Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea.

RATIONALE: Lower respiratory tract infections (LRTI) during the first 2 years of life increase the risk of pediatric obstructive sleep apnea (OSA), but whether this risk varies by LRTI severity is unknown. METHODS: We analyzed data from 2962 children, aged 0-5 years, with early-life LRTI requiring hospitalization (severe LRTI, n = 235), treated as outpatients (mild LRTI, n = 394) and without LRTI (reference group, n = 2333) enrolled in the Boston Birth Cohort. Kaplan-Meier survival estimates and Cox proportional hazards models adjusted by pertinent covariables were used to evaluate the risk of pediatric OSA. RESULTS: Compared to children without LRTI, those with mild LRTI were at a higher risk of having OSA (hazard ratio [HR] 1.44, 95% confidence interval [CI]: 1.01-2.05), and those with severe LRTI were at the highest risk (HR 2.06, 95% CI: 1.41-3.02), independently of relevant covariables (including maternal age, race, gestational age, and type of delivery). Additional risk factors linked to a higher risk of OSA included prematurity (HR 1.34, 95% CI 1.01-1.77) and maternal obesity (HR 1.82, 95% CI 1.32-2.52). The time elapsed between LRTI and OSA diagnosis was similar in mild and severe LRTI cases, with medians of 23 and 25.5 months, respectively (p = .803). CONCLUSION: Infants with severe early-life LRTI have a higher risk of developing OSA, and surveillance strategies to identify OSA need to be particularly focused on this group. OSA monitoring should continue throughout the preschool years as it may develop months or years after the initial LRTI hospitalization.

Comparing the Clinical Courses of Children With Human Rhinovirus/Enterovirus to Children With Other Respiratory Viruses in the Outpatient Setting.

BACKGROUND: While infections caused by rhinoviruses and enteroviruses are common among children, the entirety of their clinical impact remains elusive. We compared the clinical outcomes of children with rhinovirus/enterovirus infections to other common respiratory viruses in outpatient settings. METHODS: We conducted a retrospective analysis of nasopharyngeal samples singly positive for human rhinovirus/enterovirus (HRV/ENT), influenza A/B (FLU) or respiratory syncytial virus (RSV) from patients ≤17 years submitted for clinical testing via multiplex polymerase chain reaction between 2016 and 2019. We evaluated the following outpatient outcomes: days of respiratory symptoms before testing; visits for respiratory symptoms; receipt of a breathing treatment; receipt of antibiotics and hospital admission. Statistical analyses were conducted controlling for age and comorbid conditions. RESULTS: There were 1355 positive samples included in this analysis (HRV/ENT: n = 743, FLU: n = 303 and RSV: n = 309). Compared to HRV/ENT, children with FLU had 28% fewer days of respiratory symptoms (ß: -0.32; 95% confidence interval: -0.46 to -0.18; P < 0.001), fewer visits for respiratory symptoms, and significantly decreased odds of receiving a breathing treatment or antibiotics, and admission to the hospital. Children with RSV had a similar number of days of respiratory symptoms, outpatient visits and odds of hospital admission, but significantly increased odds of receiving a breathing treatment and antibiotics compared to those with HRV/ENT. CONCLUSION: Clinicians should have a high level of vigilance when managing children with positive respiratory viral testing for HRV/ENT given the potential for clinical outcomes similar to and, in some instances, worse than known highly pathogenic viruses.

Aerodigestive clinic reduces emergency department and primary care utilization and increases access to ancillary and specialty care.

OBJECTIVE: The study aimed to evaluate the effect of the aerodigestive clinic (ADC) on healthcare utilization. STUDY DESIGN: Retrospective quality improvement project; before and after. SETTING: The ADC at Tripler Army Medical Center (TAMC) in Honolulu, HI. METHODS: We retrospectively analyzed the electronic medical records of children ≤17 years old seen in the ADC at TAMC between April 2015 and June 2019. The number of emergency department (ED), primary care (PC), specialty care (SC), ancillary care (AC), and teleconsult (TC) encounters were tallied before and after one year of the initial intake visit. RESULTS: A total of 261 children were included during the study period. Comparing visits before aerodigestive evaluation to after aerodigestive evaluation, the total number of visits before and after were similar with significant changes in the distribution of encounters. The total number of ED (-38%) and PC (-40%) visits decreased significantly (p < 0.001 for both). The total number of other visits were found to have non-significant increases. PC visits accounted for nearly one-third (31%) of all visits prior to the initial ADC visit, but only 19% of visits after. PC visits decreased for all age groups. ED visits decreased by nearly half (-48.1%) for ages 1-17, but there was no change for <1-year olds. CONCLUSION: There is a statistically significant reduction in the number of emergency department and primary care visits for patients seen in a multidisciplinary ADC. The distribution of visits differed strongly among age groups. These findings emphasize the positive impact that the multidisciplinary clinic has on healthcare utilization for pediatric aerodigestive patients.

Respiratory Viral Pathogens Among U.S. Military Personnel at a Medical Treatment Facility in Hawaii From 2014 to 2019.

