Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak.

Importance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, Setting, and Participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure: Respiratory syncytial virus. Main Outcomes and Measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and Relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children.

Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence. Design, Setting, and Participants: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry. Exposure: Administration of steroids within 2 days of admission. Main Outcomes and Measures: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. Results: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators. Conclusions and Relevance: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

SARS-CoV-2 With Concurrent Respiratory Viral Infection as a Risk Factor for a Higher Level of Care in Hospitalized Pediatric Patients.

OBJECTIVE: As of early 2021, there have been over 3.5 million pediatric cases of SARS-CoV-2, including 292 pediatric deaths in the United States. Although most pediatric patients present with mild disease, they are still at risk for developing significant morbidity requiring hospitalization and intensive care unit (ICU) level of care. This study was performed to evaluate if the presence of concurrent respiratory viral infections in pediatric patients admitted to the hospital with SARS-CoV-2 was associated with an increased rate of ICU level of care. DESIGN: A multicenter, international, noninterventional, cross-sectional study using data provided through The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study database. SETTING: The medical ward and ICU of 67 participating hospitals. PATIENTS: Pediatric patients younger than 18 years hospitalized with SARS-CoV-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 922 patients were included. Among these patients, 391 required ICU level care and 31 had concurrent non-SARS-CoV-2 viral coinfection. In a multivariate analysis, after accounting for age, positive blood culture, positive sputum culture, preexisting chronic medical conditions, the presence of a viral respiratory coinfection was associated with need for ICU care (odds ratio, 3.6; 95% confidence interval, 1.6-9.4; P < 0.01). CONCLUSIONS: This study demonstrates an association between concurrent SARS-CoV-2 infection with viral respiratory coinfection and the need for ICU care. Further research is needed to identify other risk factors that can be used to derive and validate a risk-stratification tool for disease severity in pediatric patients with SARS-CoV-2.

Gastrointestinal Manifestations in Hospitalized Children With Acute SARS-CoV-2 Infection and Multisystem Inflammatory Condition: An Analysis of the VIRUS COVID-19 Registry.

BACKGROUND: Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C). METHODS: Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality. RESULTS: Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes. CONCLUSIONS: GI involvement is common in hospitalized children with acute COVID-19 and MIS-C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C.

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).

The Impact of Obesity on Disease Severity and Outcomes Among Hospitalized Children With COVID-19.

OBJECTIVE: To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children. METHODS: This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay. RESULTS: Data from 795 patients (96.4% United States) from 45 sites were analyzed, including 251 (31.5%) with obesity and 544 (68.5%) without. A higher proportion of patients with obesity were adolescents, of Hispanic ethnicity, and had other comorbidities. Those with obesity were also more likely to be diagnosed with multisystem inflammatory syndrome in children (35.7% vs 28.1%, P = .04) and had higher ICU admission rates (57% vs 44%, P < .01) with more critical illness (30.3% vs 18.3%, P < .01). Obesity had more impact on acute COVID-19 severity than on multisystem inflammatory syndrome in children presentation. The adjusted odds ratio for critical illness with obesity was 3.11 (95% confidence interval: 1.8-5.3). Patients with obesity had longer adjusted length of stay (exponentiated parameter estimate 1.3; 95% confidence interval: 1.1-1.5) compared with patients without obesity but did not have increased mortality risk due to COVID-19 (2.4% vs 1.5%, P = .38). CONCLUSION: In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness.

Resources and Costs Associated With Repeated Admissions to PICUs.

OBJECTIVE: To determine the costs and hospital resource use from all PICU patients readmitted with a PICU stay within 12 months of hospital index discharge. DESIGN: Cross-sectional, retrospective cohort study using Pediatric Health Information System. SETTING: Fifty-two tertiary children's hospitals. SUBJECTS: Pediatric patients under 18 years old admitted to the PICU from January 1, 2016, to December 31, 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and costs of care were compared between those with readmission requiring PICU care and those with only a single PICU admission per annum. In this 2-year cohort, there were 239,157 index PICU patients of which 36,970 (15.5%) were readmitted and required PICU care during the 12 months following index admission. The total hospital cost for all index admissions and readmissions was $17.3 billion, of which 21.5% ($3.71 billion) were incurred during a readmission stay involving care in the PICU; of the 3,459,079 hospital days, 20.3% (702,200) were readmission days including those where PICU care was required. Of the readmitted patients, 11,703 (30.0%) received only PICU care, accounting for $662 million in costs and 110,215 PICU days. Although 43.6% of all costs were associated with patients who required readmission, these patients only accounted for 15.5% of the index patients and 28% of index hospitalization expenditures. More patients in the readmitted group had chronic complex conditions at index discharge compared with those not readmitted (83.9% vs 54.9%; p < 0.001). Compared with those discharged directly to home without home healthcare, patients discharged to a skilled nursing facility had 18% lower odds of readmission (odds ratio 0.82 [95% CI, 0.75-0.89]; p < 0.001) and those discharged home with home healthcare had 43% higher odds of readmission (odds ratio, 1.43 [95% CI, 1.36-1.51]; p < 0.001). CONCLUSIONS: Repeated admissions with PICU care resulted in significant direct medical costs and resource use for U.S. children's hospitals.

