Multiomic Analysis of Neuroinflammation and Occult Infection in Sudden Infant Death Syndrome.

Importance: Antemortem infection is a risk factor for sudden infant death syndrome (SIDS)-the leading postneonatal cause of infant mortality in the developed world. Manifestations of infection and inflammation are not always apparent in clinical settings or by standard autopsy; thus, enhanced resolution approaches are needed. Objective: To ascertain whether a subset of SIDS cases is associated with neuroinflammation and occult infection. Design, Setting, and Participants: In this case-control study, postmortem fluids from SIDS cases and controls collected between July 2011 and November 2018 were screened for elevated inflammatory markers, specifically cerebrospinal fluid (CSF) neopterin and CSF and serum cytokines. CSF, liver, and brain tissue from SIDS cases with elevated CSF neopterin were subjected to metagenomic next-generation sequencing (mNGS) to probe for infectious pathogens. Brainstem tissue from a subset of these cases was analyzed by single-nucleus RNA sequencing (snRNAseq) to measure cell type-specific gene expression associated with neuroinflammation and infection. All tissue and fluid analyses were performed from April 2019 to January 2023 in a pathology research laboratory. Included was autopsy material from infants dying of SIDS and age-matched controls dying of known causes. Exposures: There were no interventions or exposures. Main Outcomes and Measures: CSF neopterin levels were measured by high-performance liquid chromatography. Cytokines were measured by multiplex fluorometric assay. mNGS was performed on liver, CSF, brain, and brainstem tissue. snRNAseq was performed on brainstem tissue. Results: A cohort of 71 SIDS cases (mean [SD] age, 55.2 [11.4] postconceptional weeks; 42 male [59.2%]) and 20 controls (mean [SD] age, 63.2 [16.9] postconceptional weeks; 11 male [55.0%]) had CSF and/or serum available. CSF neopterin was screened in 64 SIDS cases and 15 controls, with no exclusions. Tissues from 6 SIDS cases were further analyzed. For CSF neopterin measures, SIDS samples were from infants with mean (SD) age of 54.5 (11.3) postconceptional weeks (38 male [59.4%]) and control samples were from infants with mean (SD) age of 61.5 (17.4) postconceptional weeks (7 male [46.7%]). A total of 6 SIDS cases (9.3%) with high CSF neopterin were identified, suggestive of neuroinflammation. mNGS detected human parechovirus 3 (HPeV3) in tissue and CSF from 1 of these 6 cases. snRNAseq of HPeV3-positive brainstem tissue (medulla) revealed dramatic enrichment of transcripts for genes with predominately inflammatory functions compared with 3 age-matched SIDS cases with normal CSF neopterin levels. Conclusions and Relevance: Next-generation molecular tools in autopsy tissue provide novel insight into pathogens that go unrecognized by normal autopsy methodology, including in infants dying suddenly and unexpectedly.

A Quality Improvement Initiative to Improve Discharge Timeliness and Documentation.

INTRODUCTION: Discharge communication is critical for the continuity of patient care. However, discharge summaries are often not available in time for follow-up visits, and the content is inconsistent. We aimed to decrease the average time to discharge summary completion by 25%, reduce deficiencies (information errors) by 50%, and increase discharge summary template use to >80% in 6 months. METHODS: A pediatric interprofessional team used quality improvement methods to identify barriers and implement interventions, including discharge summary completion time expectation, electronic health record discharge summary template changes addressing gaps, and training. Notable changes to the template included embedded writing tips to guide writers and specific template choices for common diagnoses to standardize content. The primary outcome measure was the mean discharge summary completion time. Secondary measures were the percentage of discharge summaries with deficiencies and the rate of template use. RESULTS: After interventions, the mean discharge summary completion time decreased by 70% (from 71.5 to 21.8 hours). Discharge summary deficiencies decreased 44% (from 4.5% to 2.5%), and template use increased from 62% to 97%. CONCLUSION: Quality improvement methods and a newly designed electronic health record-discharge summary template were used to dramatically improve discharge summary timeliness and standardize content to streamline continuity of care.

Hyponatremia in Patients With Multisystem Inflammatory Syndrome in Children.

