Temperament and sex as moderating factors of the effects of exposure to maternal depression on telomere length in early childhood.

Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of exposure to maternal depression on telomere length in early childhood. Telomere length has emerged as a potentially important biomarker of current and future health, with possible mechanistic involvement in the onset of various disease states. Participants comprised a community sample of children followed from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy, 2 years, and 3 years. Maternal depressive symptoms and the child temperament traits of negative affectivity, surgency/extraversion, and regulation/effortful control were assessed via maternal report at each timepoint. Analyses revealed a 3-way interaction among surgency/extraversion, sex, and maternal depressive symptoms, such that higher surgency/extraversion was associated with shorter telomere length specifically among males exposed to elevated maternal depressive symptoms. These findings suggest that temperament and sex influence children's susceptibility to the effects of maternal depression on telomere dynamics in early life.

Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3.

BACKGROUND: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete. OBJECTIVE: We sought to determine phenotypic factors associated with FEV1 throughout childhood in the Severe Asthma Research Program 3 pediatric cohort. METHODS: Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV1 and prebronchodilator FEV1/forced vital capacity. RESULTS: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV1 include baseline Feno (B, -49 mL/log2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV1; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV1 over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV1 at each successive year. CONCLUSIONS: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV1 over time. Boys with recurrent exacerbations are at high risk of lower FEV1 through childhood.

The IL-4Rα Q576R polymorphism is associated with increased severity of atopic dermatitis and exaggerates allergic skin inflammation in mice.

BACKGROUND: Atopic dermatitis (AD) is characterized by TH2-dominated skin inflammation and systemic response to cutaneously encountered antigens. The TH2 cytokines IL-4 and IL-13 play a critical role in the pathogenesis of AD. The Q576->R576 polymorphism in the IL-4 receptor alpha (IL-4Rα) chain common to IL-4 and IL-13 receptors alters IL-4 signaling and is associated with asthma severity. OBJECTIVE: We sought to investigate whether the IL-4Rα R576 polymorphism is associated with AD severity and exaggerates allergic skin inflammation in mice. METHODS: Nighttime itching interfering with sleep, Rajka-Langeland, and Eczema Area and Severity Index scores were used to assess AD severity. Allergic skin inflammation following epicutaneous sensitization of mice 1 or 2 IL-4Rα R576 alleles (QR and RR) and IL-4Rα Q576 (QQ) controls was assessed by flow cytometric analysis of cells and quantitative RT-PCR analysis of cytokines in skin. RESULTS: The frequency of nighttime itching in 190 asthmatic inner-city children with AD, as well as Rajka-Langeland and Eczema Area and Severity Index scores in 1116 White patients with AD enrolled in the Atopic Dermatitis Research Network, was higher in subjects with the IL-4Rα R576 polymorphism compared with those without, with statistical significance for the Rajka-Langeland score. Following epicutaneous sensitization of mice with ovalbumin or house dust mite, skin infiltration by CD4+ cells and eosinophils, cutaneous expression of Il4 and Il13, transepidermal water loss, antigen-specific IgE antibody levels, and IL-13 secretion by antigen-stimulated splenocytes were significantly higher in RR and QR mice compared with QQ controls. Bone marrow radiation chimeras demonstrated that both hematopoietic cells and stromal cells contribute to the mutants' exaggerated allergic skin inflammation. CONCLUSIONS: The IL-4Rα R576 polymorphism predisposes to more severe AD and increases allergic skin inflammation in mice.

Risk for internalizing symptom development in young children: Roles of child parasympathetic reactivity and maternal depression and anxiety exposure in early life.

