Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells.

Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific laminar positions within visual cortex, and, for most types, the cells mapping to a t-type exhibit consistent electrophysiological and morphological properties. These properties display both discrete and continuous variation among t-types. Through multimodal integrated analysis, we define 28 met-types that have congruent morphological, electrophysiological, and transcriptomic properties and robust mutual predictability. We identify layer-specific axon innervation pattern as a defining feature distinguishing different met-types. These met-types represent a unified definition of cortical GABAergic interneuron types, providing a systematic framework to capture existing knowledge and bridge future analyses across different modalities.

Human neocortical expansion involves glutamatergic neuron diversification.

The neocortex is disproportionately expanded in human compared with mouse1,2, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth3. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer's disease4,5. Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease.

Prevalence and Genetic Diversity of Adenovirus 40/41, Astrovirus, and Sapovirus in Children with Acute Gastroenteritis in Kansas City 2011-2016.

BACKGROUND: Most U.S. acute gastroenteritis (AGE) episodes in children are attributed to norovirus, whereas very little information is available on adenovirus 40/41 (AdV40/41), astrovirus or sapovirus. The New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based AGE surveillance in young children. METHODS: We tested and typed stool specimens collected between December 2011 to June 2016 from one NVSN site in Kansas City for the three viruses, and calculated hospitalization and emergency department (ED) detection rate. RESULTS: Of 3,205 collected specimens, 2,453 (76.5%) were from AGE patients (339 inpatients and 2,114 ED patients) and 752 (23.5%) were from healthy controls (HC). In AGE patients, astrovirus was detected in 94 (3.8%), sapovirus in 252 (10.3%) and AdV40/41 in 101 (4.5%) of 2249 patients. In HC, astrovirus was detected in 13 (1.7%) and sapovirus in 15 (2.0%) specimens. Astrovirus type 1 (37.7%) and genogroup I sapoviruses (59.3%) were most prevalent.Hospitalization rates were 5 (AdV40/41), 4 (astrovirus) and 8 (sapovirus) per 100,000 children <11 years old, whereas ED rates were 2.4 (AdV40/41), 1.9 (astrovirus) and 5.3 (sapovirus) per 1000 children <5 years old. CONCLUSIONS: Overall, AdV40/41, astrovirus, and sapovirus were detected in 18.6% of AGE in a large pediatric hospital in Kansas City.

Premature pubarche in Prader-Willi syndrome: Risk factors and consequences.

OBJECTIVES: Children with Prader-Willi Syndrome (PWS) may develop premature pubarche (PP). We investigated the frequency of PP, and its potential precursors and sequelae, in PWS. DESIGN, PATIENTS AND MEASUREMENTS: A chart review of children with PWS treated at our institution between 1990 and 2021 was performed. PP was defined as Tanner stage 2 (TS2) pubic hair in girls <8 and boys <9 years old. Demographic, anthropometric, and laboratory data were collected to assess predisposing factors and consequences of PP in comparison to patients with PWS who had normal pubarche (NP). RESULTS: Analysis included 43 children with PWS, 23 (53.5%) with PP and 20 (46.5%) with NP. Median age at pubarche was 7.0 years in PP group and 10.0 years in NP group. Age at pubarche was not correlated with age of recombinant human growth hormone (rhGH) initiation, body mass index (BMI) z-score, or homeostasis model assessment of insulin resistance (HOMA-IR) at pubarche. BMI z-score at pubarche was modestly correlated with degree of pubarchal BA advancement (p = 0.033). Those with PP were more likely to have a lower high-density lipoprotein (HDL) (1.05 mmol/L vs. 1.41 mmol/L in the NP group, p = 0.041). The difference between target and final height did not differ between groups (p = 0.507). CONCLUSION: PP is common in PWS but does not compromise final height in comparison to the NP group. Obesity and insulin resistance were not associated with PP in children with PWS, contrary to what has been seen in obese children without PWS.

Clinically Significant Treatment Delay in Pediatric Scaphoid Fractures.

