Evaluation of a clinical decision support strategy to increase seasonal influenza vaccination among hospitalized children before inpatient discharge

Importance: Hospitalized children are at increased risk of influenza-related complications, yet influenza vaccine coverage remains low among this group. Evidence-based strategies about vaccination of vulnerable children during all health care visits are especially important during the COVID-19 pandemic. Objective: To design and evaluate a clinical decision support (CDS) strategy to increase the proportion of eligible hospitalized children who receive a seasonal influenza vaccine prior to inpatient discharge. Design, Setting, and Participants: This quality improvement study was conducted among children eligible for the seasonal influenza vaccine who were hospitalized in a tertiary pediatric health system providing care to more than half a million patients annually in 3 hospitals. The study used a sequential crossover design from control to intervention and compared hospitalizations in the intervention group (2019-2020 season with the use of an intervention order set) with concurrent controls (2019-2020 season without use of an intervention order set) and historical controls (2018-2019 season with use of an order set that underwent intervention during the 2019-2020 season). Interventions: A CDS intervention was developed through a user-centered design process, including (1) placing a default influenza vaccine order into admission order sets for eligible patients, (2) a script to offer the vaccine using a presumptive strategy, and (3) just-in-time education for clinicians addressing vaccine eligibility in the influenza order group with links to further reference material. The intervention was rolled out in a stepwise fashion during the 2019-2020 influenza season. Main Outcomes and Measures: Proportion of eligible hospitalizations in which 1 or more influenza vaccines were administered prior to discharge. Results: Among 17 740 hospitalizations (9295 boys [52%]), the mean (SD) age was 8.0 (6.0) years, and the patients were predominantly Black (n = 8943 [50%]) or White (n = 7559 [43%]) and mostly had public insurance (n = 11 274 [64%]). There were 10 997 hospitalizations eligible for the influenza vaccine in the 2019-2020 season. Of these, 5449 (50%) were in the intervention group, and 5548 (50%) were concurrent controls. There were 6743 eligible hospitalizations in 2018-2019 that served as historical controls. Vaccine administration rates were 31% (n = 1676) in the intervention group, 19% (n = 1051) in concurrent controls, and 14% (n = 912) in historical controls (P \u3c .001). In adjusted analyses, the odds of receiving the influenza vaccine were 3.25 (95% CI, 2.94-3.59) times higher in the intervention group and 1.28 (95% CI, 1.15-1.42) times higher in concurrent controls than in historical controls. Conclusions and Relevance: This quality improvement study suggests that user-centered CDS may be associated with significantly improved influenza vaccination rates among hospitalized children. Stepwise implementation of CDS interventions was a practical method that was used to increase quality improvement rigor through comparison with historical and concurrent controls

Putting teeth into the developmental origins hypothesis: A longitudinal study of early childhood malnutrition, enamel hypoplasia and adolescent health in Amazonian Bolivia

