Protocol for the air purification for eosinophilic COPD study (APECS): a randomised controlled trial of home air filtration by HEPA.

INTRODUCTION: Exposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have higher levels of airway inflammation, greater responsiveness to anti-inflammatory steroid inhalers and a greater lung function response to PM pollution exposure compared with those with lower eosinophil levels. This study will evaluate if reducing home PM exposure by high-efficiency particulate air (HEPA) air filtration improves respiratory health in eosinophilic COPD. METHODS AND ANALYSIS: The Air Purification for Eosinophilic COPD Study (APECS) is a double-blinded randomised placebo-controlled trial that will enrol 160 participants with eosinophilic COPD living in the area of Boston, Massachusetts. Real and sham air purifiers will be placed in the bedroom and living rooms of the participants in the intervention and control group, respectively, for 12 months. The primary trial outcome will be the change in forced expiratory volume in 1 s (FEV1). Lung function will be assessed twice preintervention and three times during the intervention phase (at 7 days, 6 months and 12 months postrandomisation). Secondary trial outcomes include changes in (1) health status by St. George's Respiratory Questionnaire; (2) respiratory symptoms by Breathlessness, Cough and Sputum Scale (BCSS); and (3) 6-Minute Walk Test (6MWT). Inflammatory mediators were measured in the nasal epithelial lining fluid (NELF). Indoor PM will be measured in the home for the week preceding each study visit. The data will be analysed to contrast changes in outcomes in the intervention and control groups using a repeated measures framework. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of Beth Israel Deaconess Medical Centre (protocol #2019P0001129). The results of the APECS trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION: NCT04252235. Version: October 2023.

NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils.

Neutrophil extracellular traps (NETs) not only counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptor-mediated apoptosis promote gasdermin E (GSDME)-dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end of life for neutrophils.

High plasma IL-6 levels may enhance the adverse effects of mouse allergen exposure in urban schools on asthma morbidity in children.

BACKGROUND: Few data on the relationships between environmental exposures, asthma morbidity, and systemic IL-6 inflammation exist. OBJECTIVE: We sought to determine whether baseline plasma IL-6 level is associated with increased asthma morbidity in children exposed to mouse allergen in inner-city classrooms. METHODS: Data from the longitudinal School Inner-City Asthma Studies of 215 children with asthma, aged 4 to 14 years and recruited from urban elementary schools, were analyzed. Given the unknown threshold of IL-6 risk levels and skewness of the distribution, the children were stratified into tertiles as follows: low baseline IL-6 level (<0.013 pg/mL), moderate baseline IL-6 level (0.013-0.302 pg/mL), and high baseline IL-6 level (>0.302 pg/mL). Relationships between plasma IL-6 level and body mass index (BMI) percentile, inflammatory markers, lung function, mouse allergen exposure, and asthma outcomes were assessed. RESULTS: Cross-sectional analysis demonstrated that increasing IL-6 level was associated with higher BMI percentile (P < .0001), C-reactive protein level (P = .0006), and blood neutrophil count (P = .0024). IL-6 was not associated with type 2 inflammatory markers, including blood eosinophil count, allergic sensitization, or fractional exhaled nitric oxide level. Longitudinal analysis showed that children with high IL-6 levels had a higher number of days with asthma symptoms than did those children with moderate (incidence rate ratio = 1.74 [95% CI = 1.10-2.77]; P = .0187) or low (incidence rate ratio =1.83 [95% CI = 1.21-2.77]; P = .0043) IL-6 levels. Children with high IL-6 levels who were exposed to increasing levels of mouse allergen exhibited lower ratios of FEV1 value to forced vital capacity than did children with moderate IL-6 levels (ß = -0.0044 [95% CI = -0.0073 to -0.0015]; pairwise interaction P = .0028) or low IL-6 levels (ß = -0.0042 [95% CI = - 0.0070 to -0.0013]; pairwise interaction P = .0039). CONCLUSIONS: Inner-city children with asthma and high plasma IL-6 levels are more likely to have an increased BMI, elevated C-reactive protein level, elevated blood neutrophil count, and greater asthma symptoms. High IL-6 level appears to increase susceptibility to the effects of classroom exposure to mouse allergen on lung function in urban children.

