Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.

BACKGROUND: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. METHODS: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. RESULTS: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. CONCLUSIONS: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.

Disparities in Cytomegalovirus Infection Rates by Race and Ethnicity among Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients at a Single Center.

Previous literature has reported cytomegalovirus (CMV) infection rate disparities among racial/ethnic groups of hematopoietic cell transplantation (HCT) recipients. Because race and ethnicity categorizations are social constructs unlikely to affect biological systems, it is likely there are covariates on the pathway to CMV detection, known as mediators, that can explain the observed disparity. Recent developments in mediation analysis methods enable the analysis of time-to-event outcomes, allowing an investigation of these disparities to also consider the timing of CMV infection detection relative to HCT. This study aimed to explore whether racial and ethnic CMV infection disparities existed within a population of HCT recipients at our center, and whether clinical covariates explained any observed association. The study cohort included all recipients of allogeneic HCT performed at the Children's Hospital of Philadelphia between January 2004 and April 2017 who were CMV PCR-negative pretransplantation, had known donor/recipient CMV serology, and were under blood CMV PCR surveillance. Subjects were followed for 100 days post-HCT. Accelerated failure time models using subject's reported race/ethnicity, dichotomized into non-Hispanic White (NHW) and non-NHW, and exposure and time to CMV detection as outcomes examined whether selected clinical factors-donor/recipient CMV serostatus, recipient age, indication for HCT, hematopoietic cell source, match quality-mediated any identified exposure-outcome association. The analysis included 348 HCTs performed in 335 subjects, with 86 episodes (24.7%) in which CMV was detected via PCR analysis. The accelerated failure time model without mediators estimated that non-NHW subjects had fewer CMV-free survival days (time ratio, .21; 95% confidence interval, .10 to .44). Any hypothesized mediator mediated at most 5% of the total association between race/ethnicity and time to CMV detection. Non-NHW HCT recipients had fewer CMV-free survival days than NHW recipients; none of the clinical factors hypothesized to mediate this association accounted for a significant component of total association. Further research should focus on nonclinical factors influenced by systemic racism to better understand their effect on CMV infection among HCT recipients.

Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.

BACKGROUND: The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed. METHODS: We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age-matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations. RESULTS: We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4 days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition. DISCUSSION: Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric-specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions.

Evolution of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroprevalence among employees of a US academic children's hospital during coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study open to adult employees at the Children's Hospital of Philadelphia, conducted April 20-December 17, 2020. METHODS: Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity. RESULTS: In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03-3.68), Black race (HR, 2.70; 95% CI, 1.24-5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71-6.88) were associated with statistically significant increased risk for seropositivity. CONCLUSIONS: Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.

Prevalence and Severity of Food Allergies Among US Adults.

Importance: Food allergy is a costly, potentially life-threatening condition. Although studies have examined the prevalence of childhood food allergy, little is known about prevalence, severity, or health care utilization related to food allergies among US adults. Objective: To provide nationally representative estimates of the distribution, severity, and factors associated with adult food allergies. Design, Setting, and Participants: In this cross-sectional survey study of US adults, surveys were administered via the internet and telephone from October 9, 2015, to September 18, 2016. Participants were first recruited from NORC at the University of Chicago's probability-based AmeriSpeak panel, and additional participants were recruited from the non-probability-based Survey Sampling International (SSI) panel. Exposures: Demographic and allergic participant characteristics. Main Outcomes and Measures: Self-reported food allergies were the main outcome and were considered convincing if reported symptoms to specific allergens were consistent with IgE-mediated reactions. Diagnosis history to specific allergens and food allergy-related health care use were also primary outcomes. Estimates were based on this nationally representative sample using small-area estimation and iterative proportional fitting methods. To increase precision, AmeriSpeak data were augmented by calibration-weighted, non-probability-based responses from SSI. Results: Surveys were completed by 40 443 adults (mean [SD] age, 46.6 [20.2] years), with a survey completion rate of 51.2% observed among AmeriSpeak panelists (n = 7210) and 5.5% among SSI panelists (n = 33 233). Estimated convincing food allergy prevalence among US adults was 10.8% (95% CI, 10.4%-11.1%), although 19.0% (95% CI, 18.5%-19.5%) of adults self-reported a food allergy. The most common allergies were shellfish (2.9%; 95% CI, 2.7%-3.1%), milk (1.9%; 95% CI, 1.8%-2.1%), peanut (1.8%; 95% CI, 1.7%-1.9%), tree nut (1.2%; 95% CI, 1.1%-1.3%), and fin fish (0.9%; 95% CI, 0.8%-1.0%). Among food-allergic adults, 51.1% (95% CI, 49.3%-52.9%) experienced a severe food allergy reaction, 45.3% (95% CI, 43.6%-47.1%) were allergic to multiple foods, and 48.0% (95% CI, 46.2%-49.7%) developed food allergies as an adult. Regarding health care utilization, 24.0% (95% CI, 22.6%-25.4%) reported a current epinephrine prescription, and 38.3% (95% CI, 36.7%-40.0%) reported at least 1 food allergy-related lifetime emergency department visit. Conclusions and Relevance: These data suggest that at least 10.8% (>26 million) of US adults are food allergic, whereas nearly 19% of adults believe that they have a food allergy. Consequently, these findings suggest that it is crucial that adults with suspected food allergy receive appropriate confirmatory testing and counseling to ensure food is not unnecessarily avoided and quality of life is not unduly impaired.

