Search

Background The goal of Project Austin, an initiative to improve emergency care for rural children who are medically complex (CMC), is to provide an Emergency Information Form (EIF) to their parents/caregivers, to local Emergency Medical Services, and Emergency Departments. EIFs are standard forms recommended by the American Academy of Pediatrics that provide pre-planned rapid response instructions, including medical conditions, medications, and care recommendations, for emergency providers. Our objective is to describe the workflows and perceived utility of the provided emergency information forms (EIFs) in the acute medical management of CMC. Methods We sampled from two key stakeholder groups in the acute management of CMC: four focus groups with emergency medical providers from rural and urban settings and eight key informant interviews with parents/caregivers enrolled in an emergency medical management program for CMC. Transcripts were thematically analyzed in NVivo© by two coders using a content analysis approach. The thematic codes were combined into a codebook and revised the themes present through combining relevant themes and developing of sub-themes until they reached consensus. Results All parents/caregivers interviewed were enrolled in Project Austin and had an EIF. Emergency medical providers and parents/caregivers supported the usage of EIFs for CMC. Parents/caregivers also felt EIFs made emergency medical providers more prepared for their child. Providers identified that EIFs helped provide individualized care, however they were not confident the data was current and so felt unsure they could rely on the recommendations on the EIF. Conclusion EIFs are an easy way to engage parents, caregivers, and emergency medical providers about the specifics of a care for CMC during an emergency. Timely updates and electronic access to EIFs could improve their value for medical providers.

Introduction. Pediatric clinical trials are difficult to conduct, leading to off-label use of medication in children based on results of trials with adults. As a unique population, children deserve to have appropriately tested therapies. The purpose of this study was to evaluate pediatric caregivers’ beliefs and perceived barriers to participation in clinical trials. Methods. The study was completed within the Sunflower Pediatric Clinical Trials Research Extension (SPeCTRE), an affiliate of the IDeA States Pediatric Clinical Trials Network (ISPCTN). This was a cross-sectional survey, adapted from the Pediatric Research Participation Questionnaire. A convenience sample of pediatric caregivers was recruited in three areas of a highly rural Midwestern state between 2017 and 2018. Results. A total of 159 caregivers completed surveys; the majority (72.3%) were previously familiar with clinical trials, but

Objective To assess whether disparities in asthma care and outcomes based on insurance type existed before a national quality improvement (QI) collaborative, and to determine the effects of the collaborative on these disparities. Methods Secondary analysis of data from Pathways for Improving Pediatric Asthma Care (PIPA), a national collaborative to standardize emergency department (ED) and inpatient asthma management. PIPA included children aged 2 to 17 with a diagnosis of asthma. Disparities were examined based on insurance status (public vs private). Outcomes included guideline adherence and health care utilization measures, assessed for 12 months before and 15 months after the start of PIPA. Results We analyzed 19,204 ED visits and 11,119 hospitalizations from 89 sites. At baseline, children with public insurance were more likely than those with private insurance to receive early administration of corticosteroids (52.3% vs 48.9%, P= .01). However, they were more likely to be admitted (20.0% vs 19.4%, P = .01), have longer inpatient length of stay (31 vs 29 hours, P = .01), and have a readmission/ED revisit within 30 days (7.4% vs 5.6%, P = .02). We assessed the effects of PIPA on these disparities by insurance status and found no significant changes across 6 guideline adherence and 4 health care utilization measures. Conclusion At baseline, children with public insurance had higher asthma health care utilization than those with private insurance, despite receiving more evidence-based care. The PIPA collaborative did not affect pre-existing disparities in asthma outcomes. Future research should identify effective strategies for leveraging QI to better address disparities.

Background Coronavirus disease 2019 (COVID-19) vaccines demonstrate excellent effectiveness against infection, severe disease, and death. However, pediatric COVID-19 vaccination rates lag among individuals from rural and other medically underserved communities. The research objective of the current protocol is to determine the effectiveness of a vaccine communication mobile health (mHealth) application (app) on parental decisions to vaccinate their children against COVID-19. Methods Custodial parents/caregivers with ≥ 1 child eligible for COVID-19 vaccination who have not yet received the vaccine will be randomized to download one of two mHealth apps. The intervention app will address logistical and motivational barriers to pediatric COVID-19 vaccination. Participants will receive eight weekly push notifications followed by two monthly push notifications (cues to action) regarding vaccinating their child. Through branching logic, users will access customized content based on their locality, degree of rurality-urbanicity, primary language (English/Spanish), race/ethnicity, and child’s age to address COVID-19 vaccine knowledge and confidence gaps. The control app will provide push notifications and information on general pediatric health and infection prevention and mitigation strategies based on recommendations from the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC). The primary outcome is the proportion of children who complete COVID-19 vaccination series. Secondary outcomes include the proportion of children who receive ≥ 1 dose of COVID-19 vaccine and changes in parent/caregiver scores from baseline to immediately post-intervention on the modified WHO SAGE Vaccine Hesitancy Scale adapted for the COVID-19 vaccine. Discussion The COVID-19 pandemic inflicts disproportionate harm on individuals from underserved communities, including those in rural settings. Maximizing vaccine uptake in these communities will decrease infection rates, severe illness, and death. Given that most US families from these communities use smart phones, mHealth interventions hold the promise of broad uptake. Bundling multiple mHealth vaccine uptake interventions into a single app may maximize the impact of deploying such a tool to increase COVID-19 vaccination. The new knowledge to be gained from this study will directly inform future efforts to increase COVID-19 vaccination rates across diverse settings and provide an evidentiary base for app-based vaccine communication tools that can be adapted to future vaccine-deployment efforts. Clinical trials registration ClinicalTrials.gov NCT05386355. Registered on May 23, 2022.

