Viral Coinfections in Kawasaki Disease: A Meta-analysis.

CONTEXT: Viral infections are suspected triggers in Kawasaki disease (KD); however, a specific viral trigger has not been identified. OBJECTIVES: In children with KD, to identify (1) overall prevalence of viral infections; (2) prevalence of specific viruses; and (3) whether viral positivity was associated with coronary artery aneurysms (CAAs) or refractoriness to intravenous immunoglobin (IVIG). DATA SOURCES: We searched Embase, Medline, and Cochrane databases and gray literature. STUDY SELECTION: Eligible studies were conducted between 1999 and 2019, and included children diagnosed with KD who underwent viral testing. DATA EXTRACTION: Two investigators independently reviewed full-text articles to confirm eligibility, extract data, appraise for bias, and assess evidence quality for outcomes using the Grading of Recommendations Assessment Development and Evaluation criteria. We defined viral positivity as number of children with a positive viral test divided by total tested. Secondary outcomes were CAA (z score ≥2.5) and IVIG refractoriness (fever ≥36 hours after IVIG). RESULTS: Of 3189 unique articles identified, 54 full-text articles were reviewed, and 18 observational studies were included. Viral positivity weighted mean prevalence was 30% (95% confidence interval [CI], 14-51) and varied from 5% to 66%, with significant between-study heterogeneity. Individual virus positivity was highest for rhinovirus (19%), adenovirus (10%), and coronavirus (7%). Odds of CAA (odds ratio, 1.08; 95% CI, 0.75-1.56) or IVIG refractoriness (odds ratio, 0.88; 95% CI, 0.58-1.35) did not differ on the basis of viral status. LIMITATIONS: Low or very low evidence quality. CONCLUSIONS: Viral infection was common with KD but without a predominant virus. Viral positivity was not associated with CAAs or IVIG refractoriness.

Diagnostic testing for evaluation of brief resolved unexplained events.

BACKGROUND: Since the publication of the American Academy of Pediatrics (AAP) clinical practice guideline for brief resolved unexplained events (BRUEs), a few small, single-center studies have suggested low yield of diagnostic testing in infants presenting with such an event. We conducted this large retrospective multicenter study to determine the role of diagnostic testing in leading to a confirmatory diagnosis in BRUE patients. METHODS: Secondary analysis from a large multicenter cohort derived from 15 hospitals participating in the BRUE Quality Improvement and Research Collaborative. The study subjects were infants < 1 year of age presenting with a BRUE to the emergency departments (EDs) of these hospitals between October 1, 2015, and September 30, 2018. Potential BRUE cases were identified using a validated algorithm that relies on administrative data. Chart review was conducted to confirm study inclusion/exclusion, AAP risk criteria, final diagnosis, and contribution of test results. Findings were stratified by ED or hospital discharge and AAP risk criteria. For each patient, we identified whether any diagnostic test contributed to the final diagnosis. We distinguished true (contributory) results from false-positive results. RESULTS: Of 2036 patients meeting study criteria, 63.2% were hospitalized, 87.1% qualified as AAP higher risk, and 45.3% received an explanatory diagnosis. Overall, a laboratory test, imaging, or an ancillary test supported the final diagnosis in 3.2% (65/2036, 95% confidence interval [CI] 2.7%-4.4%) of patients. Out of 5163 diagnostic tests overall, 1.1% (33/2897, 95% CI 0.8%-1.5%) laboratory tests and 1.5% (33/2266, 95% CI 1.0%-1.9%) of imaging and ancillary studies contributed to a diagnosis. Although 861 electrocardiograms were performed, no new cardiac diagnoses were identified during the index visit. CONCLUSIONS: Diagnostic testing to explain BRUE including for those with AAP higher risk criteria is low yield and rarely contributes to an explanation. Future research is needed to evaluate the role of testing in more specific, at-risk populations.

Association of Models of Care for Kawasaki Disease With Utilization and Cardiac Outcomes.