Thesis (Ph.D.)--University of Washington, 2016-06Adult teeth may chronologically reflect early childhood experience because enamel on the permanent teeth calcifies incrementally during early childhood and is sensitive to physiological stress. Defects in the enamel do not repair after occurrence or during the life course, leaving a permanent biological mark of physiological insults that occurred during early childhood. These characteristics suggest enamel defects may serve as a useful biomarker of chronic malnutrition and thus predictor of long-term health. This dissertation sought to investigate associations between malnutrition-related early childhood exposures and dental enamel hypoplasia (EH) and to evaluate EH as a predictor of adolescent anthropometrics and biomarkers. We conducted analyses using data from 349 Tsimane’ adolescents in Amazonian Bolivia, collected between 2002-2010 and in 2015. In 2015, we examined EH in the permanent maxillary incisors and mandibular canines using digital photography from which the following measures of EH were abstracted: occurrence (any, none), extent of occurrence (2/3 of the tooth surface) and estimated age at occurrence (1, 2, 3, 4 years of age). Data on malnutrition-related early childhood exposures (1-4 years of age) were collected between 2002 and 2010, including stunted growth (height-for-age z-scores, HAZ), underweight (weight-for-age z-scores, WAZ), anemia (hemoglobin), immune activation (c-reactive protein) and parasitic gastrointestinal infection (hookworm infection). Adolescent outcomes (10-17 years of age) were collected in 2015 and included anthropometrics (height, weight, body mass index (BMI)) and biomarkers (hemoglobin (Hb), glycated hemoglobin (HbA1c), white blood cell count (WBC) and blood pressure). First, we evaluated the reliability of EH measurement using digital photographs and the Modified DDE (developmental defects in the enamel) Index by investigating inter- and intra-rater reliability and evaluating the frequency of EH detection across examiners for systemic biases. Next, we investigated associations between several malnutrition-related childhood exposures and EH in the permanent central maxillary incisors using multivariate log-binomial and ordinal logistic regression as well as generalized estimating equations (GEE). Finally, we investigated EH in the permanent central maxillary incisors (as a marker of early childhood experience) in relation to anthropometrics and biomarkers in adolescence using multivariate linear regression. We further evaluated the accuracy of EH in the permanent central maxillary incisors as a marker of chronic malnutrition and utility as a predictor of subsequent health outcomes compared to growth stunting through sensitivity, specificity and receiver operating characteristics (ROC) analyses. Our evaluation of the digital photographs revealed a rough, cobblestone-like EH pattern in the tooth surface that was particularly prevalent in the study sample (92.3%) and was thus the focus of this project. EH detection was most common on the central maxillary incisors (87%) compared to the lateral maxillary incisors (63%) and mandibular canines (26%). The intra-examiner reliability for detecting EH occurrence on the central maxillary incisors was very good (mean kappa=0.77) and greater than the lateral maxillary incisors (mean kappa=0.68) and mandibular canines (mean kappa=0.49). However, the inter-examiner reliability was fair to poor, though the inter-examiner reliability was also better for the maxillary incisors (mean kappa= 0.29) than the mandibular canines (mean kappa=0.17). The study sample had a high prevalence of childhood malnutrition, demonstrated by prevalence of stunted linear growth (75.2%), anemia (56.9%), elevated immune activation (39.1%), and gastrointestinal hookworm infection (49.6%) between 1 and 4 years of age. Results indicated an association between average childhood HAZ (PR=0.98, 95% CI: 0.95, 1.00), CRP levels (PR=1.01, 95% CI: 1.00, 1.03) and presence of gastrointestinal hookworm infection (OR=0.28, 95% CI: 0.08, 0.94 for 2/3 of the tooth affected by EH) and EH, though some of the point estimates lacked statistical precision. Extent of the tooth surface affected by EH seemed to be an important measure of EH as it related to early childhood exposures, particularly for average HAZ and hookworm infection. Greater extent of EH on the tooth surface was also associated with adolescent outcomes, including shorter height (-0.14 HAZ, 95% CI: -0.24, -0.03 and -1.35 cm, 95% CI: -2.21, -0.50), lower weight (-0.98 kg, 95% CI: -1.73, -0.23), lower Hb (-0.36 g/dL, 95% CI: -0.59, -0.13), lower HbA1c (-0.04 %A1c, 95% CI: -0.08, -0.00), and higher WBC count (0.74 109/L, 95% CI: 0.35, 1.14) but not BMI-for-age z-score or blood pressure. EH extent was associated with anemia (PR=1.08, 95% CI: 1.00, 1.18) and elevated WBC count (PR=1.12, 95% CI: 1.01, 1.26) based on public health and clinically-relevant thresholds. When evaluated against growth stunting as the “gold standard” (HAZ< -2.0: prevalence = 62.3% in childhood and 34.1% in adolescence), EH had high sensitivity (93% in childhood, 96% in adolescence) and low specificity (11% in childhood, 10% in adolescence). EH extent was a more accurate marker of childhood stunting (AUC 0.56) than EH occurrence (AUC 0.52) due to increased specificity (0.36 vs. 0.11). The addition of EH extent to a set of markers for childhood stunting (gender and adolescent HAZ) only slightly improved the AUC (0.77 vs. 0.76, p=ns). The AUC for adolescent WBC count was greater for EH extent (AUC 0.61) than for childhood HAZ (AUC 0.58, p=ns) and adolescent HAZ (AUC 0.59, p=ns). Addition of EH extent to sets of markers for adolescent health outcomes (age, gender, childhood HAZ and adolescent HAZ) improved the AUC for nearly all outcomes. In conclusion, we detected an EH pattern that was nearly ubiquitous in the study sample, but the rough, cobblestone-like hypoplastic pattern does not fit the typical linear/grooved pattern described in the overwhelming majority of the malnutrition literature. The pattern does not provide evidence in support of a systemic cause. Intra-examiner reliability results suggest that digital photography is a reproducible method for capturing EH, particularly for the central maxillary incisors. The inter-examiner reliability results bring into question the reliability of the digital photography method, but may be explained by systemic biases between the examiners, the subjective measures included in the Modified DDE Index, insufficient examiner training, and the very high prevalence of EH in the study sample. Improvements in examiner training and the measurement index used to classify EH would likely improve inter-examiner reliability. We provided evidence in support of a relationship between early childhood chronic malnutrition (HAZ), immune activation (CRP), parasitic infection (helminth infection) and EH and between EH extent and several adverse anthropometric and biomarker measures, including shorter height and lower weight, lower hemoglobin and greater WBC count. Given that chronic malnutrition and adverse health outcomes are associated with increased mortality, our findings are in line with the bioarchaeological findings. EH extent also seemed to capture a childhood exposure relevant to adolescent HAZ, hemoglobin and WBC count outcomes above and beyond that of childhood anthropometrics. Although not a strong proxy measure for chronic malnutrition, EH extent may be an important measure for predicting adolescent health outcomes. EH extent may serve as a useful proxy measure of childhood experience among adolescents in settings where childhood stunting data is not available. Furthermore, EH extent may capture childhood exposures relevant to adolescent health outcomes, particularly WBC count, that are not captured by childhood or adolescent HAZ and may thus be a useful addition to the “toolkit” of chronic malnutrition markers. This project makes a unique contribution to the existing literature because it prospectively recorded multiple early childhood exposures (beyond height or stunted growth) and had the minimum follow-up time necessary for full eruption of the permanent dentition to demonstrate an association between malnutrition-related childhood exposures, EH in the permanent dentition and adverse adolescent health outcomes. Subsequent work that builds on this project will be directed toward improving measurement of EH, including further characterization of the spectrum of enamel defects observed in the human dentition, systematically investigating EH etiology across populations and further developing EH as a useful predictor of long-term health by evaluating additional health outcomes, associations in more populations and employing advanced methodology