Sustained Improvement in Tracheal Intubation Safety Across a 15-Center Quality-Improvement Collaborative: An Interventional Study From the National Emergency Airway Registry for Children Investigators.

OBJECTIVES: To evaluate the effect of a tracheal intubation safety bundle on adverse tracheal intubation-associated events across 15 PICUs. DESIGN: Multicenter time-series study. SETTING: PICUs in the United States. PATIENTS: All patients received tracheal intubations in ICUs. INTERVENTIONS: We implemented a tracheal intubation safety bundle as a quality-improvement intervention that includes: 1) quarterly site benchmark performance report and 2) airway safety checklists (preprocedure risk factor, approach, and role planning, preprocedure bedside "time-out," and immediate postprocedure debriefing). We define each quality-improvement phase as baseline (-24 to -12 mo before checklist implementation), benchmark performance reporting only (-12 to 0 mo before checklist implementation), implementation (checklist implementation start to time achieving > 80% bundle adherence), early bundle adherence (0-12 mo), and sustained (late) bundle adherence (12-24 mo). Bundle adherence was defined a priori as greater than 80% of checklist use for tracheal intubations for 3 consecutive months. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the adverse tracheal intubation-associated event, and secondary outcomes included severe tracheal intubation-associated events, multiple tracheal intubation attempts, and hypoxemia less than 80%.From January 2013 to December 2015, out of 19 participating PICUs, 15 ICUs (79%) achieved bundle adherence. Among the 15 ICUs, the adverse tracheal intubation-associated event rates were baseline phase: 217/1,241 (17.5%), benchmark reporting only phase: 257/1,750 (14.7%), early 0-12 month complete bundle compliance phase: 247/1,591 (15.5%), and late 12-24 month complete bundle compliance phase: 137/1,002 (13.7%). After adjusting for patient characteristics and clustering by site, the adverse tracheal intubation-associated event rate significantly decreased compared with baseline: benchmark: odds ratio, 0.83 (0.72-0.97; p = 0.016); early bundle: odds ratio, 0.80 (0.63-1.02; p = 0.074); and late bundle odds ratio, 0.63 (0.47-0.83; p = 0.001). CONCLUSIONS: Effective implementation of a quality-improvement bundle was associated with a decrease in the adverse tracheal intubation-associated event that was sustained for 24 months.

Development of an o-pthalaldehyde (OPA) assay to measure protein content in Ricin Vaccine E. coli (RVEc™).

A recombinant ricin vaccine from E. coli (RVEc™), was developed at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) and assessed in an FDA sponsored Phase 1a clinical trial. At the maximum dosage, two of the study participants developed physiological responses that were elevated to the level of severe adverse reactions. To stay within safe dosing guidelines, the FDA recommended that an assay be developed to accurately quantify the recombinant protein content in the vaccine. The RVEc™ vaccine Final Drug Product (FDP) contains the adjuvant Alhydrogel®, which by its colloidal nature interferes with most conventional protein assay methods. We decided to develop an assay measuring RVEc™ FDP using o-pthalaldehyde (OPA) reagent. The OPA reagent reacts to the primary amines and lysine side chains of proteins in the presence of a thiol under alkaline conditions with a quantifiable fluorescent signature, but does not react with Alhydrogel®. Protein content in the RVEc™ FDP can be determined by comparing the fluorescence of the test sample to the fluorescence of a standard curve of defined concentration. Each phase of the assay was tested to optimize and simplify the assay procedure. The accuracy, specificity, reproducibility, and stability of the assay were evaluated. Results indicated that the optimized and modified OPA assay was simple and able to quantify antigen concentration from a standard curve in the 25 µg/mL-600 µg/mL range. The assay accuracy and coefficient of variation (CV) was 95% and less than 8%, respectively, when determining the ricin protein content in the 200 µg/mL vialed RVEc™ FDP. The assay was simple to perform and used conventional laboratory equipment. This assay could be adapted to measure the protein content in the FDP of other vaccines, but with the proviso that each step of the assay would need to be optimized for each antigen.