The Public Health Impact of Parent-Reported Childhood Food Allergies in the United States.

: media-1vid110.1542/5840360268001PEDS-VA_2018-1235Video Abstract BACKGROUND: Childhood food allergy (FA) is a life-threatening chronic condition that substantially impairs quality of life. This large, population-based survey estimates childhood FA prevalence and severity of all major allergenic foods. Detailed allergen-specific information was also collected regarding FA management and health care use. METHODS: A survey was administered to US households between 2015 and 2016, obtaining parent-proxy responses for 38 408 children. Prevalence estimates were based on responses from NORC at the University of Chicago's nationally representative, probability-based AmeriSpeak Panel (51% completion rate), which were augmented by nonprobability-based responses via calibration weighting to increase precision. Prevalence was estimated via weighted proportions. Multiple logistic regression models were used to evaluate FA predictors. RESULTS: Overall, estimated current FA prevalence was 7.6% (95% confidence interval: 7.1%-8.1%) after excluding 4% of children whose parent-reported FA reaction history was inconsistent with immunoglobulin E-mediated FA. The most prevalent allergens were peanut (2.2%), milk (1.9%), shellfish (1.3%), and tree nut (1.2%). Among food-allergic children, 42.3% reported ≥1 severe FA and 39.9% reported multiple FA. Furthermore, 19.0% reported ≥1 FA-related emergency department visit in the previous year and 42.0% reported ≥1 lifetime FA-related emergency department visit, whereas 40.7% had a current epinephrine autoinjector prescription. Prevalence rates were higher among African American children and children with atopic comorbidities. CONCLUSIONS: FA is a major public health concern, affecting ∼8% of US children. However, >11% of children were perceived as food-allergic, suggesting that the perceived disease burden may be greater than previously acknowledged.

SMART (Student Media-based Asthma Research Team): Engaging Adolescents to Understand Asthma in Their Communities.

BACKGROUND: Asthma rates in Chicago exceed national averages and disproportionately affect minority adolescents. We collaborated with students in a neighborhood with high asthma prevalence to better understand community factors impacting asthma. OBJECTIVES: To evaluate the impact of our Student Media-based Asthma Research Team (SMART) program on student, parent, and student-peer outcomes related to asthma. METHODS: Students with asthma (n = 11), their parents (n = 9), and student-peers (n = 91) participated in a school-based asthma intervention grounded in community-based participatory research (CBPR) principles and completed multiple pre-/post-intervention questionnaires. RESULTS: After the program, participants significantly increased (p < 0.05) asthma-related quality of life (QOL), asthma control, emotional support, and empowerment. Parents significantly increased their QOL and student-peers showed significant improvements in asthma knowledge. CONCLUSIONS: This novel intervention-which used participatory media as a vehicle through which children learn about their own asthma and share their findings with parents and peers-was successful in engaging adolescents to improve asthma management and community support.