Intergenerational transmission of internalizing disorders (anxiety and depression) is well documented, but the responsible pathways are underspecified. One possible mechanism is via programming of the child's parasympathetic nervous system (PNS). For example, maternal depression and anxiety, via multiple pathways, may heighten child PNS reactivity, which has been linked to increased risk for internalizing disorders. Heightened PNS reactivity also may sensitize a child to their environment, increasing the vulnerability to developing psychopathology when exposed to stressors, such as maternal psychopathology. In a prospective longitudinal study of mother-child dyads (N = 446), we examined relations among maternal depression and anxiety symptoms when children were infants and aged 3 and 5 years, child respiratory sinus arrythmia (RSA) reactivity (measure of PNS reactivity) at 3 years, and child internalizing symptoms at age 5 years. Consistent with an adaptive calibration perspective, analyses tested the roles of child RSA reactivity as both a mediator and a moderator of associations between maternal and child symptoms. Greater child RSA reactivity in response to a fearful video predicted higher internalizing symptoms among children exposed to higher levels of maternal depression or anxiety symptoms at age 5 years (moderation effects). Child RSA reactivity did not mediate relations between maternal depression or anxiety symptoms in infancy and child internalizing symptoms at age 5 years. The results suggest that heightened PNS reactivity may represent a biological vulnerability to stressful environments early in life: When coupled with maternal depression or anxiety exposure, child PNS reactivity may promote the development of internalizing psychopathology in early childhood.

HEPA filtration intervention in classrooms may improve some students' asthma.

OBJECTIVE: The School Inner-City Asthma Intervention Study 2 (SICAS 2) tested interventions to reduce exposures in classrooms of students with asthma. The objective of this post-hoc analysis was limited to evaluating the effect of high-efficiency particulate (HEPA) filtration interventions on mold levels as quantified using the Environmental Relative Moldiness Index (ERMI) and the possible improvement in the students' asthma, as quantified by spirometry testing. METHODS: Pre-intervention dust samples were collected at the beginning of the school year from classrooms and corresponding homes of students with asthma (n = 150). Follow-up dust samples were collected in the classrooms at the end of the HEPA or Sham intervention. For each dust sample, ERMI values and the Group 1 and Group 2 mold levels (components of the ERMI metric) were quantified. In addition, each student's lung function was evaluated by spirometry testing, specifically the percentage predicted forced expiratory volume at 1 sec (FEV1%), before and at the end of the intervention. RESULTS: For those students with a higher Group 1 mold level in their pre-intervention classroom than home (n = 94), the FEV1% results for those students was significantly (p < 0.05) inversely correlated with the Group 1 level in their classrooms. After the HEPA intervention, the average Group 1 and ERMI values were significantly lowered, and the average FEV1% test results significantly increased by an average of 4.22% for students in HEPA compared to Sham classrooms. CONCLUSIONS: HEPA intervention in classrooms reduced Group 1 and ERMI values, which corresponded to improvements in the students' FEV1% test results.

Associations among maternal lifetime trauma, psychological symptoms in pregnancy, and infant stress reactivity and regulation.

Maternal trauma has intergenerational implications, including worse birth outcomes, altered brain morphology, and poorer mental health. Research investigating intergenerational effects of maternal trauma on infant stress reactivity and regulation is limited. Maternal mental health during pregnancy may be a contributor: psychopathology is a sequela of trauma exposure and predictor of altered self-regulatory capacity in offspring of affected mothers. We assessed associations among maternal lifetime trauma and infant stress responsivity, mediated by psychological symptoms in pregnancy. Mothers reported lifetime trauma history and anxiety, depressive, and posttraumatic stress symptoms during pregnancy. At infant age 6 months, stress reactivity and regulation were assessed via maternal behavior ratings (Infant Behavior Questionnaire-Revised, IBQ-R) and behavioral (negative mood) and physiological (respiratory sinus arrhythmia, RSA) markers during a laboratory stressor (Still-Face Paradigm). Maternal trauma was directly associated with lower infant physiological regulation and indirectly associated with lower levels of both infant behavioral and physiological regulation via higher maternal anxiety during pregnancy. Maternal trauma was also indirectly associated with higher infant reactivity via higher maternal anxiety during pregnancy. Post hoc analyses indicated differential contributions of maternal prenatal versus postnatal anxiety to infant outcomes. Findings highlight potential contributory mechanisms toward maladaptive child stress response, which has been associated with poor behavioral, cognitive, and academic outcomes.

Comorbidities Associated with Hospitalization and Progression Among Adolescents with Symptomatic Coronavirus Disease 2019.