INTRODUCTION: Acute respiratory diseases account for a substantial number of outpatient visits and hospitalizations among U.S. military personnel, significantly affecting mission readiness and military operations. We conducted a retrospective analysis of respiratory viral pathogen (RVP) samples collected from U.S. military personnel stationed in Hawaii and tested at Tripler Army Medical Center from January 2014 to May 2019 in order to describe the etiology, distribution, and seasonality of RVP exposure in a military population. MATERIALS AND METHODS: Samples were analyzed by viral culture or multiplex PCR. Distribution of respiratory viruses over time was analyzed as well as subject demographic and encounter data. Presenting signs and symptoms were evaluated with each RVP. RESULTS: A total of 2,576 military personnel were tested, of which 726 (28.2%) were positive for one or more RVP. Among positive tests, the three most common viral pathogens detected were influenza A (43.0%), rhinovirus (24.5%), and parainfluenza (7.6%). Symptoms were generally mild and most frequently included cough, fever, and body aches. CONCLUSION: Our study evaluated respiratory virus prevalence, seasonality, and association with clinical symptoms for military personnel in an urban tropical setting in Oahu, HI, over a 5-year period. We show that viral prevalence and seasonality in Hawaii are distinct from those of the CONUS. Results contribute to the broader understanding of seasonality, clinical manifestation, and demographics of RVP among active duty military personnel stationed in Hawaii.

Respiratory Viral Pathogens in Children Evaluated at Military Treatment Facilities in Oahu, Hawaii From 2014 to 2018: Seasonality and Climatic Factors.

Five-year retrospective analysis of respiratory viruses in children less than 18 years old at Tripler Army Medical Center and outlying clinics in Oahu. Respiratory syncytial virus and influenza A showed pronounced seasonality with peaks from September to December and December to March, respectively. Results provide a better understanding of the timing of viral preventive strategies in Oahu.

Patient-oriented online resources in pediatric surgery: Are we failing the readability test?

BACKGROUND: The study aim was to evaluate the readability of patient-oriented resources in pediatric surgery from children's hospitals in the US. METHODS: The websites of 30 children's hospitals were evaluated for information on 10 common pediatric surgical procedures. Hospitals of varying characteristics including bed number, geographic location and ACS Children's Surgery Verification (CSV) were selected for the study. Readability scores were calculated using validated algorithms, and text was assigned an overall grade level. RESULTS: Of 195 patient-oriented resources identified, only three (2%) were written at or below the recommended sixth grade level. Larger hospitals provided patient information at a higher grade level than medium and smaller sized centers (10.7 vs 9.3 vs 9.0 respectively, p < 0.001). Hospital size also correlated with availability of information, with large and medium sized hospitals having information more often. Hospitals with ACS CSV had information available more often, and written at a lower grade level, compared to nonverified centers (78% vs 62%, p = 0.023; 9.0 vs 10.0, p = 0.013). CONCLUSION: Most hospital provided patient-oriented resources in pediatric surgery are written at a grade level well above the national guidelines. Centers with ACS CSV status have improved availability and readability of this material, while larger hospitals have improved availability, but decreased readability. TYPE OF STUDY: Modeling study. LEVEL OF EVIDENCE: III.

First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors.

PURPOSE: The NHS-IL12 immunocytokine is composed of two IL12 heterodimers fused to the NHS76 antibody. Preclinical studies have shown that this antibody targets IL12 to regions of tumor necrosis by binding histones on free DNA fragments in these areas, resulting in enhanced antitumor activity. The objectives of this phase I study were to determine the maximum tolerated dose (MTD) and pharmacokinetics of NHS-IL12 in subjects with advanced solid tumors. PATIENTS AND METHODS: Subjects (n = 59) were treated subcutaneously with NHS-IL12 in a single ascending-dose cohort followed by a multiple ascending-dose cohort (n = 37 with every 4-week dosing). RESULTS: The most frequently observed treatment-related adverse events (TRAE) included decreased circulating lymphocytes, increased liver transaminases, and flu-like symptoms. Of the grade ≥3 TRAEs, all were transient and only one was symptomatic (hyperhidrosis). The MTD is 16.8 µg/kg. A time-dependent rise in IFNγ and an associated rise in IL10 were observed following NHS-IL12. Of peripheral immune cell subsets evaluated, most noticeable were increases in frequencies of activated and mature natural killer (NK) cells and NKT cells. Based on T-cell receptor sequencing analysis, increases in T-cell receptor diversity and tumor-infiltrating lymphocyte density were observed after treatment where both biopsies and peripheral blood mononuclear cells were available. Although no objective tumor responses were observed, 5 subjects had durable stable disease (range, 6-30+ months). CONCLUSIONS: NHS-IL12 was well tolerated up to a dose of 16.8 µg/kg, which is the recommended phase II dose. Early clinical immune-related activity warrants further studies, including combination with immune checkpoint inhibitors.See related commentary by Lyerly et al., p. 9.