Factors Affecting Peripheral Intravenous Catheter Placement During Pediatric Trauma Resuscitation.

INTRODUCTION: Intravenous access is required for resuscitation of injured patients but may be delayed in children because of challenges associated with peripheral intravenous (PIV) catheter placement. Early identification of factors predisposing patients to difficult PIV placement can assist in deciding strategies for timely intravenous access. METHODS: We conducted a retrospective, video-based review of injured children and adolescents treated between April 2018 and May 2019. Patient demographic, physiological, injury, and resuscitation characteristics were obtained from the patient record, including age, race, weight, injury type, Injury Severity Score, initial systolic blood pressure, initial Glasgow Coma Score, intubation status, activation level, and presence of prearrival notification. Video review was used to determine the time to PIV placement, the number of attempts required, the purpose for additional access, and the reason for abandonment of PIV placement. Multivariable regressions were used to determine factors associated with successful placement. RESULTS: During the study period, 154 consented patients underwent attempts at PIV placement in the trauma bay. Placement was successful in 139 (90.3%) patients. Older patients (OR [odds ratio]: 0.9, 95% confidence interval [CI]: 0.9, 0.9) and patients who required the highest level activation response (OR: 0.0, 95% CI: 0.0, 0.3) were less likely to have an attempt at PIV placement abandoned. Children with nonblunt injuries (OR: 11.6, 95% CI: 1.3, 119.2) and pre-existing access (OR: 39.6, 95% CI: 7.0, 350.6) were more likely to have an attempt at PIV placement abandoned. Among patients with successful PIV placement, the time required for establishing PIV access was faster as age increased (-0.5 s, 95% CI: -1.1, -0.0). CONCLUSIONS: Younger age was associated with abandonment of PIV attempts and, when successful, increased time to placement. Strategies to improve successful PIV placement and alternate routes of access should be considered early to prevent treatment delays in younger children.

Discovering interpretable medical process models: A case study in trauma resuscitation.

Understanding the actual work (i.e., "work-as-done") rather than theorized work (i.e., "work-as-imagined") during complex medical processes is critical for developing approaches that improve patient outcomes. Although process mining has been used to discover process models from medical activity logs, it often omits critical steps or produces cluttered and unreadable models. In this paper, we introduce a TraceAlignment-based ProcessDiscovery method called TAD Miner to build interpretable process models for complex medical processes. TAD Miner creates simple linear process models using a threshold metric that optimizes the consensus sequence to represent the backbone process, and then identifies both concurrent activities and uncommon-but-critical activities to represent the side branches. TAD Miner also identifies the locations of repeated activities, an essential feature for representing medical treatment steps. We conducted a study using activity logs of 308 pediatric trauma resuscitations to develop and evaluate TAD Miner. TAD Miner was used to discover process models for five resuscitation goals, including establishing intravenous (IV) access, administering non-invasive oxygenation, performing back assessment, administering blood transfusion, and performing intubation. We quantitively evaluated the process models with several complexity and accuracy metrics, and performed qualitative evaluation with four medical experts to assess the accuracy and interpretability of the discovered models. Through these evaluations, we compared the performance of our method to that of two state-of-the-art process discovery algorithms: Inductive Miner and Split Miner. The process models discovered by TAD Miner had lower complexity and better interpretability than the state-of-the-art methods, and the fitness and precision of the models were comparable. We used the TAD process models to identify (1) the errors and (2)the best locations for the tentative steps in knowledge-driven expert models. The knowledge-driven models were revised based on the modifications suggested by the discovered models. The improved modeling using TAD Miner may enhance understanding of complex medical processes.

Pathogen-Specific Effects of Probiotics in Children With Acute Gastroenteritis Seeking Emergency Care: A Randomized Trial.

