Stratification of risk for emergent intracranial abnormalities in children with headaches: a Pediatric Emergency Care Applied Research Network (PECARN) study protocol.

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA in children with headaches based on clinically sensible and reliable variables. METHODS AND ANALYSIS: Prospective cohort study of 28 000 children with headaches presenting to any of 18 EDs in the Pediatric Emergency Care Applied Research Network (PECARN). We include children aged 2-17 years with a chief complaint of headache. We exclude children with a clear non-intracranial alternative diagnosis, fever, neuroimaging within previous year, neurological or developmental condition such that patient history or physical examination may be unreliable, Glasgow Coma Scale score<14, intoxication, known pregnancy, history of intracranial surgery, known structural abnormality of the brain, pre-existing condition predisposing to an intracranial abnormality or intracranial hypertension, head injury within 14 days or not speaking English or Spanish. Clinicians complete a standardised history and physical examination of all eligible patients. Primary outcome is the presence of an EIA as determined by neuroimaging or clinical follow-up. We will use binary recursive partitioning and multiple regression analyses to create and internally validate the risk stratification model. ETHICS AND DISSEMINATION: Ethics approval was obtained for all participating sites from the University of Utah single Institutional Review Board. A waiver of informed consent was granted for collection of ED data. Verbal consent is obtained for follow-up contact. Results will be disseminated through international conferences, peer-reviewed publications, and open-access materials.

Factors Associated With Improved Pediatric Resuscitative Care in General Emergency Departments.

OBJECTIVES: To describe the quality of pediatric resuscitative care in general emergency departments (GEDs) and to determine hospital-level factors associated with higher quality. METHODS: Prospective observational study of resuscitative care provided to 3 in situ simulated patients (infant seizure, infant sepsis, and child cardiac arrest) by interprofessional GED teams. A composite quality score (CQS) was measured and the association of this score with modifiable and nonmodifiable hospital-level factors was explored. RESULTS: A median CQS of 62.8 of 100 (interquartile range 50.5-71.1) was noted for 287 resuscitation teams from 175 emergency departments. In the unadjusted analyses, a higher score was associated with the modifiable factor of an affiliation with a pediatric academic medical center (PAMC) and the nonmodifiable factors of higher pediatric volume and location in the Northeast and Midwest. In the adjusted analyses, a higher CQS was associated with modifiable factors of an affiliation with a PAMC and the designation of both a nurse and physician pediatric emergency care coordinator, and nonmodifiable factors of higher pediatric volume and location in the Northeast and Midwest. A weak correlation was noted between quality and pediatric readiness scores. CONCLUSIONS: A low quality of pediatric resuscitative care, measured using simulation, was noted across a cohort of GEDs. Hospital factors associated with higher quality included: an affiliation with a PAMC, designation of a pediatric emergency care coordinator, higher pediatric volume, and geographic location. A weak correlation was noted between quality and pediatric readiness scores.

Comprehensiveness of Testing Among Herpes Simplex Virus Infected Infants: A Multicenter Cohort Study.

Despite clear testing recommendations for herpes simplex virus (HSV) infection in infants, few data exist on the comprehensiveness of HSV testing in practice. In a 23-center study of 112 infants with confirmed HSV disease, less than one-fifth had all recommended testing performed, highlighting the need for increased awareness of and adherence to testing recommendations for this vulnerable population.

Predictors of Invasive Herpes Simplex Virus Infection in Young Infants.

OBJECTIVES: To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection. METHODS: In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively. RESULTS: Of all infants included, 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] <14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with >28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43). CONCLUSIONS: A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.

Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus.