OBJECTIVES: Describe the prevalence of different care models for children with Kawasaki disease (KD) and evaluate utilization and cardiac outcomes by care model. METHODS: Multicenter, retrospective cohort study of children aged 0 to 18 hospitalized with KD in US children's hospitals from 2017 to 2018. We classified hospital model of care via survey: hospitalist primary service with as-needed consultation (Model 1), hospitalist primary service with automatic consultation (Model 2), or subspecialist primary service (Model 3). Additional data sources included administrative data from the Pediatric Health Information System database supplemented by a 6-site chart review. Utilization outcomes included laboratory, medication and imaging usage, length of stay, and readmission rates. We measured the frequency of coronary artery aneurysms (CAAs) in the full cohort and new CAAs within 12 weeks in the 6-site chart review subset. RESULTS: We included 2080 children from 44 children's hospitals; 21 hospitals (48%) identified as Model 1, 19 (43%) as Model 2, and 4 (9%) as Model 3. Model 1 institutions obtained more laboratory tests and had lower overall costs (P < .001), whereas echocardiogram (P < .001) and immune modulator use (P < .001) were more frequent in Model 3. Secondary outcomes, including length of stay, readmission rates, emergency department revisits, CAA frequency, receipt of anticoagulation, and postdischarge CAA development, did not differ among models. CONCLUSIONS: Modest cost and utilization differences exist among different models of care for KD without significant differences in outcomes. Further research is needed to investigate primary service and consultation practices for KD to optimize health care value and outcomes.

Variation in Dexamethasone Dosing and Use Outcomes for Inpatient Croup.

OBJECTIVES: Evaluate the association between dexamethasone dosing and outcomes for children hospitalized with croup. METHODS: This study was nested within a multisite prospective cohort study of children aged 6 months to 6 years admitted to 1 of 5 US children's hospitals between July 2014 and June /2016. Multivariable linear and logistic mixed-effects regression models were used to examine the association between the number of dexamethasone doses (1 vs >1) and outcomes (length of stay [LOS], cost, and 30-day same-cause reuse). All multivariable analyses included a site-specific random effect to account for clustering within hospital and were adjusted for age, sex, race and ethnicity, presenting severity, medical complexity, insurance, caregiver education, and hospital. In cost analyses, we controlled for LOS. RESULTS: Among 234 children hospitalized with croup, patient characteristics did not differ by number of doses. The proportion receiving >1 dose varied by hospital (range 27.9%-57.1%). In adjusted analyses, >1 dose was not associated with same-cause reuse (odds ratio 0.87 [95% confidence interval (CI): 0.26 to 2.95]) but was associated with 45% longer LOS (relative risk = 1.45 [95% CI: 1.30 to 1.62]). When we controlled for LOS, >1 dose was not associated with differential cost ($-31.2 [95% CI $-424.4 to $362.0]). Eighty-two (35%) children received dexamethasone before presentation. CONCLUSIONS: We found significant interhospital variation in dexamethasone dosing and LOS. When we controlled for severity on presentation, >1 dexamethasone dose was associated with longer LOS but not reuse. Although incomplete adjustment for severity is one possible explanation, some providers may routinely keep children hospitalized to administer multiple dexamethasone doses.

Antibiotic Regimens and Associated Outcomes in Children Hospitalized With Staphylococcal Scalded Skin Syndrome.