Impact of Failure of Noninvasive Ventilation on the Safety of Pediatric Tracheal Intubation.

OBJECTIVES: Noninvasive ventilation is widely used to avoid tracheal intubation in critically ill children. The objective of this study was to assess whether noninvasive ventilation failure was associated with severe tracheal intubation-associated events and severe oxygen desaturation during tracheal intubation. DESIGN: Prospective multicenter cohort study of consecutive intubated patients using the National Emergency Airway Registry for Children registry. SETTING: Thirteen PICUs (in 12 institutions) in the United States and Canada. PATIENTS: All patients undergoing tracheal intubation in participating sites were included. Noninvasive ventilation failure group included children with any use of high-flow nasal cannula, continuous positive airway pressure, or bilevel noninvasive ventilation in the 6 hours prior to tracheal intubation. Primary tracheal intubation group included children without exposure to noninvasive ventilation within 6 hours before tracheal intubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Severe tracheal intubation-associated events (cardiac arrest, esophageal intubation with delayed recognition, emesis with aspiration, hypotension requiring intervention, laryngospasm, pneumothorax, pneumomediastinum) and severe oxygen desaturation (< 70%) were recorded prospectively. The study included 956 tracheal intubation encounters; 424 tracheal intubations (44%) occurred after noninvasive ventilation failure, with a median of 13 hours (interquartile range, 4-38 hr) of noninvasive ventilation. Noninvasive ventilation failure group included more infants (47% vs 33%; p < 0.001) and patients with a respiratory diagnosis (56% vs 30%; p < 0.001). Noninvasive ventilation failure was not associated with severe tracheal intubation-associated events (5% vs 5% without noninvasive ventilation; p = 0.96) but was associated with severe desaturation (15% vs 9% without noninvasive ventilation; p = 0.005). After controlling for baseline differences, noninvasive ventilation failure was not independently associated with severe tracheal intubation-associated events (p = 0.35) or severe desaturation (p = 0.08). In the noninvasive ventilation failure group, higher FIO2 before tracheal intubation (≥ 70%) was associated with severe tracheal intubation-associated events. CONCLUSIONS: Critically ill children are frequently exposed to noninvasive ventilation before intubation. Noninvasive ventilation failure was not independently associated with severe tracheal intubation-associated events or severe oxygen desaturation compared to primary tracheal intubation.

Implementation of a "threat and error" model in complex neonatal cardiac surgery patients to identify quality improvement opportunities.

INTRODUCTION: Neonates undergoing surgery for congenital heart disease are vulnerable to adverse events. Conventional quality improvement processes centring on mortality and significant morbidity leave a gap in the identification of systematic processes that, though not directly linked to an error, may still contribute to adverse outcomes. Implementation of a multidisciplinary "flight path" process for surgical patients may be used to identify modifiable threats and errors and generate action items, which may lead to quality improvement. METHODS: A retrospective review of our neonatal "flight path" initiative was performed. Within 72 hours of a cardiac surgery, a meeting of the multidisciplinary patient care team occurs. A "flight path" is generated, graphically illustrating the patient's hospital course. Threats, errors, or unintended consequences are identified. Action items are generated, and a working group is formed to address the items. A patient's flight path is updated weekly until discharge. The errors and action items are logged into a database, which is analysed quarterly to identify trends. RESULTS: Thirty one patients underwent flight path review over a 1-year period; 22.5% (N = 7) of patients had an error-free "flight." Eleven action items were generated - four from identified errors and seven from identified threats. Nine action items were completed. CONCLUSIONS: Flight path reviews of congenital cardiac patients can be generated with few resources and aid in the detection of quality improvement opportunities. The regular multidisciplinary meetings that occur as a part of the flight path review process can promote inter-professional teamwork.

Assessment of an Unplanned Extubation Bundle to Reduce Unplanned Extubations in Critically Ill Neonates, Infants, and Children.

