamero D
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- Humans, Infant, Newborn, Cytomegalovirus isolation & purification, Hearing Loss, Sensorineural diagnosis, Hearing Loss, Sensorineural prevention & control, Hearing Loss, Sensorineural virology, Saliva virology, Cytomegalovirus Infections complications, Cytomegalovirus Infections congenital, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections virology, Neonatal Screening methods
- Abstract
Congenital cytomegalovirus (CMV) infection is the leading infectious cause of childhood disability, in particular sensorineural hearing loss (SNHL). Timeliness of diagnosis is crucial, since the presence of CMV in any compartment (eg, blood, urine, or saliva) after age 21 days can mean postnatal acquisition of infection, particularly in breastfed infants. Given these issues, there is considerable interest in implementation of screening programmes-either universal screening (where all newborns are tested) or targeted screening. Targeted screening is typically based on the outcome of a newborn hearing screen, and can be influenced in some strategies by findings of other signs suggestive of congenital CMV. Universal screening is likely to have the greatest overall benefit. Early identification of congenital CMV allows for interventions such as antiviral therapy (when indicated) and enables anticipatory audiological monitoring that facilitates timely detection of delayed-onset SNHL. However, there are debates about the effectiveness of screening programmes. Most infants with congenital CMV are unaffected and do not appear to be at risk for adverse neurodevelopment outcomes, except for SNHL. Screening can, therefore, raise unwarranted concern among parents and clinicians in these cases. The best clinical sample for diagnostic testing is unclear. PCR testing of saliva is sensitive but has a risk of yielding false-positive results in infants without congenital CMV. Resolving the technological issues has improved the sensitivity of dried blood spot (DBS) PCR but the technique remains suboptimum. An advantage to DBS PCR testing is that an infrastructure exists to add this test to existing newborn screening programmes. In this Review, the advantages and disadvantages of congenital CMV screening are discussed, along with high-priority areas for future research that will inform and direct this rapidly evolving field., Competing Interests: Declaration of interests MRS reports grant support to the University of Minnesota, but no personal honoraria, from Moderna. MRS reports advisory board consultancy work for GSK vaccines. DB-G reports consulting fees from Moderna and honoraria for lectures and educational activities from MSD and Medscape., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2025
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26. Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis.
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Sligl WI, Yan C, Round J, Wang X, Chen JZ, Boehm C, Fong K, Crick K, Clua MG, Codan C, Dingle TC, Prosser C, Chen G, Tse-Chang A, Garros D, Zygun D, Opgenorth D, Conly JM, Doig CJ, Lau VI, and Bagshaw SM
- Abstract
Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis., Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective. Two intensive care units in Alberta with 727 adult critically ill patients were included. Our bundled intervention was compared with pre-implementation standard care. We collected healthcare resource use and estimated unit costs in 2022 Canadian dollars (CAD) over a time horizon from study entry to hospital discharge or death. We calculated the incremental net monetary benefit (iNMB) of the intervention group compared with the pre-intervention group. The primary outcome was cost per sepsis case. Secondary outcomes included readmission rates, Clostridioides difficile infections, mortality, and lengths of stay. Uncertainty was investigated using cost-effectiveness acceptability curves, cost-effectiveness plane scatterplots, and sensitivity analyses., Results: Mean (standard deviation [SD]) cost per index hospital admission was CAD $83,251 ($107,926) for patients in the intervention group and CAD $87,044 ($104,406) for the pre-intervention group, though the difference ($3,793 [$7,897]) was not statistically significant. Costs were higher in the pre-intervention group for antibiotics, readmissions, and C. difficile infections. The intervention group had a lower mean expected cost; $110,580 ($108,917) compared with pre-intervention ($125,745 [$113,210]), with a difference of $15,165 ($8278). There were no statistically significant differences in quality adjusted life years (QALYs) between groups. The iNMB of the intervention group compared with pre-intervention was greater than $15,000 for willingness-to-pay (WTP) per QALY values of between $0 and $100,000. In our sensitivity analysis, the intervention was most likely to be cost-effective in roughly 56% of simulations at all WTP thresholds., Conclusions: Our bundled intervention of ASP, PCT, and BCID among adult critically ill patients with sepsis was potentially cost-effective, but with substantial decision uncertainty., Competing Interests: Declarations. Funding: Funding was provided through a partnership grant between Alberta Innovates, Alberta Health Services, and bioMérieux. The investigators designed the study, wrote the manuscript, and vouch for the accuracy and completeness of the data and analyses. The funding organizations and partners were not involved in implementation or management of the study, in the analysis of data, or in the decision to submit the manuscript for publication. Competing Interests: Jeff Round is an editorial board member of PharmacoEconomics Open. He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. John Conly was an invited speaker at a symposium on antimicrobial resistance co-hosted by the University of Toronto and bioMérieux Canada in 2022. All other authors have no relevant conflicts to declare. Availability of Data and Material: The data that support the findings of this study are available upon reasonable request if permitted by Alberta Health Services; restrictions may apply. The anonymized model is publicly available on request. Ethics Approval and Consent to Participate: The study was approved by the Institutional Review Boards (IRBs) at the University of Alberta (Pro00101420) and the University of Calgary (REB17-2244). Individual patient consent was waived by both IRBs given the study was classified as a quality improvement initiative. Consent for Publication: Not applicable. Code Availability: The decision tree model was conducted using TreeAge software and the statistical analysis was conducted in R. Both files are included as supplementary material. Author Contributions: Conceptualization: C.D., D.Z., D.O., J.M.C., J.C., S.B., J.R., V.L., W.S. Data curation: K.C., C.B., M.G., C.C., T.D., C.P., A.T., D.G., D.O., J.M.C., J.C., K.F., W.S. Formal Analysis: X.W., C.Y., C.D., D.O., J.M.C., J.C., S.B., J.R., V.L., W.S. Funding acquisition: D.Z., D.O., S.B., W.S. Investigation: K.C., C.B., M.G., C.C., T.D., C.P., C.Y., G.C., A.T., D.G., C.D., D.Z., D.O., J.M.C., J.C., K.F., J.R., V.L., S.B., W.S. Methodology: X.W., C.Y., G.C., C.D., J.M.C., J.C., S.B., J.R., V.L., W.S. Project administration: D.Z., D.O., S.B., W.S. Resources: D.Z., D.O., S.B., W.S. Software: D.O., J.C., X.W. Supervision: S.B., W.S. Validation: S.B., W.S. Visualization: S.B., W.S. Writing—original draft: C.Y., C.D., J.M.C., S.B., J.R., V.L., S.B., W.S. Writing—reviewing and editing: K.C., C.B., M.G., C.C., T.D., C.P., C.Y., G.C., A.T., D.G., C.D., D.Z., D.O., J.M.C., J.C., K.F., J.R., V.L., S.B., W.S., (© 2024. The Author(s).)
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- 2025
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27. Etiology and Outcomes of Acute Infectious Conjunctivitis in Children.
