Pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.

Background: New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.

Methods: We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days.

Epidemiology and outcomes of bacterial meningitis in the neonatal intensive care unit.

Objective: Examine pathogen distribution, antibiotic resistance patterns, and hospital outcomes of infants with bacterial meningitis in neonatal intensive care units (NICUs) in the US from 2013-2018.

Study Design: Infants were divided into 2 groups based on age at the time of meningitis: early-onset (0-3 days) and late-onset (>3 days). We compared demographics, clinical characteristics, epidemiology, hospital outcomes, distribution of organisms and resistance, and blood culture timing relative to cerebrospinal fluid culture.

Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units.

Background: Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. We aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis.

Postdiscontinuation Antibiotic Exposure in Hospitalized Infants at Risk for Late-onset Sepsis in the Neonatal Intensive Care Unit.

Background: In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unknown.

Methods: This retrospective cohort study of simulated antibiotic exposures used published population pharmacokinetic models within drug-specific neonatal intensive care unit cohorts of preterm and term infants, postnatal age 7-60 days and exposed to cefepime, piperacillin-tazobactam or tobramycin.

Exploring the role of digital tools in rare disease management: An interview-based study.

While digital tools, such as the Internet, smartphones, and social media, are an important part of modern society, little is known about the specific role they play in the healthcare management of individuals and caregivers affected by rare disease. Collectively, rare diseases directly affect up to 10% of the global population, suggesting that a significant number of individuals might benefit from the use of digital tools. The purpose of this qualitative interview-based study was to explore: (a) the ways in which digital tools help the rare disease community; (b) the healthcare gaps not addressed by current digital tools; and (c) recommended digital tool features.

Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial.

Importance: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

Objective: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

Design, Setting, And Participants: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021.

Assessing microbiome population dynamics using wild-type isogenic standardized hybrid (WISH)-tags.

Microbiomes feature recurrent compositional structures under given environmental conditions. However, these patterns may conceal diverse underlying population dynamics that require intrastrain resolution. Here we developed a genomic tagging system, termed wild-type isogenic standardized hybrid (WISH)-tags, that can be combined with quantitative polymerase chain reaction and next-generation sequencing for microbial strain enumeration.

mBARq: a versatile and user-friendly framework for the analysis of DNA barcodes from transposon insertion libraries, knockout mutants, and isogenic strain populations.

Motivation: DNA barcoding has become a powerful tool for assessing the fitness of strains in a variety of studies, including random transposon mutagenesis screens, attenuation of site-directed mutants, and population dynamics of isogenic strain pools. However, the statistical analysis, visualization, and contextualization of the data resulting from such experiments can be complex and require bioinformatic skills.

Results: Here, we developed mBARq, a user-friendly tool designed to simplify these steps for diverse experimental setups.

Direct-to-participant recruitment of mothers and infants: A strategic approach during challenging pandemic times.

Under traditional circumstances, most clinical trials rely on in-person operations to identify, recruit, and enroll study participants and to complete study-related visits. During unusual circumstances, such as the COVID-19 pandemic, the typical clinical trial model is challenged and forced to explore alternative approaches to implementing study recruitment, participant enrollment, and data collection strategies. One such alternative is a direct-to-participant approach which leverages electronic resources and relevant technological devices (, smart phones) available to researchers and patients.

Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing.

The global loss of heterochromatin during ageing has been observed in eukaryotes from yeast to humans, and this has been proposed as one of the causes of ageing. However, the cause of this age-associated loss of heterochromatin has remained enigmatic. Here we show that heterochromatin markers, including histone H3K9 di/tri-methylation and HP1, decrease with age in muscle stem cells (MuSCs) as a consequence of the depletion of the methyl donor S-adenosylmethionine (SAM).

Development, implementation, and dissemination of operational innovations across the trial innovation network.

Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations.

Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants.

Background: We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU).

Methods: We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies.

Diagnostic Utility of Cerebrospinal Fluid White Blood Cell Components for the Identification of Bacterial Meningitis in Infants.

Background: To evaluate the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU).

Methods: We identified a cohort of infants discharged from a Pediatrix NICU between 1997 and 2020 who did not have an immunodeficiency, had at least 1 CSF culture collected within the first 120 days of life, and at least 1 CSF laboratory specimen obtained on the day of culture collection. We only included an infant's first CSF culture and excluded cultures from CSF reservoirs and those growing contaminants or nonbacterial organisms.

Leveraging School Infection Data to Address Community COVID-19 Data Gaps.

Background: At-home COVID-19 tests became available in the USA in April 2021 with widespread use by January 2022; however, the lack of infrastructure to report test results to public health agencies created a gap in public health data. Kindergarten through grade 12 (K-12) schools often tracked COVID-19 cases among students and staff; leveraging school data may have helped bridge data gaps.

Methods: We examined infection rates reported by school districts to ABC Science Collaborative with corresponding community rates from March 15, 2021 to June 3, 2022.

Impact of the COVID-19 Pandemic on Pediatric Preventive Health Care Among North Carolina Children Enrolled in Medicaid.

Background: Children enrolled in private insurance had reduced preventive health care during the coronavirus disease 2019 (COVID-19) pandemic. However, the impact of the pandemic on children enrolled in Medicaid has been minimally described.

Methods: We used an administrative claims database from North Carolina Medicaid to evaluate the rates of well-child visits and immunization administration for children ≤14 months of age, and used a quasi-Poisson regression model to estimate the rate ratio (RR) of each outcome during the pandemic period (3/15/2020 through 3/15/2021) compared with the pre-pandemic period (3/15/2019 through 3/14/2020).

Late-Onset Sepsis Evaluation and Empiric Therapy in Extremely Low Gestational Age Newborns.

Background: Little is known about late-onset sepsis (LOS) evaluations in extremely low gestational age newborns (ELGANs). We describe frequencies of LOS evaluation in ELGANs, infant characteristics, and empiric therapy choices during evaluations.

Methods: Cohort study of infants 22-28 weeks gestational age (GA) discharged from 243 centers from 2009 to 2018, excluding infants with congenital anomalies, discharged or deceased prior to postnatal day (PND) 2, or admitted after PND 2.

School Absenteeism as a Marker for Community COVID-19 Rates.

Background: Reported community transmission rates of coronavirus disease 2019 (COVID-19) may not be accurate, particularly since at-home testing has become widely available. School absenteeism may serve as a marker of broader community COVID-19 transmission.

Methods: We performed an observational study of North Carolina kindergarten through 12th grade schools participating in the ABC Science Collaborative that offered in-school instruction, and contributed severe acute respiratory syndrome coronavirus 2 data for at least 2 of 4 weeks monthly for the 2021-2022 academic year.