Autoantibodies against type I interferons (IFNs) occur in approximately 10% of adults with life-threatening COVID-19. The frequency of anti-IFN autoantibodies in children with severe sequelae of SARS-CoV-2 infection is unknown.To quantify anti-Type I IFN autoantibodies in a multi-center cohort of children with severe COVID-19, Multisystem Inflammatory Syndrome in Children (MIS-C), and mild SARS-CoV-2 infections.Circulating anti-IFNa2 antibodies were measured by a radioligand binding assay. Whole exome sequencing (WES), RNA-sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFNα2 autoantibodies exceeding the assay's positive control.Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only one had high levels of anti-IFNα2 antibodies. Anti-IFNα2 autoantibodies were not detected in patients treated with intravenous immunoglobulin prior to sample collection. WES identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of NF-kB essential for non-canonical NF-kB signaling. Her peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity.High levels of anti-IFNα2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare, but can occur in patients with inborn errors of immunity.Anti-IFNα2 autoantibodies should prompt diagnostic evaluation for inborn errors of immunity if identified in children or adolescents.

BACKGROUND AND OBJECTIVES Recommendations for parenteral antibiotic therapy duration in bacterial meningitis in young infants are based predominantly on expert consensus. Prolonged durations are generally provided for proven and suspected meningitis and are associated with considerable costs and risks. The objective of the study was to review the literature on the duration of parenteral antibiotic therapy and outcomes of bacterial meningitis in infants METHODS We searched PubMed, Embase, and the Cochrane Library for publications until May 31, 2021. Eligible studies were published in English and included infants RESULTS Thirty-two studies were included: 1 randomized controlled trial, 25 cohort studies, and 6 case series. The randomized controlled trial found no difference in treatment failure rates between 10 and 14 days of therapy. One cohort study concluded that antibiotic courses >21 days were not associated with improved outcomes as compared with shorter courses. The remaining studies had small sample sizes and/or did not stratify outcomes by therapy duration. Meta-analysis was not possible because of the heterogeneity of the treatments and reported outcomes. CONCLUSIONS Rigorous, prospective clinical trial data are lacking to determine the optimal parenteral antibiotic duration in bacterial meningitis in young infants. Given the associated costs and risks, there is a pressing need for high-quality comparative effectiveness research to further study this question.

OBJECTIVE Variation in bronchiolitis management by race and ethnicity within emergency departments (EDs) has been described in single-center and prospective studies, but large-scale assessments across EDs and inpatient settings are lacking. Our objective is to describe the association between race and ethnicity and bronchiolitis management across 37 U.S. freestanding children's hospitals from 2015 to 2018. METHODS Using the Pediatric Health Information System, we analyzed ED and inpatient visits from November 2015 to November 2018 of children with bronchiolitis 3 to 24 months old. Rates of use for specific diagnostic tests and therapeutic measures were compared across the following race/ethnicity categories: 1) non-Hispanic White (NHW), 2) non-Hispanic Black (NHB), 3) Hispanic, and 4) other. The subanalyses of ED patients only and children < 1 year old were performed. Mixed-effect logistic regression was performed to compare the adjusted odds of receiving specific test/treatment using NHW children as the reference group. RESULTS A total of 134,487 patients met inclusion criteria (59% male, 28% NHB, 26% Hispanic). Adjusted analysis showed that NHB children had higher odds of receiving medication associated with asthma (odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.22 to 1.32) and lower odds of receiving diagnostic tests (blood cultures, complete blood counts, viral testing, chest x-rays; OR = 0.78, 95% CI = 0.75 to 0.81) and antibiotics (OR = 0.58, 95% CI = 0.52 to 0.64) than NHW children. Hispanic children had lower odds of receiving diagnostic testing (OR = 0.94, 95% CI = 0.90 to 0.98), asthma-associated medication (OR = 0.92, 95% CI = 0.88 to 0.96), and antibiotics (OR = 0.74, 95% CI = 0.66 to 0.82) compared to NHW children. CONCLUSION NHB children more often receive corticosteroid and bronchodilator therapies; NHW children more often receive antibiotics and chest radiography. Given that current guidelines generally recommend supportive care with limited diagnostic testing and medical intervention, these findings among NHB and NHW children represent differing patterns of overtreatment. The underlying causes of these patterns require further investigation.

OBJECTIVES: Most children in the United States receive treatment in community hospitals, but descriptions of clinical practice patterns in pediatric care in this setting are lacking. Our objectives were to compare clinical practice patterns primarily between community and university-affiliated hospitals and secondarily by number of pediatric beds before and during participation in a national practice standardization project. METHODS: We performed a retrospective secondary analysis on data from 126 hospitals that participated in the American Academy of Pediatrics’ Value in Inpatient Pediatrics Reducing Excessive Variability in the Infant Sepsis Evaluation project, a national quality improvement project conducted to improve care for well-appearing febrile infants aged 7 to 60 days. Four use measures were compared by hospital type and by number of non-ICU pediatric beds. RESULTS: There were no differences between community and university-affiliated hospitals in the odds of hospital admission, average length of stay, or odds of cerebrospinal fluid culture. The odds of chest radiograph at community hospitals were higher only during the baseline period. There were no differences by number of pediatric beds in odds of admission or average length of stay. For hospitals with ≤30 pediatric beds, the odds of chest radiograph were higher and the odds of cerebrospinal fluid culture were lower compared with hospitals >50 beds during both study periods. CONCLUSIONS: In many key aspects, care for febrile infants does not differ between community and university-affiliated hospitals. Clinical practice may differ more by number of pediatric beds.