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Frost HM, Jenkins TC, Meece JC, Savor-Price C, Wilson ML, Keith A, Stein A, Morin T, Cosgrove S, Kiernan M, Sebastian T, and Dominguez SR
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- Humans, Male, Female, Case-Control Studies, Child, Preschool, Child, Infant, Acute Disease, Haemophilus Infections drug therapy, Haemophilus Infections epidemiology, Haemophilus Infections diagnosis, Treatment Outcome, Conjunctivitis, Bacterial drug therapy, Conjunctivitis, Bacterial microbiology, Conjunctivitis, Bacterial epidemiology, Anti-Bacterial Agents therapeutic use, Haemophilus influenzae isolation & purification
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Objective: To determine the causes of conjunctivitis and whether clinical presentations and outcomes differ by pathogen., Study Design: This multicenter, case-control study enrolled 390 children (194 cases, 196 controls) whose conjunctival samples were tested for bacterial and viral pathogens. Caregivers completed surveys tracking symptoms, antibiotic use, school attendance, and adverse events. The outcomes analyzed included the prevalence of microorganisms detected by polymerase chain reaction in cases vs controls, symptoms, rate of resolution by day 5, school/childcare attendance, and parent-reported antibiotic-related adverse incidents., Results: Most cases (148, 76%) and controls (112, 57%) had bacteria identified, although only detection of Haemophilus influenzae was associated with conjunctivitis (aOR 4.59, 95% CI 2.86, 7.37). Purulent discharge was associated with H influenzae (aOR 2.47, 95% CI 1.23, 5.01) and occurred in 92 (77%) cases in which H influenzae was detected and 39 (53%) in which H influenzae was not detected. Improvement (186, 96%) and resolution (166, 86%) were observed by day 5 for most children and did not differ on the basis of ophthalmic antibiotic use. Caregivers reported antibiotic-associated adverse events for 21 (20%) children, with 8 (8%) requiring a medical visit., Conclusions: Only H influenzae was significantly associated with conjunctivitis. Symptoms did not differ in children with or without bacteria detected by polymerase chain reaction. Independent of antibiotic use, most children experienced resolution by day 5, but parents reported adverse events in 20% of children treated with topical antibiotics, underscoring the importance of judicious prescribing., Competing Interests: Declaration of Competing Interest This work was funded by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under award number K23HD099925. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health. The authors have no relevant conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2025
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28. Increased risk of hospitalization among children who were HIV-exposed and uninfected compared to population controls.
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Brochon J, Ducruet T, Taillefer S, Lamarre V, Renaud C, Metras ME, Karatzios C, Puyat JH, Singer J, Valois S, Soudeyns H, Boucoiran I, and Kakkar F
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- Humans, Female, Male, Longitudinal Studies, Infant, Child, Preschool, Infant, Newborn, Quebec epidemiology, Risk Factors, Incidence, Risk Assessment, Child, Pregnancy, Hospitalization statistics & numerical data, HIV Infections epidemiology
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Objectives: While studies have demonstrated increased morbidity and mortality risk in infancy among children who are HIV-exposed and uninfected (CHEU), longitudinal data are limited. The objective of this study was to assess long-term risk of hospitalization among CHEU compared to children who are HIV-unexposed and uninfected (CHUU), and determine risk factors for hospitalization among CHEU., Design: A longitudinal cohort study (1988-2015) linking the Centre maternel et infantile sur le SIDA cohort (Montreal, Quebec) to administrative data from the Régie de l'assurance maladie du Québec (RAMQ), a universal health insurance provider in the province of Quebec., Methods: CHEU from the CMIS cohort were matched 1 : 3 by age, sex, and postal code with CHUU controls from the RAMQ database. Incidence and causes of hospitalization between CHEU and CHUU were compared using Poisson regression., Results: Seven hundred twenty-six CHEU were matched to 2178 CHUU. Risk of first hospitalization was significantly higher among CHEU at 1 year (incidence rate ratio [IRR] 2.22 [1.86-2.66]), 5 years (IRR 1.62 [1.39-1.90]), and over the lifespan (IRR 1.55 [1.33-1.81]). Among CHEU, significant risk factors for hospitalization on univariate regression analysis included birth year before 2005, prematurity, small for gestational age (SGA), detectable maternal viral load (dVL) at delivery, and maternal hepatitis C co-infection. In the adjusted analysis, small for gestational age and dVL remained significant risk factors., Conclusion: CHEU had a higher rate of hospitalization than CHUU controls across their lifespan. Significant risk factors included SGA and detectable maternal dVL, suggesting a need for enhanced pediatric care for these children., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2025
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29. Shorter antibiotic courses for respiratory tract infections.
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Tariq J and Banerjee R
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Competing Interests: We declare no competing interests.
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- 2025
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30. Superior persistence of ustekinumab compared to anti-TNF in vedolizumab-experienced inflammatory bowel diseases patients: a real-world cohort study.
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Chiu HY, Kuo CJ, Lai MW, Wu RC, Chen CM, Chiu CT, Pan YB, Chiu CH, and Le PH
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- Humans, Female, Male, Retrospective Studies, Adult, Middle Aged, Infliximab therapeutic use, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor Inhibitors therapeutic use, Inflammatory Bowel Diseases drug therapy, Medication Adherence statistics & numerical data, Treatment Outcome, Ustekinumab therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Gastrointestinal Agents therapeutic use, Crohn Disease drug therapy, Adalimumab therapeutic use, Colitis, Ulcerative drug therapy
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Background/aims: The increasing use of biologic therapies for moderate to severe inflammatory bowel disease (IBD) highlights the importance of optimal treatment sequencing, particularly after vedolizumab (VDZ) exposure. Studies comparing the effectiveness of ustekinumab (UST) and antitumor necrosis factor (anti-TNF) agents post-VDZ are limited., Methods: This retrospective study analyzed VDZ-experienced IBD patients treated with UST or anti-TNF (adalimumab and infliximab) from May 2019 to January 2024. We conducted a comparative analysis of the 52-week treatment persistence between UST and anti-TNF therapies, while also identifying independent predictors that influence 52-week persistence., Results: The study included 110 participants, with 40 diagnosed with ulcerative colitis (UC) and 70 with Crohn's disease (CD). Demographics were comparable across treatment groups. The primary discontinuation reason for VDZ was secondary non-response. Kaplan-Meier analysis revealed that UST demonstrated superior 52-week persistence in overall IBD, CD and UC patients, compared to anti-TNF. Cox regression analysis also showed UST's superiority in overall IBD (HR: 0.15, 95% CI: 0.05-0.45, p < 0.001), CD (HR: 0.09, 95% CI: 0.01-0.68, p = 0.02), and UC (HR: 0.28, 95% CI: 0.08-0.996, p = 0.049). The independent predictors for 52-week treatment persistence are Crohn's disease (Odds Ratio: 7.151, 95% CI: 1.763-28.995, p = 0.006) and UST treatment (Odds Ratio: 7.912, 95% CI: 1.789-34.992, p = 0.006). Notably, UST required more frequent dosing adjustments than anti-TNF, although both treatments exhibited comparable safety profiles., Conclusions: UST demonstrated superior 52-week treatment persistence in IBD patients previously treated with VDZ compared to anti-TNF agents, albeit with a need for more frequent dose adjustments., Competing Interests: Declarations. Ethical approval and consent to participate: The study was approved by the Institutional Review Board (IRB) of the Chang Gung Medical Foundation (approval document No. 202400030B0: “Diagnosis, Treatment, and Prognosis of Inflammatory Bowel Disease”). The IRB waived the requirement for signed informed consent from individual patients for reviewing medical records in the electronic medical record system as it was a retrospective study. Consent for publication: Not applicable. Financial disclosures: This study was not funded by grants or other financial sponsors. The authors have no financial arrangements for the company whose products are discussed in this manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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31. Safety, tolerability, and efficacy of intranasally-administered detoxified LTh(αK) in mild-to-moderate COVID-19 patients: A randomized, double-blinded, placebo-controlled phase 2 study.