ARCH: Large-scale Knowledge Graph via Aggregated Narrative Codified Health Records Analysis.

Objective: Electronic health record (EHR) systems contain a wealth of clinical data stored as both codified data and free-text narrative notes, covering hundreds of thousands of clinical concepts available for research and clinical care. The complex, massive, heterogeneous, and noisy nature of EHR data imposes significant challenges for feature representation, information extraction, and uncertainty quantification. To address these challenges, we proposed an efficient Aggregated naRrative Codified Health (ARCH) records analysis to generate a large-scale knowledge graph (KG) for a comprehensive set of EHR codified and narrative features. Methods: The ARCH algorithm first derives embedding vectors from a co-occurrence matrix of all EHR concepts and then generates cosine similarities along with associated p-values to measure the strength of relatedness between clinical features with statistical certainty quantification. In the final step, ARCH performs a sparse embedding regression to remove indirect linkage between entity pairs. We validated the clinical utility of the ARCH knowledge graph, generated from 12.5 million patients in the Veterans Affairs (VA) healthcare system, through downstream tasks including detecting known relationships between entity pairs, predicting drug side effects, disease phenotyping, as well as sub-typing Alzheimer's disease patients. Results: ARCH produces high-quality clinical embeddings and KG for over 60,000 EHR concepts, as visualized in the R-shiny powered web-API (https://celehs.hms.harvard.edu/ARCH/). The ARCH embeddings attained an average area under the ROC curve (AUC) of 0.926 and 0.861 for detecting pairs of similar EHR concepts when the concepts are mapped to codified data and to NLP data; and 0.810 (codified) and 0.843 (NLP) for detecting related pairs. Based on the p-values computed by ARCH, the sensitivity of detecting similar and related entity pairs are 0.906 and 0.888 under false discovery rate (FDR) control of 5%. For detecting drug side effects, the cosine similarity based on the ARCH semantic representations achieved an AUC of 0.723 while the AUC improved to 0.826 after few-shot training via minimizing the loss function on the training data set. Incorporating NLP data substantially improved the ability to detect side effects in the EHR. For example, based on unsupervised ARCH embeddings, the power of detecting drug-side effects pairs when using codified data only was 0.15, much lower than the power of 0.51 when using both codified and NLP concepts. Compared to existing large-scale representation learning methods including PubmedBERT, BioBERT and SAPBERT, ARCH attains the most robust performance and substantially higher accuracy in detecting these relationships. Incorporating ARCH selected features in weakly supervised phenotyping algorithms can improve the robustness of algorithm performance, especially for diseases that benefit from NLP features as supporting evidence. For example, the phenotyping algorithm for depression attained an AUC of 0.927 when using ARCH selected features but only 0.857 when using codified features selected via the KESER network[1]. In addition, embeddings and knowledge graphs generated from the ARCH network were able to cluster AD patients into two subgroups, where the fast progression subgroup had a much higher mortality rate. Conclusions: The proposed ARCH algorithm generates large-scale high-quality semantic representations and knowledge graph for both codified and NLP EHR features, useful for a wide range of predictive modeling tasks.

Effect of radon exposure on asthma morbidity in the School Inner-City Asthma study.

BACKGROUND: Radon may have a role in obstructive lung disease outside its known carcinogenicity. Little is known about radon's effects on asthma morbidity. OBJECTIVE: To determine the effect of radon on fractional exhaled nitric oxide (FE NO), asthma symptom-days, and lung function in inner-city asthmatic school children. METHODS: Two hundred ninety-nine school-aged asthmatic children enrolled in the School Inner-City Asthma Study (SICAS-1) were followed. One and two-month averaged radon was assessed using a spatiotemporal model predicting zip code-specific monthly exposures. FE NO and spirometry were measured twice during the academic year. Asthma symptoms were assessed four times during the academic year. The interaction between indoor radon exposure (Bq/m3 ) and seasonality predicting log-transformed FE NO, forced expiratory volume in 1 s (FEV1 ) % predicted, forced vital capacity (FVC) % predicted, FEV1 /FVC, and asthma symptom-days was evaluated. RESULTS: Participants with high radon exposure had greater change in FE NO from warm to cold periods compared to low radon exposure (interaction p = 0.0013). Participants with >50th percentile radon exposure experience significant FE NO increase from warm to cold weather ( ß $\beta $ = 0.29 [95% confidence interval [CI]: 0.04-0.54], p = 0.0240). We report a positive association between radon 1-month moving average (incidence rate ratio [IRR] = 1.01, p = 0.0273) and 2-month moving average (IRR = 1.01, p = 0.0286) with maximum asthma symptom-days (n = 299, obs = 1167). CONCLUSIONS: In asthmatic children, radon may be associated with increased asthma morbidity, suggesting radon may be a modifiable environmental risk factor for airway inflammation.

