Bronchiolitis hospitalizations in rural New England: clues to disease prevention.

Background: An improved understanding of the clinico-epidemiology of bronchiolitis hospitalizations, a clinical surrogate of respiratory syncytial virus (RSV) disease, is critical to inform public health strategies for mitigating the in-patient burden of bronchiolitis in early life. Methods: A retrospective chart review was conducted of all bronchiolitis first admissions (N = 295) to the Children's Hospital at Dartmouth-Hitchcock, CHaD, between 1 November 2010 and 31 October 2017 using the relevant International Classification of Diseases (ICD)-9 and ICD-10 codes for this illness. Abstracted data included laboratory confirmation of RSV infection, severity of illness, duration of hospitalization, age at admission in days, weight at admission, prematurity, siblings, and relevant medical pre-existing conditions. Results: Admissions for bronchiolitis were strongly associated with age of the child, the calendar month of an infant's birth, and the presence of older children in the family. Medical risk factors associated with admission included premature birth and underlying cardiopulmonary disease. Conclusion: The very early age of hospitalization emphasizes the high penetration of RSV in the community, by implication the limited protection afforded by maternal antibody, and the complexity of protecting infants from this infection. Plain Language Summary: Although risks for respiratory syncytial virus (RSV)/bronchiolitis hospitalization are well described, few studies have examined, with precision, the age-related frequency and severity of RSV/bronchiolitis. We also explore the implications of RSV clinico-epidemiology for our understanding of the pathogenesis of the disease and development of optimal approaches to prevention.

Capacity Building for a New Multicenter Network Within the ECHO IDeA States Pediatric Clinical Trials Network.

Introduction: Research capacity building is a critical component of professional development for pediatrician scientists, yet this process has been elusive in the literature. The ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN) seeks to implement pediatric trials across medically underserved and rural populations. A key component of achieving this objective is building pediatric research capacity, including enhancement of infrastructure and faculty development. This article presents findings from a site assessment inventory completed during the initial year of the ISPCTN. Methods: An assessment inventory was developed for surveying ISPCTN sites. The inventory captured site-level activities designed to increase clinical trial research capacity for pediatrician scientists and team members. The inventory findings were utilized by the ISPCTN Data Coordinating and Operations Center to construct training modules covering 3 broad domains: Faculty/coordinator development; Infrastructure; Trials/Research concept development. Results: Key lessons learned reveal substantial participation in the training modules, the importance of an inventory to guide the development of trainings, and recognizing local barriers to clinical trials research. Conclusions: Research networks that seek to implement successfully completed trials need to build capacity across and within the sites engaged. Our findings indicate that building research capacity is a multi-faceted endeavor, but likely necessary for sustainability of a unique network addressing high impact pediatric health problems. The ISPCTN emphasis on building and enhancing site capacity, including pediatrician scientists and team members, is critical to successful trial implementation/completion and the production of findings that enhance the lives of children and families.

IDeA States Pediatric Clinical Trials Network for Underserved and Rural Communities.

The National Institutes of Health's Environmental Influences on Child Health Outcomes (ECHO) program aims to study high-priority and high-impact pediatric conditions. This broad-based health initiative is unique in the National Institutes of Health research portfolio and involves 2 research components: (1) a large group of established centers with pediatric cohorts combining data to support longitudinal studies (ECHO cohorts) and (2) pediatric trials program for institutions within Institutional Development Awards states, known as the ECHO Institutional Development Awards States Pediatric Clinical Trials Network (ISPCTN). In the current presentation, we provide a broad overview of the ISPCTN and, particularly, its importance in enhancing clinical trials capabilities of pediatrician scientists through the support of research infrastructure, while at the same time implementing clinical trials that inform future health care for children. The ISPCTN research mission is aligned with the health priority conditions emphasized in the ECHO program, with a commitment to bringing state-of-the-science trials to children residing in underserved and rural communities. ISPCTN site infrastructure is critical to successful trial implementation and includes research training for pediatric faculty and coordinators. Network sites exist in settings that have historically had limited National Institutes of Health funding success and lacked pediatric research infrastructure, with the initial funding directed to considerable efforts in professional development, implementation of regulatory procedures, and engagement of communities and families. The Network has made considerable headway with these objectives, opening two large research studies during its initial 18 months as well as producing findings that serve as markers of success that will optimize sustainability.