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Cheng CY, Su YS, Chen CL, Chang M, Huang SW, Huang PN, Shih SR, Hsu YS, and Chiu CH
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- Humans, Middle Aged, Male, Double-Blind Method, Female, Adult, Aged, COVID-19 Drug Treatment, Young Adult, Treatment Outcome, Taiwan, Immunologic Factors administration & dosage, Immunologic Factors adverse effects, Immunologic Factors therapeutic use, Bacterial Toxins, Escherichia coli Proteins, Administration, Intranasal, Enterotoxins administration & dosage, Enterotoxins adverse effects, COVID-19 therapy, SARS-CoV-2
- Abstract
The objective of the study was to assess the safety, tolerability, and potential efficacy of intranasally administered AD17002, a detoxified form of Escherichia coli heat-labile enterotoxin, in treating individuals with mild-to-moderate coronavirus disease of 2019 (COVID-19). In this randomized, double-blinded, and placebo-controlled phase 2a study, a total of 30 adults aged 20-70 years with mild-to-moderate COVID-19 were recruited from three medical centers in Taiwan in 2022-2023. The trial comprised two cohorts, and participants were randomly assigned to receive intranasal administrations of either three doses of AD17002 immunomodulator or a placebo formulation buffer. Outcome analyses were conducted on the intention-to-treat set, and the safety set that included all randomized participants exposed to the AD17002. The proportion of cycle threshold (C t ) ≥30 and time to the recovery of key symptoms were assessed. An exploratory study was conducted to analyze the integrity of the viral genome after treatment. Administering 20 μg of AD17002 three times, either at 1-week or 1-day intervals, proved to be safe and well tolerated in subjects with mild-to-moderate COVID-19. AD17002 demonstrated a rapid and positive outcome in reducing the viral load in patients receiving the treatment. Impact of AD17002 treatment was further supported by the analysis of viral genome integrity following the treatment. The enhancement in clinical recovery by AD17002 within 5 days after symptom onset was observed but did not achieve statistical significance. According to the results, intranasal administration of AD17002 was safe, well-tolerated, and potentially effective for treating mild-to-moderate COVID-19.
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- 2024
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32. Transition to Enteral Triazole Antifungal Therapy for Pediatric Invasive Candidiasis: Secondary Analysis of a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.
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Bucayu RFT, Boge CLK, Yildirim I, Avilés-Robles M, Vora SB, Berman DM, Sharma TS, Sung L, Castagnola E, Palazzi DL, Danziger-Isakov L, Yin DE, Roilides E, Maron G, Tribble AC, Soler-Palacin P, López-Medina E, Romero J, Belani K, Arrieta AC, Carlesse F, Nolt D, Halasa N, Dulek D, Rajan S, Muller WJ, Ardura MI, Pong A, Gonzalez BE, Salvatore CM, Huppler AR, Aftandilian C, Abzug MJ, Chakrabarti A, Green M, Lutsar I, Knackstedt ED, Johnson SK, Steinbach WJ, Fisher BT, and Wattier RL
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- Humans, Child, Female, Male, Child, Preschool, Adolescent, Infant, Administration, Intravenous, Triazoles therapeutic use, Triazoles administration & dosage, Cohort Studies, Treatment Outcome, Antifungal Agents therapeutic use, Antifungal Agents administration & dosage, Candidiasis, Invasive drug therapy
- Abstract
Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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33. Assessment of recurrent fever among children undergoing tonsillectomy.
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Espahbodi M, Edwards KM, Goudy SL, Penn EB Jr, and Manthiram K
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- Humans, Male, Female, Child, Child, Preschool, Adolescent, Syndrome, Follow-Up Studies, Tonsillectomy adverse effects, Fever etiology, Recurrence, Tonsillitis surgery, Lymphadenitis surgery, Pharyngitis etiology, Stomatitis, Aphthous surgery
- Abstract
Background: Recurrent tonsillitis is a common indication for tonsillectomy in children and has phenotypic overlap with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. We sought to characterize symptoms associated with PFAPA among children undergoing tonsillectomy., Methods: Parents/guardians of children undergoing tonsillectomy at Vanderbilt Children's Hospital over a six-week period were queried regarding symptoms of recurrent fever. Follow-up questionnaires were administered 3 and 12 months after tonsillectomy., Results: 82% (120/147) of patients who underwent tonsillectomy during the study period participated. Provider-documented indications for tonsillectomy were obstructive sleep apnea in 88% and recurrent tonsillitis in 33%. 11% (13/120) reported[Formula: see text]6 episodes of stereotypical fever in a one-year period. During febrile episodes among these 13 subjects, 11 had tonsillitis, 5 had cervical adenitis, 3 had aphthous stomatitis, and three reported regular and predictable episode timing. In addition, participants with ≥3 episodes/year of recurrent febrile tonsillitis (N = 33) had a significantly higher prevalence of recurrent aphthous ulcers than those without recurrent tonsillitis (24% vs. 9%, p = 0.04). All participants, including those with recurrent fever, reported fewer febrile tonsillitis episodes one year after tonsillectomy., Conclusions: In our survey of children undergoing tonsillectomy, a subpopulation had frequent, stereotypical fever episodes with recurrent tonsillitis, aphthous stomatitis, or regular timing like patients with PFAPA. Although we cannot diagnose such patients with PFAPA in this limited retrospective study, pediatricians and otolaryngologists evaluating patients for tonsillectomy should be aware of the clinical signs of PFAPA that may warrant additional evaluation and therapeutic approaches., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Vanderbilt University (protocol number 140323). Informed consent/assent was obtained from parents and/or subjects. Consent for publication: Not applicable. Competing interests: KME receives grant funding from the CDC and NIH, serves as a consultant to BioNet and IBM on unrelated research, and serves on Data Safety and Monitoring Boards for Merck, Pfizer, Moderna, Roche, Seqirus, Sanofi, and X-4 Pharma. The authors report no other conflicts of interest., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2024
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34. A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose.
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Rostad CA, Yildirim I, Kao C, Yi J, Kamidani S, Peters E, Stephens K, Gibson T, Hsiao HM, Singh K, Spearman P, McCracken C, Agbakoba V, Tomashek KM, Goll JB, Gelber CE, Johnson RA, Lee S, Maner-Smith K, Bosinger S, Ortlund EA, Chen X, Anderson LJ, Wrammert J, Suthar M, Rouphael N, and Anderson EJ
- Abstract
Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.S. adults and evaluated the safety, reactogenicity and immunogenicity of homologous and heterologous MVA-BN®-Filo and Ad26.ZEBOV prime-boost schedules followed in select arms by MVA-BN®-Filo boost at 1 year (NCT02891980). We found that all vaccine regimens had acceptable safety and reactogenicity. The heterologous prime-boost strategy elicited superior Ebola binding and neutralizing antibody, antibody-dependent cellular cytotoxicity (ADCC), and cellular responses compared to homologous prime-boost. The MVA-BN®-Filo boost administered at 1 year resulted in robust humoral and cellular responses that persisted through 6-month follow-up. Overall, our data demonstrated that a heterologous Ad26.ZEBOV/MVA-BN®-Filo prime-boost was safe and immunogenic and established immunologic memory primed to respond after re-exposure. Clinicaltrials.gov, NCT02891980, registered September 1, 2016., Competing Interests: Competing interests: E.J.A has consulted for Pfizer, Sanofi Pasteur, GSK, Janssen, Moderna, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi-Pasteur, Janssen, and Micron. He also serves on a safety monitoring board for Kentucky BioProcessing, Inc. and Sanofi Pasteur. He serves on a data adjudication board for WCG and ACI Clinical. His institution has also received funding from NIH to conduct clinical trials of COVID-19 vaccines. He is now employed by Moderna and has stock/stock options. N.R. has consulted for EMMES, Moderna, Sanofi, Seqirus, GSK, and ICON and her institution receives funds to conduct clinical research unrelated to this manuscript from Pfizer, Sanofi, Quidel, Lilly, Merck, and Vaccine Company as well as NIH to conduct translational clinical studies and interventional clinical trials. C.A.R.’s institution has received funds to conduct clinical research unrelated to this manuscript from BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. Her institution has received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. She is co-inventor on patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. with royalties received. I.Y. reported research funding from the Centers for Disease Control and Prevention, National Institutes of Health, and Gates Foundation; funding to her institution to conduct clinical research from Merck, Moderna, Pfizer outside the submitted work; honorarium for advisory board from Merck and Sanofi Pasteur. All other authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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35. The Benefits of COVID-19 Vaccination for Pregnant Patients Hospitalized with Respiratory Symptoms: A Retrospective Cohort Study in South Brazil.