OBJECTIVE: To identify subgroups likely to benefit from monoclonal antibody and antiviral therapy by evaluating the relationship between comorbidities and hospitalization among US adolescents with symptomatic coronavirus disease 2019 (COVID-19). STUDY DESIGN: We analyzed the relationship between presence of comorbidities and need for hospitalization within 28 days of COVID-19 diagnosis for adolescents aged 12-17 years listed in the Pediatric COVID-19 US registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes, immunosuppressive disease or treatment, sickle cell disease (SCD), heart disease, neurologic disease/neurodevelopmental disorders, and pulmonary disease (excluding patients with mild asthma). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization. RESULTS: A total of 1877 patients met our inclusion criteria, of whom 284 (15%) were hospitalized within 28 days of their COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: SCD (aOR, 6.9; 95% CI, 3.0-15.9), immunocompromising condition (aOR, 6.4; 95% CI, 3.8-10.8), obesity (aOR, 3.2; 95% CI, 2.1-4.9), diabetes (aOR, 3.0; 95% CI, 1.4-6.2), neurologic disease (aOR, 2.8; 95% CI, 1.8-4.3), and pulmonary disease (excluding mild asthma) (aOR, 1.9; 95% CI, 1.2-3.1). Heart disease and CKD were not independently associated with hospitalization. CONCLUSIONS: SCD, immunocompromising conditions, obesity, diabetes, neurologic disease, and pulmonary disease (excluding mild asthma) were associated with hospitalization for symptomatic COVID-19. Adolescents with acute COVID-19 and these comorbidities should be prioritized for consideration of therapy to avert hospitalization.

A common IL-4 receptor variant promotes asthma severity via a Treg cell GRB2-IL-6-Notch4 circuit.

BACKGROUND: The mechanisms by which genetic and environmental factors interact to promote asthma remain unclear. Both the IL-4 receptor alpha chain R576 (IL-4RαR576) variant and Notch4 license asthmatic lung inflammation by allergens and ambient pollutant particles by subverting lung regulatory T (Treg ) cells in an IL-6-dependent manner. OBJECTIVE: We examined the interaction between IL-4RαR576 and Notch4 in promoting asthmatic inflammation. METHODS: Peripheral blood mononuclear cells (PBMCs) of asthmatics were analyzed for T helper type 2 cytokine production and Notch4 expression on Treg cells as a function of IL4RR576 allele. The capacity of IL-4RαR576 to upregulate Notch4 expression on Treg cells to promote severe allergic airway inflammation was further analyzed in genetic mouse models. RESULTS: Asthmatics carrying the IL4RR576 allele had increased Notch4 expression on their circulating Treg cells as a function of disease severity and serum IL-6. Mice harboring the Il4raR576 allele exhibited increased Notch4-dependent allergic airway inflammation that was inhibited upon Treg cell-specific Notch4 deletion or treatment with an anti-Notch4 antibody. Signaling via IL-4RαR576 upregulated the expression in lung Treg cells of Notch4 and its downstream mediators Yap1 and beta-catenin, leading to exacerbated lung inflammation. This upregulation was dependent on growth factor receptor-bound protein 2 (GRB2) and IL-6 receptor. CONCLUSION: These results identify an IL-4RαR576-regulated GRB2-IL-6-Notch4 circuit that promotes asthma severity by subverting lung Treg cell function.

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.

Understanding How Perfectionism Impacts Intensive Interdisciplinary Pain Treatment Outcomes: A Nonrandomized Trial.

OBJECTIVE: Several factors are known to impact response to the intensive interdisciplinary pain treatment (IIPT) program described in this study, yet no research has explored the role of perfectionism. This secondary data analysis explored direct and indirect relations between perfectionism and functional disability (primary outcome) and pain severity (secondary outcome) after IIPT, with pain catastrophizing and fear of pain as mediators. METHODS: Youth (N = 253) aged 8-21 with chronic pain and associated disability completed pre- and post-IIPT measures of self-oriented perfectionism (SOP), socially prescribed perfectionism (SPP), pain catastrophizing, fear of pain, functional disability, and pain characteristics for routine clinical care and this nonrandomized trial. Eight mediated models were run for the two predictors, two mediators, and two outcomes. RESULTS: Pretreatment perfectionism (SOP and SPP) led to greater reductions in pain catastrophizing over the course of IIPT, which resulted in lower pain severity (ß = -.02 [CI = -0.07, -0.01] for SOP and ß = -.02 [CI = -0.06, -0.003] for SPP) and less functional disability (ß = -.06 [CI = -0.13, -0.01] for SOP and ß = -.06 [CI = -0.14, -0.01] for SPP). Independent of pain catastrophizing, pretreatment SPP was directly associated with more posttreatment functional disability (ß = .16 [CI = 0.05, 0.27]). Fear of pain was not a mediator. CONCLUSIONS: Findings suggest perfectionism has the potential to negatively impact IIPT outcomes. However, when perfectionistic youth with chronic pain learn to manage pain-related distress, they benefit. Results highlight the importance of assessing for and treating perfectionism and pain-related distress in youth with chronic pain.

