Clinical Impact of Multiplex Molecular Diagnostic Testing in Children With Acute Gastroenteritis Presenting to an Emergency Department: A Multicenter Prospective Study.

BACKGROUND: Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. METHODS: We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7-10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion . During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. RESULTS: Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval, .70-.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P = .22). CONCLUSIONS: Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285.

Exploring the association between cognitive activity and symptom resolution following concussion in adolescents aged 11-17 years.

OBJECTIVE: As opposed to postconcussion physical activity, the potential influence of cognitive activity on concussion recovery is not well characterised. This study evaluated the intensity and duration of daily cognitive activity reported by adolescents following concussion and examined the associations between these daily cognitive activities and postconcussion symptom duration. METHODS: This study prospectively enrolled adolescents aged 11-17 years with a physician-confirmed concussion diagnosis within 72 hours of injury from the emergency department and affiliated concussion clinics. Participants were followed daily until symptom resolution or a maximum of 45 days postinjury to record their daily cognitive activity (intensity and duration) and postconcussion symptom scores. RESULTS: Participants (n=83) sustained their concussion mostly during sports (84%), had a mean age of 14.2 years, and were primarily male (65%) and white (72%). Participants reported an average of 191 (SD=148), 166 (SD=151) and 38 (SD=61) minutes of low-intensity, moderate-intensity and high-intensity daily cognitive activity postconcussion while still being symptomatic. Every 10 standardised minutes per hour increase in moderate-intensity or high-intensity cognitive activities postconcussion was associated with a 22% greater rate of symptom resolution (adjusted hazard ratio (aHR) 1.22, 95% CI 1.01 to 1.47). Additionally, each extra day's delay in returning to school postconcussion was associated with an 8% lower rate of symptom resolution (aHR 0.92, 95% CI 0.85 to 0.99). CONCLUSION: In adolescents with concussion, more moderate-high intensity cognitive activity is associated with faster symptom resolution, and a delayed return to school is associated with slower symptom resolution. However, these relationships may be bidirectional and do not necessarily imply causality. Randomised controlled trials are needed to determine if exposure to early cognitive activity can promote concussion recovery in adolescents.

Longitudinal trajectories of posttraumatic headache after pediatric mild traumatic brain injury.

OBJECTIVE: This prospective, longitudinal cohort study examined the trajectory, classification, and features of posttraumatic headache after pediatric mild traumatic brain injury. METHODS: Children (N = 213; ages 8.00 to 16.99 years) were recruited from two pediatric emergency departments <24 hours of sustaining a mild traumatic brain injury or mild orthopedic injury. At 10 days, three months, and six months postinjury, parents completed a standardized questionnaire that was used to classify premorbid and posttraumatic headache as migraine, tension-type headache, or not otherwise classified. Multilevel mixed effects models were used to examine posttraumatic headache rate, severity, frequency, and duration in relation to group, time postinjury, and premorbid headache, controlling for age, sex, and site. RESULTS: PTH risk was greater after mild traumatic brain injury than mild orthopedic injury at 10 days (odds ratio = 197.41, p < .001) and three months postinjury (odds ratio = 3.50, p = .030), especially in children without premorbid headache. Posttraumatic headache was more frequent after mild traumatic brain injury than mild orthopedic injury, ß (95% confidence interval) = 0.80 (0.05, 1.55). Groups did not differ in other examined headache features and classification any time postinjury. CONCLUSIONS: Posttraumatic headache risk increases after mild traumatic brain injury relative to mild orthopedic injury for approximately three months postinjury, but is not clearly associated with a distinct phenotype.

Intranasal fentanyl and discharge from the emergency department among children with sickle cell disease and vaso-occlusive pain: A multicenter pediatric emergency medicine perspective.

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n = 75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, p < .001). The rapid onset of action and ease of delivery without intravenous access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with SCD presenting with VOE in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study.

Radiographic pneumonia in young febrile infants presenting to the emergency department: secondary analysis of a prospective cohort study.