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Hernandez CJ, Sundar KG, Echegaray F, Cambou MC, Yang LZ, Segura ER, Gonçalves de Melo M, Santos BR, Varella IRDS, and Nielsen-Saines K
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Objectives: SARS-CoV-2 infection is a known risk factor for adverse health outcomes in pregnancy, affecting both maternal and neonatal health. Mounting evidence suggests that even a single dose of an approved COVID-19 vaccine protects against severe SARS-CoV-2 infection and is safe for both pregnant persons and neonates. Southern Brazil was heavily affected by the COVID-19 pandemic, and the protective effects of the vaccine on maternal and neonatal health are not well described. This study aims to examine the protective effects of maternal COVID-19 vaccination on both maternal and neonatal outcomes following SARS-CoV-2 infection during pregnancy., Methods: This is a retrospective cohort study that leveraged medical data from a tertiary center in South Brazil to compare maternal and infant outcomes between hospitalized pregnant persons with and without SARS-CoV-2 infection between 1 March 2020, and 1 March 2023., Results: In total, 524 patients were enrolled, including 275 pregnant patients with confirmed SARS-CoV-2 infection and 249 without infection. SARS-CoV-2 infection was associated with maternal ventilator support (adjusted Risk Ratio [aRR] = 1.48, 95% Confidence Interval [95% CI]: 1.08-2.03), while receipt of at least one dose of COVID-19 vaccine was associated with protection against maternal sepsis (aRR = 0.14, 95% CI: 0.03-0.56), intensive care unit (ICU) admission (aRR = 0.27, 95% CI: 0.10-0.68), need for ventilator support (aRR = 0.60, 95% CI: 0.43-0.84), infant admission to the neonatal intensive care unit (NICU) (aRR = 0.62, 95% CI: 0.47-0.82), and neonatal respiratory distress (aRR = 0.60, 95% CI: 0.43-0.83)., Conclusions: These findings further underscore the importance of maternal vaccination against COVID-19 during pregnancy. Even one dose of vaccine was protective against a variety of maternal and neonatal outcomes. Prenatal care should encourage COVID-19 vaccination in pregnancy.
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- 2024
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36. Prevalence and sequelae of asymptomatic Clostridioides difficile colonization in children with inflammatory bowel disease.
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Reasoner SA, Zhang LS, Bernard R, Edwards KM, and Nicholson MR
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Colonization by Clostridioides difficile is common in children with inflammatory bowel disease (IBD) and complicates both the management of IBD and the diagnosis of C. difficile infection (CDI). There is a paucity of data on rates, risk factors, and outcomes associated with asymptomatic C. difficile colonization in children with IBD. We enrolled and prospectively followed 87 children with IBD without acute gastrointestinal symptoms. Twelve patients (13.8%) tested positive for C. difficile and were considered to have asymptomatic colonization. Elevated white blood cell count was associated with C. difficile colonization based on univariate regression. Three of the 12 (25%) C. difficile colonized patients were diagnosed with CDI in the 90 days following screening for C. difficile, versus 0 of the 75 who tested negative for C. difficile (p = 0.002). This data set the stage for further longitudinal tracking of children with IBD for C. difficile colonization and associated outcomes., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
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- 2024
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37. SARS-CoV-2 ORF8 drives osteoclastogenesis in preexisting immune-mediated inflammatory diseases.
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Melano I, Azamor T, Caetano CC, Meyer NM, Onwubueke C, Visperas A, Familiar-Macedo D, Salem GM, Soos BL, Calabrese CM, Choi YJ, Chen S, Choi Y, Wu X, Vasconcelos Z, Comhair SA, Nielsen-Saines K, Calabrese LH, Husni ME, Jung JU, Piuzzi NS, Foo SS, and Chen W
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- Humans, Male, Osteoclasts immunology, Osteoclasts metabolism, Female, Middle Aged, Viral Proteins metabolism, Osteoblasts metabolism, Osteoblasts immunology, Cytokines metabolism, Biomarkers blood, Bone Resorption immunology, Aged, Coronavirus Infections immunology, Coronavirus Infections virology, RANK Ligand metabolism, Adult, Inflammation immunology, Betacoronavirus immunology, COVID-19 immunology, COVID-19 complications, SARS-CoV-2, Osteogenesis immunology, Arthritis, Rheumatoid immunology
- Abstract
Patients with immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis (RA) are at higher risk for severe COVID-19 and long-term complications in bone health. Emerging clinical evidence demonstrated that SARS-CoV-2 infection reduces bone turnover and promotes bone loss, but the mechanism underlying worsened bone health remains elusive. This study sought to identify specific immune mediators that exacerbated preexisting IMIDs after SARS-CoV-2 exposure. Plasma samples from 4 groups were analyzed: healthy, IMID only, COVID-19 only, and COVID-19 + IMID. Using high-throughput multiplexed proteomics, we profiled 1,500 protein biomarkers and identified 148 unique biomarkers in COVID-19 patients with IMIDs, including elevated inflammatory cytokines (e.g., IL-17F) and bone resorption markers. Long-term circulating SARS-CoV-2 ORF8, a virulence factor for COVID-19, was detected in the COVID + IMID group. RA was one of the most common IMIDs in our study. ORF8 treatment of RA-derived human osteoblasts (RA-hOBs) increased levels of inflammatory (TNF, IL6, CCL2) and bone resorption (RANKL/osteoprotegerin ratio) markers compared with healthy controls. Supernatants from ORF8-treated RA-hOBs drove the differentiation of macrophages into osteoclast-like cells. These findings suggest that SARS-CoV-2 exposure can exacerbate IMIDs through ORF8-driven inflammation and osteoclastogenesis, highlighting potential therapeutic targets for managing COVID-19-induced bone pathologies.
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- 2024
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38. Use of the moving epidemic method to guide the launch of palivizumab immunization campaigns for respiratory syncytial virus in Québec, Canada.