Integrated and diurnal indices of maternal pregnancy cortisol in relation to sex-specific parasympathetic responsivity to stress in infants.

Maternal hypothalamic-pituitary-adrenal axis activity may prenatally program sex-specific stress-response pathways. We investigated associations between maternal cortisol during pregnancy and infant parasympathetic responsivity to stress among 204 mother-infant pairs. Cortisol indices included 3rd trimester hair cortisol, as well as diurnal slope and area under the curve, derived from saliva samples collected during pregnancy. Mother-infant dyads participated in the Repeated Still-Face Paradigm (SFP-R) at age 6 months. We calculated respiration-adjusted respiratory sinus arrhythmia (RSAc ), an indicator of parasympathetic activation, from infant respiration and cardiac activity measured during the SFP-R. We used multivariable linear mixed models to examine each cortisol index in relation to infant RSAc and investigated sex differences using cross-product terms. Diurnal cortisol indices were not associated with RSAc . There was no association between hair cortisol and baseline RSAc . However, hair cortisol was associated with sex-specific changes in RSAc over the SFP-R such that, among girls, parasympathetic withdrawal was reduced with increasing prenatal exposure to cortisol. Consistently higher levels of prenatal cortisol exposure may lead to dampened parasympathetic responsivity to stress during infancy, particularly among girls. Maternal hair cortisol may be particularly valuable for studying the effects of prenatal cortisol exposure on infant autonomic reactivity.

Proximity to major roadways and asthma symptoms in the School Inner-City Asthma Study.

BACKGROUND: Traffic proximity has been associated with adverse respiratory health outcomes. Less is known about the combined impact of residential and school exposures on pediatric asthma. OBJECTIVE: We sought to use spatial analysis methodology to analyze residential and school proximity to major roadways and pediatric asthma morbidity. METHODS: The School Inner-City Asthma Study (n = 350) recruited school-aged children with asthma. Each participant's school and home addresses were geocoded, and distances from major roadways were measured to calculate a composite measure accounting for both home and school traffic exposure. Generalized estimating equation models were clustered by subject and adjusted for age, race/ethnicity, sex, income, environmental tobacco smoke, controller medication, upper respiratory tract infections, and seasonality. RESULTS: The majority of participants (62%) attended schools within 100 m from major roadways, and 40% also resided within 100 m of major roadways. In multivariate analyses major roadway proximity was independently associated with increased asthma symptom days. At greater than the threshold of 100 m, children had 29% less odds of a symptom day over the past 2 weeks for each 100-m increase in distance from a major roadway (odds ratio, 0.71; 95% CI, 0.58-0.87; P < .01). Children farther from a major roadway also had significantly less reported health care use (odds ratio, 0.63; 95% CI, 0.47-0.85; P < .01) and were significantly less likely to have poor asthma control (odds ratio, 0.80; 95% CI, 0.69-0.94; P < .01). There was not a meaningful association between distance to a major roadway and lung function outcomes. CONCLUSIONS: Proximity to a major roadway, a composite measure of home and school exposure but primarily driven by home exposure, was associated with greater asthma morbidity. More studies are needed to evaluate the independent effect of school distance to a roadway on asthma morbidity.

Obesity may enhance the adverse effects of NO2 exposure in urban schools on asthma symptoms in children.