Team Science Process Builds Research Coordinators' Voices in a National Pediatric Clinical Trials Network.

Geographically-dispersed teams have become the norm in clinical research collaborations. The Institutional Development Awards (IDeA) Program, first authorized by Congress in 1993 and managed by the National Institute of General Medical Sciences, has been developed for the purpose of broadening the geographic distribution of National Institutes of Health (NIH) funding for biomedical and behavioral research by enhancing the competitiveness for research funding of institutions located in states in which the aggregate success rate for grant applications to the NIH has historically been low. The IDeA States are composed of the Commonwealth of Puerto Rico and the following 23 states: Alaska, Arkansas, Delaware, Hawaii, Idaho, Kansas, Kentucky, Louisiana, Maine, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, South Carolina, South Dakota, Vermont, West Virginia, Wyoming. The Environmental influences on Child Health Outcomes (ECHO) research program's IDeA States Pediatric Clinical Trials Network (ISPCTN) was formed in 2016 with 24 sites within the IDeA states to provide clinical trial access to children in rural and underserved communities while building research capacity and infrastructure. In order to become effective, the network research coordinators used many methods to become more cohesive and productive. One of those methods was the use of Team Science.

Training as an Intervention to Decrease Medical Record Abstraction Errors Multicenter Studies.

Studies often rely on medical record abstraction as a major source of data. However, data quality from medical record abstraction has long been questioned. Electronic Health Records (EHRs) potentially add variability to the abstraction process due to the complexity of navigating and locating study data within these systems. We report training for and initial quality assessment of medical record abstraction for a clinical study conducted by the IDeA States Pediatric Clinical Trials Network (ISPCTN) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) using medical record abstraction as the primary data source. As part of overall quality assurance, study-specific training for medical record abstractors was developed and deployed during study start-up. The training consisted of a didactic session with an example case abstraction and an independent abstraction of two standardized cases. Sixty-nine site abstractors from thirty sites were trained. The training was designed to achieve an error rate for each abstractor of no greater than 4.93% with a mean of 2.53%, at study initiation. Twenty-three percent of the trainees exceeded the acceptance limit on one or both of the training test cases, supporting the need for such training. We describe lessons learned in the design and operationalization of the study-specific, medical record abstraction training program.

Frequency of Desaturation and Association With Hemodynamic Adverse Events During Tracheal Intubations in PICUs.

OBJECTIVES: Oxygen desaturation during tracheal intubation is known to be associated with adverse ICU outcomes in critically ill children. We aimed to determine the occurrence and severity of desaturation during tracheal intubations and the association with adverse hemodynamic tracheal intubation-associated events. DESIGN: Retrospective cohort study as a part of the National Emergency Airway Registry for Children Network's quality improvement project from January 2012 to December 2014. SETTING: International PICUs. PATIENTS: Critically ill children younger than 18 years undergoing primary tracheal intubations in the ICUs. INTERVENTIONS: tracheal intubation processes of care and outcomes were prospectively collected using standardized operational definitions. We defined moderate desaturation as oxygen saturation less than 80% and severe desaturation as oxygen saturation less than 70% during tracheal intubation procedures in children with initial oxygen saturation greater than 90% after preoxygenation. Adverse hemodynamic tracheal intubation-associated event was defined as cardiac arrests, hypo or hypertension requiring intervention, and dysrhythmia. MEASUREMENTS AND MAIN RESULTS: A total of 5,498 primary tracheal intubations from 31 ICUs were reported. Moderate desaturation was observed in 19.3% associated with adverse hemodynamic tracheal intubation-associated events (9.8% among children with moderate desaturation vs 4.4% without desaturation; p < 0.001). Severe desaturation was observed in 12.9% of tracheal intubations, also significantly associated with hemodynamic tracheal intubation-associated events. After adjusting for patient, provider, and practice factors, the occurrence of moderate desaturation was independently associated with hemodynamic tracheal intubation-associated events: adjusted odds ratio 1.83 (95% CI, 1.34-2.51; p < 0.001). The occurrence of severe desaturation was also independently associated with hemodynamic tracheal intubation-associated events: adjusted odds ratio 2.16 (95% CI, 1.54-3.04; p < 0.001). Number of tracheal intubation attempts was also significantly associated with the frequency of moderate and severe desaturations (p < 0.001). CONCLUSIONS: In this large tracheal intubation quality improvement database, we found moderate and severe desaturation are reported among 19% and 13% of all tracheal intubation encounters. Moderate and severe desaturations were independently associated with the occurrence of adverse hemodynamic events. Future quality improvement interventions may focus to reduce desaturation events.