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Raad C, Ouldali N, Lebel M, Paquette M, Gilca R, Papenburg J, Lewin A, and Renaud C
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Objective: The COVID-19 pandemic disrupted the seasonal transmission pattern of respiratory syncytial virus (RSV), challenging the launch of palivizumab immunization campaigns. This study explored the performance of the moving epidemic method (MEM) to guide the launch of such campaigns., Methods: Data were collected through a continuous RSV surveillance system (07/2013‒03/2022) in Québec, Canada. Two strategies were compared: (1) a "preestablished" approach according to which each annual campaign began on November 1 and ended upon the earliest week with an RSV positivity rate ≤ 10% after March 31; and (2) MEM, according to which each annual campaign began and ended upon meeting an epidemic threshold of RSV positivity. We estimated the proportion of RSV cases that would be covered depending on the approach used for each RSV epidemic., Results: From seasons 2013-2014 through 2019-2020, RSV cases peaked between weeks 1 and 8, and all epidemic curves overlapped with an intraclass correlation coefficient (ICC) of 0.83. From 2013-2014 through 2019-2020, the epidemic periods determined by MEM and the preestablished approach covered similar proportions of RSV cases (MEM = 91.6%, preestablished = 90.7%) and had a similar duration (MEM = 21.3 weeks, preestablished = 21.7 weeks). With MEM, the 2021-2022 epidemic period started at week 29 and ended at week 51, covering 95.7% of cases. With the preestablished approach, the epidemic period started at week 44 and ended at week 8, covering 28.3% of cases., Conclusion: During normal RSV seasons, MEM is an effective alternative to the preestablished approach. However, MEM appears significantly more robust to disruptions of RSV's seasonal pattern., Competing Interests: Declarations. Conflict of interest: Papenburg reports personal fees and research grants to his institution from Merck. Gilca reports financial support to her institution from Quebec Ministry of Health for an active hospital-based surveillance of respiratory viruses in Quebec. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s) under exclusive license to The Canadian Public Health Association.)
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- 2024
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39. Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study.
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Jaganath D, Nabeta P, Nicol MP, Castro R, Wambi P, Zar HJ, Workman L, Lodha R, Singh UB, Bavdekar A, Sanghavi S, Trollip A, Mace A, Bonnet M, Lounnas M, de Haas P, Tiemersma E, Alland D, Banada P, Cattamanchi A, Ruhwald M, Wobudeya E, and Denkinger CM
- Abstract
Background: Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis (TB), but there are limited data on their accuracy, acceptability and usability., Methods: We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with three methods: Stool Processing Kit (SPK), Simple One-Step (SOS), and Optimized Sucrose Flotation (OSF). Children <15 years old with presumptive TB had respiratory specimen testing with Xpert Ultra and culture. Stool was tested using Xpert Ultra after processing with each method. We compared the accuracy of each method to a microbiological reference standard (MRS) and a composite reference standard (CRS). We surveyed the laboratory staff to assess acceptability and usability of the methods., Results: We included 607 children, of whom the median age was 3.5 years (IQR 1.3-7), 48% were female, and 15.5% were HIV positive. Against the MRS, the sensitivities of SPK, SOS and OSF were 36.9% (95% CI 28.6-45.8), 38.6% (95% CI 17.2-51), and 31.3% (95% CI 20.2-44.1), respectively. The specificities of SPK, SOS and OSF were 98.2% (95% CI 96.4-99.3), 97.3% (95% CI 93.7-99.1) and 97.1% (95% CI 93.3-99), respectively. Laboratory staff reported that the methods were acceptable and usable, but SOS was most feasible to implement in a peripheral facility. Sensitivity increased among children who were culture-positive (55-77.3%) and was low (13-16.7%) against the CRS., Conclusions: Stool processing methods for Xpert Ultra were acceptable, usable, and performed similarly, with highest sensitivity among children with culture-positive TB., Competing Interests: For potential conflicts of interest, MPN, DA, PB and FIND were involved in the development of SPK, PD and ET for SOS, and MB and ML for OSF. DA holds patents related to tuberculosis detection and drug treatment, and receives royalty payments for one or more of these patents that have been licensed by Rutgers University to Cepheid. The other authors declare no conflicts of interest.
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- 2024
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40. Pediatric SARS-CoV-2 long term outcomes study (PECOS): cross sectional analysis at baseline.
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Montealegre Sanchez GA, Arrigoni LE, Yonts AB, Rubenstein KB, Bost JE, Wolff MT, Barrix MC, Bandettini WP, Boateng B, Bulas DI, Burklow TR, Carlyle KP, Chen M, Das S, Dewar RL, Dixon AA, Edu MA, Falik RL, Geslak ML, Gierdalski M, Harahsheh AS, Herbert LJ, Highbarger J, Huq SR, Ko A, Koumbourlis AC, Lacey SR, Lipton AJ, Monaghan M, Ndour AS, Olivieri LJ, Pillai DK, Rehm CA, Sable CA, Sachdev V, Thurm AE, Truong UT, Turkbey EB, Vilain E, Weyers S, White JS, Williams AA, Zember J, Liang CJ, Delaney M, Batshaw ML, Notarangelo LD, Wessel DL, Barron K, and DeBiasi RL
- Abstract
Background: PECOS is an ongoing study aimed to characterize long-term outcomes following pediatric SARS-CoV-2 infection., Methods: This is a cross-sectional analysis of infected and uninfected cohorts at baseline. Participants (0-21 years) with laboratory-confirmed SARS-CoV-2 infection were enrolled as infected. Uninfected were defined as individuals without history or laboratory evidence of SARS-CoV-2 infection. Outcome measures included demographics, medical history, review of symptoms, physical exam, cardiopulmonary evaluation and validated psychological and developmental surveys. Primary outcomes were cohort comparisons for abnormalities on all measures., Results: 654 participants (541 infected, 113 uninfected) completed baseline visits by June 30, 2023. Infected participants were more likely to report constitutional (OR: 2.24), HEENT (OR: 3.74); respiratory (OR: 2.41), or gastrointestinal (OR: 2.58) symptoms. Infected had worse scores in domains of Pain, Fatigue, Global Health, Physical and Cognitive functioning, Mobility and Sleep disturbances when compared to uninfected controls using Patient Reported Outcomes. Cardiopulmonary findings were similar among cohorts., Conclusions: The first report of this ongoing longitudinal study demonstrates that infected participants were more likely to report symptoms compared to uninfected controls, which may affect performance and quality of life of these individuals. Longitudinal data will increase understanding of long-term effects of SARS-CoV-2 infection in children., Clinicaltrials: gov Identifier: NCT04830852 IMPACT: This study establishes a large, diverse, prospective, longitudinal, multi-center cohort of children with history of SARS-CoV-2 infection compared to an uninfected cohort to be followed for 3 years. Cross-sectional cohort analysis at study entry showed infected participants were more likely to report constitutional, respiratory, and GI symptoms compared to uninfected controls. Infected participants were more likely to have significantly worse parent-reported performance in 6 of 10 Patient Reported Outcome Measures domains. Continued study of this cohort will help identify clinical sequelae of COVID-19, characterize the immune response to SARS-CoV-2 infection, and identify potential genetic/immunologic factors associated with long-term outcomes., Competing Interests: Competing interests: The authors declare no competing interests. Informed consent: Written Informed Consent was obtained from all participants ≥18 years of age and at least one parent or legal guardian per participant <18 years of age. Written Assent was obtained for all participants 12–17 years of age., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2024
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41. Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis.