BACKGROUND: Sparse data address the effects of nitrogen dioxide (NO2) exposure in inner-city schools on obese students with asthma. OBJECTIVE: We sought to evaluate relationships between classroom NO2 exposure and asthma symptoms and morbidity by body mass index (BMI) category. METHODS: The School Inner-City Asthma Study enrolled students aged 4 to 13 years with asthma from 37 inner-city schools. Students had baseline determination of BMI percentile. Asthma symptoms, morbidity, pulmonary inflammation, and lung function were monitored throughout the subsequent academic year. Classroom NO2 data, linked to enrolled students, were collected twice per year. We determined the relationship between classroom NO2 levels and asthma outcomes by BMI stratification. RESULTS: A total of 271 predominantly black (35%) or Hispanic students (35%) were included in analyses. Fifty percent were normal weight (5-84th BMI percentile), 15% overweight (≥85-94th BMI percentile), and 35% obese (≥95th BMI percentile). For each 10-parts per billion increase in NO2, obese students had a significant increase in the odds of having an asthma symptom day (odds ratio [OR], 1.86; 95% CI, 1.15-3.02) and in days caregiver changed plans (OR, 4.24; 95% CI, 2.33-7.70), which was significantly different than normal weight students who exhibited no relationship between NO2 exposure and symptom days (OR, 0.90; 95% CI, 0.57-1.42; pairwise interaction P = .03) and change in caregiver plans (OR, 1.37; 95% CI, 0.67-2.82; pairwise interaction P = .02). Relationships between NO2 levels and lung function and fractional exhaled nitric oxide did not differ by BMI category. If we applied a conservative Holm-Bonferroni correction for 16 comparisons (obese vs normal weight and overweight vs normal weight for 8 outcomes), these findings would not meet statistical significance (all P > .003). CONCLUSIONS: Obese BMI status appears to increase susceptibility to classroom NO2 exposure effects on asthma symptoms in inner-city children. Environmental interventions targeting indoor school NO2 levels may improve asthma health for obese children. Although our findings would not remain statistically significant after adjustment for multiple comparisons, the large effect sizes warrant future study of the interaction of obesity and pollution in pediatric asthma.

Effect of School Integrated Pest Management or Classroom Air Filter Purifiers on Asthma Symptoms in Students With Active Asthma: A Randomized Clinical Trial.

Importance: School and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known. Objective: To determine whether use of a school-wide integrated pest management (IPM) program or high-efficiency particulate air (HEPA) filter purifiers in the classrooms improve asthma symptoms in students with active asthma. Design, Setting, and Participants: Factorial randomized clinical trial of a school-wide IPM program and HEPA filter purifiers in the classrooms was conducted from 2015 to 2020 (School Inner-City Asthma Intervention Study). There were 236 students with active asthma attending 41 participating urban elementary schools located in the Northeastern US who were randomized to IPM by school and HEPA filter purifiers by classroom. The date of final follow-up was June 20, 2020. Interventions: The school-wide IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for school staff. Infestation was assessed every 3 months, with additional treatments as needed. Control schools received no IPM, cleaning, or education. Classroom portable HEPA filter purifiers were deployed and the filters were changed every 3 months. Control classrooms received sham HEPA filters that looked and sounded like active HEPA filter purifiers. Randomization was done independently (split-plot design), with matching by the number of enrolled students to ensure a nearly exact 1:1 student ratio for each intervention with 118 students randomized to each group. Participants, investigators, and those assessing outcomes were blinded to the interventions. Main Outcomes and Measures: The primary outcome was the number of symptom-days with asthma during a 2-week period. Symptom-days were assessed every 2 months during the 10 months after randomization. Results: Among the 236 students who were randomized (mean age, 8.1 [SD, 2.0] years; 113 [48%] female), all completed the trial. At baseline, the 2-week mean was 2.2 (SD, 3.9) symptom-days with asthma and 98% of the classrooms had detectable levels of mouse allergen. The results were pooled because there was no statistically significant difference between the 2 interventions (P = .18 for interaction). During a 2-week period, the mean was 1.5 symptom-days with asthma after use of the school-wide IPM program vs 1.9 symptom-days after no IPM across the school year (incidence rate ratio, 0.71 [95% CI, 0.38-1.33]), which was not statistically significantly different. During a 2-week period, the mean was 1.6 symptom-days with asthma after use of HEPA filter purifiers in the classrooms vs 1.8 symptom-days after use of sham HEPA filter purifiers across the school year (incidence rate ratio, 1.47 [95% CI, 0.79-2.75]), which was not statistically significantly different. There were no intervention-related adverse events. Conclusions and Relevance: Among children with active asthma, use of a school-wide IPM program or classroom HEPA filter purifiers did not significantly reduce symptom-days with asthma. However, interpretation of the study findings may need to consider allergen levels, particle exposures, and asthma symptoms at baseline. Trial Registration: ClinicalTrials.gov Identifier: NCT02291302.