BACKGROUND: It is unknown if probiotics exert pathogen-specific effects in children with diarrhea secondary to acute gastroenteritis. METHODS: Analysis of patient-level data from 2 multicenter randomized, placebo controlled trials conducted in pediatric emergency departments in Canada and the United States. Participants were 3-48 months with >3 diarrheal episodes in the preceding 24 hours and were symptomatic for <72 hours and <7 days in the Canadian and US studies, respectively. Participants received either placebo or a probiotic preparation (Canada-Lactobacillus rhamnosus R0011/Lactobacillus helveticus R0052; US-L. rhamnosus GG). The primary outcome was post-intervention moderate-to-severe disease (ie, ≥9 on the Modified Vesikari Scale [MVS] score). RESULTS: Pathogens were identified in specimens from 59.3% of children (928/1565). No pathogen groups were less likely to experience an MVS score ≥9 based on treatment allocation (test for interaction = 0.35). No differences between groups were identified for adenovirus (adjusted relative risk [aRR]: 1.42; 95% confidence interval [CI]: .62, 3.23), norovirus (aRR: 0.98; 95% CI: .56, 1.74), rotavirus (aRR: 0.86; 95% CI: .43, 1.71) or bacteria (aRR: 1.19; 95% CI: .41, 3.43). At pathogen-group and among individual pathogens there were no differences in diarrhea duration or the total number of diarrheal stools between treatment groups, regardless of intervention allocation or among probiotic sub-groups. Among adenovirus-infected children, those administered the L. rhamnosus R0011/L. helveticus R0052 product experienced fewer diarrheal episodes (aRR: 0.65; 95% CI: .47, .90). CONCLUSIONS: Neither probiotic product resulted in less severe disease compared to placebo across a range of the most common etiologic pathogens. The preponderance of evidence does not support the notion that there are pathogen specific benefits associated with probiotic use in children with acute gastroenteritis. CLINICAL TRIALS REGISTRATION: NCT01773967 and NCT01853124.

Pregnancy outcomes in patients with congenital myasthenic syndromes.

INTRODUCTION/AIMS: The congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited disorders that affect neuromuscular junction transmission. Data on pregnancy outcomes in women with CMS are limited due to their infrequency. In this study we explored pregnancy with CMS in a large cohort of women attending a national specialty clinic in England. METHODS: All women with CMS who had a documented pregnancy were invited to complete a questionnaire assessing clinical status during pregnancy and postpartum, pregnancy outcomes, fetal outcomes, and medication use during pregnancy. RESULTS: Among 16 women with CMS (acetylcholine receptor deficiency [CHRNE], slow channel syndrome [CHRNA1], DOK7, RAPSYN and glycosylation [DPAGT1 and GFPT1]), 27 pregnancies were recorded: 26 single pregnancies and 1 twin pregnancy. Symptom worsening was reported in 63% of pregnancies, but recovery to baseline function was seen in all but one patient. Miscarriage and cesarean section occurred in 31% and 33% of the women, respectively. Over half of the patients continued taking their medication during pregnancy, which included pyridostigmine (n = 10), 3,4-diaminopyridine (n = 9), ephedrine (n = 3), salbutamol (n = 3), and quinidine (n = 1). No fetal malformations were recorded. DISCUSSION: Our results show that clinical worsening during pregnancy was common but rarely persistent. The majority of women with CMS can safely plan pregnancy, but close follow-up is required from their neurology and obstetric teams. Although we identified no safety concerns, continued medication use should be reviewed on a case-by-case basis.

Videographic Assessment of Tracheal Intubation Technique in a Network of Pediatric Emergency Departments: A Report by the Videography in Pediatric Resuscitation (VIPER) Collaborative.

STUDY OBJECTIVE: We sought to describe the tracheal intubation technique across a network of children's hospitals and explore the association between intubation technical adjuncts and first-attempt success as well as between laryngoscopy duration and the incidence of hypoxemia. METHODS: We conducted a prospective observational study in 4 tertiary pediatric emergency departments of the Videography in Pediatric Resuscitation Collaborative. Children undergoing tracheal intubation captured on video were eligible for inclusion. Data on intubator background, patient characteristics, technical characteristics (eg, use of videolaryngoscopy and apneic oxygenation), and procedural outcomes were obtained through a video review. RESULTS: We obtained complete data on first attempts in 494 patients. The first-attempt success rate was 67%, the median laryngoscopy duration was 35 seconds (interquartile range 25 to 40), and hypoxemia occurred in 15% of the patients. Videolaryngoscopy was used for at least a part of the procedure in 48% of the attempts, and it had no association with success or the incidence of hypoxemia. Attempts in which videolaryngoscopy was used for the entire procedure (compared with direct laryngoscopy for the entire procedure) had a longer duration (the difference between the medians was 6 seconds; 95% confidence interval, 1 to 12 seconds). Intubation attempts longer than 45 seconds had a greater incidence of hypoxemia (29% versus 6%). Furthermore, apneic oxygenation was used in 8% of the first attempts. CONCLUSION: Among children undergoing tracheal intubation in a group of pediatric emergency departments, first-attempt success occurred in 67% of the patients. Videolaryngoscopy use was associated with longer laryngoscopy durations but was not associated with success or the incidence of hypoxemia.

