The bronchiolitis severity score: An assessment of face validity, construct validity, and interobserver reliability.

OBJECTIVE: To assess face validity, interobserver reliability, and the ability to discriminate escalations of care within 24-h of admission (late rescues) for the bronchiolitis severity score (BSS) for children hospitalized for acute bronchiolitis. HYPOTHESES: The BSS will yield variable face validity, have clinically relevant interobserver reliability (kappa > 0.7), and distinguish late rescues during hospitalization. METHODS: We performed a combined retrospective and prospective, mixed methods study where (1) interobserver agreement was prospectively assessed by overall and subcategory congruence (kappa) calculations, (2) face value were qualitatively assessed from aggregate questionnaire responses, and (3) construct validity for late rescues were assessed using receiver operator characteristic (ROC) curve analyses. RESULTS: Face validity, assessed from 39 questionnaire respondents, were generally positive for BSS utility, reliability, and usability. The BSS exhibited weak interobserver reliability (kappa = 0.22, 95% confidence interval [CI]: 0.11-0.31) calculated from 72 sequential, blinded calculations. Retrospectively, 181 children less than 2 years of age admitted to the general pediatric ward for acute bronchiolitis from November 2017 to April 2019 were identified of which 18 (9.9%) experienced late rescues. Admission BSS values were no different for children with and without late rescues (6[3,6] vs. 4[3,6]; p = .09). An ROC curve analysis revealed an area under the curve of 0.61 (95% CI: 0.48-0.75; threshold ≥6 with sensitivity = 56%, specificity = 69%) for BSS to discriminate late rescues. CONCLUSION: Although clinicians expressed favorable perceptions of BSS face and content validity, we noted weak interobserver reliability and limited construct validity. Further development and validation are needed to strengthen the BSS before routine use.

The Utility of Head Computed Tomography in the Evaluation of Apparent Life-Threatening Event.

OBJECTIVE: This study aimed to evaluate the diagnostic utility of empiric head computed tomography (CT) in apparent life threatening event (ALTE). METHODS: This was a retrospective chart review of children younger than 12 months presenting to an urban pediatric hospital and its suburban satellite for an ALTE from October 2009 to December 2012. The ALTE cases were identified as having had a diagnosis of ALTE (International Classification of Diseases, 9th Revision 799.82) or as having had a constellation of studies performed consistent with our institutional protocol for ALTE evaluation. Exclusion criteria were known trauma and cases lacking an identifiable ALTE feature on review. RESULTS: There were 631 cases identified, of which 617 met inclusion and exclusion criteria. Of those, 537 had a head CT performed. Five patients were identified with clinically important head CT findings: a case of congenital toxoplasmosis, a case of intraventricular hemorrhage, and 3 cases of nonaccidental trauma (NAT). One of the NAT patients had a bruise on his forehead; the other patients had no historical, physical examination, and other laboratory or radiologic findings to raise concern for significant finding on head CT. The rate of clinically significant findings and occult clinically significant findings was 5/537 (0.93%) (95% confidence interval, 0.30%-2.16%; number needed to treat = 108) and 4/537 (0.75%) (95% confidence interval, 0.20%-1.90%; number needed to treat = 135), respectively. CONCLUSIONS: The rate of clinically important head CT findings in ALTE evaluation was relatively rare, at 0.93%. Given the severe consequences of missing these cases, these data establish a role for empiric head CT in the evaluation of ALTE.

Phosphorylation of RyR2 and shortening of RyR2 cluster spacing in spontaneously hypertensive rat with heart failure.

As a critical step toward understanding the role of abnormal intracellular Ca(2+) release via the ryanodine receptor (RyR(2)) during the development of hypertension-induced cardiac hypertrophy and heart failure, this study examines two questions: 1) At what stage, if ever, in the development of hypertrophy and heart failure is RyR(2) hyperphosphorylated at Ser(2808)? 2) Does the spatial distribution of RyR(2) clusters change in failing hearts? Using a newly developed semiquantitative immunohistochemistry method and Western blotting, we measured phosphorylation of RyR(2) at Ser(2808) in the spontaneously hypertensive rat (SHR) at four distinct disease stages. A major finding is that hyperphosphorylation of RyR(2) at Ser(2808) occurred only at late-stage heart failure in SHR, but not in age-matched controls. Furthermore, the spacing between RyR(2) clusters was shortened in failing hearts, as predicted by quantitative model simulation to increase spontaneous Ca(2+) wave generation and arrhythmias.

Robust gene expression with amplified RNA from biopsy-sized human heart tissue.

The need to assess heart failure at an early stage highlights the importance of accurate microarray analysis using small tissue samples. To test our ability to obtain high quality RNA from biopsy-sized cardiac specimens, amplification was performed on RNA from biopsy-sized samples of left ventricle (LV) tissue from one explanted failing human heart and one non-failing heart. Two methods were used: one-cycle (1C) amplification of 1.6 microg of RNA, and two-cycle (2C) amplification of 50 ng of RNA. The resulting cRNA was hybridized to Affymetrix GeneChip arrays. Over 65% of all differentially expressed genes for failing vs non-failing hearts were concordant between 1C and 2C RNA amplification. Differentially expressed genes between 1C and 2C RNA amplification in our study were highly correlated (R(2) = 0.957 and changes in gene expression agreed with prior studies on genes and heart failure; e.g., decreased alpha-myosin heavy chain and alpha-tropomyosin, as well as increased expression of insulin-like growth factor). Two cycles of amplification from cardiac biopsies will permit accurate transcription profiling of heart failure at pre-symptomatic stages. Ability to measure gene expression from nanogram amounts of RNA will provide new opportunities to predict progression to symptomatic heart failure, and to identify potential targets for therapy.