Importance: Unplanned extubations (UEs) in children contribute to significant morbidity and mortality, with an arbitrary benchmark target of less than 1 UE per 100 ventilator days. However, there have been no multicenter initiatives to reduce these events. Objective: To determine if a multicenter quality improvement initiative targeting all intubated neonatal and pediatric patients is associated with a reduction in UEs and morbidity associated with UE events. Design, Setting, and Participants: This multicenter quality improvement initiative enrolled patients from pediatric, neonatal, and cardiac intensive care units (ICUs) in 43 participating children's hospitals from March 2016 to December 2018. All patients with an endotracheal tube requiring mechanical ventilation were included in the study. Interventions: Participating hospitals implemented a quality improvement bundle to reduce UEs, which included standardized anatomic reference points and securement methods, protocol for high-risk situations, and multidisciplinary apparent cause analyses. Main Outcomes and Measures: The main outcome measures for this study included bundle compliance with each factor tested and UE rates on the center level and on the cohort level. Results: Among the 43 children's hospitals, the quality improvement initiative was associated with an aggregate 24.1% reduction in UE events, from a baseline rate of 1.135 UEs per 100 ventilator days to 0.862 UEs per 100 ventilator days. Across ICU settings studied, the pediatric ICU and neonatal ICU demonstrated centerline shifts, with an absolute reduction in events of 20.6% (from a baseline rate of 0.729 UEs per 100 ventilator days to 0.579 UEs per 100 ventilator days) and 17.6% (from a baseline rate of 1.555 UEs per 100 ventilator days to 1.282 UEs per 100 ventilator days), respectively. Most UEs required reintubation within 1 hour (mean of 120 of 206 events per month [58.3%]), followed by UEs that did not require reintubation (mean of 78 of 206 events per month [37.9%]) and UEs that resulted in cardiovascular collapse (mean of 8 of 206 events per month [3.9%]). Cardiovascular collapse events represented the most significant consequence of UE studied, and the collaborative reduced these UE events by 36.6%, from a study baseline rate of 0.041 UEs per 100 ventilator days to 0.026 UEs per 100 ventilator days. Conclusions and Relevance: This multicenter quality improvement initiative was associated with a reduction in UEs across different pediatric populations in diverse settings. A significant reduction in event rate and rate of harm (cardiovascular collapse) was observed, which was sustained over the time course of the intervention. This quality improvement process and UE bundle may be considered standard of care for pediatric hospitals in the future.

Depression and Anxiety Screening in Adolescents With Diabetes.

Adolescents with diabetes are at increased risk for depression and anxiety, which when untreated negatively affects diabetes control. During a 6-month period, the Patient Health Questionnaire for Depression and Anxiety (PHQ-4) screening tool was utilized. Those with a positive screen then completed the Patient Health Questionnaire for Adolescents (PHQ-A) and the Generalized Anxiety Disorder 7-item (GAD-7) scale. In this article, we report on the correlations in outcomes between the PHQ-4 and the PHQ-A and GAD-7 and its clinical utility for determining the need for standard versus acute behavioral health care. Over 6 months, 77 patients aged 10 to 18 years screened positive on the PHQ-4. Thirty-two patients had positive screening with the PHQ-A and/or the GAD-7. Thoughts of self-harm were reported by 13 (40%), with 1 experiencing current/active symptoms. The PHQ-4 as a screening tool was able to identify adolescents with symptoms of depression and/or anxiety who would benefit from further evaluation by a behavioral health provider.

Impact of Kamishibai Card Process on Compliance With the Central Venous Line Maintenance Bundle.

BACKGROUND: The Kamishibai Card (K-Card) process is a storytelling methodology designed to help identify barriers and remove or redesign them. PURPOSE: The purpose of this study was to evaluate the effectiveness of the K-Card process for central venous line (CVL) maintenance bundle compliance in a pediatric intensive care unit. METHODS: A retrospective evaluation of the implementation of the K-Card process was performed using a pretest and posttest design. RESULTS: A total of 1003 central venous catheter maintenance observations were completed during the study period. A statistically significant change was noted in one element of the CVL maintenance bundle, tubing timed and dated. The most frequent cause for noncompliance with the CVL maintenance bundle was incomplete communication during handoff, followed by device associated factors (failure of device, use of device, and availability of device). CONCLUSIONS: The K-Card process had a positive impact on CVL maintenance bundle compliance in the study setting.

Standardized Implementation of Evidence-based Guidelines to Decrease Blood Transfusions in Pediatric Intensive Care Units.

