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1.
AIDS Care ; 35(3): 447-452, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36285336

RESUMO

Evidence suggests an increasing number of US families are adopting internationally born children with HIV (IACH). Little is known about the experiences of adoptive parents, particularly how they help children navigate adolescence. Many adopted children may have additional needs as they mature into adolescence. Forty-four parents of 51 IACH were recruited from three pediatric infectious disease clinics and social media sites. The majority identified as white (n = 43), Christian (n = 38), and female (n = 43). Mean age of adoptees was 10.1 years (range 3-19, 33 females, 25 from African countries, and Russia, Ukraine, China, Haiti, Columbia, Estonia). Participants completed semi-structured audio-recorded interviews focused on experienced and potential challenges as their child matures. Interviews were coded for emergent themes. Findings identified universal concerns about sexuality. Some parents had not yet discussed sex with their child due to age/level of maturity. Others stated they had "the talk" and some emphasized the importance of abstinence before marriage while others highlighted the importance of comprehensive sex education and open communication. Finally, parents acknowledged that HIV was a manageable illness and hoped their children lived long healthy lives. Medical and mental health clinicians can support families as their child transitions into adolescence.


Assuntos
Infecções por HIV , Criança , Humanos , Adolescente , Feminino , Pré-Escolar , Infecções por HIV/psicologia , HIV , Saúde Reprodutiva , Pesquisa Qualitativa , Pais/psicologia
2.
Am J Physiol Lung Cell Mol Physiol ; 320(6): L1147-L1157, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33851876

RESUMO

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Patients with severe bronchiolitis had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand the totality of mechanisms of adverse outcomes in viral bronchiolitis.


Assuntos
Bronquiolite Viral/virologia , Antígenos de Histocompatibilidade Menor/farmacologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Transcriptoma/efeitos dos fármacos , Bronquiolite Viral/sangue , Humanos , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sincicial Respiratório Humano/patogenicidade , Índice de Gravidade de Doença , Transcriptoma/imunologia , Viroses/tratamento farmacológico , Viroses/virologia
3.
J Pediatr ; 229: 33-40, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33075369

RESUMO

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.


Assuntos
COVID-19/terapia , Protocolos Clínicos , Padrões de Prática Médica/estatística & dados numéricos , Síndrome de Resposta Inflamatória Sistêmica/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticoagulantes/uso terapêutico , Antirreumáticos/uso terapêutico , Aspirina/uso terapêutico , COVID-19/diagnóstico , Criança , Estudos Transversais , Glucocorticoides/uso terapêutico , Heparina/uso terapêutico , Hospitais , Humanos , Imunoglobulinas Intravenosas , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Inquéritos e Questionários , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Estados Unidos/epidemiologia , Vasoconstritores/uso terapêutico
5.
AIDS ; 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39411892

RESUMO

OBJECTIVE: Bictegravir is increasingly prescribed as a co-formulated tablet with tenofovir alafenamide and emtricitabine to pregnant persons with HIV (PWH) despite limited pregnancy and birth outcome data. We sought to provide birth outcome data following exposure to bictegravir during pregnancy. DESIGN: We conducted a descriptive analysis of infants born to pregnant PWH 18-45 years of age enrolled in at least one Pediatric HIV/AIDS Cohort Study (PHACS)-affiliated study who received bictegravir for ≥7 days during pregnancy and completed follow-up through delivery. METHODS: The outcomes of interest were gestational age at birth, preterm birth (<37 weeks' gestation), gestational-age adjusted birth weight (BWZ) and length (BLZ) z-scores, small for gestational age (SGA, birthweight <10th percentile), congenital anomalies, neonatal deaths in the first 28 days of life, and infant HIV status. RESULTS: A total of 177 infants born to 170 unique PWH were exposed to bictegravir for ≥7 days during gestation; 55% were exposed to bictegravir from the time of conception. Median gestational age at birth was 38.1 weeks. The prevalence of preterm birth was 15.8% and SGA was 9.3%. Mean BWZ and BLZ were -0.48 and 0.03. No neonatal deaths or perinatal HIV transmissions were reported. Among 126 infants exposed to first-trimester bictegravir, 7 (5.6%) had major congenital anomalies with no specific pattern suggestive of a syndrome. CONCLUSIONS: These findings provide preliminary data without significant safety concerns for fetal bictegravir exposure in this United States cohort. Comparative data and continued surveillance of outcomes among infants exposed to bictegravir during gestation are warranted.