The objective of this paper was to determine inhaled corticosteroid (IC) use in infants with bronchopulmonary dysplasia (BPD), define the interhospital variation of IC administration to infants with BPD, and compare clinical, demographic, and hospital factors associated with IC use. Using the Pediatric Health Information System database, a retrospective multicenter cohort of 4,551 infants born at32 weeks of gestation with developing BPD was studied. The clinical, demographic, and hospital characteristics of infants exposed and not exposed to ICs were compared. IC use varied markedly between hospitals, ranging from 0 to 66% of infants with BPD exposed to ICs. Increased annual BPD census was not associated with IC use. In total, 25% (1,144 out of 4,551) of patients with BPD and 43% (536 out of 1,244) of those with severe BPD received ICs. Increased IC exposure was associated with lower birth weight and gestational age, days on respiratory support, need for positive pressure ventilation at 36-week postmenstrual age, need for tracheostomy, and increased use of systemic steroids, bronchodilators, and diuretics. IC exposure is common in infants with BPD, with substantial interhospital variability. IC use was associated with more severe disease. Hospital experience did not account for the wide variability in IC use by the hospital. Further research into the effects of ICs use is urgently needed to help guide their use in this vulnerable population.· The risks and benefits of IC use in infants with BPD are incompletely understood.. · IC use is common in infants with BPD (25%) and severe BPD (43%) varies widely by hospital (0-66% of patients with BPD received an IC).. · Hospital experience did not account for the wide interhospital variation in IC use..

OBJECTIVES: Assess trends in inpatient acute gastroenteritis (AGE) management across children’s hospitals and identify elements of AGE management associated with resource use. METHODS: We examined inpatient stays for children 6 months to 18 years hospitalized with AGE from 2009 to 2018 using the Pediatric Health Information System database. We characterized demographics, hospital-level resource use (ie, medications, laboratories, and imaging), and outcomes (ie, cost per case, 14-day revisit rates, and length of stay [LOS]). We compared demographic characteristics and resource use between 2009 to 2013 and 2014 to 2018 using χ2 and Wilcoxon rank-sum tests. We grouped hospitals on the basis of 2009 use of each resource and trended use over time using logistic regression. Annual change in mean cost and LOS were estimated by using models of log-transformed data. RESULTS: Across 32 354 hospitalizations at 38 hospitals, there was a high use of electrolyte testing (85.4%) and intravenous fluids (84.1%) without substantial changes over time. There were significant reductions in the majority of laboratory, medication, and imaging resources across hospitals over the study period. The most notable reductions were for rotavirus and stool testing. Many hospitals saw a decrease in LOS, with only 3 noting an increased revisit rate. Reductions in cost per case over time were most associated with decreases in imaging, laboratory testing, and LOS. CONCLUSIONS: Significant variation in resource use for children hospitalized with AGE coupled with high use of resources discouraged in AGE guidelines highlights potential opportunities to improve resource use that may be addressed in future AGE guidelines and quality improvement initiatives.

OBJECTIVE Management of febrile infants 60 days and younger for suspected serious infection varies widely. Clinical practice guidelines (CPGs) are intended to improve clinician adherence to evidence-based practices. In 2011, a CPG for managing febrile infants was implemented in an urban children's hospital with simultaneous release of an electronic order set and algorithm to guide clinician decisions for managing infants for suspected serious bacterial infection. The objective of the present study was to determine the association of CPG implementation with order set use, clinical practices, and clinical outcomes. METHODS Records of febrile infants 60 days and younger from February 1, 2009, to January 31, 2013, were retrospectively reviewed. Clinical documentation, order set use, clinical management practices, and outcomes were compared pre-CPG and post-CPG release. RESULTS In total, 1037 infants pre-CPG and 930 infants post-CPG implementation were identified. After CPG release, more infants 29 to 60 days old underwent lumbar puncture (56% vs 62%, P = 0.02). Overall antibiotic use and duration of antibiotic use decreased for infants 29 to 60 days (57% vs 51%, P = 0.02). Blood culture and urine culture obtainment remained unchanged for older infants. Diagnosed infections, hospital readmissions, and length of stay were unchanged. Electronic order sets were used in 80% of patient encounters. CONCLUSIONS Antibiotic use and lumbar puncture performance modestly changed in accordance with CPG recommendations provided in the electronic order set and algorithm, suggesting that the presence of embedded prompts may affect clinician decision-making. Our results highlight the potential usefulness of these decision aids to improve adherence to CPG recommendations.

ImportanceTo our knowledge, there are no published randomized clinical trials of recruitment strategies. Rigorously evaluated successful recruitment strategies for children are needed.ObjectiveTo evaluate the feasibility of 2 recruitment methods for enrolling rural children through primary care clinics to assess whether either or both methods are sufficiently effective for enrolling participants into a clinical trial of a behavioral telehealth intervention for children with overweight or obesity.Design, Setting, and ParticipantsThis cluster-randomized clinical trial of 2 recruitment methods was conducted at 4 primary care clinics in 4 separate states. Each clinic used both recruitment methods in random order. Clinic eligibility criteria included at least 40% pediatric patients with Medicaid coverage and at least 100 potential participants. Eligibility criteria for children included a rural home address, age 6 to 11 years, and body mass index at or above the 85th percentile. Recruitment began February 3, 2020, and randomization of participants occurred on August 17, 2020. Data were analyzed from October 3, 2021, to April 21, 2022.InterventionsTwo recruitment methods were assessed: the active method, for which a list of potential participants seen within the past year at each clinic was generated through the electronic health record and consecutively approached by research staff based on visit date to the clinic, and the traditional method, for which recruitment included posters, flyers, social media, and press release. Clinics were randomized to the order in which the 2 methods were implemented in 4-week periods, followed by a 4-week catch-up period using the method found most effective in previous periods.Main Outcomes and MeasuresFor each recruitment method, the number and proportion of randomized children among those who were approached was calculated.ResultsA total of 104 participants were randomized (58 girls [55.8%]; mean age, 9.3 [95% CI, 9.0-9.6] years). Using the active method, 535 child-parent dyads were approached and 99 (18.5% [95% CI, 15.3%-22.1%]) were randomized. Using the traditional method, 23 caregivers expressed interest, and 5 (21.7% [95% CI, 7.5%-43.7%]) were randomized. All sites reached full enrollment using the active method and no sites achieved full enrollment using the traditional method. Mean time to full enrollment was 26.3 (range, 21.0-31.0) days.Conclusions and RelevanceThis study supports the use of the active approach with local primary care clinics to recruit children with overweight and obesity from rural communities into clinical trials.Trial RegistrationClinicalTrials.gov Identifier: NCT04142034