INTRODUCTION: Despite evidence that red blood cell (RBC) transfusions may be associated with more harm than benefit, current transfusion practices vary significantly. This multicenter, quality improvement study aimed to sustainably decrease the rate of RBC transfusions in pediatric intensive care units (PICUs). METHODS: This 16-month prospective study included 5 PICUs. We implemented a standardized project plan including education, bedside tools, real-time reminders, and email feedback. We collected data from consecutive transfusions during pre-implementation (Phase I), postimplementation (Phase II), and post-stabilization phases (Phase III). RESULTS: Of the 2,064 RBC transfusions, we excluded 35% (N = 729) from analysis in patients undergoing extracorporeal membrane oxygenation. Transfusion/1,000 admissions improved throughout the study periods from a baseline 209.6 -199.8 in Phase II and 195.8 in Phase III (P value < 0.05). There were fewer transfusions outside of the hemoglobin threshold guideline, decreasing from 81% of transfusions outside of guidelines in Phase I to 74% in Phases II and III, P < 0.05. Study phase, site, co-management status, service of requesting provider, admit reason, previous transfusion status, and age were associated with transfusion above guideline threshold. CONCLUSIONS: Multicenter collaboration can successfully deploy a standardized plan that adheres to implementation science principles to sustainably decrease the rate of RBC transfusion outside of guideline thresholds. However, we did not decrease the total number of transfusions in our study. The complexity of multiple specialties co-managing patients is common in the contemporary PICU. Educational initiatives aimed at one specialty may have limited effectiveness in a multifaceted system of care.

Downward Trend in Pediatric Resident Laryngoscopy Participation in PICUs.

OBJECTIVES: As of July 2013, pediatric resident trainee guidelines in the United States no longer require proficiency in nonneonatal tracheal intubation. We hypothesized that laryngoscopy by pediatric residents has decreased over time, with a more pronounced decrease after this guideline change. DESIGN: Prospective cohort study. SETTING: Twenty-five PICUs at various children's hospitals across the United States. PATIENTS: Tracheal intubations performed in PICUs from July 2010 to June 2016 in the multicenter tracheal intubation database (National Emergency Airway Registry for Children). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Prospective cohort study in which all primary tracheal intubations occurring in the United States from July 2010 to June 2016 in the multicenter tracheal intubation database (National Emergency Airway Registry for Children) were analyzed. Participating PICU leaders were also asked to describe their local airway management training for residents. Resident participation trends over time, stratified by presence of a Pediatric Critical Care Medicine fellowship and airway training curriculum for residents, were described. A total of 9,203 tracheal intubations from 25 PICUs were reported. Pediatric residents participated in 16% of tracheal intubations as first laryngoscopists: 14% in PICUs with a Pediatric Critical Care Medicine fellowship and 34% in PICUs without one (p < 0.001). Resident participation decreased significantly over time (3.4% per year; p < 0.001). The decrease was significant in ICUs with a Pediatric Critical Care Medicine fellowship (p < 0.001) but not in ICUs without one (p = 0.73). After adjusting for site-level clustering, patient characteristics, and Pediatric Critical Care Medicine fellowship presence, the Accreditation Council for Graduate Medical Education guideline change was not associated with lower participation by residents (odds ratio, 0.86; 95% CI, 0.59-1.24; p = 0.43). The downward trend of resident participation was similar regardless of the presence of an airway curriculum for residents. CONCLUSION: Laryngoscopy by pediatric residents has substantially decreased over time. This downward trend was not associated with the 2013 Accreditation Council for Graduate Medical Education change in residency requirements.

A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A.

Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC50 values ⩽1µM and 11 effective at ⩽2µM in an ex vivo assay.

Family Presence During Pediatric Tracheal Intubations.