Maternal Allostatic Load, Caretaking Behaviors, and Child Dental Caries Experience:A Cross-Sectional Evaluation of Linked Mother-Child Data From the Third National Health and Nutrition Examination Survey

Objectives. We evaluated the associations between chronic maternal stress measured by allostatic load (AL), maternal caretaking behaviors, and child dental caries experience. We also assessed the role of socioeconomic status in these associations. Methods. We used data from the Third National Health and Nutrition Examination Survey (1988–1994). We included children aged 2 to 6 years who linked to a maternal record (n = 716 maternal–child pairs). The main exposure was maternal AL index (0, 1, or ≥ 2). The primary outcome of interest was child dental caries experience (none or any). We evaluated the association between maternal AL and (1) maternal caretaking behaviors, and (2) child caries status and the role of socioeconomic status in these relationships. Results. Children of mothers with an AL index of at least 2 were significantly more likely to have not been breastfed and to have dental caries than were children of mothers with a normal AL before adjusting for measures of socioeconomic status. Conclusions. Maternal chronic stress, indicated by elevation in markers of AL, has an important role in child caretaking behaviors and in children’s oral health

Baseline characteristics of children in the International PANS Registry (IPR) Epidemiology Study

Purpose The International PANS Registry (IPR) Epidemiology Study is a registry-based, longitudinal study. We designed this study to improve phenotyping and characterisation of children with paediatric acute-onset neuropsychiatric syndrome (PANS) and PANS-like features and facilitate multidisciplinary and translational health research. This cohort provides new opportunities to address unresolved research questions related to the broad spectrum of heterogenous PANS-like conditions.Participants Inclusion in the IPR Epidemiology Study remains open indefinitely via IPR enrolment online. Participants include children with PANS or who have PANS-like features and their healthy siblings. We collected cross-sectional survey data based on parent report, including details on phenotypic traits and characteristics that, to our knowledge, have not been previously collected for this patient population. We describe the baseline characteristics of cases and their healthy siblings here.Findings to date The IPR Epidemiology Study currently includes 1781 individuals (1179 cases, 602 siblings; from 1010 households). Many households include a sibling (n=390, 39%) and some include multiple cases (n=205, 20%). Mean enrolment age was 11.3±4.3 years for cases and 10.1±5.3 for siblings. Leading PANS-like features include anxiety (94%), emotional lability (92%) and obsessions (90%). Onsets were sudden and dramatic (27%), gradual with a subsequent sudden and dramatic episode (68%) or a gradual progression (5%). The mean age at early signs/symptom onset was 4 years and 7 years at sudden and dramatic increases, respectively. Infection/illness was the most common suspected symptom trigger (84%). Nearly all cases had been treated with antibiotics (88%) and/or non-steroidal anti-inflammatory drugs (79%). Parents reported immune-related conditions in cases (18%) and their nuclear, biological family (48%; 39% in biological mothers).Future plans Future plans include increasing sample size, collecting longitudinal survey data, recruiting appropriate study controls and expanding the scope of the database, prioritising medical record data integration and creating a linked biorepository. Secondary data analyses will prioritise identifying subgroups by phenotypic traits, maternal health and disease characteristics

Rationale and design for the International PANS Registry (IPR; pediatric acute-onset neuropsychiatric syndrome)