Buprenorphine treatment receipt characteristics and retention among people who inject drugs at Integrated Care Centers in India.

BACKGROUND: India is facing overlapping opioid injection and HIV epidemics among people who inject drugs (PWID) in several cities. Integrated Care Centers (ICCs) provide single-venue HIV and substance use services to PWID. We evaluated PWID engagement in daily observed buprenorphine treatment at 7 ICCs to inform interventions. METHODS: We analyzed 1-year follow-up data for PWID initiating buprenorphine between 1 January - 31 December 2018, evaluating receipt frequency, treatment interruptions (no buprenorphine receipt for 60 consecutive days with subsequent re-engagement), and drop-out (no buprenorphine receipt for 60 consecutive days without re-engagement). Using descriptive statistics, we explored differences between ICCs in the opioid-endemic Northeast region and ICCs in the emerging opioid epidemic North/Central region. We used a multivariable logistic regression model to determine predictors of treatment drop-out by 6 months. RESULTS: 1312 PWID initiated buprenorphine (76% North/Central ICCs vs. 24% Northeast ICCs). 31% of PWID in North/Central, and 25% in Northeast ICCs experienced ≥ 1 treatment interruption in 1 year. Over 6 months, 48% of PWID in North/Central vs. 60% in Northeast ICCs received buprenorphine ≤ 2 times/week (p < 0.0001). A third of PWID in North/Central vs. half in Northeast ICCs experienced treatment drop-out by 6 months (p < 0.001). In the multivariable model, living in Northeast cities was associated with increased odds of drop-out while counseling receipt was associated with decreased odds. CONCLUSIONS: Retention among PWID initiating buprenorphine at ICCs was comparable to global reports. However, regional heterogeneity in retention, and low daily buprenorphine receipt suggest patient-centered interventions adapted to regional contexts are urgently needed.

Clinical Assessment of Mechanical Allodynia in Youth With Complex Regional Pain Syndrome: Development and Preliminary Validation of the Pediatric Tactile Sensitivity Test of Allodynia (Pedi-Sense).

Youth with complex regional pain syndrome (CRPS) commonly experience mechanical allodynia and disability. Assessment of mechanical allodynia is typically binary (present or absent), making it difficult to assess the quality and degree of mechanical allodynia before and after treatment. This study developed and validated the Pediatric Tactile Sensitivity Test of Allodynia (Pedi-Sense) to provide an easy way for rehabilitation clinicians to evaluate mechanical allodynia before and after intensive interdisciplinary pain treatment. The 6 Pedi-Sense items demonstrated adequate internal consistency reliability (CR) at admission (CR = .956) and discharge (CR = .973), reasonably fit the hypothesized linear model of stimulus intensity (P < .0001), and significantly loaded onto a single latent factor, mechanical allodynia (P < .0001), at admission and discharge. Pedi-Sense scores significantly correlated with disability (rs = .40; P = .004) and pain catastrophizing (rs = .33; P = .017) at admission. The Pedi-Sense appeared responsive to intervention as participants' total scores improved by 1.44 points (95% CI: .72, 2.15) after IIPT interventions that included daily tactile desensitization. However, test-retest and interrater reliability and the specific contribution of desensitization treatment to the overall success of multi-modal pain rehabilitation still needs to be evaluated. PERSPECTIVE: This article presents the development and preliminary validation of a novel clinical assessment of static and dynamic mechanical allodynia. The Pediatric Tactile Sensitivity Test of Allodynia (Pedi-Sense) allows rehabilitation clinicians to easily evaluate mechanical allodynia at the bedside with minimal training and simple equipment to guide desensitization treatment in clinical settings.

Clinician factors associated with delayed diagnosis of appendicitis.