Promoters and Barriers to Implementation of Tracheal Intubation Airway Safety Bundle: A Mixed-Method Analysis.

OBJECTIVES: To describe promoters and barriers to implementation of an airway safety quality improvement bundle from the perspective of interdisciplinary frontline clinicians and ICU quality improvement leaders. DESIGN: Mixed methods. SETTING: Thirteen PICUs of the National Emergency Airway Registry for Children network. INTERVENTION: Remote or on-site focus groups with interdisciplinary ICU staff. Two semistructured interviews with ICU quality improvement leaders with quantitative and qualitative data-based feedbacks. MEASUREMENTS AND MAIN RESULTS: Bundle implementation success (compliance) was defined as greater than or equal to 80% use for tracheal intubations for 3 consecutive months. ICUs were classified as early or late adopters. Focus group discussions concentrated on safety concerns and promoters and barriers to bundle implementation. Initial semistructured quality improvement leader interviews assessed implementation tactics and provided recommendations. Follow-up interviews assessed degree of acceptance and changes made after initial interview. Transcripts were thematically analyzed and contrasted by early versus late adopters. Median duration to achieve success was 502 days (interquartile range, 182-781). Five sites were early (median, 153 d; interquartile range, 146-267) and eight sites were late adopters (median, 783 d; interquartile range, 773-845). Focus groups identified common "promoter" themes-interdisciplinary approach, influential champions, and quality improvement bundle customization-and "barrier" themes-time constraints, competing paperwork and quality improvement activities, and poor engagement. Semistructured interviews with quality improvement leaders identified effective and ineffective tactics implemented by early and late adopters. Effective tactics included interdisciplinary quality improvement team involvement (early adopter: 5/5, 100% vs late adopter: 3/8, 38%; p = 0.08); ineffective tactics included physician-only rollouts, lack of interdisciplinary education, lack of data feedback to frontline clinicians, and misconception of bundle as research instead of quality improvement intervention. CONCLUSIONS: Implementation of an airway safety quality improvement bundle with high compliance takes a long time across diverse ICUs. Both early and late adopters identified similar promoter and barrier themes. Early adopter sites customized the quality improvement bundle and had an interdisciplinary quality improvement team approach.

Rooming-In to Treat Neonatal Abstinence Syndrome: Improved Family-Centered Care at Lower Cost.

BACKGROUND AND OBJECTIVE: The incidence and associated costs of neonatal abstinence syndrome (NAS) have recently risen sharply; newborns with NAS occupy 4% of NICU beds. We implemented a coordinated program for NAS including standardized protocols for scoring, medications and weaning, and a calm rooming-in environment, to improve family-centered care and to decrease both length of stay (LOS) and hospital costs. METHODS: In early 2013, a multidisciplinary quality improvement team began consecutive plan-do-study-act (PDSA) cycles. We trained nurses in modified Finnegan scoring, ensured scoring only after on-demand feeds during skin-to-skin care, and standardized physician score interpretation. We provided prenatal family education, increased family involvement in symptom monitoring and nonpharmacologic treatment, and treated otherwise healthy infants on the inpatient pediatric unit instead of in the NICU. We measured outcomes using statistical process control methods. RESULTS: At baseline, 46% of inborn infants at-risk for NAS were treated with morphine; by 2015, this decreased to 27%. Adjunctive use of phenobarbital decreased from 13% to 2% in the same period. Average LOS for morphine-treated newborns decreased from 16.9 to 12.3 days, average hospital costs per treated infant decreased from $19 737 to $8755, and costs per at-risk infant dropped from $11 000 to $5300. Cumulative morphine dose decreased from 13.7 to 6.6 mg per treated newborn. There were no adverse events, and 30-day readmission rates remained stable. CONCLUSIONS: A coordinated, standardized NAS program safely reduced pharmacologic therapy, LOS, and hospital costs. Rooming-in with family and decreased use of NICU beds were central to achieved outcomes.

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.

Site-level variance for adverse tracheal intubation-associated events across 15 North American PICUs: a report from the national emergency airway registry for children*.