PURPOSE: Pediatric scaphoid fractures present to treatment in a delayed manner 8% to 29% of the time. The indications for cast immobilization in this population are not clear. The definition of a clinically important treatment delay is based only on anecdotal reports. Successful treatment with a cast may be more desirable than surgical intervention. However, it remains unclear what clinical and radiographic factors may predict success with casting. METHODS: A retrospective analysis of all scaphoid fractures treated at a single pediatric hospital was performed to identify fracture characteristics, the presence of cystic change, treatment method, and healing rate. A cut-point analysis was performed to determine the number of days of treatment delay, predictive of casting failure. Kaplan-Meier assessments were performed to determine the differences in time in cast. Characteristics of the delayed group were described and stratified by treatment success or failure. RESULTS: After review, 254 patients met the inclusion criteria. Cut-point analysis determined that a presentation delay of ≥21 days was associated with failure to unite with casting. The median time in the cast for the acute and delayed groups was not significantly different. The casting union rate of delayed fractures was less than acute fractures (75.0% vs 97.0%). CONCLUSIONS: Delayed presentation of scaphoid fractures 21 days or more after injury predicts a greater risk of casting failure; however, the union rate remains high with comparable time in cast. Cast immobilization for scaphoid fractures presenting 21 days or more after injury is a reasonable option. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognosis IV.

Injuries Following COVID-19 Infection in Academy-level Male Youth Soccer Players.

BACKGROUND: Injury epidemiology data are key to injury prevention strategy development. Most such data surrounding the COVID-19 pandemic compare team injury data during the pandemic to that before the pandemic; few investigate injuries by infection status and even less involve academy-level organizations. We hypothesized that in male youth developmental academy-level soccer players, the rate of injury would be higher following COVID-19 infection than in the uninfected. METHODS: Retrospective cohort study involving 141 male youth athletes from a single midwestern US developmental soccer academy during the spring 2022 soccer season. Injury data was gathered prospectively and analyzed retrospectively. Injury rate (incidence per 1000 playing hours), type, location, severity, mechanism, and mode of play were compared between COVID-19-positive and -negative athletes. RESULTS: Thirty-four (24.11%) of 141 athletes tested positive for COVID-19. Of those 34, 20 (58.8%) sustained at least 1 injury, totaling 30 injuries. Of the 107 (75.89%) uninfected athletes, 30 (28.04%) sustained at least 1 injury, totaling 37 injuries. COVID-19-positive athletes sustained injuries at higher rates (7.10, 95% CI: 4.79-10.14) than uninfected athletes (2.71, 95% CI: 1.91-3.74), with an infected to uninfected adjusted injury rate ratio of 2.08 (95% CI: 1.20-3.59, P=0.008). COVID-19 positive players were 2.78 times more likely to sustain an injury following their infection than uninfected players (95% CI: 1.14-6.96, P=0.026). There were no significant differences in injury type (P=0.515), location (P=0.319), severity (P=0.679), mechanism (P=0.225), or mode of play (P=0.557) between groups. CONCLUSIONS: Among academy-level youth soccer athletes, injury rate increased significantly after COVID-19 infection; injury patterns were similar. LEVEL OF EVIDENCE: II - Retrospective cohort study.

A Comparison of Pathogen Detection and Risk Factors among Symptomatic Children with Gastroenteritis Compared with Asymptomatic Children in the Post-rotavirus Vaccine Era.