The International PANS Registry (IPR) is the first centralized, epidemiologic database of children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and PANS-like features and their siblings. PANS is a relatively new umbrella syndrome that lacks diagnostic biomarkers and is characterized by a set of working criteria. The failure to find a diagnostic biomarker is likely due to underpowered studies and inherent biological heterogeneity within PANS. Until the IPR was established, a critical barrier to large-scale longitudinal studies had been the absence of a large-scale epidemiologic study and a centralized database of children with PANS and PANS-like features. The IPR was created to serve as a translational health tool to accelerate research on the broad spectrum of complex pediatric neuroimmune conditions with the long-term goal of enabling a paradigm shift in this field from symptom-based evaluation and treatment towards biology-based diagnoses, treatments, screening, and surveillance. To date, the IPR has registered 1,666 families (3,247 children) and is the largest database in the world that gathers in-depth information on children with PANS and PANS-like features and their siblings. Enrollment in the IPR is open and ongoing; longitudinal follow up is planned. Participating families enroll their children with PANS and PANS-like features and their healthy siblings in the IPR via an online survey platform. The selection criteria for IPR enrollment are intentionally less restrictive than the current working criteria for PANS to generate a large recruitment pool and enable study of the broad spectrum of PANS-like conditions. The IPR is designed to enable ancillary study recruitment based on detailed selection criteria and to grow and expand in scope in the future. The IPR team is committed to data sharing and invites collaborators who will leverage existing data from the IPR database and extend knowledge in an area beyond the original scope of the IPR.This study was funded by the Pediatric Research & Advocacy Initiative (PRAI; https://praikids.org/), a 501c3 nonprofit organization founded by the patient community

Shades of Decay: The Meanings of Tooth Discoloration and Deterioration to Mexican Immigrant Caregivers of Young Children

The objective of this article is to investigate parental understanding of tooth discoloration and decay and their related care seeking for young, Mexican-American children. The research design entailed semi-structured, face-to-face interviews conducted in Spanish with a convenience sample of 37 Mexican immigrant mothers of young children in a low-income urban neighborhood. Five major color terms - white, off-white, yellow, brown, and black - were used to describe tooth discoloration, the causes of which were mainly unrecognized or attributed to poor oral hygiene and exposure to sweet substances. Mothers also described three major levels of deterioration of the structural integrity of teeth due to caries, from stains to decayed portions to entirely rotten. A trend was observed between use of darker discoloration terms and extensive carious lesions. Teeth described as both dark in color and structurally damaged resulted in seeking of professional care. The paper concludes with the finding that Spanish terms used to describe tooth discoloration and carious lesions are broad and complex. Mexican immigrant mothers' interpretations of tooth discoloration and decay may differ from dental professionals' and result in late care seeking. Increased understanding between dental practitioners and caregivers is needed to create educational messages about the early signs of tooth decay

Maternal exposure to urinary polycyclic aromatic hydrocarbons (PAH) in pregnancy and childhood asthma in a pooled multi-cohort study

Background: Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may increase risk of pediatric asthma, but existing human studies are limited. Objectives: We estimated associations between gestational PAHs and pediatric asthma in a diverse US sample and evaluated effect modification by child sex, maternal asthma, and prenatal vitamin D status. Methods: We pooled two prospective pregnancy cohorts in the ECHO PATHWAYS Consortium, CANDLE and TIDES, for an analytic sample of N = 1296 mother–child dyads. Mono-hydroxylated PAH metabolites (OH-PAHs) were measured in mid-pregnancy urine. Mothers completed the International Study on Allergies and Asthma in Childhood survey at child age 4–6 years. Poisson regression with robust standard errors was used to estimate relative risk of current wheeze, current asthma, ever asthma, and strict asthma associated with each metabolite, adjusted for potential confounders. We used interaction models to assess effect modification. We explored associations between OH-PAH mixtures and outcomes using logistic weighted quantile sum regression augmented by a permutation test to control Type 1 errors. Results: The sociodemographically diverse sample spanned five cities. Mean (SD) child age at assessment was 4.4 (0.4) years. While there was little evidence that either individual OH-PAHs or mixtures were associated with outcomes, we observed effect modification by child sex for most pairs of OH-PAHs and outcomes, with adverse associations specific to females. For example, a 2-fold increase in 2-hydroxy-phenanthrene was associated with current asthma in females but not males (RRfemale = 1.29 [95 % CI: 1.09, 1.52], RRmale = 0.95 [95 % CI: 0.79, 1.13]; pinteraction = 0.004). There was no consistent evidence of modification by vitamin D status or maternal asthma. Discussion: This analysis, the largest cohort study of gestational PAH exposure and childhood asthma to date, suggests adverse associations for females only. These preliminary findings are consistent with hypothesized endocrine disruption properties of PAHs, which may lead to sexually dimorphic effects