OBJECTIVE: Tracheal intubation in PICUs is associated with adverse tracheal intubation-associated events. Patient, provider, and practice factors have been associated with tracheal intubation-associated events; however, site-level variance and the association of site-level characteristics on tracheal intubation-associated event outcomes are unknown. We hypothesize that site-level variance exists in the prevalence of tracheal intubation-associated events and that site characteristics may affect outcomes. DESIGN: Prospective observational cohort study. SETTING: Fifteen PICUs in North America. SUBJECTS: Critically ill pediatric patients requiring tracheal intubation. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Tracheal intubation quality improvement data were collected in 15 PICUs from July 2010 to December 2011 using a National Emergency Airway Registry for Children with robust site-specific compliance. Tracheal intubation-associated events and severe tracheal intubation-associated events were explicitly defined a priori. We analyzed the association of site-level variance with tracheal intubation-associated events using univariate analysis and adjusted for previously identified patient- and provider-level risk factors. Analysis of 1,720 consecutive intubations revealed an overall prevalence of 20% tracheal intubation-associated events and 6.5% severe tracheal intubation-associated events, with considerable site variability ranging from 0% to 44% tracheal intubation-associated events and from 0% to 20% severe tracheal intubation-associated events. Larger PICU size (> 26 beds) was associated with fewer tracheal intubation-associated events (18% vs 23%, p = 0.006), but the presence of a fellowship program was not (20% vs 18%, p = 0.58). After adjusting for patient and provider characteristics, both PICU size and fellowship presence were not associated with tracheal intubation-associated events (p = 0.44 and p = 0.18, respectively). Presence of mixed ICU with cardiac surgery was independently associated with a higher prevalence of tracheal intubation-associated events (25% vs 15%; p < 0.001; adjusted odds ratio, 1.81; 95% CI, 1.29-2.53; p = 0.01). Substantial site-level variance was observed in medication use, which was not explained by patient characteristic differences. CONCLUSIONS: Substantial site-level variance exists in tracheal intubation practice, tracheal intubation-associated events, and severe tracheal intubation-associated events. Neither PICU size nor fellowship training program explained site-level variance. Interventions to reduce tracheal intubation-associated event prevalence and severity will likely need to be contextualized to variability in individual ICUs patients, providers, and practice.

Biomarkers and genetics of brain injury risk in diabetic ketoacidosis: A pilot study.

Diabetic ketoacidosis (DKA) is the primary cause of death for children with diabetes, especially when complicated by cerebral edema. Central nervous system (CNS) involvement is common, however the mechanism of, and predictors of CNS dysfunction/injury are largely unknown. In this observational pilot study, blood was collected from pediatric DKA patients at three time points (consent, 12 hr and 24 hr after beginning treatment), to test genetic markers, ribonucleic acid expression and plasma biomarkers reflecting inflammation (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and cerebral dysfunction and/or possible injury (S100ß, glial fibrillary acidic protein [GFAP]). Thirty patients were enrolled in the study. The average age was 11.3 yr, 73% were new onset diabetes and 53% were female. Forty percent exhibited abnormal mentation (Glasgow Coma Scale <15), consistent with CNS dysfunction. IL-6 and TNF-α were elevated in plasma, suggesting systemic inflammation. GFAP was measurable in 45% of patients and correlated positively with GCS. Only two patients had detectable levels of S100ß. In conclusion, children with DKA often present with evidence of acute neurologic dysfunction or injury. We have demonstrated the feasibility of exploring genetic and biochemical markers of potential importance in the pathophysiology of CNS dysfunction and/or possible injury in DKA. We have identified IL-6, TNF-α and GFAP as potentially important markers for further exploration. A larger, follow-up study will help to better understand the extent and type of CNS injury in DKA as well as the mechanism underlying this dysfunction/injury.

Empiric antibiotics are justified for infants with respiratory syncytial virus lower respiratory tract infection presenting with respiratory failure: a prospective study and evidence review.