OBJECTIVE: To quantify the association between early neurologic recovery, practice pattern variation, and endotracheal intubation during established status epilepticus, we performed a secondary analysis within the cohort of patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). METHODS: We evaluated factors associated with the endpoint of endotracheal intubation occurring within 120 minutes of ESETT study drug initiation. We defined a blocked, stepwise multivariate regression, examining 4 phases during status epilepticus management: (1) baseline characteristics, (2) acute treatment, (3) 20-minute neurologic recovery, and (4) 60-minute recovery, including seizure cessation and improving responsiveness. RESULTS: Of 478 patients, 117 (24.5%) were intubated within 120 minutes. Among high-enrolling sites, intubation rates ranged from 4% to 32% at pediatric sites and 19% to 39% at adult sites. Baseline characteristics, including seizure precipitant, benzodiazepine dosing, and admission vital signs, provided limited discrimination for predicting intubation (area under the curve [AUC] 0.63). However, treatment at sites with an intubation rate in the highest (vs lowest) quartile strongly predicted endotracheal intubation independently of other treatment variables (adjusted odds ratio [aOR] 8.12, 95% confidence interval [CI] 3.08-21.4, model AUC 0.70). Site-specific variation was the factor most strongly associated with endotracheal intubation after adjustment for 20-minute (aOR 23.4, 95% CI 6.99-78.3, model AUC 0.88) and 60-minute (aOR 14.7, 95% CI 3.20-67.5, model AUC 0.98) neurologic recovery. CONCLUSIONS: Endotracheal intubation after established status epilepticus is strongly associated with site-specific practice pattern variation, independently of baseline characteristics, and early neurologic recovery and should not alone serve as a clinical trial endpoint in established status epilepticus. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT01960075.

Improving Pediatric Readiness in General Emergency Departments: A Prospective Interventional Study.

OBJECTIVE: To describe the impact of a national interventional collaborative on pediatric readiness within general emergency departments (EDs). STUDY DESIGN: A prospective, multicenter, interventional study measured pediatric readiness in general EDs before and after participation in a pediatric readiness improvement intervention. Pediatric readiness was assessed using the weighted pediatric readiness score (WPRS) on a 100-point scale. The study protocol extended over 6 months and involved 3 phases: (1) a baseline on-site assessment of pediatric readiness and simulated quality of care; (2) pediatric readiness interventions; and (3) a follow-up on-site assessment of WPRS. The intervention phase included a benchmarking performance report, resources toolkits, and ongoing interactions between general EDs and academic medical centers. RESULTS: Thirty-six general EDs were enrolled, and 34 (94%) completed the study. Four EDs (11%) were located in Canada, and the rest were in the US. The mean improvement in WPRS was 16.3 (P < .001) from a baseline of 62.4 (SEM = 2.2) to 78.7 (SEM = 2.1), with significant improvement in the domains of administration/coordination of care; policies, protocol, and procedures; and quality improvement. Six EDs (17%) were fully adherent to the protocol timeline. CONCLUSIONS: Implementing a collaborative intervention model including simulation and quality improvement initiatives is associated with improvement in WPRS when disseminated to a diverse group of general EDs partnering with their regional pediatric academic medical centers. This work provides evidence that innovative collaboration facilitated by academic medical centers can serve as an effective strategy to improve pediatric readiness and processes of care.

Performance of the Modified Boston and Philadelphia Criteria for Invasive Bacterial Infections.

BACKGROUND: The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated. METHODS: We assembled a multicenter cohort of infants 29 to 60 days of age who had cerebrospinal fluid (CSF) and blood cultures obtained. We report the performance of the modified Boston criteria (peripheral white blood cell count [WBC] ≥20 000 cells per mm3, CSF WBC ≥10 cells per mm3, and urinalysis with >10 WBC per high-power field or positive urine dip result) and modified Philadelphia criteria (peripheral WBC ≥15 000 cells per mm3, CSF WBC ≥8 cells per mm3, positive CSF Gram-stain result, and urinalysis with >10 WBC per high-power field or positive urine dip result) for the identification of invasive bacterial infections (IBIs). We defined IBI as bacterial meningitis (growth of pathogenic bacteria from CSF culture) or bacteremia (growth from blood culture). RESULTS: We applied the modified Boston criteria to 8344 infants and the modified Philadelphia criteria to 8131 infants. The modified Boston criteria identified 133 of the 212 infants with IBI (sensitivity 62.7% [95% confidence interval (CI) 55.9% to 69.3%] and specificity 59.2% [95% CI 58.1% to 60.2%]), and the modified Philadelphia criteria identified 157 of the 219 infants with IBI (sensitivity 71.7% [95% CI 65.2% to 77.6%] and specificity 46.1% [95% CI 45.0% to 47.2%]). The modified Boston and Philadelphia criteria misclassified 17 of 53 (32.1%) and 13 of 56 (23.3%) infants with bacterial meningitis, respectively. CONCLUSIONS: The modified Boston and Philadelphia criteria misclassified a substantial number of infants 29 to 60 days old with IBI, including those with bacterial meningitis.