OBJECTIVE: To describe demographics, pathogen distribution/seasonality, and risk factors in children seeking care for acute gastroenteritis (AGE) at a midwestern US emergency department during 5 postrotavirus vaccine years (2011-2016), and further, to compare the same data with matched healthy controls (HC). STUDY DESIGN: AGE and HC participants <11 years old enrolled in the New Vaccine Surveillance Network study between December 2011 to June 2016 were included. AGE was defined as ≥3 diarrhea episodes or ≥1 vomiting episode. Each HC's age was similar to an AGE participant's age. Pathogens were analyzed for seasonality effects. Participant risk factors for AGE illness and pathogen detections were compared between HC and a matched subset of AGE cases. RESULTS: One or more organisms was detected in 1159 of 2503 children (46.3%) with AGE compared with 99 of 537 HC (17.3%). Norovirus was detected most frequently among AGE (n = 568 [22.7%]) and second-most frequently in HC (n = 39 [6.8%]). Rotavirus was the second most frequently detected pathogen among AGE (n = 196 [7.8%]). Children with AGE were significantly more likely to have reported a sick contact compared with HC, both outside the home (15.6% vs 1.4%; P < .001) and inside the home (18.6% vs 2.1%; P < .001). Daycare attendance was higher among children with AGE (41.4%) compared with HC (29.5%; P < .001). The Clostridium difficile detection rate was slightly higher among HC (7.0%) than AGE (5.3%). CONCLUSIONS: Norovirus was the most prevalent pathogen among children with AGE. Norovirus was detected in some HC, suggesting potential asymptomatic shedding among HC. The proportion of AGE participants with a sick contact was approximately 10 times greater than that of HC.

Humoral and cellular response to the COVID-19 vaccine in immunocompromised children.

BACKGROUND: A suboptimal response to the 2-dose COVID-19 vaccine series in the immunocompromised population prompted recommendations for a 3rd primary dose. We aimed to determine the humoral and cellular immune response to the 3rd COVID-19 vaccine in immunocompromised children. METHODS: Prospective cohort study of immunocompromised participants, 5-21 years old, who received 2 prior doses of an mRNA COVID-19 vaccine. Humoral and CD4/CD8 T-cell responses were measured to SARS-CoV-2 spike antigens prior to receiving the 3rd vaccine dose and 3-4 weeks after the 3rd dose was given. RESULTS: Of the 37 participants, approximately half were solid organ transplant recipients. The majority (86.5%) had a detectable humoral response after the 2nd and 3rd vaccine doses, with a significant increase in antibody levels after the 3rd dose. Positive T-cell responses increased from being present in 86.5% to 100% of the cohort after the 3rd dose. CONCLUSIONS: Most immunocompromised children mount a humoral and cellular immune response to the 2-dose COVID-19 vaccine series, which is significantly augmented after receiving the 3rd vaccine dose. This supports the utility of the 3rd vaccine dose and the rationale for ongoing emphasis for vaccination against COVID-19 in this population. IMPACT: Most immunocompromised children mount a humoral and cellular immune response to the 2-dose COVID-19 vaccine series, which is significantly augmented after receiving the 3rd vaccine dose. This is the first prospective cohort study to analyze both the humoral and T-cell immune response to the 3rd COVID-19 primary vaccine dose in children who are immunocompromised. The results of this study support the utility of the 3rd vaccine dose and the rationale for ongoing emphasis for vaccination against COVID-19 in the immunosuppressed pediatric population.

Admission Pa o2 and Mortality Among PICU Patients and Select Diagnostic Subgroups.

OBJECTIVES: Evaluate the relationship between admission Pa o2 and mortality in a large multicenter dataset and among diagnostic subgroups. DESIGN: Retrospective cohort study. SETTING: North American PICUs participating in Virtual Pediatric Systems, LLC (VPS), 2015-2019. PATIENTS: Noncardiac patients 18 years or younger admitted to a VPS PICU with admission Pa o2 . INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirteen thousand seventy-one patient encounters were included with an overall mortality of 13.52%. Age categories were equally distributed among survivors and nonsurvivors with the exception of small differences among neonates and adolescents. Importantly, there was a tightly fitting quadratic relationship between admission Pa o2 and mortality, with the highest mortality rates seen among hypoxemic and hyperoxemic patients (likelihood-ratio test p < 0.001). This relationship persisted after adjustment for illness severity using modified Pediatric Index of Mortality 3 scores. A similar U-shaped relationship was demonstrated among patients with diagnoses of trauma, head trauma, sepsis, renal failure, hemorrhagic shock, and drowning. However, among the 1,500 patients admitted following cardiac arrest, there was no clear relationship between admission Pa o2 and mortality. CONCLUSIONS: In a large multicenter pediatric cohort, admission Pa o2 demonstrates a tightly fitting quadratic relationship with mortality. The persistence of this relationship among some but not all diagnostic subgroups suggests the pathophysiology of certain disease states may modify the hyperoxemia association.

