Early MicroRNA and Metabolite Changes Post-ACL Reconstruction Surgery.

OBJECTIVES: Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA's natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males. METHODS: A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2-weeks, and 6-weeks post-surgery (129 biospecimens in total). High throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre- versus 2- and 6-weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed. RESULTS: Levels of 46 miRNAs were increased at 2-weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2-weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2-weeks (log2-fold-change 0.71, 95%CI 0.22,1.20) and 6-weeks (log2-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2-weeks (log2-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6-weeks (log2-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2-weeks post-surgery in females compared to males: L-leucine (-1.44, 95%CI -1.75,-1.13), g-guanidinobutyrate (-1.27, 95%CI 1.54,-0.99), creatinine (-1.17, 95%CI -1.44,-0.90), 2-methylbutyrylcarnitine (-1.76, 95%CI -2.17,-1.35), and leu-pro (-1.13, 95%CI -1.44,-0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males. CONCLUSION: MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.

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.

SCRATCH Trial: An Initiative to Reduce Excess Use of High-Flow Nasal Cannula.

OBJECTIVES: We aimed to reduce unnecessary use of high-flow nasal cannula (HFNC) at lower flow rates through the implementation of a standard daily trial off HFNC at a medium-sized academic center. METHODS: We used an interprofessional quality improvement collaboration to develop and implement interventions to reduce HFNC waste in children aged 1 month to 24 months with bronchiolitis who were admitted to the inpatient ward or ICU. Key interventions included development and implementation of the Simple Cannula/Room Air Trial for Children (SCRATCH Trial), a standard trial off HFNC for eligible infants. Process measures were selected as metrics of use of the newly developed trial. The primary outcome measure was hours of treatment with ≤8 L per minute (LPM) of HFNC. Additional outcome measures included total hours of treatment with HFNC and length of stay. RESULTS: A total of 271 patients were included in this study, 131 in the preimplementation group and 140 in the postimplementation group. The mean hours of treatment below our a priori determined waste line (≤8 LPM of HFNC) decreased from 36.3 to 16.8 hours after SCRATCH Trial implementation, and mean length of stay decreased from 4.1 to 3.0 days. CONCLUSIONS: The SCRATCH Trial was successfully implemented across hospital units, with a significant reduction in hours on ≤8 LPM of flow. Rapid discontinuation of HFNC appears feasible and may be associated with a shorter length of stay.

Preventability of 7-Day Versus 30-Day Readmissions at an Academic Children's Hospital.

BACKGROUND AND OBJECTIVES: The 30-day readmission rate is a common quality metric used by Medicare for adult patients. However, studies in pediatrics have shown lower readmission rates and potentially less preventability. Therefore, some question the utility of the 30-day readmission time frame in pediatrics. Our objective was to describe the characteristics of patients readmitted within 30 days of discharge over a 1-year period and determine the preventability of readmissions occurring 0 to 7 vs 8 to 30 days after discharge from a pediatric hospitalist service at an academic children's hospital. METHODS: Retrospective chart review and hospital administrative data were used to gather medical characteristics, demographics, and process-level metrics for readmitted patients between July 1, 2015, and June 30, 2016. All readmissions were reviewed by 2 senior authors and assigned a preventability category. Subgroup analysis comparing preventability in 0-to-7- and 8-to-30-day readmissions groups was performed. Qualitative thematic analysis was performed on readmissions deemed preventable. RESULTS: Of 1523 discharges that occurred during the study period, 49 patients, with 65 distinct readmission encounters, were readmitted for an overall 30-day readmission rate of 4.3% (65 of 1523). Twenty-eight percent (9 of 32) of readmissions within 7 days of discharge and 12.1% (4 of 33) occurring 8 to 30 days after discharge were deemed potentially preventable (P = .13). Combined, the 30-day preventable readmission rate was 20% (13 of 65). CONCLUSIONS: We identified a possible association between preventability and time to readmission. If confirmed by larger studies, the 7-day, rather than 30-day, time frame may represent a better quality metric for readmitted pediatric patients.

Bronchiolitis.

OBJECTIVES: After completing this article, readers should be able to: 1. Recognize the clinical presentation of bronchiolitis. 2. Be aware of the recommendations made in the current American Academy of Pediatrics clinical practice guideline for diagnosis and management of bronchiolitis. 3. Describe the role of laboratory testing in the diagnosis of bronchiolitis. 4. Delineate the efficacy of current therapeutic interventions in the treatment of bronchiolitis. 5. Discuss the evaluation for serious bacterial infections in patients who have bronchiolitis. 6. Outline the prognosis and risk of recurrent wheezing in patients diagnosed with bronchiolitis.