OBJECTIVE: The lack of evidence-based criteria to guide chest radiograph (CXR) use in young febrile infants results in variation in its use with resultant suboptimal quality of care. We sought to describe the features associated with radiographic pneumonias in young febrile infants. STUDY DESIGN: Secondary analysis of a prospective cohort study in 18 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Febrile (≥38°C) infants aged ≤60 days who received CXRs were included. CXR reports were categorised as 'no', 'possible' or 'definite' pneumonia. We compared demographics, clinical signs and laboratory tests among infants with and without pneumonias. RESULTS: Of 2612 infants, 568 (21.7%) had CXRs performed; 19 (3.3%) had definite and 34 (6%) had possible pneumonias. Patients with definite (4/19, 21.1%) or possible (11/34, 32.4%) pneumonias more frequently presented with respiratory distress compared with those without (77/515, 15.0%) pneumonias (adjusted OR 2.17; 95% CI 1.04 to 4.51). There were no differences in temperature or HR in infants with and without radiographic pneumonias. The median serum procalcitonin (PCT) level was higher in the definite (0.7 ng/mL (IQR 0.1, 1.5)) vs no pneumonia (0.1 ng/mL (IQR 0.1, 0.3)) groups, as was the median absolute neutrophil count (ANC) (definite, 5.8 K/mcL (IQR 3.9, 6.9) vs no pneumonia, 3.1 K/mcL (IQR 1.9, 5.3)). No infants with pneumonia had bacteraemia. Viral detection was frequent (no pneumonia (309/422, 73.2%), definite pneumonia (11/16, 68.8%), possible pneumonia (25/29, 86.2%)). Respiratory syncytial virus was the predominant pathogen in the pneumonia groups and rhinovirus in infants without pneumonias. CONCLUSIONS: Radiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonias, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias.

Nasopharyngeal Codetection of Haemophilus influenzae and Streptococcus pneumoniae Shapes Respiratory Syncytial Virus Disease Outcomes in Children.

BACKGROUND: The role of nasopharyngeal bacteria in respiratory syncytial virus (RSV) disease has been underestimated. We measured the frequency and burden of respiratory bacteria in the upper respiratory tract of infants with RSV infection over 7 respiratory seasons, and their impact on clinical outcomes. METHODS: Children <2 years old with mild (outpatients, n=115) or severe (inpatients, n=566) RSV infection, and matched healthy controls (n=161) were enrolled. Nasopharyngeal samples were obtained for RSV, Streptococcus pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, and Haemophilus influenzae detection and quantitation by PCR. Multivariable models were constructed to identify variables predictive of severe disease. RESULTS: S. pneumoniae, H. influenzae, and M. catarrhalis, but not S. aureus, were detected more frequently in RSV-infected children (84%) than healthy controls (46%; P<.001). Detection of S. pneumoniae and/or H. influenzae was associated with fever, more frequent antibiotic treatment, worse radiologic findings, and higher neutrophil counts (P<.01). In adjusted analyses, S. pneumoniae/H. influenzae codetection was independentlyassociated with greater odds of hospitalization, higher disease severity scores, need for supplemental oxygen, and longer hospitalization. CONCLUSIONS: Nasopharyngeal codetection of S. pneumoniae and H. influenzae in infants with RSV infection is associated with increased disease severity.

Novel urine biomarkers to distinguish UTI from culture-negative pyuria.

BACKGROUND: Emergency departments (EDs) often rely on urinalysis (UA) to rapidly identify urinary tract infections (UTIs) in children. However, the suboptimal test characteristics of UA can lead to false-positive results. Novel urinary biomarkers may increase the diagnostic precision of UA. In this study, we compared the concentrations of 6 pre-selected proteins: BH3 interacting domain death agonist (BID), B-cell lymphoma 6 protein, ras GTPase-activating protein 1, cathepsin S (CTSS), 3-hydroxyanthranilate 3,4-dioxygenase, and transgelin-2. METHODS: In a pediatric ED, we prospectively enrolled 167 children with UA and urine culture collected. Pyuria was defined as either ≥ 5 white blood cells per high-power field on microscopy or positive leukocyte esterase (LE). The urine culture was considered positive if it yielded ≥ 50,000 colony-forming units per milliliter of any single urinary pathogen. Urine protein levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine. RESULTS: BID was significantly higher in the UTI group compared to the culture-negative pyuria group with a mean ratio of 1.42 (95% confidence interval (CI), 1.15, 1.76) when uncorrected for creatinine concentration. When corrected for creatinine concentration, CTSS was significantly elevated in the UTI group compared to the culture-negative pyuria group with a mean ratio of 2.11 (95% CI, 1.39, 3.21). CONCLUSIONS: BID and CTSS concentrations were elevated in the urine of children with UTI compared to those with culture-negative pyuria. These proteins deserve further research into their utility to serve as novel biomarkers for UTI.