Appropriateness of Diagnosis and Management for Otitis Media With Effusion in Pediatric Urgent Care Clinics.

BACKGROUND: Otitis media with effusion (OME)'s clinical presentation is often confused with acute otitis media (AOM) by clinicians. Despite OME guidelines recommending watchful waiting with no antibiotics, rates of antibiotic use remain elevated. The aim of this study was to determine the clinician diagnosis validity and the rates of antibiotics prescribed among pediatric OME patients evaluated in 3 urgent care clinics within a pediatric health care system. METHODS: We retrospectively reviewed a random sample of encounters for children aged 0 to 18 years with a billing diagnosis of OME in 2019. We recorded clinical symptoms, antibiotic prescribed, and the clinicians' diagnosis. We used the American Academy of Pediatrics guidelines to assign an AOM diagnosis and compared those with the clinicians' final diagnoses using Pearson χ 2 . RESULTS: Of the 912 eligible charts, clinicians' final diagnoses were as follows: AOM for 271 (29.7%) patients, OME for 638 (70.0%) patients, and no ear pathology for 3 (0.3%) patients. Antibiotics were prescribed for 519 (56.9%) patients; of those, only 242 (46.6%) had a final clinician diagnosis of AOM. Antibiotic prescribing rates were higher when a clinician diagnosed AOM compared with OME (89.3% vs 43.2%; P < 0.001). Per American Academy of Pediatrics guidelines, up to 273 (29.9%) patients qualified for an AOM diagnosis, but those were not the same as those diagnosed with AOM by clinicians ( P < 0.001). CONCLUSIONS: When evaluating children with a billing diagnosis of OME, a third fit a diagnosis of AOM. Clinicians commonly misdiagnosed AOM, but also prescribed antibiotics to almost half of those they diagnose with OME.

A Description of the Imaging Innovations for Placental Assessment in Response to Environmental Pollution Study.

OBJECTIVE: The aim of Placental Assessment in Response to Environmental Pollution Study (PARENTs) was to determine whether imaging of the placenta by novel multiparametric magnetic resonance imaging (MRI) techniques in early pregnancy could help predict adverse pregnancy outcomes (APOs) due to ischemic placental disease (IPD). Additionally, we sought to determine maternal characteristics and environmental risk factors that contribute to IPD and secondary APOs. STUDY DESIGN: Potential patients in their first trimester of pregnancy, who agreed to MRI of the placenta and measures of assessment of environmental pollution, were recruited into PARENTs, a prospective population-based cohort study. Participants were seen at three study visits during pregnancy and again at their delivery from 2015 to 2019. We collected data from interviews, chart abstractions, and imaging. Maternal biospecimens (serum, plasma, and urine) at antepartum study visits and delivery specimens (placenta, cord, and maternal blood) were collected, processed, and stored. The primary outcome was a composite of IPD, which included any of the following: placental abruption, hypertensive disease of pregnancy, fetal growth restriction, or a newborn of small for gestational age. RESULTS: In this pilot cohort, of the 190 patients who completed pregnancy to viable delivery, 50 (26%) developed IPD. Among demographic characteristics, having a history of prior IPD in multiparous women was associated with the development of IPD. In the multiple novel perfusion measurements taken of the in vivo placenta using MRI, decreased high placental blood flow (mL/100 g/min) in early pregnancy (between 14 and 16 weeks) was found to be significantly associated with the later development of IPD. CONCLUSION: Successful recruitment of the PARENTs prospective cohort demonstrated the feasibility and acceptability of the use of MRI in human pregnancy to study the placenta in vivo and at the same time collect environmental exposure data. Analysis is ongoing and we hope these methods will assist researchers in the design of prospective imaging studies of pregnancy. KEY POINTS: · MRI was acceptable and feasible for the study of the human placenta in vivo.. · Functional imaging of the placenta by MRI showed a significant decrease in high placental blood flow.. · Measures of environmental exposures are further being analyzed to predict IPD..