The Champagne Tap: Time to Pop the Cork?

BACKGROUND: A "champagne tap" is a lumbar puncture with no cerebrospinal fluid (CSF) red blood cells (RBCs). Clinicians disagree whether the absence of CSF white blood cells (WBCs) is also required. AIMS: As supervising providers frequently reward trainees after a champagne tap, we investigated how varying the definition impacted the frequency of trainee accolades. MATERIALS & METHODS: We performed a secondary analysis of a retrospective cross-sectional study of infants ≤60 days of age who had a CSF culture performed in the emergency department (ED) at one of 20 centers participating in a Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC) endorsed study. Our primary outcomes were a champagne tap defined by either a CSF RBC count of 0 cells/mm3 regardless of CSF WBC count or both CSF RBC and WBC counts of 0 cells/mm3 . RESULTS: Of the 23,618 eligible encounters, 20,358 (86.2%) had both a CSF RBC and WBC count obtained. Overall, 3,147 (13.3%) had a CSF RBC count of 0 cells/mm3 and 377 (1.6%) had both CSF WBC and RBC counts of 0 cells/mm3 (relative rate 8.35, 95% confidence interval 7.51 to 9.27). CONCLUSIONS: In infants, a lumbar puncture with a CSF RBC count of 0 cells/mm3 regardless of the CSF WBC count occurred eight-times more frequently than one with both CSF WBC and RBC counts of 0 cells/mm3 . A broader champagne tap definition would allow more frequent recognition of procedural success, with the potential to foster a supportive community during medical training, potentially protecting against burnout.

Pediatric stroke in the emergency department.

Strokes are more commonly seen in adults but also occur in the pediatric population. Similar to adult strokes, pediatric strokes are considered medical emergencies and require prompt diagnosis and treatment to maximize favorable outcomes. Unfortunately, the diagnosis of stroke in children is often delayed, commonly because of parental delay or failure to consider stroke in the differential diagnosis. Children, especially young children, often present differently than adults. Much of the treatment for pediatric strokes has been adapted from adult guidelines but the optimal treatment has not been clearly defined. In this article, we review pediatric strokes and the most recent recommendations for treatment.

Management of Pain After Pediatric Trauma.

OBJECTIVES: The primary objective of this study was to evaluate the management of pain after traumatic injury in the pediatric emergency department (ED) as measured by time to analgesic administration and pain resolution, stratified by triage acuity level. METHODS: This is a retrospective descriptive study evaluating the management of children who presented with pain after injury to an urban level 1 trauma center. Consecutive enrollment of 1000 patients identified by ICD-9 codes that included all injuries or external causes for injury (700-999 and all E codes) and who had pain identified by triage pain assessment was performed. For analysis, patients were grouped according to triage level. RESULTS: Fifty-one percent (511/1000) of patients achieved pain resolution, and an additional 20% (200/1000) of patients had documented improvement in pain score during their ED visit. Triage acuity level 1 group received medications the fastest with a median time of 12 minutes (interquartile range, 10-53 minutes); 65.3% of patients (653/1000) received a pain medication during their ED visit; 54.3% of these patients received oral medications only. Average time to intravenous line placement was 2 hours 35 minutes (SD, 2 hours 55 minutes). Only 1.9% of patients received any medications prior to arrival. CONCLUSIONS: Higher-acuity patients received initial pain medications and had initial pain score decrease before lower-acuity patients. Given the retrospective nature of the study, we were unable to clearly identify barriers that contributed to delay in or lack of pain treatment in our patient population.

Objective Evaluation of a Simulation Course for Residents in the Pediatric Emergency Medicine Department: Breaking Bad News.