Oral Ondansetron Administration in Children Seeking Emergency Department Care for Acute Gastroenteritis: A Patient-Level Propensity-Matched Analysis.

STUDY OBJECTIVE: This study aimed to explore oral ondansetron usage and impact on outcomes in clinical practice. METHODS: This observational study was a planned secondary analysis of 2 trials conducted in 10 US and 6 Canadian institutions between 2014 and 2017. Children 3 to 48 months old with gastroenteritis and ≥3 episodes of vomiting in the 24 hours preceding emergency department (ED) presentation were included. Oral ondansetron was administered at the discretion of the provider. The principal outcomes were intravenous fluid administration and hospitalization at the index visit and during the subsequent 72 hours and diarrhea and vomiting frequency during the 24 hours following the ED visit. RESULTS: In total, 794 children were included. The median age was 16.0 months (interquartile range 10.0 to 26.0), and 50.1% (398/794) received oral ondansetron. In propensity-adjusted analysis (n=528), children administered oral ondansetron were less likely to receive intravenous fluids at the index visit (adjusted odds ratio [aOR] 0.50; 95% confidence interval [CI] 0.29 to 0.88). There were no differences in the frequencies of intravenous fluid administration within the first 72 hours (aOR 0.65; 95% CI 0.39 to 1.10) or hospitalization at the index visit (aOR 0.31; 95% CI 0.09 to 1.10) or the subsequent 72 hours (aOR 0.52; 95% CI 0.21 to 1.28). Episodes of vomiting (aRR 0.86; 95% CI 0.63 to 1.19) and diarrhea (aRR 1.11; 95% CI 0.93 to 1.32) during the 24 hours following ED discharge also did not differ. CONCLUSION: Among preschool-aged children with gastroenteritis seeking ED care, oral ondansetron administration was associated with a reduction in index ED visit intravenous fluid administration; it was not associated with intravenous fluids administered within 72 hours, hospitalization, or vomiting and diarrhea in the 24 hours following discharge.

Derivation of the Pediatric Acute Gastroenteritis Risk Score to Predict Moderate-to-Severe Acute Gastroenteritis.

OBJECTIVES: Although most acute gastroenteritis (AGE) episodes in children rapidly self-resolve, some children go on to experience more significant and prolonged illness. We sought to develop a prognostic score to identify children at risk of experiencing moderate-to-severe disease after an index emergency department (ED) visit. METHODS: Data were collected from a cohort of children 3 to 48 months of age diagnosed with AGE in 16 North American pediatric EDs. Moderate-to-severe AGE was defined as a Modified Vesikari Scale (MVS) score ≥9 during the 14-day post-ED visit. A clinical prognostic model was derived using multivariable logistic regression and converted into a simple risk score. The model's accuracy was assessed for moderate-to-severe AGE and several secondary outcomes. RESULTS: After their index ED visit, 19% (336/1770) of participants developed moderate-to-severe AGE. Patient age, number of vomiting episodes, dehydration status, prior ED visits, and intravenous rehydration were associated with MVS ≥9 in multivariable regression. Calibration of the prognostic model was strong with a P value of 0.77 by the Hosmer-Lemenshow goodness-of-fit test, and discrimination was moderate with an area under the receiver operator characteristic curve of 0.68 (95% confidence interval [CI] 0.65-0.72). Similarly, the model was shown to have good calibration when fit to the secondary outcomes of subsequent ED revisit, intravenous rehydration, or hospitalization within 72 hours after the index visit. CONCLUSIONS: After external validation, this new risk score may provide clinicians with accurate prognostic insight into the likely disease course of children with AGE, informing disposition decisions, anticipatory guidance, and follow-up care.