Group A Streptococcal Pharyngitis Testing Appropriateness in Pediatric Acute Care Settings.

OBJECTIVE: Acute pharyngitis is one of the most common causes of ambulatory clinic visits; however, group A Streptococcus accounts for less than a third. National guidelines recommend against streptococcal testing in patients with viral features. This study aims to assess the rate of inappropriate streptococcal rapid antigen detection tests (RADT)s in children evaluated in urgent care clinics (UCC)s and emergency department (ED)s at a children's hospital. METHODS: We retrospectively reviewed charts of 10% of children 3 years or older with RADTs ordered between April and September 2018 at EDs and UCCs. The test was determined to be inappropriate if the patient had no sore throat and/or had 2 or more viral symptoms: rhinorrhea/congestion, cough, diarrhea, hoarseness, conjunctivitis, or viral exanthem. RESULTS: Over the study period, 7678 RADTs were performed, of which 7024 (91.2%) were in children 3 years or older. We evaluated 708 charts and found 44% of RADTs were inappropriate. The predicted probability of inappropriate RADT was highest among patients with a triaged reason for visit for respiratory complaints (70.5%), viral upper respiratory tract infection (69.7%), and rash (61.3%). Of the inappropriate RADTs, 20.1% were positive, whereas 32.2% of the appropriate RADTs were positive. CONCLUSION: Quality improvement initiatives are needed to decrease the rate of inappropriate RADTs in pediatric UCC and ED settings.

Improving Emergency Department Use of Safety-Net Antibiotic Prescriptions for Acute Otitis Media.

OBJECTIVES: Acute otitis media (AOM) is the most common reason for pediatric antibiotic prescriptions. The 2013 American Academy of Pediatrics' AOM guidelines recommend observation for nonsevere AOM. Our aim was to increase the percentage safety-net antibiotic prescription (SNAP) offered to patients 6 months of age or older diagnosed with AOM in 2 pediatric emergency departments (EDs) from a baseline of 0.5% to 15% in 20 months. METHODS: This is a quality improvement study at a quaternary pediatric medical center with 2 locations, both with EDs. A random chart review revealed that 27.5% of patients diagnosed with AOM in the ED would qualify for a SNAP, but only 0.5% were offered it. Quality improvement interventions were designed to improve safety-net antibiotic prescribing. Both EDs conducted multiple interventions, including algorithm development, provider education, and electronic medical record aids. The primary outcome measure was the percentage of patients offered a SNAP for AOM. RESULTS: A total of 8226 children 6 months of age or older were diagnosed with AOM in our 2 EDs during the 20-month intervention period. The percentage offered a SNAP increased at both EDs. One ED had a single shift in the mean to 7.9%, whereas the other had 2 shifts in the mean, an initial shift to 5.1% and a second to 7.3%. Providers consistently used the algorithm and electronic medical record aids. CONCLUSIONS: Safety-net antibiotic prescriptions in conjunction with parent education was effective in reducing the use of immediate antibiotic prescriptions in children with AOM in 2 pediatric EDs. Offering a SNAP can reduce unnecessary use of antibiotics, which in turn may decrease antibiotic-related adverse events and antibiotic resistance.

Impact of Rapid Influenza Molecular Testing on Management in Pediatric Acute Care Settings.