INTRODUCTION: Breaking bad news (BBN), especially in the pediatric emergency medicine department, requires significant skill and delicacy due to the acute context of a busy emergency department (ED) and the lack of prior rapport with the patients and families. Pediatric literature on breaking bad news has mostly focused on pediatric oncology and pediatric critical care, with limited literature focused on pediatric emergency medicine. Review of the literature also reveals that most existing studies solely assess the learners' self-ratings of efficacy and comfort, and far fewer studies objectively evaluate learners' actual performance using simulation. Our objectives for this study was to use an objective assessment tool to assess residents' breaking bad news skills, pre- and post-simulation training, specifically in the setting of a pediatric emergency medicine department. METHODS: 34 residents were evaluated on their performance in breaking bad news via videotaped simulation encounters before and after teaching intervention. The "Modified Breaking Bad News Assessment Scale" (mBAS) was used as the assessment tool. A paired t-test analysis was conducted to examine the mean difference in pre- and post-simulation scores in each of the five mBAS domains. RESULTS: Breaking bad news performance score improves one to two weeks post-intervention, and was statistically significant in three of five domains. CONCLUSION: Our study shows that breaking bad news is a teachable skill that can be improved by simulated education in the pediatric emergency medicine department. This study demonstrates the utility of simulation course in improving breaking bad news skills in the pediatric emergency medicine department. Future work in developing focused simulation curriculums is important to improve provider communication skills and patient-physician relationships.

Application of the Bacterial Meningitis Score for Infants Aged 0 to 60 Days.

In 4292 infants aged ≤60 days with cerebrospinal fluid (CSF) pleocytosis, the bacterial meningitis score had excellent sensitivity (121 of 121 [100.0%] [95% confidence interval, 96.5%-100.0%]) but low specificity (66 of 4171 [1.6%] [95% confidence interval, 1.3%-2.0%]) and therefore should not be applied clinically to infants in this age group.

Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation.

BACKGROUND: Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed. METHODS: We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture. The primary outcome was the proportion of encounters in which HSV infection was identified. Secondary outcomes included frequency of central nervous system (CNS) and disseminated HSV, and HSV testing and treatment patterns. RESULTS: Of 26 533 eligible encounters, 112 infants had HSV identified (0.42%, 95% confidence interval [CI]: 0.35%-0.51%). Of these, 90 (80.4%) occurred in weeks 1 to 4, 10 (8.9%) in weeks 5 to 6, and 12 (10.7%) in weeks 7 to 9. The median age of HSV-infected infants was 14 days (interquartile range: 9-24 days). HSV infection was more common in 0 to 28-day-old infants compared with 29- to 60-day-old infants (odds ratio 3.9; 95% CI: 2.4-6.2). Sixty-eight (0.26%, 95% CI: 0.21%-0.33%) had CNS or disseminated HSV. The proportion of infants tested for HSV (35%; range 14%-72%) and to whom acyclovir was administered (23%; range 4%-53%) varied widely across sites. CONCLUSIONS: An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger.

OBJECTIVE: To determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. STUDY DESIGN: We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005-2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result. RESULTS: Of 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89-1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57-0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0-0.4). CONCLUSIONS: Although enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one-third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.

Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial.

IMPORTANCE: Benzodiazepines are considered first-line therapy for pediatric status epilepticus. Some studies suggest that lorazepam may be more effective or safer than diazepam, but lorazepam is not Food and Drug Administration approved for this indication. OBJECTIVE: To test the hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, randomized clinical trial was conducted from March 1, 2008, to March 14, 2012. Patients aged 3 months to younger than 18 years with convulsive status epilepticus presenting to 1 of 11 US academic pediatric emergency departments were eligible. There were 273 patients; 140 randomized to diazepam and 133 to lorazepam. INTERVENTIONS: Patients received either 0.2 mg/kg of diazepam or 0.1 mg/kg of lorazepam intravenously, with half this dose repeated at 5 minutes if necessary. If status epilepticus continued at 12 minutes, fosphenytoin was administered. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was cessation of status epilepticus by 10 minutes without recurrence within 30 minutes. The primary safety outcome was the performance of assisted ventilation. Secondary outcomes included rates of seizure recurrence and sedation and times to cessation of status epilepticus and return to baseline mental status. Outcomes were measured 4 hours after study medication administration. RESULTS: Cessation of status epilepticus for 10 minutes without recurrence within 30 minutes occurred in 101 of 140 (72.1%) in the diazepam group and 97 of 133 (72.9%) in the lorazepam group, with an absolute efficacy difference of 0.8% (95% CI, -11.4% to 9.8%). Twenty-six patients in each group required assisted ventilation (16.0% given diazepam and 17.6% given lorazepam; absolute risk difference, 1.6%; 95% CI, -9.9% to 6.8%). There were no statistically significant differences in secondary outcomes except that lorazepam patients were more likely to be sedated (66.9% vs 50%, respectively; absolute risk difference, 16.9%; 95% CI, 6.1% to 27.7%). CONCLUSIONS AND RELEVANCE: Among pediatric patients with convulsive status epilepticus, treatment with lorazepam did not result in improved efficacy or safety compared with diazepam. These findings do not support the preferential use of lorazepam for this condition. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00621478.