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Bennett JC, Deloria Knoll M, Kagucia EW, Garcia Quesada M, Zeger SL, Hetrich MK, Yang Y, Herbert C, Ogyu A, Cohen AL, Yildirim I, Winje BA, von Gottberg A, Viriot D, van der Linden M, Valentiner-Branth P, Suga S, Steens A, Skoczynska A, Sinkovec Zorko N, Scott JA, Savulescu C, Savrasova L, Sanz JC, Russell F, Ricketson LJ, Puentes R, Nuorti JP, Mereckiene J, McMahon K, McGeer A, Mad'arová L, Mackenzie GA, MacDonald L, Lepp T, Ladhani SN, Kristinsson KG, Kozakova J, Klein NP, Jayasinghe S, Ho PL, Hilty M, Heyderman RS, Hasanuzzaman M, Hammitt LL, Guevara M, Grgic-Vitek M, Gierke R, Georgakopoulou T, Galloway Y, Diawara I, Desmet S, De Wals P, Dagan R, Colzani E, Cohen C, Ciruela P, Chuluunbat U, Chan G, Camilli R, Bruce MG, Brandileone MC, Bigogo G, Ampofo K, O'Brien KL, Feikin DR, and Hayford K
- Abstract
Background: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages., Methods: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial)., Findings: Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product., Interpretation: Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites., Funding: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project., Competing Interests: Declaration of interests KH reports employment at Pfizer from Oct 26, 2020. MDK reports grants from Merck and Pfizer, and personal fees from Merck. JAS reports grants from the Bill & Melinda Gates Foundation, the Wellcome Trust, the UK Medical Research Council, and the National Institute of Health Research. M-CCB reports lecture fees from MSD. ASk reports grants and personal fees from MSD and Pfizer. MvdL reports support from, membership on advisory boards for, and speakers honoraria from Pfizer and Merck. SD reports a grant from Pfizer. KA reports a grant from Merck. AvG reports research funding from Pfizer, and attendance at advisory board meetings for Pfizer and Merck. AM reports research support to her institution from Pfizer and Merck, and honoraria for advisory board membership from GSK, Merck, and Pfizer. SNL performs contract research for GSK, Pfizer, and Sanofi Pasteur on behalf of St George's University of London, with no personal remuneration. IY reports membership of an mRNA-1273 study group, and funding to her institution to conduct clinical research from BioFire, MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi Pasteur, and Micron. RD reports grants or research support from Pfizer, MSD, and Medimmune; scientific consultancy for Pfizer, MeMed, MSD, and BiondVax; participation on advisory boards of Pfizer, MSD, and BiondVax; and being a speaker for Pfizer. LLH reports research grants to her institution from GSK, Pfizer, and Merck. JK reports an unrestricted grant-in-aid from Pfizer Canada. MHi reports reimbursement for advisory boards from MSD; and an investigator-initiated research grant from Pfizer paid to his institution. JCS reports assistance from Pfizer for attending scientific meetings. NPK reports research support from Pfizer, GSK, Sanofi Pasteur, Merck, and Protein Sciences (now Sanofi Pasteur). CC reports research support to her institution from Sanofi Pasteur. KGK reports grants from GSK. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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42. Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis.
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Garcia Quesada M, Peterson ME, Bennett JC, Hayford K, Zeger SL, Yang Y, Hetrich MK, Feikin DR, Cohen AL, von Gottberg A, van der Linden M, van Sorge NM, de Oliveira LH, de Miguel S, Yildirim I, Vestrheim DF, Verani JR, Varon E, Valentiner-Branth P, Tzanakaki G, Sinkovec Zorko N, Setchanova LP, Serhan F, Scott KJ, Scott JA, Savulescu C, Savrasova L, Reyburn R, Oishi K, Nuorti JP, Napoli D, Mwenda JM, Muñoz-Almagro C, Morfeldt E, McMahon K, McGeer A, Mad'arová L, Mackenzie GA, Eugenia León M, Ladhani SN, Kristinsson KG, Kozakova J, Kleynhans J, Klein NP, Kellner JD, Jayasinghe S, Ho PL, Hilty M, Harker-Jones MA, Hammitt LL, Grgic-Vitek M, Gilkison C, Gierke R, French N, Diawara I, Desmet S, De Wals P, Dalby T, Dagan R, Corcoran M, Colzani E, Chanto Chacón G, Castilla J, Camilli R, Ang M, Ampofo K, Almeida SCG, Alarcon P, O'Brien KL, and Deloria Knoll M
- Abstract
Background: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally., Methods: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years)., Findings: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV., Interpretation: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact., Funding: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project., Competing Interests: Declaration of interests MDK reports grants from Merck and Pfizer and personal fees from Merck. KH reports employment at Pfizer from Oct 26, 2020. AvG reports funding from Pfizer and attendance at advisory board meetings for Pfizer and Merck. MvdL reports support, membership of advisory boards, and speakers honoraria from Pfizer and Merck. NMvS reports speaker and service fees from MSD and GSK, and holding a patent (WO 2013/020090 A3) with royalties paid to herself and to the University of California San Diego (inventors: Nina van Sorge and Victor Nizet). IY reports membership of an mRNA-1273 study group, and funding to her institution from BioFire, MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi Pasteur, and Micron. EV reports grants from the French Public Health Agency, Pfizer, and Merck. JAS reports grants from the Bill & Melinda Gates Foundation, the Wellcome Trust, the UK Medical Research Council, and the National Institute for Health and Care Research. CM-A reports grants from Pfizer and speaker fees from Pfizer and MSD. AM reports research support to her institution from Pfizer and Merck, and honoraria for advisory board membership from GSK, Merck, and Pfizer. SNL reports contract research for GSK, Pfizer, and Sanofi Pasteur on behalf of St George's University of London, with no personal remuneration. NPK reports research support from Pfizer, GSK, Sanofi Pasteur, Merck, and Protein Sciences (now Sanofi Pasteur). JDK reports an unrestricted grant-in-aid from Pfizer Canada. MH reports reimbursement for advisory boards from MSD; and an investigator-initiated research grant paid to his institution from Pfizer. LLH reports research grants to her institution from GSK, Pfizer, and Merck. SD reports a grant from Pfizer. RD reports grants and research support from Pfizer, MSD, and MedImmune; consultancy for Pfizer, MeMed, MSD, BiondVax, and GSK; participation on advisory boards for Pfizer, MSD, BiondVax, and GXRD; and having been a speaker for Pfizer, AstraZeneca, and GSK. MC reports a professional fee, an unrestricted research grant, and an Investigator Initiated Reward (W1243730) from Pfizer Ireland. KA reports a grant from Merck. SCGA reports a travel grant from Pfizer. KGK reports grants from GSK. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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43. Pneumococcal Endophthalmitis: A Rare Threat Observed Years After Glaucoma Surgery.
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Seyhanli D, Cakil Guzin A, Kasikci Mermer ET, Ayhan Z, Ural Fatihoglu O, Karadag Oncel E, and Belet N
- Abstract
Competing Interests: The authors have no funding or conflicts of interest to disclose.
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44. Metabolic capabilities are highly conserved among human nasal-associated Corynebacterium species in pangenomic analyses.