OBJECTIVES: To measure the impact of rapid influenza real-time qualitative reverse transcriptase polymerase chain reaction (RT-PCR) on patient management in busy pediatric emergency department (ED) and urgent care clinic settings. STUDY DESIGN: We developed a brief, elective survey that clinicians completed when an influenza RT-PCR order was placed in the ED or urgent care clinic between February 18, 2019, and March 13, 2019. We captured the clinical suspicion for influenza, intended management plans, and actual management plans once influenza RT-PCR results were available. RESULTS: We evaluated 339 encounters, of which 164 (48.4%) had a positive influenza RT-PCR. Clinical suspicion for influenza was a nonsignificant predictor for influenza PT-PCR positivity (P = .126). After rapid influenza RT-PCR results were available, clinicians changed their original plans in 44.5% of influenza RT-PCR positive vs 92.6% of influenza RT-PCR negative cases (P < .0001). Change in plans for antiviral use was observed in 26% of influenza positive vs 77% of influenza negative cases (P < .0001). A total of 135 antiviral prescriptions were avoided in patients with negative influenza RT-PCR. CONCLUSIONS: Implementation of a rapid and accurate influenza RT-PCR in the acute care setting is important to systematically diagnose influenza in children and improve outpatient management decisions, because clinical suspicion for influenza is inaccurate. A negative influenza RT-PCR decreases unnecessary antiviral use and has the potential for significant cost savings.

In Vivo Submillisecond Two-Photon Optogenetics with Temporally Focused Patterned Light.

To better examine circuit mechanisms underlying perception and behavior, researchers need tools to enable temporally precise control of action-potential generation of individual cells from neuronal ensembles. Here we demonstrate that such precision can be achieved with two-photon (2P) temporally focused computer-generated holography to control neuronal excitability at the supragranular layers of anesthetized and awake visual cortex in both male and female mice. Using 2P-guided whole-cell or cell-attached recordings in positive neurons expressing any of the three opsins ReaChR, CoChR, or ChrimsonR, we investigated the dependence of spiking activity on the opsin's channel kinetics. We found that in all cases the use of brief illumination (≤10 ms) induces spikes of millisecond temporal resolution and submillisecond precision, which were preserved upon repetitive illuminations up to tens of hertz. To reach high temporal precision, we used a large illumination spot covering the entire cell body and an amplified laser at high peak power and low excitation intensity (on average ≤0.2 mW/µm2), thus minimizing the risk for nonlinear photodamage effects. Finally, by combining 2P holographic excitation with electrophysiological recordings and calcium imaging using GCaMP6s, we investigated the factors, including illumination shape and intensity, opsin distribution in the target cell, and cell morphology, which affect the spatial selectivity of single-cell and multicell holographic activation. Parallel optical control of neuronal activity with cellular resolution and millisecond temporal precision should make it easier to investigate neuronal connections and find further links between connectivity, microcircuit dynamics, and brain functions.SIGNIFICANCE STATEMENT Recent developments in the field of optogenetics has enabled researchers to probe the neuronal microcircuit with light by optically actuating genetically encoded light-sensitive opsins expressed in the target cells. Here, we applied holographic light shaping and temporal focusing to simultaneously deliver axially confined holographic patterns to opsin-positive cells in the living mouse cortex. Parallel illumination efficiently induced action potentials with high temporal resolution and precision for three opsins of different kinetics. We extended the parallel optogenetic activation at low intensity to multiple neurons and concurrently monitored their calcium dynamics. These results demonstrate fast and temporally precise in vivo control of a neuronal subpopulation, opening new opportunities for revealing circuit mechanisms underlying brain functions.

Appropriateness of Antibiotic Prescribing in United States Children's Hospitals: A National Point Prevalence Survey.

BACKGROUND: Studies estimate that 30%-50% of antibiotics prescribed for hospitalized patients are inappropriate, but pediatric data are limited. Characterization of inappropriate prescribing practices for children is needed to guide pediatric antimicrobial stewardship. METHODS: Cross-sectional analysis of antibiotic prescribing at 32 children's hospitals in the United States. Subjects included hospitalized children with ≥ 1 antibiotic order at 8:00 am on 1 day per calendar quarter, over 6 quarters (quarter 3 2016-quarter 4 2017). Antimicrobial stewardship program (ASP) physicians and/or pharmacists used a standardized survey to collect data on antibiotic orders and evaluate appropriateness. The primary outcome was the percentage of antibiotics prescribed for infectious use that were classified as suboptimal, defined as inappropriate or needing modification. RESULTS: Of 34 927 children hospitalized on survey days, 12 213 (35.0%) had ≥ 1 active antibiotic order. Among 11 784 patients receiving antibiotics for infectious use, 25.9% were prescribed ≥ 1 suboptimal antibiotic. Of the 17 110 antibiotic orders prescribed for infectious use, 21.0% were considered suboptimal. Most common reasons for inappropriate use were bug-drug mismatch (27.7%), surgical prophylaxis > 24 hours (17.7%), overly broad empiric therapy (11.2%), and unnecessary treatment (11.0%). The majority of recommended modifications were to stop (44.7%) or narrow (19.7%) the drug. ASPs would not have routinely reviewed 46.1% of suboptimal orders. CONCLUSIONS: Across 32 children's hospitals, approximately 1 in 3 hospitalized children are receiving 1 or more antibiotics at any given time. One-quarter of these children are receiving suboptimal therapy, and nearly half of suboptimal use is not captured by current ASP practices.

