Reducing Antibiotic Duration for Uncomplicated UTI in the Pediatric Emergency Department.

BACKGROUND: Short-duration (3-5 days) antibiotic treatment of uncomplicated urinary tract infection (uUTI) in children >24 months of age is equivalent to longer-duration antibiotic treatment, with added benefits of antibiotic stewardship. At our pediatric emergency department (ED), 13% of 5- to 18-year-old patients discharged with uUTI received ≤5 days of antibiotics. We aimed to increase short-duration prescriptions in patients with uUTI from 13% to >50% over 12 months. METHODS: This quality improvement project was conducted from January 2021 to August 2022. Complicated UTI was excluded. Interventions included education, practice feedback, and electronic health record changes. The outcome measure, the proportion of children treated with a short antibiotic duration, was studied by using p-charts. Antibiotic days saved were calculated. Revisits with UTI within 14 days of confirmed uUTI treated with short-duration antibiotics (balancing measure) were analyzed by using Fisher's exact test. RESULTS: In 1292 (n = 363 baseline, 929 post-intervention) eligible patients treated for uUTI, shorter antibiotic duration increased from 13% to 91%. We met our 50% aim within 2 months, with continued improvement leading to an additional centerline shift. Consequently, 2619 antibiotic days were saved. Two of 334 (0.6%) patients returned (P = NS) within 14 days of the index visit with a culture-positive uUTI. CONCLUSIONS: By using education, feedback, and electronic health record changes, we decreased antibiotic duration in children discharged from the ED for uUTI without a significant increase in return visits with UTI. These interventions can be expanded to wider age groups and other outpatient settings.

Evaluation and validation of a prediction model for extubation success in very preterm infants.

OBJECTIVE: To perform an external validation of a publicly available model predicting extubation success in very preterm infants. STUDY DESIGN: Retrospective study of infants born <1250 g at a single center. Model performance evaluated using the area under the receiver operating characteristic curve (AUROC) and comparing observed and expected probabilities of extubation success, defined as survival ≥5 d without an endotracheal tube. RESULTS: Of 177 infants, 120 (68%) were extubated successfully. The median (IQR) gestational age was 27 weeks (25-28) and weight at extubation was 915 g (755-1050). The model had acceptable discrimination (AUROC 0.72 [95% CI 0.65-0.80]) and adequate calibration (calibration slope 0.96, intercept -0.06, mean observed-to-expected difference in probability of extubation success -0.08 [95% CI -0.01, -0.15]). CONCLUSIONS: The extubation success prediction model has acceptable performance in an external cohort. Additional prospective studies are needed to determine if the model can be improved or how it can be used for clinical benefit.

Caffeine for preterm infants: Fixed standard dose, adjustments for age or high dose?

Caffeine is an effective treatment for apnea of prematurity and has several important benefits, including decreasing respiratory morbidity and motor impairment. In this article, we focus on the dose of caffeine. We review the evidence regarding the efficacy and safety of standard caffeine dosing and alternative dosing approaches, including the use of high dose caffeine and routine dose adjustments for age. Current evidence suggests high dose caffeine may provide additional benefit in reducing the risk of bronchopulmonary dysplasia and extubation failure, but may also increase the risk of cerebellar hemorrhage and seizures. Increasing the standard caffeine citrate dose every 1-2 weeks to a goal dose of 8 mg per kilogram every 24 h may help maintain therapeutic effect. We conclude by highlighting the need for additional trials before high dose caffeine is routinely used.

Transfusion-related Gut Injury and Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) accounts for 10% of deaths in neonatal intensive care units. Several causal mechanisms are likely to lead to a final common disease phenotype. This article summarizes recent data on NEC following red blood cell (RBC) transfusion, with a focus on the most recent literature and ongoing trials. It highlights potential mechanisms from preclinical and human physiologic studies. It also discusses the role of feeding during RBC transfusion and the risk of NEC. Ongoing randomized trials will provide important data on how liberal or conservative approaches to RBC transfusion influence the risk of NEC.

Epidemiology of Necrotizing Enterocolitis: New Considerations Regarding the Influence of Red Blood Cell Transfusions and Anemia.

This article summarizes available evidence on the relationship between red blood cell transfusion and anemia, and necrotizing enterocolitis (NEC). We review recent studies that highlight the uncertainty of the effect of red blood cell transfusion on NEC and the potential role of anemia. We also discuss potential pathophysiologic effects of both red blood cell transfusion and anemia and highlight strategies to prevent anemia and red blood cell transfusion. We also discuss ongoing randomized trials that are likely to provide important new evidence to guide red blood cell transfusion practices.

Optimizing Caffeine Use and Risk of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review, Meta-analysis, and Application of Grading of Recommendations Assessment, Development, and Evaluation Methodology.