The Challenge of Bioinequality: Addressing the Health Impact of Unequal Treatment Through Law.

Global social movements for justice have called for better legal responses to the harms of inequality. These inequalities have traditionally been dealt with in the political sphere and legal measures to address them have taken little account of emerging knowledge about the biological impact of unequal treatment. We use the concept 'bioinequalities' to foreground the relationship increasingly articulated in studies that show that social stress and trauma associated with unequal treatment have a significant epigenetic and intergenerational impact on the body. This article proposes a way to address the health harms that result from inequality by drawing on the existing concept of the 'hostile environment' in sexual harassment jurisprudence in Australia. Our 'bioinequality' approach focuses on the way that inequality operates in and as a hostile and harmful environment for the embodied and embedded beings that live in it. We examine the possibilities of using the concept of a hostile environment to more effectively address discriminatory harms alongside a positive duty to create non-hostile environments. In so doing we offer a broader, bioscientifically informed approach that can inform equality laws in other jurisdictions.

Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children.

BACKGROUND: Acute gastroenteritis develops in millions of children in the United States every year, and treatment with probiotics is common. However, data to support the use of probiotics in this population are limited. METHODS: We conducted a prospective, randomized, double-blind trial involving children 3 months to 4 years of age with acute gastroenteritis who presented to one of 10 U.S. pediatric emergency departments. Participants received a 5-day course of Lactobacillus rhamnosus GG at a dose of 1×1010 colony-forming units twice daily or matching placebo. Follow-up surveys were conducted daily for 5 days and again 14 days after enrollment and 1 month after enrollment. The primary outcome was moderate-to-severe gastroenteritis, which was defined as an illness episode with a total score on the modified Vesikari scale of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease), within 14 days after enrollment. Secondary outcomes included the duration and frequency of diarrhea and vomiting, the duration of day-care absenteeism, and the rate of household transmission (defined as the development of symptoms of gastroenteritis in previously asymptomatic household contacts). RESULTS: Among the 971 participants, 943 (97.1%) completed the trial. The median age was 1.4 years (interquartile range, 0.9 to 2.3), and 513 participants (52.9%) were male. The modified Vesikari scale score for the 14-day period after enrollment was 9 or higher in 55 of 468 participants (11.8%) in the L. rhamnosus GG group and in 60 of 475 participants (12.6%) in the placebo group (relative risk, 0.96; 95% confidence interval, 0.68 to 1.35; P=0.83). There were no significant differences between the L. rhamnosus GG group and the placebo group in the duration of diarrhea (median, 49.7 hours in the L. rhamnosus GG group and 50.9 hours in the placebo group; P=0.26), duration of vomiting (median, 0 hours in both groups; P=0.17), or day-care absenteeism (median, 2 days in both groups; P=0.67) or in the rate of household transmission (10.6% and 14.1% in the two groups, respectively; P=0.16). CONCLUSIONS: Among preschool children with acute gastroenteritis, those who received a 5-day course of L. rhamnosus GG did not have better outcomes than those who received placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01773967 .).

Association Between Diarrhea Duration and Severity and Probiotic Efficacy in Children With Acute Gastroenteritis.

INTRODUCTION: It is unclear whether the alleged efficacy of probiotics in childhood acute gastroenteritis depends on the duration and severity of symptoms before treatment. METHODS: Preplanned secondary analysis of 2 randomized placebo-controlled trials in children 3-48 months of age was conducted in 16 emergency departments in North America evaluating the efficacy of 2 probiotic products (Lactobacillus rhamnosus GG and a combination probiotic: L. rhamnosus and L. helveticus). Participants were categorized in severity groups according to the duration (<24, 24-<72, and ≥72 hours) and the frequency of diarrhea episodes in the 24 hours (≤3, 4-5, and ≥6) before presentation. We used regression models to assess the interaction between pretreatment diarrhea severity groups and treatment arm (probiotic or placebo) in the presence of moderate-to-severe gastroenteritis (Modified Vesikari Scale score ≥9). Secondary outcomes included diarrhea frequency and duration, unscheduled healthcare provider visits, and hospitalization. RESULTS: A total of 1,770 children were included, and 882 (50%) received a probiotic. The development of moderate-to-severe gastroenteritis symptoms after the initiation of treatment did not differ between groups (probiotic-18.4% [162/882] vs placebo-18.3% [162/888]; risk ratio 1.00; 95% confidence interval 0.87, 1.16; P = 0.95). There was no evidence of interaction between baseline severity and treatment (P = 0.61) for the primary or any of the secondary outcomes: diarrhea duration (P = 0.88), maximum diarrheal episodes in a 24-hour period (P = 0.87), unscheduled healthcare visits (P = 0.21), and hospitalization (P = 0.87). DISCUSSION: In children 3-48 months with acute gastroenteritis, the lack of effect of probiotics is not explained by the duration of symptoms or frequency of diarrheal episodes before presentation.