BACKGROUND AND OBJECTIVES Effective communication between inpatient and primary care providers (PCPs) is important for safe transition of care for hospitalized patients. In 2017, communication with PCPs was prioritized for the pediatric hospital medicine division. Our primary aim was to improve documented attempted communication with PCPs within 72 hours of discharge from 41% to at least 60% by January 1, 2018, and maintain this performance through 2019. METHODS This study included all inpatient encounters discharged by a pediatric hospital medicine provider from March 2017 to April 2020. An electronic health record phrase debuted March 2017. Successful documentation was defined as any attempt to contact the PCP, regardless of whether actual communication occurred. Group and individual audit and feedback occurred in July 2017 to April 2020. Provider communication was financially incentivized in July 2018 to June 2019. An annotated P-chart for the proportion of encounters with documented PCP communication occurring within 72 hours was established. Special-cause variation was determined by using Shewhart rules. RESULTS The mean proportion of encounters with documented PCP communication increased from 41% at baseline (March 2017 through July 2017) to 60% in August 2017 and 66% in December 2017. After the financial incentive was removed in July 2019, documentation decreased to 54%. Phone calls with clinic staff were the most common communication method (40% to 71%). Direct conversations with the PCP occurred rarely (0% to 3%). CONCLUSIONS Even when coupled with audit and feedback with EHR interventions, our work suggests that shifting to external financial motivation may hinder sustainability of behavior change to improve attempted documented PCP communication.

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children’s participation in state-of-the-art clinical trials.

OBJECTIVE: To evaluate the individual-level impact of an electronic clinical support (ECDS) tool, PedsGuide, on febrile infant clinical decision making and cognitive load. METHODS: A counterbalanced, prospective, cross-over simulation study was performed amongst attending and trainee physicians. Participants performed simulated febrile infant cases with use of PedsGuide and with standard reference text. Cognitive load was assessed using the NASA-Task Load Index (NASA-TLX) which determines mental, physical, temporal demand, effort, frustration, and performance. Usability was assessed with the System Usability Scale (SUS). Scores on cases and NASA-TLX scores were compared between condition states. RESULTS: A total of 32 participants completed the study. Scores on febrile infant cases using PedsGuide were higher compared to standard reference text (89% vs. 72%, p=0.001). NASA-TLX scores were lower (i.e. more optimal) with use of PedsGuide vs. control (mental 6.34 vs. 11.8, p

The role of the urinalysis (UA) in the management of young, febrile infants is controversial. To assess how frequently infants are treated for urinary tract infection (UTI) despite having normal UA values and to compare the characteristics of infants treated for UTI who have positive versus negative UAs, we reviewed 20,570 wellappearing febrile infants 7-60 days of age evaluated at 124 hospitals in the United States who were included in a national quality improvement project. Of 19,922 infants without bacteremia and meningitis, 2,407 (12.1%) were treated for UTI, of whom 2,298 (95.5%) had an initial UA performed. UAs were negative in 337/2,298 (14.7%) treated subjects. The proportion of infants treated for UTI with negative UAs ranged from 0%-35% across hospitals. UA-negative subjects were more likely to have respiratory symptoms and less likely to have abnormal inflammatory markers than UA+ subjects, indicating that they are mounting less of an inflammatory response to their underlying illness and/or might have contaminated specimens or asymptomatic bacteriuria.

BackgroundClinical trials are the gold standard for assessing the effectiveness and safety of treatments. The objective of the current study was to assess provider opinions regarding implementing pediatric clinical trials in various practice settings across Kansas. MethodsThe study was completed within the Sunflower Pediatric Clinical Trials Research Extension (SPeCTRE), an affiliate of the IDeA States Pediatric Clinical Trials Network (ISPCTN). A cross-sectional, 36-item survey was administered to a state-wide convenience sample targeting health care providers and clinic staff. ResultsA total of 119 health care providers and clinic staff completed surveys; 31% were physicians. Physicians were more likely than other clinic staff to have experience with clinical trials (correlation coefficient [CC]=0.270, p=0.004). When compared to urban respondents, rural providers were less supportive of recruitment for clinical trials in their practices (CC=-0.251, p=0.008) and more likely to feel comfortable referring patients for clinical trials involving treatments that their insurance did not cover (CC=0.302, p=0.001).ConclusionA range of rural and urban health care professionals support the performance of pediatric clinical trials but identify several barriers as well. These results will support future pediatric clinical trials across the country including Kansas.TRIAL REGISTRATION: NA

Objective To determine utilization and impacts of a mobile electronic clinical decision support (mECDS) on pediatric asthma care quality in emergency department and inpatient settings. Methods We conducted an observational study of a mECDS tool that was deployed as part of a multi-dimensional, national quality improvement (QI) project focused on pediatric asthma. We quantified mECDS utilization using cumulative screen views over the study period in the city in which each participating site was located. We determined associations between mECDS utilization and pediatric asthma quality metrics using mixed-effect logistic regression models (adjusted for time, site characteristics, site-level QI project engagement, and patient characteristics). Results The tool was offered to clinicians at 75 sites and used on 286 devices; cumulative screen views were 4191. Children’s hospitals and sites with greater QI project engagement had higher cumulative mECDS utilization. Cumulative mECDS utilization was associated with significantly reduced odds of hospital admission (OR: 0.95, 95% CI: 0.92–0.98) and higher odds of caregiver referral to smoking cessation resources (OR: 1.08, 95% CI: 1.01–1.16). Discussion We linked mECDS utilization to clinical outcomes using a national sample and controlling for important confounders (secular trends, patient case mix, and concomitant QI efforts). We found mECDS utilization was associated with improvements in multiple measures of pediatric asthma care quality. Conclusion mECDS has the potential to overcome barriers to dissemination and improve care on a broad scale. Important areas of future work include improving mECDS uptake/utilization, linking clinicians’ mECDS usage to clinical practice, and studying mECDS’s impacts on other common pediatric conditions.