Transitional objects of grief.

BACKGROUND: Transitional objects provide security and symbolic connection with valued others when separated from them. Bereaved parents often keep, cherish and visit saved objects of their deceased child. This research examined the hypothesis that these objects behave as transitional objects of grief in bereaved mothers during three years following their infants' deaths from Sudden Infant Death Syndrome. METHODS: Questionnaires were administered asking about the presence of kept objects and momentos from their deceased infant, and the frequency, location and emotions experienced during visits to them. Diagnostic criteria for Prolonged Grief Disorder (PGD) were assessed using the Parental Bereavement Questionnaire. RESULTS: 98.6% of the mothers reported having transitional objects of grief, and most visited them more frequently than once per week regardless of PGD status. Mothers with PGD reported significantly more distress when visiting the objects, especially those visiting them privately. Mothers with PGD who felt comforted by the objects had lower risk for finding life meaningless or finding discussion about the infant intolerable. CONCLUSIONS: Transitional objects of grief are common and associated with key aspects of grief. There is a need to understand the potential therapeutic uses of transitional objects in promoting bereavement adjustment.

Pre-loss personal factors and prolonged grief disorder in bereaved mothers.

BACKGROUND: Identifying characteristics of individuals at greatest risk for prolonged grief disorder (PGD) can improve its detection and elucidate the etiology of the disorder. The Safe Passage Study, a study of women at high risk for sudden infant death syndrome (SIDS), prospectively examined the psychosocial functioning of women while monitoring their healthy pregnancies. Mothers whose infants died of SIDS were followed in bereavement. METHODS: Pre-loss data were collected from 12 000 pregnant mothers and analyzed for their associations with grief symptoms and PGD in 50 mothers whose infants died from SIDS, from 2 to 48 months after their infant's death, focusing on pre-loss risk factors of anxiety, depression, alcohol use, maternal age, the presence of other living children in the home, and previous child loss. RESULTS: The presence of any four risk factors significantly predicted PGD for 24 months post-loss (p < 0.003); 2-3 risk factors predicted PGD for 12 months (p = 0.02). PGD rates increased in the second post-loss year, converging in all groups to approximately 40% by 3 years. Pre-loss depressive symptoms were significantly associated with PGD. Higher alcohol intake and older maternal age were consistently positively associated with PGD. Predicted risk scores showed good discrimination between PGD and no PGD 6-24 months after loss (C-statistic = 0.83). CONCLUSIONS: A combination of personal risk factors predicted PGD in 2 years of bereavement. There is a convergence of risk groups to high rates at 2-3 years, marked by increased PGD rates in mothers at low risk. The risk factors showed different effects on PGD.

Association between fungal spore exposure in inner-city schools and asthma morbidity.

BACKGROUND: Home fungus exposures may be associated with development or worsening of asthma. Little is known about the effects of school/classroom fungus exposures on asthma morbidity in students. OBJECTIVE: To evaluate the association of school-based fungus exposures on asthma symptoms in both fungus-sensitized and nonsensitized students with asthma. METHODS: In this prospective study, 280 children with asthma from 37 inner-city schools were phenotypically characterized at baseline and followed-up for 1 year. Fungal spores were collected by using a Burkard air sampler twice during the school year. Clinical outcomes were evaluated throughout the school year and linked to classroom-specific airborne spore sampling. The primary outcome was days with asthma symptoms per 2-week period. RESULTS: Fungal spores were present in all classroom samples. The geometric mean of the total fungi was 316.9 spores/m3 and ranged from 15.0 to 59,345.7 spores/m3. There was variability in total fungus quantity between schools and classrooms within the same school. Mitospores were the most commonly detected fungal grouping. Investigation of the individual mitospores revealed that exposure to Alternaria was significantly associated with asthma symptom days in students sensitized to Alternaria (OR = 3.61, CI = 1.34-9.76, P = .01), but not in children not sensitized to Alternaria (OR = 1.04, CI = 0.72-1.49, P = .85). Students sensitized to Alternaria and exposed to high levels (≥75th percentile exposure) had 3.2 more symptom days per 2-week period as compared with students sensitized but exposed to lower levels. CONCLUSION: Children with asthma who are sensitized to Alternaria and exposed to this fungus in their classroom may have significantly more days with asthma symptoms than those who were sensitized and not exposed. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT01756391.