OBJECTIVES: To evaluate the association of clinician demographics and practice patterns with delayed diagnosis of appendicitis. METHODS: We included children with appendicitis at 13 regional emergency departments (EDs). We screened patients with a previous ED visit within 7 days for delayed diagnosis by chart review. We evaluated the association of clinician characteristics using logistic regression with random intercepts for site and clinician and delay as the outcome. RESULTS: Among 7,452 children with appendicitis, 105 (1.4%) had delayed diagnosis. Clinicians in the lowest quartile of obtaining blood in their general practice were more likely to have delayed diagnosis (odds ratio 4.9 compared to highest quartile, 95% confidence interval 1.8, 13.8). Clinicians' imaging rates, specialty, sex, and experience were not associated with delayed diagnosis. CONCLUSIONS: Clinicians who used more blood tests in their general practice had a lower risk of delayed diagnosis of appendicitis, possible evidence that lower risk tolerance has benefits.

Delayed diagnosis of serious paediatric conditions in 13 regional emergency departments.

OBJECTIVE: To evaluate rates, risk factors and outcomes of delayed diagnosis of seven serious paediatric conditions. METHODS: This was a retrospective, cross-sectional study of children under 21 years old visiting 13 community and tertiary emergency departments (EDs) with appendicitis, bacterial meningitis, intussusception, mastoiditis, ovarian torsion, sepsis or testicular torsion. Delayed diagnosis was defined as having a previous ED encounter within 1 week in which the condition was present per case review. Patients with delayed diagnosis were each matched to four control patients without delay by condition, facility and age. Conditional logistic regression models evaluated risk factors of delay. Complications were compared between by delayed diagnosis status. RESULTS: Among 14 972 children, delayed diagnosis occurred in 1.1% (range 0.3% for sepsis to 2.6% for ovarian torsion). Hispanic (matched OR 2.71, 95% CI 1.69 to 4.35) and non-Hispanic black (OR 2.40, 95% CI 1.21 to 4.79) race/ethnicity were associated with delayed diagnosis, whereas Asian and other race/ethnicity were not. Public (OR 2.21, 95% CI 1.42 to 3.44) and other (OR 2.43, 95% CI 1.50 to 3.93) insurance were also associated with delay. Non-English language was associated with delay (OR 1.65, 95% CI 1.02 to 2.69). Abnormal vital signs were associated with a lower likelihood of delay (OR 0.15, 95% CI 0.09 to 0.25). In an adjusted model, Hispanic race/ethnicity, other insurance, abnormal vital signs and complex chronic conditions (CCCs) were associated with delay. The odds of a complication were 2.5-fold (95% CI 1.6 to 3.8) higher among patients with a delay. CONCLUSION: Delayed diagnosis was uncommon across 13 regional EDs but was more likely among children with Hispanic ethnicity, CCCs or normal vital signs. Delays were associated with a higher risk of complications.

Atopic Dermatitis Mediates the Association Between an IL4RA Variant and Food Allergy in School-Aged Children.

BACKGROUND: Atopic dermatitis (AD) and food allergy (FA) may share genetic risk factors. It is unknown whether genetic factors directly cause FA or are mediated through AD, as the dual-allergen hypothesis suggests. OBJECTIVE: To test the hypothesis that AD mediates the relationship between an IL-4 receptor alpha chain gene (IL4RA) variant, the human IL-4 receptor alpha chain protein-R576 polymorphism, and FA. METHODS: A total of 433 children with asthma enrolled in the School Inner-City Asthma Study underwent genotyping for the IL4RA576 allele. Surveys were administered to determine FA, AD, and associated allergic responses. Mediation analysis was performed adjusting for race and ethnicity, age, sex, and household income. Multivariate models were used to determine the association between genotype and FA severity. RESULTS: AD was reported in 193 (45%) and FA in 80 children (19%). Each risk allele increased odds of AD 1.39-fold ([1.03-1.87], P = .03), and AD increased odds of FA 3.67-fold ([2.05- 6.57], P < .01). There was an indirect effect of genotype, mediated by AD, predicting FA; each risk allele increased the odds of FA by 1.13 (odds ratio [95% CI], Q/R = 1.13 [1.02-1.24], R/R = 1.28 [1.04-1.51]; P < .01). Each risk allele increased the odds of severe FA symptoms 2.68-fold ([1.26-5.71], P = .01). CONCLUSIONS: In a cohort of children with asthma, AD is part of the causal pathway between an IL4RA variant and FA. This variant is associated with increased risk of severe FA reactions. Addressing AD in children with an IL4RA polymorphism may modulate the risk of FA.