A significant percentage of clinical trials fail due to poor recruitment. Despite this, few studies exist to evaluate clinical trial recruitment strategies using a randomized approach in any population, and none exist to test recruitment strategies for trials involving children or rural populations. For clinical trials focused on weight control, evaluating retention and dose are extremely important, as poor retention can lead to biased samples and existing research shows that dose (i.e. contact hours) is directly related to patient outcome. Finally, adequacy of blinding of assessment teams is rarely reported in pediatric trials, and unblinded staff may be more likely to inadvertently bias findings. Therefore, in this feasibility trial we aim to use rigorous clinical trial methodology to assess the effectiveness of two different recruitment strategies, as well as test retention, dose, and blinding. Specifically, we describe the rationale, design, and planned implementation of a feasibility study of a rural pediatric obesity treatment trial that will be implemented in four medical clinics in four states affiliated with the Environmental influences on Child Health Outcomes IDeA States Pediatric Clinical Trials Network (ECHO ISPCTN). The primary objective is to assess recruitment rate for consecutive recruitment (approaching recently seen eligible patients in consecutive order by date seen) compared to traditional recruitment (such as posters, flyers, tear-offs), as well as to assess retention, dose, and blinding. If successful, this trial will support the implementation of a large multi-state trial directed at addressing obesity in rural children and their families recruited from their primary care clinics. Registered with ClinicalTrials.gov NCT ID NCT04142034 .

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 three 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.

OBJECTIVES:Examine the degree of seasonal variation in nonrecommended resource use for bronchiolitis management subsequent to publication of the American Academy of Pediatrics (AAP) 2014 guidelines.METHODS:We performed a multicenter retrospective cohort study using the Pediatric Health Information System database, examining patients aged 1 to 24 months, diagnosed with bronchiolitis between November 2015 and November 2018. Exclusions included presence of a complex chronic condition, admission to the PICU, hospital stay >10 days, or readmission. Primary outcomes were use rates of viral testing, complete blood count, blood culture, chest radiography, antibiotics, albuterol, and systemic steroids. Each hospital’s monthly bronchiolitis census was aggregated into hospital bronchiolitis census quartiles. Mixed-effect logistic regression was performed, comparing the primary outcomes between bronchiolitis census quartiles, adjusting for patient age, race, insurance, hospitalization status, bacterial coinfection, time since publication of latest AAP bronchiolitis guidelines, and clustering by site.RESULTS:In total, 196 902 bronchiolitis patient encounters across 50 US hospitals were analyzed. All hospitals followed a similar census pattern, with peaks during winter months and nadirs during summer months. Chest radiography, albuterol, and systemic steroid use were found to significantly increase in lower bronchiolitis census quartiles, whereas rates of viral testing significantly decreased. No significant variation was found for complete blood count testing, blood culture testing, or antibiotic use. Overall adherence with AAP guidelines increased over time.CONCLUSIONS:Resource use for patients with bronchiolitis varied significantly across hospital bronchiolitis census quartiles despite adjusting for potential known confounders. There remains a need for greater standardization of bronchiolitis management.

Background: Electronic clinical decision support (ECDS) tools are often developed within quality improvement (QI) projects to increase adherence with the latest clinical practice guidelines (CPGs).However, scalability and sustainability of ECDS beyond the time and location of their associated project are very limited. Deploying ECDS using a mobile app (mECDS) has shown the potential to be a viable method of overcoming these limitations. However, it is unclear what pattern the spread of uptake and use of such a tool might follow.Methods: In 2016, our team released a freely available mECDS as part of a national multi-site project entitled Reducing Variation in Infant Sepsis Evaluation (REVISE). For this study, we evaluated trends in weekly mECDS usage measures defined as 1) REVISE metric related screen views (MetricHits), 2) unique designated market areas (DMA) where the mECDS was used (Unique DMAs), 3) density of use or MetricHits/Unique DMAs (HitsPerDMA). Linear regressions were performed to examine the app usage trends measures across three time periods (during REVISE, 1-year post, 2-year post). Separate regression analyses were performed among DMAs that contained a REVISE site and those that did not. The number of REVISE sites in the DMA, the number of children’s hospitals in the DMA, DMA population, and season were also evaluated as confounding factors.Results: Strong growth in the number of unique DMAs and MetricHits occurred during the period of 1-year post the REVISE project. The overall usage continued to be relatively stable during the period of 2-years post. HitsPerDMA had stronger growth in DMAs with a REVISE site than those without. MetricHits were higher in DMAs with a larger population, more REVISE sites, and more children’s hospitals. There were also more MetricHits in the summer than in the winter months. Conclusions: Both temporal and spatial increases in mECDS app usage were found as evidence of a contagion method of spread. Other confounding factors may also play a role in app reach, adoption, and sustainability. Further research is needed to determine the factors driving passive diffusion and its impact on clinical practice and patient outcomes.

Effective communication of when students should attend school, stay home, and return to school is a critical function of SARS-CoV-2 symptom screening mobile intervention. We developed two visualization aids (Alternative Aid A or B, or text only) to support families in determining when their child can return to school in-person. We obtained subjective feedback from 23 potential users. Seventy-four percent (17/23) of users rated Visual A as “Easy” or “Very Easy.” Visual B was rated by 57% (13/23) of users as “Not Easy/Not Hard.” Sixty-five percent (15/23) of users rated the text description as “Easy” or “Very Easy.” Visual A was reported as their first choice in determining when a child can return to school. A calculator may be preferential to users to determine return-to-school date. Future research should evaluate the impact of the decision support visual on user behavior with determining the return-to-school date.