BACKGROUND: Controversy exists regarding the optimal antibiotic regimen for use in hospitalized children with staphylococcal scalded skin syndrome (SSSS). Various regimens may confer toxin suppression and/or additional coverage for methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S aureus (MRSA). OBJECTIVES: To describe antibiotic regimens in hospitalized children with SSSS and examine the association between antistaphylococcal antibiotic regimens and patient outcomes. DESIGN/METHODS: Retrospective cohort study of children hospitalized with SSSS using the Pediatric Health Information System database (2011-2016). Children who received clindamycin monotherapy, clindamycin plus MSSA coverage (eg, nafcillin), or clindamycin plus MRSA coverage (eg, vancomycin) were included. The primary outcome was hospital length of stay (LOS); secondary outcomes were treatment failure and cost. Generalized linear mixed-effects models were used to compare outcomes among antibiotic groups. RESULTS: Of 1,259 children included, 828 children received the most common antistaphylococcal antibiotic regimens: clindamycin monotherapy (47%), clindamycin plus MSSA coverage (33%), and clindamycin plus MRSA coverage (20%). Children receiving clindamycin plus MRSA coverage had higher illness severity (44%) compared with clindamycin monotherapy (28%) and clindamycin plus MSSA (32%) (P =.001). In adjusted analyses, LOS and treatment failure did not differ among the 3 regimens (P =.42 and P =.26, respectively). Cost was significantly lower for children receiving clindamycin monotherapy and highest in those receiving clindamycin plus MRSA coverage (mean, $4,839 vs $5,348, respectively; P <.001). CONCLUSIONS: In children with SSSS, the addition of MSSA or MRSA coverage to clindamycin monotherapy was associated with increased cost and no incremental difference in clinical outcomes.

Murine Typhus in 5 Children Hospitalized for Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is an emerging disease described in children in association with infection or epidemiological link to severe acute respiratory syndrome coronavirus 2. Signs and symptoms include fever, rash, and cardiac dysfunction; US Centers for Disease Control and Prevention have put forth broad criteria for diagnosis. The illness is serious and can progress rapidly to heart failure and death. However, findings in MIS-C are nonspecific, and there is significant overlap with other systemic illnesses, including Kawasaki disease and several viral and bacterial infections. We present 5 children admitted to a teaching hospital within an 11-day period in May 2020 for MIS-C evaluation who were later diagnosed with murine typhus. Typhus is a rickettsial infection that presents with fever and rash, and, although usually self-limited, responds well to treatment with doxycycline to shorten the course of illness. Clinical and laboratory characteristics of these children are presented to illustrate similarities to MIS-C, which can also be shared with viral, bacterial, or other regional endemic infections, as well as noninfectious inflammatory diseases. This case series serves to remind pediatric hospitalists to be vigilant to avoid premature closure on MIS-C for children admitted with fever and systemic inflammation. Maintaining a wide differential diagnosis in approaching such patients is of utmost importance as community exposure to severe acute respiratory syndrome coronavirus 2 is likely and evidence of past infection becomes commonplace.

Variation in Diagnostic Test Use and Associated Outcomes in Staphylococcal Scalded Skin Syndrome at Children's Hospitals.

OBJECTIVES: The incidence of staphylococcal scalded skin syndrome (SSSS) is rising, but current practice variation in diagnostic test use is not well described. Our aim was to describe the variation in diagnostic test use in children hospitalized with SSSS and to determine associations with patient outcomes. METHODS: We performed a retrospective (2011-2016) cohort study of children aged 0 to 18 years from 35 children's hospitals in the Pediatric Health Information System database. Tests included blood culture, complete blood count, erythrocyte sedimentation rate, C-reactive protein level, serum chemistries, and group A streptococcal testing. K-means clustering was used to stratify hospitals into groups of high (cluster 1) and low (cluster 2) test use. Associations between clusters and patient outcomes (length of stay, cost, readmissions, and emergency department revisits) were assessed with generalized linear mixed-effects modeling. RESULTS: We included 1259 hospitalized children with SSSS; 84% were ≤4 years old. Substantial interhospital variation was seen in diagnostic testing. Blood culture was the most commonly obtained test (range 62%-100%), with the most variation seen in inflammatory markers (14%-100%). Between hospital clusters 1 and 2, respectively, there was no significant difference in adjusted length of stay (2.6 vs 2.5 days; P = .235), cost ($4752 vs $4453; P = .591), same-cause 7-day readmission rate (0.8% vs 0.4%; P = .349), or emergency department revisit rates (0.1% vs 0.6%; P = .148). CONCLUSIONS: For children hospitalized with SSSS, lower use of diagnostic tests was not associated with changes in outcomes. Hospitals with high diagnostic test use may be able to reduce testing without adversely affecting patient outcomes.