Association between Age, Weight, and Dose and Clinical Response to Probiotics in Children with Acute Gastroenteritis.

BACKGROUND: Gastroenteritis is a common and impactful disease in childhood. Probiotics are often used to treat acute gastroenteritis (AGE); however, in a large multicenter randomized controlled trial (RCT) in 971 children, Lactobacillus rhamnosus GG (LGG) was no better than placebo in improving patient outcomes. OBJECTIVES: We sought to determine whether the effect of LGG is associated with age, weight z score and weight percentile adjusted for age and sex, or dose per kilogram administered. METHODS: This was a preplanned secondary analysis of a multicenter double-blind RCT of LGG 1 × 1010 CFU twice daily for 5 d or placebo in children 3-48 mo of age with AGE. Our primary outcome was moderate to severe gastroenteritis. Secondary outcomes included diarrhea and vomiting frequency and duration, chronic diarrhea, and side effects. We used multivariable linear and nonlinear models testing for interaction effects to assess outcomes by age, weight z score and weight percentile adjusted for age and sex, and dose per kilogram of LGG received. RESULTS: A total of 813 children (84%) were included in the analysis; 413 received placebo and 400 LGG. Baseline characteristics were similar between treatment groups. There were no differential interaction effects across ranges of age (P-interaction = 0.32), adjusted weight z score (P-interaction = 0.43), adjusted weight percentile (P-interaction = 0.45), or dose per kilogram of LGG received (P-interaction = 0.28) for the primary outcome. Whereas we found a statistical association favoring placebo at the extremes of adjusted weight z scores for the number of vomiting episodes (P-interaction = 0.02) and vomiting duration (P-interaction = 0.0475), there were no statistically significant differences in other secondary outcome measures (all P-interactions > 0.05). CONCLUSIONS: LGG does not improve outcomes in children with AGE regardless of the age, adjusted weight z score, and adjusted weight percentile of participants, or the probiotic dose per kilogram received. These results further strengthen the conclusions of low risk of bias clinical trials which demonstrate that LGG provides no clinical benefit in children with AGE.This trial was registered at clinicaltrials.gov as NCT01773967.

Differential item functioning of the Arm function in Multiple Sclerosis Questionnaire (AMSQ) by language, a study in six countries.

BACKGROUND: The Arm function in Multiple Sclerosis Questionnaire (AMSQ) has been developed as a self-reported measure of arm and hand functioning for patients with multiple sclerosis (MS). The AMSQ was originally developed in Dutch and to date translated into five languages (i.e. English, German, Spanish, French, and Italian). OBJECTIVE: The aim of this study was to evaluate differential item functioning (DIF) of the AMSQ in these languages. METHODS: We performed DIF analyses, using "language" as the polytomous group variable. To detect DIF, logistic regression and item response theory principles were applied. Multiple logistic regression models were evaluated. We used a pseudo R2 value of 0.02 or more as the DIF threshold. RESULTS: A total of 1733 male and female patients with all subtypes of MS were included. The DIF analysis for the whole dataset showed no uniform or non-uniform DIF on any of the 31 items. All R2 values were below 0.02. CONCLUSION: The AMSQ is validated in six languages. All items have the same meaning to MS patients in Dutch, English, German, Spanish, French, and Italian. This validation study enables use of the AMSQ in international studies, for monitoring treatment response and disease progression.

Assessment of Nonroutine Events During Intubation After Pediatric Trauma.