Adolescent alcohol use predicts cannabis use over a three year follow-up period.

Background: Alcohol and cannabis use frequently co-occur, which can result in problems from social and academic impairment to dependence (i.e., alcohol use disorder [AUD] and/or cannabis use disorder [CUD]). The Emergency Department (ED) is an excellent site to identify adolescents with alcohol misuse, conduct a brief intervention, and refer to treatment; however, given time constraints, alcohol use may be the only substance assessed due to its common role in unintentional injury. The current study, a secondary data analysis, assessed the relationship between adolescent alcohol and cannabis use by examining the National Institute of Alcohol Abuse and Alcoholism (NIAAA) two question screen's (2QS) ability to predict future CUD at one, two, and three years post-ED visit. Methods: At baseline, data was collected via tablet self-report surveys from medically and behaviorally stable adolescents 12-17 years old (n = 1,689) treated in 16 pediatric EDs for non-life-threatening injury, illness, or mental health condition. Follow-up surveys were completed via telephone or web-based survey. Logistic regression compared CUD diagnosis odds at one, two, or three-year follow-up between levels constituting a single-level change in baseline risk categorization on the NIAAA 2QS (nondrinker versus low-risk, low- versus moderate-risk, moderate- versus high-risk). Receiver operating characteristic curve methods examined the predictive ability of the baseline NIAAA 2QS cut points for CUD at one, two, or three-year follow-up. Results: Adolescents with low alcohol risk had significantly higher rates of CUD versus nondrinkers (OR range: 1.94-2.76, p < .0001). For low and moderate alcohol risk, there was no difference in CUD rates (OR range: 1.00-1.08). CUD rates were higher in adolescents with high alcohol risk versus moderate risk (OR range: 2.39-4.81, p < .05). Conclusions: Even low levels of baseline alcohol use are associated with risk for a later CUD. The NIAAA 2QS is an appropriate assessment measure to gauge risk for future cannabis use.

Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments.

OBJECTIVE: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. STUDY DESIGN: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. RESULTS: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%. CONCLUSIONS: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.

Association of Self-Paced Physical and Cognitive Activities Across the First Week Postconcussion With Symptom Resolution in Youth.

OBJECTIVE: To examine the association of objectively measured, self-paced physical and cognitive activities across the first week postconcussion with symptom resolution in youth. SETTING: Emergency department or concussion clinics. PARTICIPANTS: Youth aged 11 to 17 years with physician-confirmed concussion. DESIGN: Prospective cohort with repeated measures. MAIN MEASURES: Days from injury to symptom resolution, based on daily ratings by youth on the Post-Concussive Symptom Scale. Physical and cognitive activities were assessed using an ActiGraph and a Narrative Clip, respectively. RESULTS: A total of 83 youth participants were included (n = 54 [65%] males; mean age = 14.2 years, SD = 1.9). While self-paced daily physical and cognitive activities increased across the first week postinjury, daily postconcussion symptoms decreased. Increased daily step count was associated with an increased likelihood of early symptom resolution (hazard ratio [HR] = 1.17; 95% confidence interval [CI], 1.02-1.34). However, this association was not statistically significant after adjusting for acute postconcussion symptoms and other covariates. Greater school attendance time was associated with earlier symptom resolution (adjusted HR = 1.14; 95% CI, 1.02-1.27). CONCLUSION: Self-paced physical and cognitive activities across the first week postinjury alone neither hastened nor prolonged concussion recovery. Youth with concussion may have some latitude to determine their activity levels.

Normative and Psychometric Characteristics of the Health and Behavior Inventory Among Children With Mild Orthopedic Injury Presenting to the Emergency Department: Implications for Assessing Postconcussive Symptoms Using the Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5).