Caffeine reduces the risk of bronchopulmonary dysplasia (BPD). Optimizing caffeine use could increase therapeutic benefit. We performed a systematic-review and random-effects meta-analysis of studies comparing different timing of initiation and dose of caffeine on the risk of BPD. Earlier initiation, compared to later, was associated with a decreased risk of BPD (5 observational studies; n = 63,049, adjusted OR 0.69; 95% CI 0.64-0.75, GRADE: low quality). High-dose caffeine, compared to standard-dose, was associated with a decreased risk of BPD (3 randomized trials, n = 432, OR 0.65; 95% CI 0.43-0.97; GRADE: low quality). Higher quality evidence is needed to guide optimal caffeine use.

Tissue cell stress response to obesity and its interaction with late gestation diet.

Intrauterine growth restriction in late pregnancy can contribute to adverse long-term metabolic health in the offspring. In the present study we used an animal (sheep) model of maternal dietary manipulation in late pregnancy, combined with exposure of the offspring to a low-activity, obesogenic environment after weaning, to characterise the effects on glucose homeostasis. Dizygotic twin-pregnant sheep were either fed to 60% of requirements (nutrient restriction (R)) or fed ad libitum (~140% of requirements (A)) from 110 days gestation until term (~147 days). After weaning (~3 months of age), the offspring were kept in either a standard (in order to remain lean) or low-activity, obesogenic environment. R mothers gained less weight and produced smaller offspring. As adults, obese offspring were heavier and fatter with reduced glucose tolerance, regardless of maternal diet. Molecular markers of stress and autophagy in liver and adipose tissue were increased with obesity, with gene expression of hepatic glucose-related protein 78 (Grp78) and omental activation transcription factor 6 (Atf6), Grp78 and ER stress degradation enhancer molecule 1 (Edem1) only being increased in R offspring. In conclusion, the adverse effect of juvenile-onset obesity on insulin-responsive tissues can be amplified by previous exposure to a suboptimal nutritional environment in utero, thereby contributing to earlier onset of insulin resistance.

Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

What is the easier and more reliable dose calculation for iv phenytoin in children at risk of developing convulsive status epilepticus, 18 mg/kg or 20 mg/kg?

BACKGROUND: With the Convulsive Status Guidelines due for renewal, we wondered if a phenytoin dose of '20 mg/kg' would be easier to calculate correctly and therefore safer than the current '18 mg/kg'. An educational exercise in dose calculation was therefore undertaken to assess ease of calculation. METHOD: A standard question paper was prepared, comprising five clinical scenarios with children of varying ages and estimated body weights. Medical students, trainee doctors at registrar and senior house officer level, and consultant paediatricians were asked to complete the exercise, in private, by one of two medical students (SD, PS). Calculations were done with and without a calculator, for 18 mg/kg and for 20 mg/kg in randomised order. Speed and errors (greater than 10%) were determined. The data analysis was performed using SPSS version 18. RESULTS: All answered all 20 scenarios, giving a total of 300 answers per doctor/student group, and 300 answers per type of calculation. When comparing the 2 doses, the numbers of errors more than 10% were significantly less in 20 mg/kg dose (0.33%) as compared to the 18 mg/kg dose (9.3%) (p<0.0001). Speed off calculation was significantly decreased in 20 mg/kg dose when compared with 18 mg/kg dose, with (p<0.001) or without (p<0.0001) the calculator. Speed was more than halved and errors were much less frequent by using a calculator, for the 18 mg/kg dose but no difference with or without the calculator for 20 mg/kg dose. CONCLUSION: We recommend that the future guidelines should suggest iv Phenytoin at 20 mg/kg rather than 18 mg/kg. This will make the calculation easier and reduce the risk of significant errors.

Excess nutrient supply in early life and its later metabolic consequences.

Suboptimal nutrition in early life, both in utero and during infancy, is linked to increased risk of adult obesity and its associated adverse metabolic health problems. Excess nutrient supply during early life can lead to metabolic programming in the offspring. Such overnutrition can occur in the offspring of obese mothers, the offspring of mothers who gain excess weight during gestation, infants of diabetic mothers and infants who undergo rapid growth, particularly weight gain, during early infancy. Postnatal overnutrition is particularly detrimental for infants who are born small for gestational age, who are overfed to attain 'catch-up growth'. Potential mechanisms underlying metabolic programming that results from excess nutrition during early life include resetting of hypothalamic energy sensing and appetite regulation, altered adipose tissue insulin sensitivity and impaired brown adipose tissue function. More detailed understanding of the mechanisms involved in metabolic programming could enable the development of therapeutic strategies for ameliorating its ill effects. Research in this field could potentially identify optimal and appropriate preventative interventions for a burgeoning population at risk of increased mortality and morbidity from obesity and its concomitant metabolic conditions.