6.
Am J Infect Control ; 52(5): 614-617, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38158158

RESUMO

We quantified antibiotic prescribing for ambulatory pediatric acute respiratory illness at 22 institutions in "pre-shortage" (Jan 2019-Sep 2022) and "shortage" (Oct 2022-Mar 2023) periods for amoxicillin. While acute respiratory illness prescribing increased across settings, the proportion of amoxicillin prescriptions decreased. Variation was seen within and between institutions.

7.
Microorganisms ; 12(9)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39338537

RESUMO

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology. Within this work, we integrate a two-year genotyping window with structural biology to explore the selective pressures of SARS-CoV-2 on protein insights. Although genotype and the Spike (Surface Glycoprotein) protein continue to drift, most SARS-CoV-2 proteins have had few amino acid alterations. Within Spike, the high drift rate of amino acids involved in antibody evasion also corresponds to changes within the ACE2 binding pocket that have undergone multiple changes that maintain functional binding. The genotyping suggests selective pressure for receptor specificity that could also confer changes in viral risk. Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike.

8.
J Pediatric Infect Dis Soc ; 13(3): 159-185, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38339996

RESUMO

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , SARS-CoV-2 , Adolescente , Criança , Humanos , Antivirais/uso terapêutico , COVID-19/prevenção & controle , COVID-19/terapia , Fatores de Risco , SARS-CoV-2/fisiologia
9.
J Pediatric Infect Dis Soc ; 12(1): 43-48, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36525377

RESUMO

Approximately 50% of human immunodeficiency virus (HIV)-infected adolescents fail to achieve complete viral suppression, largely due to nonadherence to their antiretroviral drug regimens. Numerous personal, financial, and societal barriers contribute to nonadherence, which may lead to the development of HIV drug resistance. Long-acting antiretroviral drugs hold the promise of improved adherence because they remove the need for swallowing one or more pills daily. Cabotegravir (an integrase strand transfer inhibitor) and rilpivirine (a non-nucleoside reverse transcriptase inhibitor) can now be intramuscularly co-administered to HIV-infected adolescents every 4-8 weeks if they are virologically suppressed and without resistance mutations to cabotegravir or rilpivirine. Adverse effects are few and non-severe. Widespread use of this complete antiretroviral therapy may be limited by drug costs, need for sites and skilled personnel who can administer the injections, and ethical challenges. Other long-acting medications and new antiretroviral therapy delivery systems are under active investigation and show great promise.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Adolescente , Preparações Farmacêuticas , Infecções por HIV/tratamento farmacológico , Rilpivirina/efeitos adversos , Antirretrovirais/uso terapêutico
10.
Front Public Health ; 11: 1091335, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006538

RESUMO

Background: The number of internationally adopted children living with perinatally-acquired HIV (IACP) in the U.S. is increasing, yet little is known about their families' experiences navigating HIV disclosure within a community context. This paper examines the lived experiences of adoptive parents as they navigate HIV disclosure and manage stigma toward their adopted children within their broader communities. Methods: A purposive sample of parents of IACP was recruited at two pediatric infectious disease clinics and via closed Facebook groups. Parents completed two semi-structured interviews approximately one year apart. Interview questions included strategies parents used to reduce the impact of community level stigma that their child is likely to encounter as they mature. Interviews were analyzed using Sort and Sift, Think and Shift analytic approach. All parents (n = 24) identified as white and most (n = 17) had interracial families, with children adopted from 11 different countries (range: age at adoption 1-15 years; range: age at first interview 2-19 years). Results: Analyses revealed that parents serve as advocates for their child by both supporting more public HIV disclosure at times, but also applying indirect strategies such as working to improve outdated sex education material. Knowledge of HIV disclosure laws empowered parents to make informed decisions about who, if anyone, in the community needed to know their child's HIV status. Conclusion: Families with IACP would benefit from HIV disclosure support/training and community-based HIV stigma reduction interventions.