OBJECTIVE: The study sought to present normative and psychometric data and reliable change formulas for the Health and Behavior Inventory (HBI), a postconcussive symptom rating scale embedded in the Child Sport Concussion Assessment Tool 5th edition (Child SCAT5). DESIGN: Prospective cohort study with longitudinal follow-up. SETTING: Pediatric emergency departments (EDs). PARTICIPANTS: As part of 3 studies conducted in the United States and Canada between 2001 and 2019, 450 children aged 8 to 16 years with mild orthopedic injuries were recruited during ED visits and assessed postacutely (M = 9.38 days, SD = 3.31) and 1 month and 3 months postinjury. Independent variables were rater (child vs parent), sex, and age at injury. MAIN OUTCOME MEASURE: HBI ratings. METHODS: Children and parents rated children's symptoms at each time point; parents also rated children's preinjury symptoms retrospectively. Normative data (mean, SD, skewness, kurtosis, and percentiles) were computed for child and parent ratings. Internal consistency was assessed using Cronbach alpha (α), and test-retest reliability and interrater agreement were assessed with intraclass correlations (ICCs). Reliable change formulas were computed using linear regression and mixed models. RESULTS: HBI ratings were positively skewed. Mean ratings and percentiles were stable over time. Child and parent ratings demonstrated good-to-excellent internal consistency (α 0.76-0.94) and moderate-to-good test-retest reliability (ICC 0.51-0.76 between adjacent assessments). However, parent-child agreement was poor to moderate (ICC 0.31-0.69). CONCLUSIONS: The HBI demonstrates acceptable normative and psychometric characteristics. Modest parent-child agreement highlights the importance of multiple informants when assessing postconcussive symptoms. The results will facilitate the use of the HBI in research and clinical practice.

Using Dry-Erase Boards to Share Information in a Pediatric Emergency Department to Improve Family Experience of Care.

OBJECTIVES: To determine whether the use of dry-erase boards for communicating the plan of care of children evaluated in the pediatric emergency department (PED) improves the family experience of care. METHODS: Dry-erase boards were mounted at eye level in patient examination rooms. The study was conducted during a 4-week period during which physicians were instructed to use the boards on alternating weeks. During the 2 intervention weeks, they were instructed to write their name and plan of care in addition to their standard verbal communication. A questionnaire was administered to a convenience sample of caregivers that measured their perceptions of physician listening skills, time spent with the physician, their understanding of the care plan, their willingness to ask questions, likelihood to recommend the PED, and overall physician care. Differences between intervention and nonintervention weeks were analyzed using adjusted multivariable modeling taking into account clustered observations within physician. RESULTS: Surveys were completed by 672 caregivers. There were no significant differences in reported experience of care between the intervention and nonintervention weeks. During the intervention weeks, 59% of caregivers recalled use of the dry-erase boards, whereas 10% of caregivers recalled use during nonintervention weeks. Caregivers who recalled the use of dry-erase boards were more likely to report better physician listening skills, better understanding of the plan of care, and higher overall physician ratings. CONCLUSIONS: Recommending use of dry-erase boards in pediatric emergency department rooms did not increase overall measures of experience of care, although patients who recalled dry-erase board use did report higher performance. Further study could explore how to effectively and efficiently use these boards.

Discrepancies in Physician and Coroner Findings in Cases of Fatal Suspected Physical Child Abuse.

OBJECTIVES: As mandated reporters of suspected abuse, physicians must consider abuse when a child dies unexpectedly. Subsequently, a coroner or medical examiner determines the manner of death (MOD) and cause of death (COD). Accurate diagnoses and determinations are important for social safety and justice. This study described discrepancies between physicians' and coroners' findings in cases of fatal suspected physical child abuse. METHODS: This study was a single-institution, retrospective review. All children 6 years or younger who died in a pediatric emergency department from October 2006 to January 2013 with a coroner report were included in this study. Coroner reports, MODs, and CODs were reviewed. Skeletal survey results were compared with coroners' findings. RESULTS: One hundred twenty-nine children were included. The MODs included the following: undetermined, 63 (49%); accident, 32 (25%); natural, 31 (24%); and homicide, 3 (2%). Thirty-three (26%) of the 129 patients had abuse suspected at the time of death in the emergency department; in this subset, MODs were as follows: undetermined, 16 (48%); accident, 8 (24%); natural, 6 (18%); and homicide, 3 (9%). Sudden infant death syndrome or sudden unexpected death was the most common COD in all children (68, 55%). Skeletal surveys were positive in 12 children with 29 fractures identified; 8 (28%) of the 29 fractures were corroborated on autopsy findings. Of the 12 children with positive skeletal survey findings, only 1 was ruled a homicide. CONCLUSIONS: We found discrepancies between coroner determination of homicide and abuse suspected by physicians, especially among children with fractures. Improved communication between agencies in cases of fatal child abuse is needed.