BACKGROUND: Intubation in the early postinjury phase can be a high-risk procedure associated with an increased risk of mortality when delayed. Nonroutine events (NREs) are workflow disruptions that can be latent safety threats in high-risk settings and may contribute to adverse outcomes. MATERIALS AND METHODS: We reviewed videos of intubations of injured children (age<17 y old) in the emergency department occurring between 2014 and 2018 to identify NREs occurring between the decision to intubate and successful intubation ("critical window"). RESULTS: Among 34 children requiring intubation, the indications included GCS≤8 (n = 20, 58.8%), cardiac arrest (n = 6, 17.6%), airway protection (n = 5, 14.7%), and respiratory failure (n = 3, 8.8%). The median duration of the "critical window" was 7.5 min (range 1.4-27.5 min), with a median of six NREs per case in this period (range 2-30). Most NREs (n = 159, 61.9%) delayed workflow, with 31 (12.1%) of these delays each lasting more than one minute. Eighty-seven NREs (33.9%) had a potential for harm but did not lead to direct patient harm. The most common NREs directly related to the intubation process were poor positioning for intubation (n = 23, 8.9%) and difficulty passing the endotracheal tube (n = 5, 1.9%), with most being attributed to the anesthesiologist performing the intubation (n = 51, range 0-7). CONCLUSIONS: Workflow disruptions related to nonroutine events were frequent during pediatric trauma intubation and were often associated with delays and potential for patient harm. Interventions for improving the efficiency and timeliness of the critical window should focus on adherence to intubation protocol and improving communication and teamwork related to tasks in this phase.

Personal Protective Equipment Adherence of Pediatric Resuscitation Team Members During the COVID-19 Pandemic.

STUDY OBJECTIVE: During the COVID-19 pandemic, health care workers have had the highest risk of infection among essential workers. Although personal protective equipment (PPE) use is associated with lower infection rates, appropriate use of PPE has been variable among health care workers, even in settings with COVID-19 patients. We aimed to evaluate the patterns of PPE adherence during emergency department resuscitations that included aerosol-generating procedures. METHODS: We conducted a retrospective, video-based review of pediatric resuscitations involving one or more aerosol-generating procedures during the first 3 months of the COVID-19 pandemic in the United States (March to June 2020). Recommended adherence (complete, inadequate, absent) with 5 PPE items (headwear, eyewear, masks, gowns, gloves) and the duration of potential exposure were evaluated for individuals in the room after aerosol-generating procedure initiation. RESULTS: Among the 345 health care workers observed during 19 resuscitations, 306 (88.7%) were nonadherent (inadequate or absent adherence) with the recommended use of at least 1 PPE type at some time during the resuscitation, 23 (6.7%) of whom had no PPE. One hundred and forty health care workers (40.6%) altered or removed at least 1 type of PPE during the event. The aggregate time in the resuscitation room for health care workers across all events was 118.7 hours. During this time, providers had either absent or inadequate eyewear for 46.4 hours (39.1%) and absent or inadequate masks for 35.2 hours (29.7%). CONCLUSION: Full adherence with recommended PPE use was limited in a setting at increased risk for SARS-CoV-2 virus aerosolization. In addition to ensuring appropriate donning, approaches are needed for ensuring ongoing adherence with PPE recommendations during exposure.

Factors Associated With Nonadherence in an Emergency Department-based Multicenter Randomized Clinical Trial of a Probiotic in Children With Acute Gastroenteritis.

ABSTRACT: Nonadherence in clinical trials affects safety and efficacy determinations. Predictors of nonadherence in pediatric acute illness trials are unknown. We sought to examine predictors of nonadherence in a multicenter randomized trial of 971 children with acute gastroenteritis receiving a 5-day oral course of Lactobacillus rhamnosus GG or placebo. Adherence, defined as consuming all doses of the product, was reported by the parents and recorded during daily follow-up contacts. Of 943 patients with follow-up data, 766 (81.2%) were adherent. On multivariate analysis, older age (OR 1.19; 95% CI: 1.00-1.43), increased vomiting duration (OR 1.23; 95% CI: 1.05-1.45), higher dehydration score (OR 1.23, 95% CI: 1.07-1.42), and hospitalization following ED discharge (OR 4.16, 95% CI: 1.21--14.30) were factors associated with nonadherence; however, those with highest severity scores were more likely to adhere (OR 0.87, 95% CI: 0.80-0.95). These data may inform strategies and specific targets to maximize adherence in future pediatric trials.

