Variation in Inhaled Medication Use for Infants With Congenital Heart Disease and Bronchiolitis.

BACKGROUND AND OBJECTIVES: Current viral bronchiolitis guidelines exclude infants with congenital heart disease (CHD). Variations in the use of common therapeutics in this population and their associations with clinical outcomes are unknown. Our objective was to evaluate variations in (1) the use of ß-2-agonists and hypertonic saline across hospitals among infants with CHD hospitalized with bronchiolitis, and (2) hospital-level associations between medication use and outcomes. METHODS: We performed a multicenter retrospective cohort study using administrative data from 52 hospitals in the Pediatric Health Information System. We included infants ≤12 months old hospitalized from January 1, 2015 to June 30, 2019 for bronchiolitis with a secondary diagnosis of CHD. Primary exposures were the hospital-level proportion of days that patients received ß-2-agonists or hypertonic saline. Linear regression models assessed the association between the primary exposure and length of stay, 7-day readmission, mechanical ventilation use, and ICU utilization, adjusting for patient covariates and accounting for clustering by center. RESULTS: We identified 6846 index hospitalizations for bronchiolitis in infants with CHD. Overall, 43% received a ß-2-agonist, and 23% received hypertonic saline. The proportion of days with the use of ß-2-agonists (3.6% to 57.4%) and hypertonic saline (0.0% to 65.8%) varied widely across hospitals in our adjusted model. For both exposures, adjusted models revealed no association between days of use and patient outcomes. CONCLUSIONS: For children with CHD hospitalized with bronchiolitis, hospital-level use of ß-2-agonists and hypertonic saline varied widely, and their use was not associated with clinical outcomes.

Etiologies of Poor Weight Gain and Ultimate Diagnosis in Children Admitted for Growth Faltering.

BACKGROUND AND OBJECTIVES: Growth faltering (GF) (previously failure to thrive) is a common reason for hospital admission, but there is little data on whether diagnoses made during initial admission remain accurate in follow-up. We sought to characterize infants admitted for isolated GF and identify diagnoses at discharge and ultimate diagnoses determined over 2 years of follow-up, to determine how diagnoses changed. We also sought to identify patient factors on admission associated with ultimate diagnosis. METHODS: We conducted a retrospective study of children aged 2 weeks to 2 years with index admissions for GF from 2013 to 2017. We reviewed clinical data and documentation to determine discharge and ultimate diagnosis, and identify factors associated with ultimate diagnosis. RESULTS: Of 497 patients, 292 (59%) had insufficient intake, 103 (20%) had organic disease including 36 genetic disorders, 52 (11%) had mechanical feeding difficulties, and 50 (10%) had mixed or unknown diagnoses 2 years after admission. Over 90% of cases of insufficient intake were diagnosed during admission. Sixty-five percent of organic diseases, and only 39% of genetic disorders, were diagnosed during admission. Patient factors associated with genetic disorders included previous NICU stay, low birth weight, dysphagia, hypotonia, and dysmorphisms. CONCLUSIONS: Insufficient intake remains the most common diagnosis, and this diagnosis was accurately made during admission. Organic disease, especially genetic disease, was often not diagnosed during admission. Better tools are needed to identify patients with organic disease. We identified patient factors on admission associated with ultimate diagnosis, which could be used to prioritize evaluation and expedite follow-up.

Research Methods: How to Perform an Effective Peer Review.

Scientific peer review has existed for centuries and is a cornerstone of the scientific publication process. Because the number of scientific publications has rapidly increased over the past decades, so has the number of peer reviews and peer reviewers. In this paper, drawing on the relevant medical literature and our collective experience as peer reviewers, we provide a user guide to the peer review process, including discussion of the purpose and limitations of peer review, the qualities of a good peer reviewer, and a step-by-step process of how to conduct an effective peer review.

Caspase-9 is required for normal hematopoietic development and protection from alkylator-induced DNA damage in mice.

Apoptosis and the DNA damage responses have been implicated in hematopoietic development and differentiation, as well as in the pathogenesis of myelodysplastic syndromes (MDS) and leukemia. However, the importance of late-stage mediators of apoptosis in hematopoiesis and leukemogenesis has not been elucidated. Here, we examine the role of caspase-9 (Casp9), the initiator caspase of the intrinsic apoptotic cascade, in murine fetal and adult hematopoiesis. Casp9 deficiency resulted in decreased erythroid and B-cell progenitor abundance and impaired function of hematopoietic stem cells after transplantation. Mouse bone marrow chimeras lacking Casp9 or its cofactor Apaf1 developed low white blood cell counts, decreased B-cell numbers, anemia, and reduced survival. Defects in apoptosis have also been previously implicated in susceptibility to therapy-related leukemia, a disease caused by exposure to DNA-damaging chemotherapy. We found that the burden of DNA damage was increased in Casp9-deficient cells after exposure to the alkylator, N-ethyl-nitrosourea (ENU). Furthermore, exome sequencing revealed that oligoclonal hematopoiesis emerged in Casp9-deficient bone marrow chimeras after alkylator exposure. Taken together, these findings suggest that defects in apoptosis could be a key step in the pathogenesis of alkylator-associated secondary malignancies.