Radiographic Pneumonia in Febrile Infants 60 Days and Younger.

OBJECTIVE: Few prospective studies have assessed the occurrence of radiographic pneumonia in young febrile infants. We analyzed factors associated with radiographic pneumonias in febrile infants 60 days or younger evaluated in pediatric emergency departments. STUDY DESIGN: We conducted a planned secondary analysis of a prospective cohort study within 26 emergency departments in a pediatric research network from 2008 to 2013. Febrile (≥38°C) infants 60 days or younger who received chest radiographs were included. Chest radiograph reports were categorized as "no," "possible," or "definite" pneumonia. We compared demographics, Yale Observation Scale scores (>10 implying ill appearance), laboratory markers, blood cultures, and viral testing among groups. RESULTS: Of 4778 infants, 1724 (36.1%) had chest radiographs performed; 2.7% (n = 46) had definite pneumonias, and 3.9% (n = 67) had possible pneumonias. Patients with definite (13/46 [28.3%]) or possible (15/67 [22.7%]) pneumonias more frequently had Yale Observation Scale score >10 compared with those without pneumonias (210/1611 [13.2%], P = 0.002) in univariable and multivariable analyses. Median white blood cell count (WBC), absolute neutrophil count (ANC), and procalcitonin (PCT) were higher in the definite (WBC, 11.5 [interquartile range, 9.8-15.5]; ANC, 5.0 [3.2-7.6]; PCT, 0.4 [0.2-2.1]) versus no pneumonia (WBC, 10.0 [7.6-13.3]; ANC, 3.4 [2.1-5.4]; PCT, 0.2 [0.2-0.3]; WBC, P = 0.006; ANC, P = 0.002; PCT, P = 0.046) groups, but of unclear clinical significance. There were no cases of bacteremia in the definite pneumonia group. Viral infections were more frequent in groups with definite (25/38 [65.8%]) and possible (28/55 [50.9%]) pneumonias than no pneumonias (534/1185 [45.1%], P = 0.02). CONCLUSIONS: Radiographic pneumonias were uncommon, often had viruses detected, and were associated with ill appearance, but few other predictors, in febrile infants 60 days or younger.

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children aged <18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/µL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count <250 × 103/µL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/µL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.

Using quality improvement to implement the CNS/AAN quality measure on rescue medication for seizures.

OBJECTIVE: A multidisciplinary quality improvement (QI) team was established to conduct analysis of data for prescribed seizure rescue medication doses from January 2013 to December 2015 to identify and improve inappropriately low dose prescriptions. The QI team identified areas of focus for improvement opportunities and developed the project objective based on the 2017 American Academy of Neurology (AAN) and Child Neurology Society (CNS) quality measure. METHODS: Within a freestanding children's hospital, the QI team developed key drivers and implemented interventions, such as the midazolam prefilled syringe program with use of standardized dosing, electronic chart tools, monthly pharmacy review of all underdosed prescriptions, and provider and nursing education. The team created an automated monthly report to monitor prescribed seizure rescue medication dosing compliance. The year 2015 was used as the preliminary data baseline period with an average noncompliance rate of 3.5%. RESULTS: From January 2016 to December 2019, the team has decreased and sustained the noncompliance rate to an average of 0.38%. The data for the project included 12,975 seizure rescue medication prescribed by a neurology provider from January 2015 to December 2019. Compliance with properly dosed diazepam orders continues to be the largest area of opportunity. The data demonstrated a centerline shift in January 2019, moving the baseline average of 7.2% noncompliance to the current average rate of 0.22%. In comparison, underdosed midazolam orders occurred at an average rate of 0.037% in the same timeframe. SIGNIFICANCE: Using quality improvement methodologies, the team successfully and substantially decreased provider prescribed and signed underdosed rescue medication orders by an average of 89%. This QI project demonstrates successful implementation and improvement addressing the AAN/CNS quality measure of proper rescue seizure treatment dosing.

A Multiyear Cross-sectional Study of Guideline Adherence for the Timeliness of Opioid Administration in Children With Sickle Cell Pain Crisis.