Effect of Family Presence on Advanced Trauma Life Support Task Performance During Pediatric Trauma Team Evaluation.

IMPORTANCE: In many hospitals, family members are separated from their children during the early phases of trauma care. Including family members during this phase of trauma care varies by institution and is limited by concerns for adverse effects on clinical care. OBJECTIVE: The aim of this study is to evaluate the effect of family presence (FP) on advanced trauma life support primary and secondary survey task performance by pediatric trauma teams. We hypothesized that trauma care with FP would be noninferior to care when families were absent. DESIGN: We performed a retrospective video review of consecutive pediatric trauma evaluations. Family presence status was determined by availability of the family. SETTING: The study was conducted at an American College of Surgeons-designated level I pediatric trauma center that serves the Washington, DC, metropolitan area. PARTICIPANTS: Participants included patients younger than 16 years of age who met trauma activation criteria and were evaluated by the trauma team in our emergency department. OUTCOME MEASURES: We compared task performance between patients with and without FP. RESULTS: Video recordings of 135 trauma evaluations were reviewed. Family was present for 88 (65%) evaluations. Patients with FP were younger (mean age, 6.4 years [SD = 4.1] vs 9.0 years [SD = 4.9]; P < 0.001) and more likely to have sustained blunt injuries (95% vs 85%, P = 0.03). Noninferiority of frequency and timeliness of completion of all primary survey tasks were confirmed for evaluations with FP. Noninferiority of frequencies of secondary survey task completion was confirmed for most tasks except for examination of the neck, pelvis, and upper extremities. Family members did not directly interfere with patient care in any case. CONCLUSIONS: Performance of most advanced trauma life support tasks during pediatric trauma evaluation was not worsened by FP. Our data provide additional evidence supporting FP during the acute management of injured children.

A Pulse Check on Leadership and Teamwork: An Evaluation of the First 5 Minutes of Emergency Department Resuscitation During Pediatric Cardiopulmonary Arrests.

OBJECTIVES: Effective leadership and teamwork are imperative during pediatric cardiopulmonary resuscitations (CPR). The initial phase of pediatric CPR, termed the "first 5 minutes," has significant care delivery gaps in both leadership and team performance. The aim of the study was to describe the performance data of emergency department (ED) teams who performed CPR in a pediatric ED. METHODS: We conducted a retrospective video review of resuscitations involving pediatric patients younger than 21 years who presented in cardiac arrest to a tertiary pediatric ED. Descriptive statistics were used for data analysis. RESULTS: Twenty events met study inclusion criteria. Prearrival task completion included the following: estimated weight (90%), airway set-up (85%), epinephrine dose prepared (84%), defibrillator ready (75%), and intraosseous kit ready (50%). Median prearrival notification time was 5 minutes 34 seconds (interquartile range = 4:44-7:13) with no significant relationship between prearrival time and task completion. Within the first 5 minutes, the team leader provided a care summary in 84%, prioritized tasks in 95%, and assigned roles for airway management (90%), intravenous/intravenous access (63%), and CPR/pulse check (63%). Most critical tasks were completed within 1 minute; however, only 25% had defibrillator pads placed within the 5-minute window. CONCLUSIONS: Our study of leadership and teamwork during the first 5 minutes of pediatric CPR care noted wide variation in team performance. Opportunities for improvements in CPR readiness can be incorporated into education and quality programs to drive improvements in the care of future pediatric patients experiencing cardiac arrest.

IRAK1 Limits TLR3/4- and IFNAR-Driven IL-27 Production through a STAT1-Dependent Mechanism.