Factors Influencing Classroom Exposures to Fine Particles, Black Carbon, and Nitrogen Dioxide in Inner-City Schools and Their Implications for Indoor Air Quality.

BACKGROUND: School classrooms, where students spend the majority of their time during the day, are the second most important indoor microenvironment for children. OBJECTIVE: We investigated factors influencing classroom exposures to fine particulate matter (PM2.5), black carbon (BC), and nitrogen dioxide (NO2) in urban schools in the northeast United States. METHODS: Over the period of 10 y (2008-2013; 2015-2019) measurements were conducted in 309 classrooms of 74 inner-city schools during fall, winter, and spring of the academic period. The data were analyzed using adaptive mixed-effects least absolute shrinkage and selection operator (LASSO) regression models. The LASSO variables included meteorological-, school-, and classroom-based covariates. RESULTS: LASSO identified 10, 10, and 11 significant factors (p<0.05) that were associated with indoor PM2.5, BC, and NO2 exposures, respectively. The overall variability explained by these models was R2=0.679, 0.687, and 0.621 for PM2.5, BC, and NO2, respectively. Of the model's explained variability, outdoor air pollution was the most important predictor, accounting for 53.9%, 63.4%, and 34.1% of the indoor PM2.5, BC, and NO2 concentrations. School-based predictors included furnace servicing, presence of a basement, annual income, building type, building year of construction, number of classrooms, number of students, and type of ventilation that, in combination, explained 18.6%, 26.1%, and 34.2% of PM2.5, BC, and NO2 levels, whereas classroom-based predictors included classroom floor level, classroom proximity to cafeteria, number of windows, frequency of cleaning, and windows facing the bus area and jointly explained 24.0%, 4.2%, and 29.3% of PM2.5, BC, and NO2 concentrations, respectively. DISCUSSION: The adaptive LASSO technique identified significant regional-, school-, and classroom-based factors influencing classroom air pollutant levels and provided robust estimates that could potentially inform targeted interventions aiming at improving children's health and well-being during their early years of development. https://doi.org/10.1289/EHP10007.

Sex differences in the relationship of sleep-disordered breathing and asthma control among children with severe asthma.

OBJECTIVE: Children with severe asthma are underrepresented in studies of the relationship of sleep-disordered breathing (SDB) and asthma and little is known about sex differences of these relationships. We sought to determine the relationship of SDB with asthma control and lung function among boys and girls within a pediatric severe asthma cohort. METHODS: Patients attending clinic visits at the Boston Children's Hospital Pediatric Severe Asthma Program completed the Pediatric Sleep Questionnaire (PSQ), Asthma Control Test (ACT) and Spirometry. The prevalence of SDB was defined as a PSQ score >0.33. We analyzed the association between PSQ score and both ACT score and spirometry values in mixed effect models, testing interactions for age and sex. RESULTS: Among 37 subjects, mean age was 11.8 years (4.4) and 23 (62.2%) were male, the prevalence of SDB was 43.2% (16/37). Including all 80 observations, there was a moderate negative correlation between PSQ and ACT scores (r=-0.46, p < 0.001). Multivariable linear regression models revealed a significant sex interaction with PSQ on asthma control (p = 0.003), such that for each 0.10 point increase in PSQ there was a 1.88 point decrease in ACT score for females but only 0.21 point decrease in ACT score for males. A positive PSQ screen was associated with a 9.44 point (CI 5.54, 13.34, p < 0.001) lower ACT score for females and a 3.22 point (CI 0.56, 5.88, p = 0.02) lower score for males. CONCLUSIONS: SDB is common among children with severe asthma. Among children with severe asthma, SDB in girls portends to significantly worse asthma control than boys.Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.1897838.

Impact of decreasing vancomycin exposure on acute kidney injury in stem cell transplant recipients.