We report 2 patients with multisystem inflammatory syndrome in children with evidence of hyponatremia on admission. Despite fluid resuscitation and resolution of dehydration, the hyponatremia worsened. Serum and urine studies were evaluated and demonstrated evidence of syndrome of inappropriate antidiuretic hormone. Fluid restriction and anti-inflammatory therapy were initiated with resolution of hyponatremia.

Intravenous Immunoglobulin Infusion Reactions in Kawasaki Disease Patients Who Undergo Sedation.

OBJECTIVES: Although IVIG infusions are usually well tolerated, reactions can include hypotension, chills, and, rarely, anaphylactic reactions. Risk of adverse reactions correlates with dose and rate of IVIG infusion. An echocardiogram is the preferred imaging modality to detect coronary artery changes in acute Kawasaki disease (KD), but the quality of the study can be compromised if a child moves much during the imaging procedure. Thus, sedation is often required for children younger than 3 years of age. There is concern regarding coadministration of IVIG and sedatives. Therefore, the purpose of this analysis is to determine when the majority of IVIG infusion reactions occur to help find the optimal time to safely perform a sedated echocardiogram in patients with KD. METHODS: This is a retrospective, single-center analysis of patients with KD administered IVIG at Rady Children's Hospital San Diego from November 1, 2013, to October 31, 2016. RESULTS: Of the 260 subjects in this study, 34 (13%) had an IVIG infusion reaction consisting of either chills or hypotension. There were no anaphylactic reactions. All infusion reactions occurred within 4 hours of starting IVIG. No hypotension reactions occurred after 4 hours. All subjects were able to complete their IVIG infusion without any further complications. CONCLUSIONS: Given that the maximum IVIG infusion rate is reached at 1.5 hours per our hospital's policy and that the overwhelming majority of infusion reactions occurred within the first 4 hours, we found it is safe to coadminister IVIG with sedation 4 hours after initiation of IVIG infusion.

Reducing Unnecessary Testing in Uncomplicated Skin and Soft Tissue Infections: A Quality Improvement Approach.

OBJECTIVES: Skin and soft tissue infections are common pediatric diagnoses with substantial costs. Recent studies suggest blood cultures are not useful in management of uncomplicated skin and soft tissue infections (uSSTIs). Complete blood cell count, erythrocyte sedimentation rate, and C-reactive protein are also of questionable value. We aimed to decrease these tests by 25% for patients with uSSTIs admitted to the pediatric hospital medicine service within 3 months. METHODS: An interdisciplinary team led a quality improvement (QI) project. Baseline assessment included review of the literature and 12 months of medical records. Key stakeholders identified drivers that informed the creation of an electronic order set and development of a pediatric hospital medicine-emergency department collaborative QI project. The primary outcome measure was mean number of tests per patient encounter. Balancing measures included unplanned readmissions and missed diagnoses. RESULTS: Our baseline-year rate was 3.4 tests per patient encounter (573 tests and 169 patient encounters). During the intervention year, the rate decreased by 35% to 2.2 tests per patient encounter (286 tests and 130 patient encounters) and was sustained for 14 months postintervention. There were no unplanned readmissions or missed diagnoses for the study period. Order set adherence was 80% (83 out of 104) during the intervention period and sustained at 87% postintervention. CONCLUSIONS: Our interdisciplinary team achieved our aim, reducing unnecessary laboratory testing in patients with an uSSTI without patient harm. Awareness of local culture, creation of an order set, defining appropriate patient selection and testing indications, and implementation of a collaborative QI project helped us achieve our aim.

Multicenter study of viral etiology and relapse in hospitalized children with bronchiolitis.