Controlled clinical comparison of new pediatric medium with adsorbent polymeric beads (PF Plus) versus charcoal-containing PF medium in the BacT/alert blood culture system.

We conducted a controlled clinical comparison of PF Plus, the new pediatric medium with adsorbent polymeric beads, versus the charcoal-containing PF medium in the BacT/Alert blood culture system. A total of 2,381 pediatric cultures were enrolled, and 1,703 (71.5%) were deemed to be compliant and acceptable for analysis. Seventy-two cultures (4.2%) had a positive result with 80 clinically significant microorganisms. The results showed that the PF Plus medium yielded more clinically significant microorganisms than the BacT/Alert system (P < 0.05). In addition, the PF Plus bottle yielded positive results an average of 5.0 h earlier than the PF bottle for compliant clinically significant cultures (18.3 h versus 23.2 h, P = 0.004). PF Plus is an improved medium for detecting microorganisms that cause pediatric bloodstream infections.

Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): a phase 3, randomised controlled trial.

BACKGROUND: On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48-72 h with slow rewarming improved mortality in children after brain injury. METHODS: In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6-15 years, 16-17 years]) to either hypothermia (rapidly cooled to 32-33°C for 48-72 h, then rewarmed by 0·5-1·0°C every 12-24 h) or normothermia (maintained at 36·5-37·5°C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GOS-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742. FINDINGS: The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1, 2007, and Feb 28, 2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0·15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events. INTERPRETATION: Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury. FUNDING: National Institute of Neurological Disorders and Stroke and National Institutes of Health.

A randomized clinical trial of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in mild to moderately dehydrated children in the emergency department.

BACKGROUND: Alternative treatment of dehydration is needed when intravenous (IV) or oral rehydration therapy fails. Subcutaneous (SC) hydration facilitated by recombinant human hyaluronidase offers an alternative treatment for dehydration. This clinical trial is the first to compare recombinant human hyaluronidase-facilitated SC (rHFSC) rehydration with standard IV rehydration for use in dehydrated children. OBJECTIVE: This Phase IV noninferiority trial evaluated whether rHFSC fluid administration can be given safely and effectively, with volumes similar to those delivered intravenously, to children who have mild to moderate dehydration. METHODS: The study included mild to moderately dehydrated children (Gorelick dehydration score) aged 1 month to 10 years. They were randomized to receive 20 mL/kg of isotonic fluids using rHFSC or IV therapy over 1 hour and then as needed until clinically rehydrated. The primary outcome was total volume of fluid administered (emergency department [ED] plus inpatient hospitalization). Secondary outcomes included mean volume infused in the ED alone, postinfusion dehydration scores and weight changes, line placement success and time, safety, and provider and parent/guardian questionnaire. RESULTS: 148 patients (mean age, 2.3 [1.91] years]; white, 53.4%; black, 31.8%) were enrolled in the intention-to-treat population (73 rHFSC; 75 IV). The primary outcome, mean total volume infused, was 365.0 (324.6) mL in the rHFSC group over 3.1 hours versus 455.8 (597.4) mL in the IV group over 6.6 hours (P = 0.51). The secondary outcome of mean volume infused in the ED alone was 334.3 (226.40) mL in the rHFSC group versus 299.6 (252.33) mL in the IV group (P = 0.03). Dehydration scores and weight changes postinfusion were similar. Successful line placement occurred in all 73 rHFSC-treated patients and 59 of 75 (78.7%) IV-treated patients (P < 0.0001). All IV failures occurred in patients aged <3 years; rHFSC rescue was successful in all patients in whom it was attempted. Both treatments were well tolerated. Clinicians rated fluid administration as easy to perform in 94.5% (69 of 73) of the rHFSC group versus 65.3% (49 of 75) of the IV group (P < 0.001). Parents/caregivers were satisfied or very satisfied with fluid administration in 94.5% (69 of 73) of rHFSC-treated patients and 73.3% (55 of 75) of IV-treated patients. CONCLUSIONS: In mild to moderately dehydrated children, rHFSC was inferior to IV hydration for the primary outcome measure. However, rHFSC was noninferior in the ED phase of hydration. Additional benefits of rHFSC included time and success of line placement, ease of use, and satisfaction. SC hydration facilitated with recombinant human hyaluronidase represents a reasonable addition to the treatment options for children who have mild to moderate dehydration, especially those with difficult IV access. ClinicalTrials.gov identifier: NCT00773175.