STUDY OBJECTIVE: The National Heart, Lung, and Blood Institute evidence-based guidelines for timeliness of opioid administration for sickle cell disease (SCD) pain crises recommend an initial opioid within 1 hour of arrival, with subsequent dosing every 30 minutes until pain is controlled. No multisite studies have evaluated guideline adherence, to our knowledge. Our objective was to determine guideline adherence across a multicenter network. METHODS: We conducted a multiyear cross-sectional analysis of children with SCD who presented between January 1, 2016, and December 31, 2018, to 7 emergency departments (EDs) within the Pediatric Emergency Care Applied Research Network. Visits for uncomplicated pain crisis were included, defined with an International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 code for SCD crisis and receipt of an opioid, excluding visits with other SCD complications or temperature exceeding 38.5°C (101.3°F). Times were extracted from the electronic record. Guideline adherence was assessed across sites and calendar years. RESULTS: A total of 4,578 visits were included. The median time to first opioid receipt was 62 minutes (interquartile range 42 to 93 minutes); between the first and second opioid receipt, 60 minutes (interquartile range 39 to 93 minutes). Overall, 48% of visits (95% confidence interval 47% to 50%) were guideline adherent for first opioid. Of 3,538 visits with a second opioid, 15% (95% confidence interval 14% to 16%) were guideline adherent. Site variation in adherence existed for time to first opioid (range 22% to 70%) and time between first and second opioid (range 2% to 36%; both P<.001). There was no change in timeliness to first dose or time between doses across years (P>.05 for both). CONCLUSION: Guideline adherence for timeliness of SCD treatment is poor, with half of visits adherent for time to first opioid and one seventh adherent for second dose. Dissemination and implementation research/quality improvement efforts are critical to improve care across EDs.

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

BACKGROUND: To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied. METHODS: Children aged 2 months to 6 years with their first febrile UTI were randomized to corticosteroids or placebo for 3 days (both arms received antimicrobial therapy); kidney scarring was assessed using 99mTc-dimercaptosuccinic acid kidney scan 5-24 months after the initial UTI. RESULTS: We randomized 546 children of which 385 had a UTI and 254 had outcome kidney scans (instead of the 320 planned). Rates of kidney scarring were 9.8% (12/123) and 16.8% (22/131) in the corticosteroid and placebo groups, respectively (p = 0.16), corresponding to an absolute risk reduction of 5.9% (95% confidence interval: - 2.2, 14.1). CONCLUSION: While children randomized to adjuvant corticosteroids tended to develop fewer kidney scars than children who were randomized to receive placebo, a statistically significant difference was not achieved. However, the study was limited by not reaching its intended sample size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov , NCT01391793, Registered 7/12/2011 Graphical abstract.

What is the effect of a decision aid in potentially vulnerable parents? Insights from the head CT choice randomized trial.

OBJECTIVE: To test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust. METHODS: This was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy-two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site. RESULTS: The decision aid did not increase knowledge more in parents with high numeracy (P for interaction [Pint ] = 0.14) or physician trust more in parents with low health literacy (Pint  = 0.34). The decision aid decreased decisional conflict more in non-white parents (decisional conflict scale, -8.14, 95% CI: -12.33 to -3.95; Pint  = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35-14.83; Pint  = 0.04). CONCLUSIONS: Use of the Head CT Choice decision aid resulted in less decisional conflict in non-white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents.

Shared nucleotide flanks confer transcriptional competency to bZip core motifs.

Sequence-specific DNA binding recruits transcription factors (TFs) to the genome to regulate gene expression. Here, we perform high resolution mapping of CEBP proteins to determine how sequence dictates genomic occupancy. We demonstrate a fundamental difference between the sequence repertoire utilized by CEBPs in vivo versus the palindromic sequence preference reported by classical in vitro models, by identifying a palindromic motif at <1% of the genomic binding sites. On the native genome, CEBPs bind a diversity of related 10 bp sequences resulting from the fusion of degenerate and canonical half-sites. Altered DNA specificity of CEBPs in cells occurs through heterodimerization with other bZip TFs, and approximately 40% of CEBP-binding sites in primary human cells harbor motifs characteristic of CEBP heterodimers. In addition, we uncover an important role for sequence bias at core-motif-flanking bases for CEBPs and demonstrate that flanking bases regulate motif function across mammalian bZip TFs. Favorable flanking bases confer efficient TF occupancy and transcriptional activity, and DNA shape may explain how the flanks alter TF binding. Importantly, motif optimization within the 10-mer is strongly correlated with cell-type-independent recruitment of CEBPß, providing key insight into how sequence sub-optimization affects genomic occupancy of widely expressed CEBPs across cell types.