BACKGROUND: It is unclear whether the infectious etiology of severe bronchiolitis affects short-term outcomes, such as posthospitalization relapse. We tested the hypothesis that children hospitalized with rhinovirus (RV) bronchiolitis, either as a sole pathogen or in combination with respiratory syncytial virus (RSV), are at increased risk of relapse. METHODS: We performed a 16-center, prospective cohort study of hospitalized children age <2 years with bronchiolitis. During the winters of 2007-2010, researchers collected clinical data and nasopharyngeal aspirates from study participants; the aspirates were tested using real-time polymerase chain reaction. The primary outcome was bronchiolitis relapse (urgent bronchiolitis visit or scheduled visit at which additions to the bronchiolitis medications were made) during the 2 weeks after hospital discharge. RESULTS: Among 1836 enrolled children with 2-week, follow-up data, the median age was 4 months and 60% were male. Overall, 48% had sole RSV infection, 8% had sole RV infection, and 13% had RSV/RV coinfection. Compared with children with sole RSV infection, and adjusting for 10 demographic and clinical characteristics and clustering of patients within hospitals, children with sole RV infection did not differ in their likelihood of relapse (odds ratio: 0.99; 95% confidence interval: 0.52-1.90; P = 0.98), whereas those with RSV/RV coinfection were more likely to have relapse (odds ratio: 1.54; 95% confidence interval: 1.03-2.30; P = 0.03). CONCLUSIONS: In this prospective, multicenter, multiyear study of children hospitalized with bronchiolitis, we found that RSV/RV coinfection was independently associated with a higher likelihood of bronchiolitis relapse. Present data support the concept that the infectious etiology of severe bronchiolitis affects short-term outcomes.

Pediatric discharge content: a multisite assessment of physician preferences and experiences.

BACKGROUND AND OBJECTIVES: Professional medical societies endorse prompt, consistent discharge communication to primary care providers (PCPs) on discharge. However, evidence is limited about what clinical elements to communicate. Our main goal was to identify and compare the clinical elements considered by PCPs and pediatric hospitalists to be essential to communicate to PCPs within 2 days of pediatric hospital discharge. A secondary goal was to describe experiences of the PCPs and pediatric hospitalists regarding sending and receiving discharge information. METHODS: A survey of physician preferences and experiences regarding discharge communication was sent to 320 PCPs who refer patients to 16 hospitals, with an analogous survey sent to 147 hospitalists. Descriptive statistics were calculated, and χ² analyses were performed. RESULTS: A total of 201 PCPs (63%) and 71 hospitalists (48%) responded to the survey. Seven clinical elements were reported as essential by >75% of both PCPs and hospitalists: dates of admission and discharge; discharge diagnoses; brief hospital course; discharge medications; immunizations given during hospitalization; pending laboratory or test results; and follow-up appointments. PCPs reported reliably receiving discharge communication significantly less often than hospitalists reported sending it (71.8% vs 85.1%; P < .01), and PCPs considered this communication to be complete significantly less often than hospitalists did (64.9% vs 79.1%; P < .01). CONCLUSIONS: We identified 7 core clinical elements that PCPs and hospitalists consider essential in discharge communication. Consistently and promptly communicating at least these core elements after discharge may enhance PCP satisfaction and patient-level outcomes. Reported rates of transmission and receipt of this information were suboptimal and should be targeted for improvement.

Pediatric hospitalists collaborate to improve timeliness of discharge communication.

OBJECTIVES: The transition of care from hospital to primary care provider (PCP) at discharge carries the potential for significant information loss. There is evidence that the timeliness and content of discharge communication are often unreliable during this handoff. Suboptimal transitions of care at discharge have been associated with adverse outcomes, and efficient solutions are required to transform the current state. Our specific aim was the achievement 90% documentation of hospitalist-PCP communication within 2 days of hospital discharge in < 12 months. METHODS: As part of a grassroots collaborative improvement organization, pediatric hospitalist groups engaged in parallel quality improvement projects to improve the timeliness and reliability of discharge communication at their local institutions. After an initial face-to-face meeting, e-mail and regular conference calls were used to promote shared effort and learning. The study period lasted 12 months, with > 16 weeks of continuous data required for inclusion. RESULTS: The mean rate of documentation of timely discharge communication across the collaborative increased from 57% to 85% over the study period. For the 7 hospitals that were able to collect > 16 weeks of data before July 2010, the mean rate of communication was > 90%. Participants reported that the context of the collaborative contributed to their success. CONCLUSIONS: Timely hospitalist-PCP communication was inconsistent at the beginning of the study. This low-resource quality improvement collaborative was able to achieve rapid improvement and resulted in improved perceptions of quality improvement knowledge among participants.