Assuntos
Criança Adotada , Infecções por HIV , Humanos , Criança , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Revelação , Pesquisa Qualitativa , Pais
11.
J Pediatric Infect Dis Soc ; 12(6): 364-371, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37262431

RESUMO

BACKGROUND: Most antibiotic use occurs in ambulatory settings. No benchmarks exist for pediatric institutions to assess their outpatient antibiotic use and compare prescribing rates to peers. We aimed to share pediatric outpatient antibiotic use reports and benchmarking metrics nationally. METHODS: We invited institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship OutPatient (SHARPS-OP) Collaborative to contribute quarterly aggregate reports on antibiotic use from January 2019 to June 2022. Outpatient settings included emergency departments (ED), urgent care centers (UCC), primary care clinics (PCC) and telehealth encounters. Benchmarking metrics included the percentage of: (1) all acute encounters resulting in antibiotic prescriptions; (2) acute respiratory infection (ARI) encounters resulting in antibiotic prescriptions; and among ARI encounters receiving antibiotics, (3) the percentage receiving amoxicillin ("Amoxicillin index"); and (4) the percentage receiving azithromycin ("Azithromycin index"). We collected rates of antibiotic prescriptions with durations ≤7 days and >10 days from institutions able to provide validated duration data. RESULTS: Twenty-one institutions submitted aggregate reports. Percent ARI encounters receiving antibiotics were highest in the UCC (40.2%), and lowest in telehealth (19.1%). Amoxicillin index was highest for the ED (76.2%), and lowest for telehealth (55.8%), while the azithromycin index was similar for ED, UCC, and PCC (3.8%, 3.7%, and 5.0% respectively). Antibiotic duration of ≤7 days varied substantially (46.4% for ED, 27.8% UCC, 23.7% telehealth, and 16.4% PCC). CONCLUSIONS: We developed a benchmarking platform for key pediatric outpatient antibiotic use metrics drawing data from multiple pediatric institutions nationally. These data may serve as a baseline measurement for future improvement work.


Assuntos
Antibacterianos , Infecções Respiratórias , Humanos , Criança , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Benchmarking , Pacientes Ambulatoriais , Padrões de Prática Médica , Amoxicilina/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Prescrição Inadequada
12.
J Pediatric Infect Dis Soc ; 11(5): 177-185, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35107571

RESUMO

BACKGROUND: Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. CONCLUSIONS: Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.


Assuntos
Tratamento Farmacológico da COVID-19 , Guias de Prática Clínica como Assunto , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticorpos Neutralizantes , Anticorpos Antivirais , Criança , Combinação de Medicamentos , Humanos , SARS-CoV-2
13.
Pediatr Infect Dis J ; 40(8): 738-740, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33742614

RESUMO

In a cohort of 257 infants with congenital heart disease admitted to the pediatric intensive care unit, 22 infants had positive cultures for extended-spectrum beta-lactamase or AmpC Gram-negative bacteria. These infants had longer exposure to broad-spectrum antibiotics, greater support with invasive devices and longer intensive care and hospital lengths of stay.


Assuntos
Proteínas de Bactérias , Infecção Hospitalar/microbiologia , Infecções por Bactérias Gram-Negativas/complicações , Cardiopatias Congênitas/complicações , Resistência beta-Lactâmica , beta-Lactamases , Estudos de Casos e Controles , Citrobacter/enzimologia , Estudos de Coortes , Estado Terminal , Enterobacter/enzimologia , Escherichia coli/enzimologia , Feminino , Hospitais Pediátricos , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Klebsiella/enzimologia , Masculino , Prevalência , Estudos Retrospectivos , Fatores de Risco , Serratia/enzimologia
14.
Front Immunol ; 12: 790041, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925370