The Rochester criteria were developed to identify febrile infants aged 60 days or younger at low-risk of bacterial infection and do not include cerebrospinal fluid (CSF) testing. Prior studies have not specifically assessed criteria performance for bacteremia and bacterial meningitis (invasive bacterial infection). Our objective was to determine the sensitivity of the Rochester criteria for detection of invasive bacterial infection.Retrospective cohort study of febrile infants aged 60 days or younger with invasive bacterial infections evaluated at 8 pediatric emergency departments from July 1, 2012, to June 30, 2014. Potential cases were identified from the Pediatric Health Information System using International Classification of Diseases, Ninth Revision diagnosis codes for bacteremia, meningitis, urinary tract infection, and fever. Medical record review was then performed to confirm presence of an invasive bacterial infection and to evaluate the Rochester criteria: medical history, symptoms or ill appearance, results of urinalysis, complete blood count, CSF testing (if obtained), and blood, urine, and CSF culture. An invasive bacterial infection was defined as growth of pathogenic bacteria from blood or CSF culture.Among 82 febrile infants aged 60 days or younger with invasive bacterial infection, the sensitivity of the Rochester criteria were 92.7% (95% confidence interval [CI], 84.9%-96.6%) overall, 91.7% (95% CI, 80.5%-96.7%) for neonates 28 days or younger, and 94.1% (95% CI, 80.9%-98.4%) for infants aged 29 to 60 days old. Six infants with bacteremia, including 1 neonate with bacterial meningitis, met low-risk criteria.The Rochester criteria identified 92% of infants aged 60 days or younger with invasive bacterial infection. However, 1 neonate 28 days or younger with meningitis was classified as low-risk.

EP67 is a second-generation, human C5a-derived decapeptide agonist of C5a Receptor 1 (C5aR1/CD88) that selectively activates mononuclear phagocytes over neutrophils to potentiate protective innate and adaptive immune responses while potentially minimizing neutrophil-mediated toxicity. Pro(7) and N-methyl-Leu(8) (Me-Leu(8)) amino acid residues within EP67 likely induce backbone structural changes that increase potency and selective activation of mononuclear phagocytes over neutrophils vs. first-generation EP54. Low coupling efficiency between Pro(7) and Me-Leu(8) and challenging purification by HPLC, however, greatly increase scale-up costs of EP67 for clinical use. Thus, the goal of this study was to determine whether replacing Pro(7) and/or Me-Leu(8) with large-scale amenable amino acid residues predicted to induce similar structural changes (cyclohexylalanine(7) and/or leucine(8)) sufficiently preserves EP67 activity in primary human mononuclear phagocytes and neutrophils. We found that, depending on the secreted cytokine and mononuclear phagocyte, EP67 analogs had (i.) similar or lower (29 to 39%) potency and similar, increased (9.5 to 45%), or decreased (5 to 23%) efficacy for IL-6 and TNF-α secretion from mononuclear phagocytes and (ii.) similar potency and similar or decreased (21% to 24%) efficacy for myeloperoxidase secretion from human neutrophils without affecting selective activation of human mononuclear phagocytes. Thus, replacing Pro(7) and/or Me-Leu(8) with large-scale amenable amino acid residues predicted to induce similar structural changes is a suitable strategy to overcome scale-up challenges with EP67.

Objective To determine clinical, demographic, and hospital factors associated with inhaled bronchodilator (IB) use in infants with bronchopulmonary dysplasia (BPD) and specifically severe BPD. Study design Retrospective multicenter cohort study of 4986 infants born

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.

The aim of this study was to describe the variation in antibiotic prescribing practices for uncomplicated community-acquired pneumonia across the continuum of care for hospitalized pediatric patients to better inform future efforts at standardizing antibiotic therapy throughout a single hospitalization. This is a retrospective cohort study involving 4 hospitals caring for children aged 3 months to 18 years, hospitalized between January 1, 2011, and December 31, 2012, with diagnosis of uncomplicated pneumonia and without complex chronic medical conditions. Data collected include antibiotics prescribed before hospitalization, at the emergency department (ED) encounter, during hospitalization, and at hospital discharge. Six hundred nine children met inclusion criteria, with a mean age of 5.3 years and median length of stay of 2 days. Emergency department providers prescribed narrow-spectrum therapy 27% of the time, whereas discharging providers prescribed narrow-spectrum therapy 56% of the time. Third- and fourth-generation cephalosporins were less often prescribed in the preadmission setting and at discharge but were more often prescribed in the ED and inpatient setting. There was an association between inpatient prescription of broad-spectrum antibiotics when a blood culture was obtained, when broad-spectrum antibiotics were prescribed in the ED, and with increasing length of stay. Broad-spectrum antibiotic therapy for community-acquired pneumonia, especially third- and fourth-generation cephalosporins, often originates in the ED. When initiated in this setting, it is likely to be continued in the inpatient setting.

OBJECTIVES: To describe variation in the care of children hospitalized with orbital cellulitis and to determine associations with length of stay (LOS), emergency department (ED) revisits, and hospital readmissions. METHODS: By using the Pediatric Health Information System, we performed a multicenter, retrospective study of children aged 2 months to 18 years with a primary International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for orbital cellulitis from 2007 to 2014. We assessed hospital-level variation in the use of diagnostic tests, corticosteroids, and antibiotics individually and in aggregate for association with outcomes (LOS, ED revisits, readmissions) after risk-adjusting for important clinical and demographic factors. RESULTS: A total of 1828 children met inclusion criteria. Complete blood cell counts (median [interquartile range]: 81.8% [66.7–89.6]), C-reactive protein levels (57.1% [22.2–84.0]), blood cultures (57.9% [48.9–63.6]), and computed tomography imaging (74.7% [66.7–81.0]) were the most frequently performed diagnostic tests, with significant variation observed across hospitals (all P < .001). Corticosteroids were used in 29.2% of children (interquartile range: 18.4–37.5). There was significant variation in antibiotic exposure across hospitals (P < .001). Increased total diagnostic test usage was associated with increased LOS (P = .044), but not with 30-day ED revisits (P = .176) or readmissions (P = .403). CONCLUSIONS: Children hospitalized with orbital cellulitis experience wide variation in clinical management. Increased hospital-level usage is associated with increased LOS. Our findings highlight a critical need to identify treatment strategies that optimize resource use and outcomes for children hospitalized with orbital cellulitis.

