Browsing by Author "Spears, Tracy"

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    Association between simulated ketamine exposures and oxygen saturations in children.
    (International journal of pharmacokinetics, 2023-02) Commander, Sarah Jane; Gonzalez, Daniel; Kumar, Karan R; Spears, Tracy; Cohen-Wolkowiez, Michael; Zimmerman, Kanecia O; Lee, Jan Hau; Hornik, Christoph P

    Aim

    We performed a real-world data analysis to evaluate the relationship between simulated ketamine exposures and oxygen desaturation in children.

    Materials & methods

    A previously developed population pharmacokinetic model was used to simulate exposures and evaluate target attainment, as well as the association with oxygen desaturation in children ≤17 years treated with intravenous ketamine.

    Results

    In 2022 children, there was no significant association between simulated plasma ketamine concentrations and oxygen saturation; however, a higher cumulative area under the curve was associated with increased odds of progression to significant desaturation (<85%), though magnitude of effect was small.

    Conclusion

    By leveraging a population pharmacokinetic model and real-world data, we confirmed there is no relationship between simulated ketamine plasma concentration and oxygen desaturation.
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    Risk Factors for Sudden Infant Death in North Carolina.
    (Frontiers in pediatrics, 2021-01) Yamada, Merick M; Rosamilia, Michael B; Chiswell, Karen E; D'Ottavio, Alfred; Spears, Tracy; Osgood, Claire; Miranda, Marie Lynn; Forestieri, Nina; Li, Jennifer S; Landstrom, Andrew P
    Background: Sudden infant death syndrome (SIDS) is the sudden, unexplained death of infants <1 year old. SIDS remains a leading cause of death in US infants. We aim to identify associations between SIDS and race/ethnicity, birth weight/gestational age, and socioeconomic/environmental factors in North Carolina (NC) to help identify infants at risk for SIDS. Methods and Results: In this IRB-approved study, infant mortality 2007-2016 and death certificate-linked natality 2007-2014 were obtained from the NC Department of Health and Human Services. General, NC natality statistics 2007-2016 were obtained from CDC Wonder. Association between SIDS/total infant death and covariates (below) were calculated. Total infant mortality decreased 2007-2016 by an average of 14 deaths/100,000 live births per year, while SIDS incidence remained constant. Risk ratios of SIDS/total infant deaths, standardized to Non-Hispanic White, were 1.76/2.41 for Non-Hispanic Black and 0.49/0.97 for Hispanic infants. Increased SIDS risk was significantly and independently associated with male infant sex, Non-Hispanic Black maternal race/ethnicity, young maternal age, low prenatal care, gestational age <39 weeks, birthweight <2500 g, low maternal education, and maternal tobacco use (p < 0.01). Maternal previous children now deceased also trended toward association with increased SIDS risk. Conclusions: A thorough SIDS risk assessment should include maternal, socioeconomic, and environmental risk factors as these are associated with SIDS in our population.
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    Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study.
    (BMC pediatrics, 2020-12) Schneider, Simone; Bailey, Mary; Spears, Tracy; Esther, Charles R; Laughon, Matthew M; Hornik, Christoph P; Jackson, Wesley

    Background

    Pulmonary hypertension is a deadly complication of bronchopulmonary dysplasia, the most common pulmonary morbidity of prematurity. Despite these catastrophic consequences, no evidence-based therapies are available for the prevention of pulmonary hypertension in this population. Sildenafil is a potent pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of pulmonary hypertension in adults. Preclinical models suggest a beneficial effect of sildenafil on premature lungs through improved alveolarization and preserved vascular development. Sildenafil may therefore prevent the development of pulmonary hypertension associated with lung disease of prematurity by reducing pulmonary vascular remodeling and lowering pulmonary vascular resistance; however, clinical trial evidence is needed. The present study, supported by the National Institutes of Health's National Heart Lung and Blood Institute, will generate safety, pharmacokinetics, and preliminary effectiveness data on sildenafil in a population of premature infants with severe bronchopulmonary dysplasia at risk for pulmonary hypertension.

    Methods

    We have designed a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety trial of sildenafil in premature infants with severe bronchopulmonary dysplasia. We will randomize 120 premature infants < 29 weeks gestational age with severe bronchopulmonary dysplasia at 32-40 weeks postmenstrual age in a dose-escalating approach 3:1 (sildenafil: placebo) sequentially into each of 3 cohorts at ~ 30 clinical sites. Participants will receive up to 34 days of study drug, followed by 28 days of safety monitoring. The primary outcome will be safety as determined by incidence of hypotension. Secondary outcomes will include pharmacokinetics and preliminary effectiveness of sildenafil based on presence or absence of pulmonary hypertension diagnosed by echocardiography at the end of treatment period.

    Discussion

    Sildenafil is a promising intervention to prevent the development of pulmonary hypertension in premature infants with bronchopulmonary dysplasia. Clinical trials of sildenafil specifically designed for premature infants are urgently needed. The current study will make substantial contributions to scientific knowledge of the safety of sildenafil in premature infants at risk for pulmonary hypertension. Results from the study will be used by investigators to inform the design of a pivotal efficacy trial.

    Trial registration

    ClinicalTrials.gov NCT04447989 . Registered 25 June 2020.