OBJECTIVE: To evaluate the change in vancomycin days of therapy (DOT) and vancomycin-associated acute kidney injury (AKI) after an antimicrobial stewardship program (ASP) intervention to decrease vancomycin use in stable patients after hematopoietic stem cell transplantation (HSCT). DESIGN: Retrospective cohort study and quasi-experimental interrupted time series analysis. Change in unit-level vancomycin DOT per 1,000 inpatient days after the intervention was assessed using segmented Poisson regression. Subject-specific risk of vancomycin-associated AKI was evaluated using a random intercept logistic regression model with mediation analysis. SETTING: HSCT unit at a single quaternary-care pediatric hospital. PARTICIPANTS: Inpatients aged 3 months and older who underwent HSCT between January 1, 2015, and March 31, 2019 (27 months before and after the intervention) who received any dose of vancomycin. INTERVENTION: An ASP intervention in April 2017 creating a new practice guideline to decrease prolonged (>72 hours) vancomycin courses for stable HSCT patients with febrile neutropenia. RESULTS: Overall, 439 vancomycin exposures (234 before the intervention and 205 after the intervention) occurring across 300 transplants and 259 subjects were included. The mean vancomycin DOT was 307 per 1,000 inpatient days (95% confidence interval [CI], 272-342) and decreased after the intervention to 207 per 1,000 inpatient days (95% CI, 173-240). In multivariable analyses, the odds of AKI in the postintervention period were 37% lower than in the preintervention period (adjusted OR, 0.63; 95% CI, 0.42-0.95; P = .0268); 56% of the excess risk was mediated by vancomycin DOT. CONCLUSIONS: An ASP intervention successfully decreased vancomycin use after HSCT and resulted in a decrease in AKI. Reducing empiric antibiotic exposure for stable patients after HSCT can improve clinical outcomes.

Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia-a randomized controlled feeding trial.

BACKGROUND: Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption. OBJECTIVES: This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance. METHODS: After 10-14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis. RESULTS: Retention was 90%. Mean change in LPIR (scale 0-100) differed by diet in a dose-dependent fashion: Low-Carb (-5.3; 95% CI: -9.2, -1.5), Moderate-Carb (-0.02; 95% CI: -4.1, 4.1), High-Carb (3.6; 95% CI: -0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [-14.7% (95% CI: -19.5, -9.5), -2.1 (95% CI: -8.2, 4.3), and 0.2 (95% CI: -6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet. CONCLUSIONS: A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.

Air quality, Environment and Respiratory Outcomes in Bronchopulmonary Dysplasia, the AERO-BPD cohort study: design and adaptation during the SARS-CoV-2 pandemic.

INTRODUCTION: Almost half of all school-age children with bronchopulmonary dysplasia (BPD) have asthma-like symptoms and more suffer from lung function deficits. While air pollution and indoor respiratory irritants are known to affect high-risk populations of children, few studies have objectively evaluated environmental contributions to long-term respiratory morbidity in this population. This study aimed to examine the role of indoor environmental exposures on respiratory morbidity in children with BPD. METHODS AND ANALYSIS: The Air quality, Environment and Respiratory Ouctomes in BPD (AERO-BPD) study is a prospective, single-centre observational study that will enrol a unique cohort of 240 children with BPD and carefully characterise participants and their indoor home environmental exposures. Measures of indoor air quality constituents will assess the relationship of nitrogen dioxide (NO2), particulate matter (PM2.5), nitric oxide (NO), temperature and humidity, as well as dust concentrations of allergens, with concurrently measured respiratory symptoms and lung function.Adaptations to the research protocol due to the SARS-CoV-2 pandemic included remote home environment and participant assessments. ETHICS AND DISSEMINATION: Study protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. Dissemination will be in the form of peer-reviewed publications and participant information products. TRIAL REGISTRATION NUMBER: NCT04107701.