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Tran TH, F Escapa I, Roberts AQ, Gao W, Obawemimo AC, Segre JA, Kong HH, Conlan S, Kelly MS, and Lemon KP
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- Humans, Microbiota genetics, Genomics, United States, Nose microbiology, Botswana, Corynebacterium genetics, Corynebacterium metabolism, Genome, Bacterial, Phylogeny
- Abstract
Corynebact e rium species are globally ubiquitous in human nasal microbiota across the lifespan. Moreover, nasal microbiota profiles typified by higher relative abundances of Corynebacterium are often positively associated with health. Among the most common human nasal Corynebacterium species are C. propinquum , C. pseudodiphtheriticum, C. accolens , and C. tuberculostearicum . To gain insight into the functions of these four species, we identified genomic, phylogenomic, and pangenomic properties and estimated the metabolic capabilities of 87 distinct human nasal Corynebacterium strain genomes: 31 from Botswana and 56 from the United States. C. pseudodiphtheriticum had geographically distinct clades consistent with localized strain circulation, whereas some strains from the other species had wide geographic distribution spanning Africa and North America. All species had similar genomic and pangenomic structures. Gene clusters assigned to all COG metabolic categories were overrepresented in the persistent versus accessory genome of each species indicating limited strain-level variability in metabolic capacity. Based on prevalence data, at least two Corynebacterium species likely coexist in the nasal microbiota of 82% of adults. So, it was surprising that core metabolic capabilities were highly conserved among the four species indicating limited species-level metabolic variation. Strikingly, strains in the U.S. clade of C. pseudodiphtheriticum lacked genes for assimilatory sulfate reduction present in most of the strains in the Botswana clade and in the other studied species, indicating a recent, geographically related loss of assimilatory sulfate reduction. Overall, the minimal species and strain variability in metabolic capacity implies coexisting strains might have limited ability to occupy distinct metabolic niches., Importance: Pangenomic analysis with estimation of functional capabilities facilitates our understanding of the full biologic diversity of bacterial species. We performed systematic genomic, phylogenomic, and pangenomic analyses with qualitative estimation of the metabolic capabilities of four common human nasal Corynebacterium species, along with focused experimental validations, generating a foundational resource. The prevalence of each species in human nasal microbiota is consistent with the common coexistence of at least two species. We identified a notably high level of metabolic conservation within and among species indicating limited options for species to occupy distinct metabolic niches, highlighting the importance of investigating interactions among nasal Corynebacterium species. Comparing strains from two continents, C. pseudodiphtheriticum had restricted geographic strain distribution characterized by an evolutionarily recent loss of assimilatory sulfate reduction in U.S. strains. Our findings contribute to understanding the functions of Corynebacterium within human nasal microbiota and to evaluating their potential for future use as biotherapeutics., Competing Interests: The authors declare no conflict of interest.
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45. Safety and Immunogenicity of an mRNA-1273 Booster in Children.
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Berthaud V, Creech CB, Rostad CA, Carr Q, de Leon L, Dietrich M, Gupta A, Javita D, Nachman S, Pinninti S, Rathore M, Rodriguez CA, Luzuriaga K, Towner W, Yeakey A, Brown M, Zhao X, Deng W, Xu W, Zhou H, Girard B, Kelly R, Slobod K, Anderson EJ, Das R, Miller J, and Schnyder Ghamloush S
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- Humans, Child, Male, Female, Child, Preschool, Infant, Adolescent, Immunogenicity, Vaccine, Young Adult, Adult, COVID-19 Vaccines immunology, COVID-19 Vaccines adverse effects, COVID-19 Vaccines administration & dosage, Immunization, Secondary, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, COVID-19 prevention & control, COVID-19 immunology, 2019-nCoV Vaccine mRNA-1273 immunology, 2019-nCoV Vaccine mRNA-1273 administration & dosage, SARS-CoV-2 immunology
- Abstract
Background: A 2-dose mRNA-1273 primary series in children aged 6 months-5 years (25 µg) and 6-11 years (50 µg) had an acceptable safety profile and was immunogenic in the phase 2/3 KidCOVE study. We present data from KidCOVE participants who received an mRNA-1273 booster dose., Methods: An mRNA-1273 booster dose (10 µg for children aged 6 months-5 years; 25 µg for children aged 6-11 years; age groups based on participant age at enrollment) was administered ≥6 months after primary series completion. The primary safety objective was the safety and reactogenicity of an mRNA-1273 booster dose. The primary immunogenicity objective was to infer efficacy of an mRNA-1273 booster dose by establishing noninferiority of neutralizing antibody (nAb) responses after a booster in children versus nAb responses observed after the mRNA-1273 primary series in young adults (18-25 years) from the pivotal efficacy study. Data were collected from March 2022 to June 2023., Results: Overall, 153 (6 months-5 years) and 2519 (6-11 years) participants received an mRNA-1273 booster dose (median age at receipt of booster: 2 and 10 years, respectively). The booster dose safety profile was generally consistent with that of the primary series in children; no new safety concerns were identified. An mRNA-1273 booster dose elicited robust nAb responses against ancestral SARS-CoV-2 among children and met prespecified noninferiority success criteria versus responses observed after the primary series in young adults., Conclusions: Safety and immunogenicity data support administration of an mRNA-1273 booster dose in children aged 6 months to 11 years., Clinical Trials Registration: NCT04796896 (Clinicaltrials.gov)., Competing Interests: Potential conflicts of interest. M. B., X. Z., W. D., W. X., H. Z., B. G., R. K., E. J. A., R. D., J. M., and S. S. G. are employees of Moderna, Inc, and hold stock/stock options in the company. A. Y. and K. S. are consultants and were contracted by Moderna, Inc, for this study. V. B. has received institutional research support from Moderna, Inc, GSK-ViiV, Gilead Sciences, Inc, and Novavax, Inc. C. B. C. has consulted for Pfizer, Inc, Moderna, Inc, GSK plc, Vir Biotechnology, CommenseBio, Cowen Investment Management LLC, Sanofi S.A., and Guidepoint Global. C. A. Rostad has received institutional support from Moderna, Inc, BioFire, Inc, GSK plc, MedImmune, Micron Technology, Inc, Janssen Pharmaceuticals, Merck & Co, Inc, Novavax, PaxVax, Pfizer, Inc, Regeneron, Sanofi Pasteur, and from the National Institutes of Health (NIH). She is coinventor of patented respiratory syncytial (RSV) vaccine technology, which has been licensed to Meissa Vaccines, Inc. E. J. A. has consulted for Pfizer, Inc, Sanofi Pasteur, GSK plc, Janssen Pharmaceuticals, Moderna, Inc, and Medscape, and his institution received funds to conduct clinical research unrelated to this manuscript from MedImmune LLC, Regeneron Pharmaceuticals, Inc, PaxVax, Pfizer, Inc, GSK plc, Merck & Co, Inc, Sanofi Pasteur, Janssen Pharmaceuticals, and Micron Technology, Inc. E. J. A. served on a safety monitoring board for Kentucky BioProcessing, Inc, and Sanofi Pasteur. E. J. A. served on a data adjudication board for WCG and ACI Clinical and his institution received funding from the NIH to conduct clinical trials of COVID-19 vaccines. K. L. has consulted for Gilead Sciences, Inc, has received research funding from the NIH and Moderna, Inc, and has received funding for clinical research from Gilead Sciences, Inc, Moderna, Inc, and Pfizer, Inc. C. A. Rodriguez has received institutional research support from Moderna, Inc, Novavax, Inc, and Gilead Sciences, Inc. M. D. has received clinical trial funding from Moderna, Inc, and Gilead Sciences, Inc. W. T. has received institutional research support from Moderna, Inc, Pfizer, Inc, Janssen Pharmaceuticals, GSK plc, ViiV Healthcare Limited, and AstraZeneca plc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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46. Projecting the Potential Clinical and Economic Impact of HIV Prevention Resource Reallocation in Tennessee.