OBJECTIVE: Although some studies indicate a low risk of serious bacterial infection in infants with respiratory syncytial virus (RSV), these studies focused on patients who did not progress to respiratory failure. We hypothesized the composite diagnosis of concomitant bacterial pneumonia (CBP) is common in lower risk infants with RSV who present in respiratory failure. The aim of the study was to investigate the incidence of CBP in low-risk infants mechanically ventilated for RSV respiratory failure and to compare the results with other studies searched for in MEDLINE. DESIGN: Prospective, descriptive study, and literature review. Two MEDLINE searches were done using the terms 1) respiratory syncytial virus (RSV) and pneumonia, and 2) RSV, pneumonia, and antibiotics. SETTING: Tertiary pediatric intensive care unit (PICU) in the Northeast United States. PATIENTS: We prospectively enrolled 23 infants admitted to our PICU with RSV infection and respiratory failure over a 27-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All infants were intubated on arrival or soon thereafter; 22 had diagnostic tracheal aspiration performed, and 20 had blood cultures obtained shortly after admission. All had white blood cell count, temperature measured, and chest radiograph. Only one had antibiotics before culture. The length of mechanical ventilation, PICU course, and hospital stay were recorded.The primary outcome variable was the composite diagnosis of CBP as determined by the following criteria: 1) isolation of pathogenic bacteria from a tracheal aspirate, 2) blood culture, 3) chest radiograph, 4) temperature abnormality, and 5) peripheral white blood cell count. In our study, 7 infants met four criteria (probable pneumonia); 6 met three criteria (possible pneumonia); and 10 infants met less than three criteria. By tracheal aspirate criteria alone, 9 of 23 (39%) had probable pneumonia and 9 of 23 had possible pneumonia by previously published criteria. The mean length of mechanical ventilation for 7 infants who met four criteria was 10 +/- 2.7 (sem) days; for 6 infants who met three criteria, 10.5 +/- 2.1 days; and for infants who met less than three criteria 7.4 +/- 0.9 days. The mean PICU stay was 14.3 +/- 3.6 days for infants who met four criteria; 14.3 +/- 3.0 days for infants who met three criteria; and 9.9 +/- 1.4 days for infants who met less than three criteria. The mean hospital stay was 16.3 +/- 3.4 for infants who met four criteria; 18.7 +/- 2.8 days for infants who met three criteria; and 24.8 +/- 9.6 days for infants who met less than three criteria. These differences were not statistically significant. A MEDLINE search was performed using the terms 1) RSV and pneumonia, and 2) RSV, pneumonia, and antibiotics. CONCLUSIONS: While the small size of this study does not permit definitive conclusions, these data, in combination with other data from the literature, suggest that composite evidence of bacterial pneumonia in otherwise low-risk infants with RSV presenting with respiratory failure is 20% or higher and the use of empirical antibiotics for 24 to 48 hrs pending culture results may be justified and could be used until CBP is excluded.

A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation.

OBJECTIVE: To study patients with respiratory syncytial virus bronchiolitis in respiratory failure to make specific measurements reflecting airway resistance before and after treatment with commonly used agents. We hypothesized that racemic epinephrine would decrease airways resistance more effectively than levalbuterol, and levalbuterol would decrease airways resistance more effectively than racemic albuterol. Normal saline was used as a control. DESIGN: Prospective, randomized, controlled, blinded study. SETTING: Tertiary Pediatric Intensive Care Unit in a University affiliated hospital in the northeastern United States. PATIENTS: Twenty-two patients with respiratory syncytial virus bronchiolitis and in respiratory failure were enrolled. All were intubated and ventilated in a volume control mode and sedated. INTERVENTIONS: In a randomized, blinded fashion patients were given four agents: norepinephrine, levalbuterol, racemic albuterol, and normal saline at 6 hr intervals. MEASUREMENTS: As indicators of bronchodilation, peak inspiratory pressure and inspiratory respiratory system resistance were measured before and 20 mins after each agent was given. Thus, each patient acted as his/her own control. MAIN RESULTS: There were small but statistically significant decreases in peak inspiratory pressure after racemic epinephrine treatment, levalbuterol, and racemic albuterol. There was no change in peak inspiratory pressure after inhaled normal saline. Inspiratory respiratory system resistance fell significantly after all treatments, including saline. Heart rate rose significantly after inhaled bronchodilator treatments (p < 0.05 for all treatments). CONCLUSIONS: Similar statistically significant bronchodilation occurred after all three bronchodilators as indicated by a decrease in peak inspiratory pressure and respiratory system resistance, but these changes were small and probably clinically insignificant. However, side effects of bronchodilators, such as tachycardia, also occurred, and these may be clinically significant. Thus the benefit of bronchodilator treatment in these patients is small, does not differ among the drugs we studied and of questionable value.