Pediatric Intern Clinical Exposure During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Pediatric health care encounters declined during the coronavirus disease 2019 (COVID-19) pandemic, and pediatric residency programs have adapted trainee schedules to meet the needs of this changing clinical environment. We sought to evaluate the impact of the pandemic on pediatric interns' clinical exposure. METHODS: In this retrospective cohort study, we quantified patient exposure among pediatric interns from a single large pediatric residency program at a freestanding children's hospital. Patient encounters and shifts per pediatric intern in the inpatient and emergency department settings were evaluated during the COVID-19 pandemic, from March to June 2020, as compared with these 3 months in 2019. Patient encounters by diagnosis were also evaluated. RESULTS: The median number of patient encounters per intern per 2-week block declined on the pediatric hospital medicine service (37.5 vs 27.0; P < .001) and intensive care step-down unit (29.0 vs 18.8; P = .004) during the pandemic. No significant difference in emergency department encounters was observed (63.0 vs 40.5; P = .06). The median number of shifts worked per intern per 2-week block also decreased on the pediatric hospital medicine service (10.5 vs 9.5, P < .001). Across all settings, there were more encounters for screening for infectious disease and fewer encounters for respiratory illnesses. CONCLUSIONS: Pediatric interns at the onset of the COVID-19 pandemic were exposed to fewer patients and had reduced clinical schedules. Careful consideration is needed to track and supplement missed clinical experiences during the pandemic.

Improving patient education for atopic dermatitis: A randomized controlled trial of a caregiver handbook.

BACKGROUND/OBJECTIVES: Patient education is important to families' ability to manage and cope with pediatric atopic dermatitis (AD). We evaluated whether an educational handbook could improve AD symptoms, caregiver confidence in AD management skills, and AD-related quality of life. METHODS: Caregivers of children with AD ages 1 month to 16 years were randomly assigned to the intervention arm (handbook in addition to standard AD management) or the control arm (standard management alone). Caregivers completed self-report outcome questionnaires prior to a clinical visit for AD and at 3-month follow-up. RESULTS: 175 caregivers completed questionnaires at baseline and follow-up. AD symptoms measured by the Patient-Oriented Eczema Measure (POEM) improved in both the handbook and control arms. However, the decrease in the mean POEM score in the handbook arm (-4.4, 95% CI [-5.8, -3.0]) did not differ from that in the control arm (-3.4, 95% CI [-4.8, -2.03]; P = .343). Change in quality of life did not differ between study arms. Among caregivers attending a new patient visit for AD, mean confidence scores (measured from 0 to 100) increased more in the handbook arm (67 [95% CI {60, 74}] to 83 [95% CI {77, 88}]) relative to the control arm (74 [95% CI {65, 82}] to 75 [95% CI {67, 83}]; P = .012). The majority of caregivers rated the handbook as helpful in managing the child's AD. CONCLUSIONS: Despite an adequate sample size, the handbook did not improve AD symptoms more than standard management alone. The handbook improved confidence in management skills for families attending new patient visits for AD.

Asthma control and psychological health in pediatric severe asthma.

OBJECTIVES: Psychological comorbidities have been associated with asthma in adults and children, but have not been studied in a population of children with severe asthma. The aim of this study was to test the hypothesis that symptoms of anxiety or depression are highly prevalent in pediatric severe asthma and negatively effects asthma control. METHODS: Longitudinal assessments of anxiety or depression symptoms (Patient Health Questionnaire-4 [PHQ-4]), asthma control (Asthma Control Test [ACT]), and lung function were performed in a single-center pediatric severe asthma clinic. Participant data were collected during routine clinical care. Primary outcomes were ACT and forced expiratory volume in 1 s per forced vital capacity (FEV1/FVC). RESULTS: Among 43 subjects (with total 93 observations), 58.1% reported at least one anxious or depressive symptom and 18.6% had a PHQ-4 more than 2, the threshold for an abnormal test result. After adjusting for age, sex, race, and asthma medication step, there was a significant reduction in ACT for girls with PHQ-4 more than 2 (adjusted mean [SE] ACT for PHQ-4 > 2: 13.64 [0.59], ACT for PHQ-4 ≤ 2: 20.64 [1.25], p = .02) but not boys. Moreover, there was a significant differential effect of mental health impairment for girls than boys. ACT for girls with PHQ more than 2: 13.64 (0.59) compared with boys with PHQ-4 more than 2: 17.82 (0.95), adjusted mean difference ACT by sex = 4.18 points; 95% confidence interval, 0.63-7.73; p = .033. In adjusted models, there was no association between PHQ-4 more than 2 and FEV1/FVC. CONCLUSIONS: Symptoms of anxiety and depression are common. In children with severe asthma, a PHQ-4 score more than 2 is associated with worse asthma symptom control in girls, but not boys.