IMPORTANCE: Family-centered care, which supports family presence (FP) during procedures, is now a widely accepted standard at health care facilities that care for children. However, there is a paucity of data regarding the practice of FP during tracheal intubation (TI) in pediatric intensive care units (PICUs). Family presence during procedures in PICUs has been advocated. OBJECTIVE: To describe the current practice of FP during TI and evaluate the association with procedural and clinician (including physician, respiratory therapist, and nurse practitioner) outcomes across multiple PICUs. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study in which all TIs from July 2010 to March 2014 in the multicenter TI database (National Emergency Airway Registry for Children [NEAR4KIDS]) were analyzed. Family presence was defined as a family member present during TI. This study included all TIs in patients younger than 18 years in 22 international PICUs. EXPOSURES: Family presence and no FP during TI in the PICU. MAIN OUTCOMES AND MEASURES: The percentage of FP during TIs. First attempt success rate, adverse TI-associated events, multiple attempts (≥ 3), oxygen desaturation (oxygen saturation as measured by pulse oximetry <80%), and self-reported team stress level. RESULTS: A total of 4969 TI encounters were reported. Among those, 81% (n = 4030) of TIs had documented FP status (with/without). The median age of participants with FP was 2 years and 1 year for those without FP. The average percentage of TIs with FP was 19% and varied widely across sites (0%-43%; P < .001). Tracheal intubations with FP (vs without FP) were associated with older patients (median, 2 years vs 1 year; P = .04), lower Paediatric Index of Mortality 2 score, and pediatric resident as the first airway clinician (23%, n = 179 vs 18%, n = 584; odds ratio [OR], 1.4; 95% CI, 1.2-1.7). Tracheal intubations with FP and without FP were no different in the first attempt success rate (OR, 1.00; 95% CI, 0.85-1.18), adverse TI-associated events (any events: OR, 1.06; 95% CI, 0.85-1.30 and severe events: OR, 1.04; 95% CI, 0.75-1.43), multiple attempts (≥ 3) (OR, 1.03; 95% CI, 0.82-1.28), oxygen desaturation (oxygen saturation <80%) (OR, 0.97; 95% CI, 0.80-1.18), or self-reported team stress level (OR, 1.09; 95% CI, 0.92-1.31). This result persisted after adjusting for patient and clinician confounders. CONCLUSIONS AND RELEVANCE: Wide variability exists in FP during TIs across PICUs. Family presence was not associated with first attempt success, adverse TI-associated events, oxygen desaturation (<80%), or higher team stress level. Our data suggest that FP during TI can safely be implemented as part of a family-centered care model in the PICU.

A Bedside Decision Tree for Use of Saline With Endotracheal Tube Suctioning in Children.

BACKGROUND: Endotracheal tube suctioning is necessary for patients receiving mechanical ventilation. Studies examining saline instillation before suctioning have demonstrated mixed results. METHODS: A prospective study to evaluate whether saline instillation is associated with an increased risk of suctioning-related adverse events in patients 18 years old or younger requiring mechanical ventilation through an endotracheal tube for at least 48 hours when suctioned per protocol using a bedside decision tree. RESULTS: A total of 1986 suctioning episodes (1003 with saline) were recorded in 69 patients. The most common indication for use of saline was thick secretions (87% of episodes). In 586 suctioning episodes, at least 1 adverse event occurred with increased frequency in the saline group (P < .001). Normal saline was more likely to be associated with hemodynamic instability (P = .04), bronchospasm (P < .001), and oxygen desaturation (P < .001). Patient factors associated with adverse events include younger age (P < .001), a cuffed endotracheal tube (P = .001), endotracheal tube diameter of 4.0 mm or less (P < .001), respiratory or hemodynamic indication for intubation (P < .001), underlying respiratory disease (P < .001), and longer duration of mechanical ventilation (P < .001). Saline instillation (P < .001), endotracheal tube size of 4.0 mm or less (P = .03), and comorbid respiratory diseases (P = .03) were associated with an increased risk of adverse events. CONCLUSIONS: Saline instillation before endotracheal tube suctioning is associated with hemodynamic instability, bronchospasm, and transient hypoxemia. Saline should be used cautiously, especially in children with a small endotracheal tube and comorbid respiratory disease.

Critical Care Delivery: The Importance of Process of Care and ICU Structure to Improved Outcomes: An Update From the American College of Critical Care Medicine Task Force on Models of Critical Care.

In 2001, the Society of Critical Care Medicine published practice model guidelines that focused on the delivery of critical care and the roles of different ICU team members. An exhaustive review of the additional literature published since the last guideline has demonstrated that both the structure and process of care in the ICU are important for achieving optimal patient outcomes. Since the publication of the original guideline, several authorities have recognized that improvements in the processes of care, ICU structure, and the use of quality improvement science methodologies can beneficially impact patient outcomes and reduce costs. Herein, we summarize findings of the American College of Critical Care Medicine Task Force on Models of Critical Care: 1) An intensivist-led, high-performing, multidisciplinary team dedicated to the ICU is an integral part of effective care delivery; 2) Process improvement is the backbone of achieving high-quality ICU outcomes; 3) Standardized protocols including care bundles and order sets to facilitate measurable processes and outcomes should be used and further developed in the ICU setting; and 4) Institutional support for comprehensive quality improvement programs as well as tele-ICU programs should be provided.