Background FilmArray Meningitis/Encephalitis Panel (ME panel) has a 11% false positive and 2.2% false negative rate compared to conventional testing. We aim to describe characteristics, treatment decisions and outcomes in pediatric patients with discordant results between ME panel and conventional testing. Methods We conducted a multisite (n=4) retrospective review of patients < 18 years with positive cerebrospinal fluid (CSF) results by ME panel or conventional testing (CSF culture, Herpes Simplex Virus [HSV] and enterovirus [EV] PCR) from time of local ME panel implementation to February 2019. We excluded CSF obtained for non-infectious reasons. Demographic and clinical data were extracted from electronic medical records. Comparison between concordant and discordant results were made using Mann-Whitney test for continuous and Fisher’s exact test for categorical variables. Results A total of 355 patients had at least 1 positive result. Baseline characteristics and pathogens are shown in Table 1 and 2. Of the 53 bacterial pathogens identifiable by ME panel, 31 (58%) had discordant results – 29 positive by ME panel only and 2 by culture only (both E.coli). Patients with bacterial pathogens identified by ME panel only had lower CSF WBC and protein but higher CSF glucose (Table 3). Five patients with bacteria identified on ME panel only were not treated as meningitis given lack of pleocytosis, no antibiotic pretreatment and negative repeat cultures. Of these, 4 recovered without complications but one had hypoxic encephalopathy. Two patients had HSV noted in ME panel but individual PCR negative. The first was a 13-day-old with typical skin lesions and positive surface swab. The other was a 6-day old only with CSF pleocytosis. Both had abnormal neuroimaging and were treated as true cases. Of 24 who had both EV PCR and ME panel, 7 were positive by ME panel only and 3 by PCR only. Table 1: Baseline Characteristics of the Study Population Table 2: Pathogens identified via CSF Culture, ME panel or Conventional PCR Table 3: Characteristics of Discordant Results for Bacterial Pathogens Tested in ME panel Conclusion More than half of bacterial pathogens identified by ME panel did not have a corresponding positive CSF culture. No difference was noted by antibiotic pretreatment. Treatment decisions based on positive ME panel should be made in the appropriate clinical context. Likewise, a negative ME panel does not rule out infection especially when atypical organisms are suspected. Disclosures Krow Ampofo, MBChB, Merck (Grant/Research Support)

Background The ability to quickly recognize and diagnose meningitis is a critical component in its management. The use of the FilmArray Meningitis/Encephalitis (ME) panel has made pathogen identification easier and faster. Although literature exists regarding clinical and laboratory data in patients with bacterial meningitis, less is known about the characteristics of viral meningitis caused by viruses detected by the ME panel This study aims to compare differences in clinical and laboratory characteristics between viral and bacterial meningitis identified by the ME panel. Methods We conducted a multisite retrospective review of pediatric patients with cerebral spinal fluid (CSF) positive for viral or bacterial organisms from January 2015 - February 2019. Demographic, clinical, and lab characteristics were extracted from medical records. Frequencies and percentages are used to explain descriptive data. Fisher’s exact test was used for categorical data. The Mann-Whitney test was used for continuous data. Results Four hundred thirty-eight patients were included in the analysis with baseline characteristics found in Table 1. Among these, 345 and 93 patients tested positive for viral and bacterial organisms respectively. Viral organisms identified are presented in Figure 1. Patients with bacterial organisms were more likely to have a history of prematurity, a prior neurosurgical procedure, neurological symptoms at presentation, neurological complications, and death within 30 days of admission. The median serum white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin, CSF WBC count, CSF neutrophil percentage, and CSF protein were significantly higher in patients with bacterial organisms compared to viral organisms (Table 2). Table 1: Baseline Characteristics of the Study Population Figure 1: Viral organisms identified. Table 2: Comparison of Laboratory Data by CSF Pathogen Group Conclusion Patients positive for bacterial meningitis were more likely to have higher markers of infection compared to patients with viral organisms. Patients with bacterial organisms were also more likely to have death within 30 days of admission and neurological symptoms and subsequent complications, although the small number of patients limits these conclusions. These findings may help clinicians utilize clinical and laboratory data in conjunction with a ME panel result. Disclosures All Authors: No reported disclosures

Health care providers’ adherence to guidelines declines over time, and feasible strategies for sustaining adherence have not yet been identified. We assessed the long-term feasibility of various strategies for sustaining guideline adherence and described factors influencing their use. We conducted a cross-sectional survey (N = 104) of physician leaders who participated in a national collaborative to improve care of infants with suspected sepsis. Data were collected on long-term use of strategies to promote guideline adherence (use, perceived effectiveness, and barriers to use). Sixty (58%) participants from diverse hospital settings responded. There were significant declines in use of quality improvement and educational strategies, largely driven by lack of time or staff resources and competing priorities. Electronic strategies (eg, order sets) and hospital policies or guidelines were feasible to continue long-term after the collaborative ended and were perceived as effective. Clinicians and healthcare leaders should consider prioritizing these strategies in their efforts to improve care and outcomes for children in hospital settings.