Positive Impact of Routine Testing for Enterovirus and Parechovirus on Length of Hospitalization and Antimicrobial Use among Inpatients ≤6 Months of Age.

Enterovirus (EV) and parechovirus (PeV) are leading viral causes of central nervous system (CNS) infection among hospitalized neonates and young infants, yet testing for PeV is not routinely performed. The goal of our study was to determine how EV and PeV CSF RT-PCR testing impacted the duration of antibiotic use and the length of hospitalization (LOS) in children ≤6 months old with suspected CNS infection. This retrospective cohort study at Children's Mercy Kansas City evaluated data from patients ≤6 months old for whom routine CSF EV and PeV reverse transcription-PCR (RT-PCR) testing was performed during January 2011 to December 2018. Electronic data were abstracted from the electronic medical record, including demographics, systemic antimicrobial use, imaging data, herpes simplex virus (HSV) testing, and overall hospital charges. Among 1,926 patients, 345 (17.9%) were RT-PCR positive for EV and 172 (8.9%) were positive for PeV. A significantly shorter LOS was observed for patients with EV (51.6 h; P < 0.001) and PeV (66.3 h; P = 0.048) compared to patients that tested negative for both viruses (74.1 h). Discontinuation of empirical antibiotic therapy following test result availability occurred more frequently for PeV patients (57.8%; P = 0.03) and EV patients (65.4%; P < 0.001) than RT-PCR-negative patients (48.5%). Routine EV/PeV RT-PCR testing of cerebrospinal fluid (CSF) samples in children impacted care of hospitalized neonates and young infants. Rapid and prompt diagnosis has the potential to reduce antibiotic usage, length of stay, and patient charges.

Reductions in Parent Interest in Receiving Antibiotics following a 90-Second Video Intervention in Outpatient Pediatric Clinics.

OBJECTIVES: To assess the impact of a 90-second animated video on parents' interest in receiving an antibiotic for their child. STUDY DESIGN: This pre-post test study enrolled English and Spanish speaking parents (n = 1051) of children ages 1-5 years presenting with acute respiratory tract infection symptoms. Before meeting with their provider, parents rated their interest in receiving an antibiotic for their child, answered 6 true/false antibiotic knowledge questions, viewed the video, and then rated their antibiotic interest again. Parents rated their interest in receiving an antibiotic using a visual analogue scale ranging from 0 to 100, with 0 being "I definitely do not want an antibiotic," 50 "Neutral," and 100 "I absolutely want an antibiotic." RESULTS: Parents were 84% female, with a mean age of 32 ± 6.0, 26.0% had a high school education or less, 15% were black, and 19% were Hispanic. After watching the video, parents' average antibiotic interest ratings decreased by 10 points (mean, 57.0 ± 20 to M ± 21; P < .0001). Among parents with the highest initial antibiotic interest ratings (≥60), even greater decreases were observed (83.0 ± 12.0 to 63.4 ± 22; P < .0001) with more than one-half (52%) rating their interest in the low or neutral ranges after watching the video. CONCLUSIONS: A 90-second video can decrease parents' interest in receiving antibiotics, especially among those with higher baseline interest. This scalable intervention could be used in a variety of settings to reduce parents' interest in receiving antibiotics. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03037112.