IL-27 is a cytokine exerting pleiotropic immunomodulatory effects on a broad spectrum of immune cells. Optimal IL-27 production downstream of TLR3/4 ligand stimulation relies on autocrine type I IFN signaling, defining a first and second phase in IL-27 production. This work shows that IL-1 receptor-associated kinase 1 (IRAK1) limits TLR3/4- and IFNAR-induced IL-27 production. At the mechanistic level, we identified IRAK1 as a novel regulator of STAT1, IRF1, and IRF9. We found hyperactivation of STAT1 together with increased nuclear levels of IRF1 and IRF9 in IRAK1-deficient murine macrophages compared with control cells following stimulation with LPS and poly(I:C). IRAK1-deficient human microglial cells showed higher basal levels of STAT1 and STAT2 compared with control cells. Blocking the kinase activity of TBK1/IKKε in IRAK1 knockdown human microglial cells reduced the high basal levels of STAT1/2, uncovering a TBK1/IKKε kinase-dependent mechanism controlling basal levels of STAT1/2. Stimulating IRAK1 knockdown human microglial cells with IFN-ß led to increased IL-27p28 expression compared with control cells. In IRAK1-deficient murine macrophages, increased IL-27 levels were detected by ELISA following IFN-ß stimulation compared with control macrophages together with increased nuclear levels of p-STAT1, IRF1, and IRF9. Treatment of wild-type and IRAK1-deficient murine macrophages with fludarabine similarly reduced TLR3/4-induced IL-27 cytokine levels. To our knowledge, this work represents the first report placing IRAK1 in the IFNAR pathway and identifies IRAK1 as an important regulator of STAT1, controlling IL-27 production downstream of TLR3/4 and IFNAR signaling pathways.

CNS lymphoma, the Irish experience: A retrospective review of neuropathologically confirmed cases over 10 years.

BACKGROUND: Central nervous system (CNS) lymphoma is rare, representing 2% of all brain tumors. The commonest subtype is diffuse large B-cell lymphoma (DLBCL), with primary T-cell lymphomas (PCNSTL) accounting for ~ 2%. OBJECTIVE: To determine the frequency and describe the key features of CNS lymphoma over a 10-year period in an Irish population. MATERIALS AND METHODS: This retrospective review was carried out using the neuropathology database in Beaumont hospital, the largest of two national neurosurgical centers, to identify all cases of CNS lymphoma from 2007 to 2017. Clinical, radiological, morphological, immunophenotype, and molecular information was recorded where available. RESULTS: We identified 149 cases of CNS lymphoma from 2007 to 2017, which equated to a cumulative incidence rate of 0.4/100,000 persons. Median age at diagnosis was 66 years, and 46% were male. 86% were classified as DLBCL (n = 128), 10% immunodeficiency-associated CNS lymphoma (n = 15), 3% PCNSTL (n = 4), and 1% (n = 2) cases of intravascular large B-cell lymphoma. Location in declining frequency was as follows: supratentorial (n = 125), infratentorial (n = 22), spinal (n = 1), and orbital (n = 1). CONCLUSION: This is the first study in an Irish population to determine a cumulative incidence rate of CNS lymphoma, which is in line with larger international population-based registries. No significant trends in incidence rate have been observed from 2007 to 2017. DLBCL is the commonest subtype encountered. Rare variants including PCNSTL can pose a significant diagnostic challenge, and in this setting, molecular studies can be useful to confirm diagnoses.

New versus old: Implications of evolving diagnostic criteria for relapsing-remitting multiple sclerosis.

The International Panel on Diagnosis of Multiple Sclerosis (MS) recently revised the 2010 McDonald criteria and made recommendations for revision, allowing for the earliest possible, accurate diagnosis of MS. For relapsing-remitting MS, positive, unmatched cerebrospinal fluid oligoclonal bands may substitute for dissemination in time. Symptomatic lesions, including brainstem and spinal cord, may demonstrate dissemination in space or in time if enhancing (with the exception of the optic nerve). Cortical and juxtacortical lesions are equivalent. In this retrospective analysis, we applied revised criteria to 250 patients previously diagnosed with relapsing-remitting MS according to 2010 criteria and assessed for change in diagnostic times. There was a significant improvement in time to diagnosis between 2010 and 2017 groups ( p < 0.01). Median time to diagnosis according to McDonald 2010 was 7.4 months, compared with 2.3 months for McDonald 2017. Use of cerebrospinal fluid results most frequently resulted in a reduction in time to diagnosis. Symptomatic gadolinium-enhancing lesions led to earliest diagnostic times.