RESUMO

In the age of genomics, public understanding of complex scientific knowledge is critical. To combat reductionistic views, it is necessary to generate and organize educational material and data that keep pace with advances in genomics. The view that CCR5 is solely the receptor for HIV gave rise to demand to remove the gene in patients to create host HIV resistance, underestimating the broader roles and complex genetic inheritance of CCR5. A program aimed at providing research projects to undergraduates, known as CODE, has been expanded to build educational material for genes such as CCR5 in a rapid approach, exposing students and trainees to large bioinformatics databases and previous experiments for broader data to challenge commitment to biological reductionism. Our students organize expression databases, query environmental responses, assess genetic factors, generate protein models/dynamics, and profile evolutionary insights into a protein such as CCR5. The knowledgebase generated in the initiative opens the door for public educational information and tools (molecular videos, 3D printed models, and handouts), classroom materials, and strategy for future genetic ideas that can be distributed in formal, semiformal, and informal educational environments. This work highlights that many factors are missing from the reductionist view of CCR5, including the role of missense variants or expression of CCR5 with neurological phenotypes and the role of CCR5 and the delta32 variant in complex critical care patients with sepsis. When connected to genomic stories in the news, these tools offer critically needed Ethical, Legal, and Social Implication (ELSI) education to combat biological reductionism.


Assuntos
Genômica/ética , Infecções por HIV/prevenção & controle , HIV-1/patogenicidade , Receptores CCR5/genética , Internalização do Vírus , Bases de Dados Genéticas , Resistência à Doença/genética , Evolução Molecular , Predisposição Genética para Doença , Genômica/educação , Genômica/legislação & jurisprudência , Genômica/métodos , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/metabolismo , Humanos , Disseminação de Informação/ética , Disseminação de Informação/legislação & jurisprudência , Mutação de Sentido Incorreto , Receptores CCR5/metabolismo
15.
Front Immunol ; 12: 694243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335605

RESUMO

The immune response to COVID-19 infection is variable. How COVID-19 influences clinical outcomes in hospitalized patients needs to be understood through readily obtainable biological materials, such as blood. We hypothesized that a high-density analysis of host (and pathogen) blood RNA in hospitalized patients with SARS-CoV-2 would provide mechanistic insights into the heterogeneity of response amongst COVID-19 patients when combined with advanced multidimensional bioinformatics for RNA. We enrolled 36 hospitalized COVID-19 patients (11 died) and 15 controls, collecting 74 blood PAXgene RNA tubes at multiple timepoints, one early and in 23 patients after treatment with various therapies. Total RNAseq was performed at high-density, with >160 million paired-end, 150 base pair reads per sample, representing the most sequenced bases per sample for any publicly deposited blood PAXgene tube study. There are 770 genes significantly altered in the blood of COVID-19 patients associated with antiviral defense, mitotic cell cycle, type I interferon signaling, and severe viral infections. Immune genes activated include those associated with neutrophil mechanisms, secretory granules, and neutrophil extracellular traps (NETs), along with decreased gene expression in lymphocytes and clonal expansion of the acquired immune response. Therapies such as convalescent serum and dexamethasone reduced many of the blood expression signatures of COVID-19. Severely ill or deceased patients are marked by various secondary infections, unique gene patterns, dysregulated innate response, and peripheral organ damage not otherwise found in the cohort. High-density transcriptomic data offers shared gene expression signatures, providing unique insights into the immune system and individualized signatures of patients that could be used to understand the patient's clinical condition. Whole blood transcriptomics provides patient-level insights for immune activation, immune repertoire, and secondary infections that can further guide precision treatment.


Assuntos
Proteínas Sanguíneas/genética , COVID-19/imunologia , Interferon Tipo I/genética , Neutrófilos/fisiologia , SARS-CoV-2/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Hospitalização , Humanos , Imunidade , Imunidade Inata , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Transcriptoma , Adulto Jovem
16.
J Pediatric Infect Dis Soc ; 10(5): 629-634, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33388760

RESUMO

BACKGROUND: In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. CONCLUSIONS: Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Pneumonia Viral/tratamento farmacológico , Adolescente , Anticorpos Monoclonais Humanizados , COVID-19/epidemiologia , Criança , Aprovação de Drogas , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , SARS-CoV-2 , Estados Unidos/epidemiologia , United States Food and Drug Administration
17.
J Pediatric Infect Dis Soc ; 10(1): 34-48, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32918548

RESUMO

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. RESULTS: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , COVID-19/terapia , Criança , Medicina Baseada em Evidências , Humanos , Hospedeiro Imunocomprometido , Fatores de Risco , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico
18.
PLoS One ; 15(6): e0234751, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555719