Sterile cerebrospinal fluid pleocytosis in young febrile infants with urinary tract infections.

OBJECTIVES: To determine the prevalence of and to identify risk factors for sterile cerebrospinal fluid (CSF) pleocytosis in a large sample of febrile young infants with urinary tract infections (UTIs) and to describe the clinical courses of those patients. DESIGN: Secondary analysis of a multicenter retrospective review. SETTING: Emergency departments of 20 North American hospitals. Patients Infants aged 29 to 60 days with temperatures of 38.0°C or higher and culture-proven UTIs who underwent a nontraumatic lumbar puncture from January 1, 1995, through May 31, 2006. MAIN EXPOSURE: Febrile UTI. OUTCOME MEASURES: Presence of sterile CSF pleocytosis defined as CSF white blood cell count of 10/µL or higher in the absence of bacterial meningitis and clinical course and treatment (ie, presence of adverse events, time to defervescence, duration of parenteral antibiotic treatment, and length of hospitalization). RESULTS: A total of 214 of 1190 infants had sterile CSF pleocytosis (18.0%; 95% confidence interval, 15.9%-20.3%). Only the peripheral white blood cell count was independently associated with sterile CSF pleocytosis, and patients with a peripheral white blood cell count of 15/µL or higher had twice the odds of having sterile CSF pleocytosis (odds ratio, 1.97; 95% confidence interval, 1.32-2.94; P = .001). In the subset of patients at very low risk for adverse events (ie, not clinically ill in the emergency department and without a high-risk medical history), patients with and without sterile CSF pleocytosis had similar clinical courses; however, patients with CSF pleocytosis had longer parenteral antibiotics courses (median length, 4 days [interquartile range, 3-6 days] vs 3 days [interquartile range, 3-5 days]) (P = .04). CONCLUSION: Sterile CSF pleocytosis occurs in 18% of young infants with UTIs. Patients with CSF pleocytosis at very low risk for adverse events may not require longer treatment with antibiotics.

Febrile infants with urinary tract infections at very low risk for adverse events and bacteremia.

BACKGROUND: There is limited evidence from which to derive guidelines for the management of febrile infants aged 29 to 60 days with urinary tract infections (UTIs). Most such infants are hospitalized for ≥48 hours. Our objective was to derive clinical prediction models to identify febrile infants with UTIs at very low risk of adverse events and bacteremia in a large sample of patients. METHODS: This study was a 20-center retrospective review of infants aged 29 to 60 days with temperatures of ≥38°C and culture-proven UTIs. We defined UTI by growth of ≥50,000 colony-forming units (CFU)/mL of a single pathogen or ≥10,000 CFU/mL in association with positive urinalyses. We defined adverse events as death, shock, bacterial meningitis, ICU admission need for ventilator support, or other substantial complications. We performed binary recursive partitioning analyses to derive prediction models. RESULTS: We analyzed 1895 patients. Adverse events occurred in 51 of 1842 (2.8% [95% confidence interval (CI): 2.1%-3.6%)] and bacteremia in 123 of 1877 (6.5% [95% CI: 5.5%-7.7%]). Patients were at very low risk for adverse events if not clinically ill on emergency department (ED) examination and did not have a high-risk past medical history (prediction model sensitivity: 98.0% [95% CI: 88.2%-99.9%]). Patients were at lower risk for bacteremia if they were not clinically ill on ED examination, did not have a high-risk past medical history, had a peripheral band count of <1250 cells per µL, and had a peripheral absolute neutrophil count of ≥1500 cells per µL (sensitivity 77.2% [95% CI: 68.6%-84.1%]). CONCLUSION: Brief hospitalization or outpatient management with close follow-up may be considered for infants with UTIs at very low risk of adverse events.