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Borre ED, Ahonkhai AA, Chi KK, Osman A, Thayer K, Person AK, Weddle A, Flanagan CF, Pettit AC, Closs D, Cotton M, Agwu AL, Cespedes MS, Ciaranello AL, Gonsalves G, Hyle EP, Paltiel AD, Freedberg KA, and Neilan AM
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- Humans, Tennessee, Male, Female, Adult, Young Adult, Adolescent, Middle Aged, United States epidemiology, Transgender Persons, Condoms economics, Condoms statistics & numerical data, Homosexuality, Male, Pregnancy, Centers for Disease Control and Prevention, U.S., HIV Testing economics, Cost-Benefit Analysis, HIV Infections prevention & control, HIV Infections economics, HIV Infections epidemiology, Pre-Exposure Prophylaxis economics
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Background: In 2023, Tennessee replaced $6.2 M in US Centers for Disease Control and Prevention (CDC) human immunodeficiency virus (HIV) prevention funding with state funds to redirect support away from men who have sex with men (MSM), transgender women (TGW), and heterosexual Black women (HSBW) and to prioritize instead first responders (FR), pregnant people (PP), and survivors of sex trafficking (SST)., Methods: We used a simulation model of HIV disease to compare the clinical impact of Current, the present allocation of condoms, preexposure prophylaxis (PrEP), and HIV testing to CDC priority risk groups (MSM/TGW/HSBW); with Reallocation, funding instead increased HIV testing and linkage of Tennessee-determined priority populations (FR/PP/SST). Key model inputs included baseline condom use (45%-49%), PrEP provision (0.1%-8%), HIV testing frequency (every 2.5-4.8 years), and 30-day HIV care linkage (57%-65%). We assumed Reallocation would reduce condom use (-4%), PrEP provision (-26%), and HIV testing (-47%) in MSM/TGW/HSBW, whereas it would increase HIV testing among FR (+47%) and HIV care linkage (to 100%/90%) among PP/SST., Results: Reallocation would lead to 166 additional HIV transmissions, 190 additional deaths, and 843 life-years lost over 10 years. HIV testing reductions were most influential in sensitivity analysis; even a 24% reduction would result in 287 more deaths compared to Current. With pessimistic assumptions, we projected 1359 additional HIV transmissions, 712 additional deaths, and 2778 life-years lost over 10 years., Conclusions: Redirecting HIV prevention funding in Tennessee would greatly harm CDC priority populations while conferring minimal benefits to new priority populations., Competing Interests: Potential conflicts of interest . A. L. A. discloses participation on the advisory boards of Gilead, ViiV, consulting for Merck, Site principal investigator for multisite studies funded by Gilead, Merck, and 1 investigator-initiated study funded by Gilead. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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47. Staff and caregivers' perceptions of digital storytelling to increase influenza vaccine confidence in an urban safety-net healthcare system.
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Williams JTB, Ritger C, Holliman BD, Huebschmann AG, and O'Leary ST
- Abstract
Background: Myriad risk factors contribute to pediatric influenza vaccination disparities. Digital stories are compelling accounts of lived experience that have been useful in health promotion, especially in minoritized communities. Little is known about how they are perceived as a behavioral intervention to improve influenza vaccination confidence in safety-net healthcare systems., Objective: To explore staff and caregivers' perceptions of Digital Storytelling (DST) as a behavioral intervention to improve influenza vaccine confidence among caregivers of children., Methods: This qualitative study was set in two federally qualified health centers in historically Black neighborhoods in Denver, Colorado, USA. Informal group discussions with clinic staff probed perceptions of vaccine disparities, clinic priorities, and DST. Individual interviews with key staff and caregivers of children 6 months to 5 years old explored perceptions of and preferences for DST to improve vaccine confidence. Interviews were recorded and transcribed verbatim. Three researchers analyzed transcripts via directed content analysis using a deductive approach based off the IM4Equity framework. Final themes were member-checked with clinic staff, pediatric providers, and community advisors., Results: Approximately 70 staff attended informal group discussions; 13 staff and 12 caregivers participated in key informant interviews. Transcripts from group discussions (n = 6) and individual interviews (n = 23) were included in final analyses. Staff felt existing influenza vaccination strategies were inadequate, perceived digital stories meaningfully, and desired equitable implementation without responsibility for implementing them. Caregivers perceived DST as compelling, noted the importance of trusted storytellers, and suggested relatable stories from diverse caregivers could be sent via text messages in the winter to cue caregivers to action., Conclusions: In this qualitative study, staff and caregivers perceived DST favorably, with preferences specific to DST implementation in a large, diverse health system. Work to develop and implement text-based DST for pediatric influenza vaccination in this context is warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joshua T.B. Williams reports financial support was provided by National Institute of Child Health and Human Development. Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number K23HD107184. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Joshua T.B. Williams reports a relationship with Colorado Children's Immunization Coalition that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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48. Default Antibiotic Order Durations for Skin and Soft Tissue Infections in Outpatient Pediatrics: A Cluster Randomized Trial.
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Broussard KA, Chaparro JD, Erdem G, Abdel-Rasoul M, Stevens J, and Watson JR
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Background: Antibiotic durations for uncomplicated skin/soft tissue infections (SSTI) often exceed the guideline-recommended 5-7 days. We assessed the effectiveness of a default duration order panel in the Electronic Health Record (EHR) to reduce long prescriptions., Methods: Cluster randomized trial of a SSTI order panel with default antibiotic durations (implemented 12/2021), compared to a control panel (no decision support) in 14 pediatric primary care clinics. We assessed long prescription rates from 23 months before to 12 months after order panel implementation (1/2020-12/2022). Antibiotic duration was considered long if >5 days for cellulitis or drained abscess, or >7 days for undrained abscess, impetigo, or other SSTI., Results: We included 1123 and 511 encounters in intervention and control clinics, respectively. In a piecewise generalized linear model, long prescription rate decreased from 63.8% to 54.6% (absolute difference, -9.2%) in the intervention group and from 70.0% to 54.9% (absolute difference, -15.1%) in the control group. The relative change in trajectories from pre-panel to post-panel periods did not differ significantly between intervention and control groups (P = .488). Although used in only 29.4% of eligible encounters, intervention panel use had lower odds of long prescription compared to all other prescriptions (OR 0.18)., Conclusion: We did not detect an overall impact of an order panel with default durations in reducing long antibiotic prescriptions for SSTIs. When ordered from the intervention panel, prescriptions were usually guideline-concordant. Effective strategies to make choosing a default duration more automatic are necessary to further reduce long prescriptions., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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49. Electronic evaluation of infection risk from room environment and prior room occupants: the transmission from room environment events (TREE) measure.
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Rock C, Hsu YJ, Milstone AM, Salinas AB, Maragakis L, Kwon N, Cosgrove SE, Simner PJ, Virk Z, Vorsteg AH, and Klein E
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Over a 2-year period, we identified Transmission from Room Environment Events (TREE) across the Johns Hopkins Health System, where the subsequent room occupant developed the same organism with the same antimicrobial susceptibilities as the patient who had previously occupied that room. Overall, the TREE rate was 50/100,000 inpatient days.
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- 2024
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50. The structure, role, and procedures of Korean expert committee on immunization practices.
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Lim SY, Kim HW, Choe YJ, Ahn B, Kang HM, Park J, Kwon GY, Lee SH, Kwon S, and Choi EH
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Vaccination is a cornerstone of public health, preventing infectious diseases with significant contribution to human health. In South Korea, the Korea Expert Committee on Immunization Practices (KECIP) plays a pivotal role in guiding national vaccination policies. In this comprehensive review, we investigated the history, legal basis, operation, and achievements of the KECIP, highlighting its critical role in shaping the country's successful vaccination program. We analyze the KECIP's diverse responsibilities, including deliberating on national immunization programs, establishing vaccination criteria, managing targeted infectious diseases, and formulating eradication strategies. Also, we revealed its well-defined structure, specialized subcommittees, and ethical protocols that ensure transparency and integrity. Furthermore, we explored the KECIP's strategic evolution, showcasing its contributions to expanding vaccine coverage, implementing emergency approvals, and optimizing foundational vaccinations for all age groups as well as special populations including immunocompromised individuals. By combining scientific rigor, expert insights, and a commitment to public health, the KECIP had navigated the dynamic landscape of infectious disease control, contributing significantly to South Korea's impressive vaccination achievements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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