RESUMO

Perinatal factors can shape fecal microbiome patterns among pregnant women and their infants. However, there is scarce information about the effect of maternal demographics and perinatal exposures on antibiotic resistance genes (ARG) and mobile genetic element (MGE) patterns in pregnant women and infants. We examined fecal samples from pregnant women during their third trimester of pregnancy (n = 51) and 6-month-old infants (n = 40). Of the 91 participants, 72 represented 36 maternal-infant dyads, 15 were additional pregnant women, and 4 were additional infants. We assessed the effects of demographics, pre-pregnancy BMI, smoking and parity in the pregnancy resistome and the effects of demographics, delivery mode, feeding habits and prenatal antibiotic treatment on the infancy resistome. ARG and MGE richness and abundance were assessed using a SmartChip qPCR-array. Alpha diversity (Shannon and Inverse Simpson index) and beta diversity (Sorensen and Bray-Curtis index) were calculated. The Wilcoxon and the Kruskal non-parametric test were used for comparisons. There is a high variability in shared resistome patterns between pregnant women and their infants. An average of 29% of ARG and 24% of MGE were shared within dyads. Infants had significantly greater abundance and higher diversity of ARG and MGE compared to pregnant women. Pregnancy and infancy samples differed in ARG and MGE gene composition and structure. Composition of the fecal resistome was significantly associated with race in pregnant women, with non-white women having different patterns than white women, and, in infants, with extent of solid food consumption. Our data showed that the pregnancy and infancy resistome had different structure and composition patterns, with maternal race and infant solid food consumption as possible contributors to ARG. By characterizing resistome patterns, our results can inform the mechanism of antibiotic resistome development in pregnant women and their infants.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Antibacterianos/uso terapêutico , Bactérias/genética , Bactérias/isolamento & purificação , Índice de Massa Corporal , Aleitamento Materno , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Lactente , Paridade , Gravidez , Terceiro Trimestre da Gravidez , Análise de Componente Principal , Fatores de Risco , Fatores Sexuais , Fumar
19.
J Pediatric Infect Dis Soc ; 9(6): 701-715, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-32318706

RESUMO

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Criança , Humanos , Medição de Risco , Índice de Gravidade de Doença
20.
Pediatr Infect Dis J ; 38(1): 32-36, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29601446

RESUMO

BACKGROUND: Clostridium difficile infection (CDI) is one of the most common nosocomial infections in the United States, with an increasing incidence in children. Approximately 20% of pediatric patients develop recurrent infections. It's imperative to further analyze the incidence of recurrent CDI in the pediatric population and determine the most effective treatments. The primary goal of this study is to characterize children with recurrent CDI at our institution, including both hospital-acquired CDI (HA-CDI) and community-acquired CDI (CA-CDI) cases, summarize the various treatments utilized, including fecal microbiota transplant (FMT) and compare their success rates. METHODS: A retrospective cohort study of pediatric patients 1-21 years of age treated for CDI at a single institution from January 2010 to December 2014 was performed. RESULTS: There were 175 subjects with 215 separate episodes of CDI. Oral metronidazole was the most common initial treatment (145/207, 70%) followed by oral vancomycin (30/207, 15%), with recurrence rates of 30% (42/145) and 37% (11/30), respectively. Twenty-nine percent (63/215) of all initial CDI cases had at least 1 documented recurrence. Using multivariate analysis, subjects with HA-CDI were 2.6 times less likely to recur than those with CA-CDI (odds ratio: 0.39; 95% confidence interval: 0.18-0.85; P = 0.018). The overall success rate for FMT at our institution was 10/12 (83%). CONCLUSIONS: Our data show that cases of HA-CDI were less likely to recur compared with CA-CDI. Although currently reserved for multiply-recurrent cases, FMT was highly successful in our small cohort. More studies on FMT should be conducted to further evaluate its usefulness in the treatment of recurrent CDI in children.


Assuntos
Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Hospitais Pediátricos , Adolescente , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Clostridioides difficile/efeitos dos fármacos , Diarreia/microbiologia , Feminino , Humanos , Lactente , Masculino , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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