BACKGROUND:Substantial variability exists in the care of febrile, well-appearing infants. We aimed to assess the impact of a national quality initiative on appropriate hospitalization and length of stay (LOS) in this population.METHODS:The initiative, entitled Reducing Variability in the Infant Sepsis Evaluation (REVISE), was designed to standardize care for well-appearing infants ages 7 to 60 days evaluated for fever without an obvious source. Twelve months of baseline and 12 months of implementation data were collected from emergency departments and inpatient units. Ill-appearing infants and those with comorbid conditions were excluded. Participating sites received change tools, run charts, a mobile application, live webinars, coaching, and a LISTSERV. Analyses were performed via statistical process control charts and interrupted time series regression. The 2 outcome measures were the percentage of hospitalized infants who were evaluated and hospitalized appropriately and the percentage of hospitalized infants who were discharged with an appropriate LOS.RESULTS:In total, 124 hospitals from 38 states provided data on 20 570 infants. The median site improvement in percentages of infants who were evaluated and hospitalized appropriately and in those with appropriate LOS was 5.3% (interquartile range = −2.5% to 13.7%) and 15.5% (interquartile range = 2.9 to 31.3), respectively. Special cause variation toward the target was identified for both measures. There was no change in delayed treatment or missed bacterial infections (slope difference 0.1; 95% confidence interval, −8.3 to 9.1).CONCLUSIONS:Reducing Variability in the Infant Sepsis Evaluation noted improvement in key aspects of febrile infant management. Similar projects may be used to improve care in other clinical conditions.

BACKGROUND AND OBJECTIVES:To determine factors associated with cerebrospinal fluid (CSF) testing in febrile young infants with a positive urinalysis and assess the probability of delayed diagnosis of bacterial meningitis in infants treated for urinary tract infection (UTI) without CSF testing.METHODS:We performed a retrospective cohort study using data from the Reducing Excessive Variability in Infant Sepsis Evaluation quality improvement project. A total of 20 570 well-appearing febrile infants 7 to 60 days old presenting to 124 hospitals from 2015 to 2017 were included. A mixed-effects logistic regression was conducted to determine factors associated with CSF testing. Delayed meningitis was defined as a new diagnosis of bacterial meningitis within 7 days of discharge.RESULTS:Overall, 3572 infants had a positive urinalysis; 2511 (70.3%) underwent CSF testing. There was wide variation by site, with CSF testing rates ranging from 64% to 100% for infants 7 to 30 days old and 10% to 100% for infants 31 to 60 days old. Factors associated with CSF testing included: age 7 to 30 days (adjusted odds ratio [aOR]: 4.6; 95% confidence interval [CI]: 3.8–5.5), abnormal inflammatory markers (aOR: 2.2; 95% CI: 1.8–2.5), and site volume >300 febrile infants per year (aOR: 1.8; 95% CI: 1.2–2.6). Among 505 infants treated for UTI without CSF testing, there were 0 (95% CI: 0%–0.6%) cases of delayed meningitis.CONCLUSIONS:There was wide variation in CSF testing in febrile infants with a positive urinalysis. Among infants treated for UTI without CSF testing (mostly 31 to 60-day-old infants), there were no cases of delayed meningitis within 7 days of discharge, suggesting that routine CSF testing of infants 31 to 60 days old with a positive urinalysis may not be necessary.

Objective Estimate the impact on clinical practice of using a mobile device–based electronic clinical decision support (mECDS) tool within a national standardization project. Materials and Methods An mECDS tool (app) was released as part of a change package to provide febrile infant management guidance to clinicians. App usage was analyzed using 2 measures: metric hits per case (metric-related screen view count divided by site-reported febrile infant cases in each designated market area [DMA] monthly) and cumulative prior metric hits per site (DMA metric hits summed from study month 1 until the month preceding the index, divided by sites in the DMA). For each metric, a mixed logistic regression model was fit to model site performance as a function of app usage. Results An increase of 200 cumulative prior metric hits per site was associated with increased odds of adherence to 3 metrics: appropriate admission (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.18), appropriate length of stay (OR, 1.20; 95% CI, 1.12-1.28), and inappropriate chest x-ray (OR, 0.82; 95% CI, 0.75-0.91). Ten additional metric hits per case were also associated: OR were 1.18 (95% CI, 1.02-1.36), 1.36 (95% CI, 1.14-1.62), and 0.74 (95% CI, 0.62-0.89). Discussion mECDS tools are increasingly being implemented, but their impact on clinical practice is poorly described. To our knowledge, although ecologic in nature, this report is the first to link clinical practice to mECDS use on a national scale and outside of an electronic health record. Conclusions mECDS use was associated with changes in adherence to targeted metrics. Future studies should seek to link mECDS usage more directly to clinical practice and assess other site-level factors.

IMPORTANCE Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. OBJECTIVE To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. INTERVENTIONS Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200mg (n = 588), or placebo (n = 587). MAIN OUTCOMES AND MEASURES The primary outcomewas incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase���polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. RESULTS The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5%vs 15.2%; odds ratio, 0.43 [95%CI, 0.28-0.68]; P < .001; absolute risk difference, ���6.6 [95%CI, ���10.7 to ���2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). CONCLUSIONS AND RELEVANCE Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy.

Antimicrobial resistance is a global threat to human health regardless of age or geography,1 and the most rapidly modifiable cause for antimicrobial resistance is antimicrobial use.2 In the United States, 1287 antibiotic prescriptions are written for every 1000 children 0 to 2 years of age annually, up to half of which are inappropriately prescribed or completely unnecessary.3 Antimicrobial exposure is not benign and may result in far-reaching and lifelong ramifications for child health and development, including risks of adverse drug events,4 Clostridium difficile infection,5 and long-term risks for developing obesity.6 Given the impact of inappropriate antimicrobial use on human health, it is no surprise that antimicrobial stewardship is an emerging focus of national and international health agencies7 and regulatory agencies, such as The Joint Commission.8 In the United States, laws mandating the development and implementation of antimicrobial stewardship programs (ASPs) have already been passed in California and Missouri. As stated in the Missouri law, “each hospital and ambulatory surgical center, excluding mental health facilities, shall establish an antibiotic stewardship program for evaluating the judicious use of antibiotics, especially antibiotics that are the last line of defense against resistant infections.”9 Hospitals that treat both children and adults may face greater challenges to implementing ASPs than freestanding …