Nitrogen dioxide exposure in school classrooms of inner-city children with asthma.

BACKGROUND: Ambient and home exposure to nitrogen dioxide (NO2) causes asthma symptoms and decreased lung function in children with asthma. Little is known about the health effects of school classroom pollution exposure. OBJECTIVE: We aimed to determine the effect of indoor classroom NO2 on lung function and symptoms in inner-city school children with asthma. METHODS: Children enrolled in the School Inner-City Asthma Study were followed for 1 academic year. Subjects performed spirometry and had fraction of exhaled nitric oxide values measured twice during the school year at school. Classroom NO2 was collected by means of passive sampling for 1-week periods twice per year, coinciding with lung function testing. Generalized estimating equation models assessed lung function and symptom relationships with the temporally nearest classroom NO2 level. RESULTS: The mean NO2 value was 11.1 ppb (range, 4.3-29.7 ppb). In total, exposure data were available for 296 subjects, 188 of whom had complete spirometric data. At greater than a threshold of 8 ppb of NO2 and after adjusting for race and season (spirometry standardized by age, height, and sex), NO2 levels were associated highly with airflow obstruction, such that each 10-ppb increase in NO2 level was associated with a 5% decrease in FEV1/forced vital capacity ratio (ß = -0.05; 95% CI, -0.08 to -0.02; P = .01). Percent predicted forced expiratory flow between the 25th and 75th percentile of forced vital capacity was also inversely associated with higher NO2 exposure (ß = -22.8; 95% CI, -36.0 to -9.7; P = .01). There was no significant association of NO2 levels with percent predicted FEV1, fraction of exhaled nitric oxide, or asthma symptoms. Additionally, there was no effect modification of atopy on lung function or symptom outcomes. CONCLUSION: In children with asthma, indoor classroom NO2 levels can be associated with increased airflow obstruction.

Impact of school peanut-free policies on epinephrine administration.

BACKGROUND: Children with food allergies spend a large proportion of time in school but characteristics of allergic reactions in schools are not well studied. Some schools self-designate as peanut-free or have peanut-free areas, but the impact of policies on clinical outcomes has not been evaluated. OBJECTIVE: We sought to determine the effect of peanut-free policies on rates of epinephrine administration for allergic reactions in Massachusetts public schools. METHODS: In this retrospective study, we analyzed (1) rates of epinephrine administration in all Massachusetts public schools and (2) Massachusetts public school nurse survey reports of school peanut-free policies from 2006 to 2011 and whether schools self-designated as "peanut-free" based on policies. Rates of epinephrine administration were compared for schools with or without peanut-restrictive policies. RESULTS: The percentage of schools with peanut-restrictive policies did not change significantly in the study time frame. There was variability in policies used by schools self-designated as peanut-free. No policy was associated with complete absence of allergic reactions. Both self-designated peanut-free schools and schools banning peanuts from being served in school or brought from home reported allergic reactions to nuts. Policies restricting peanuts from home, served in schools, or having peanut-free classrooms did not affect epinephrine administration rates. Schools with peanut-free tables, compared to without, had lower rates of epinephrine administration (incidence rate per 10,000 students 0.2 and 0.6, respectively, P = .009). CONCLUSIONS: These data provide a basis for evidence-based school policies for children with food allergies. Further studies are required before decisions can be made regarding peanut-free policies in schools.

A Randomized Trial of Displaying Paid Price Information on Imaging Study and Procedure Ordering Rates.

BACKGROUND: Prior studies have demonstrated how price transparency lowers the test-ordering rates of trainees in hospitals, and physician-targeted price transparency efforts have been viewed as a promising cost-controlling strategy. OBJECTIVE: To examine the effect of displaying paid-price information on test-ordering rates for common imaging studies and procedures within an accountable care organization (ACO). DESIGN: Block randomized controlled trial for 1 year. SUBJECTS: A total of 1205 fully licensed clinicians (728 primary care, 477 specialists). INTERVENTION: Starting January 2014, clinicians in the Control arm received no price display; those in the intervention arms received Single or Paired Internal/External Median Prices in the test-ordering screen of their electronic health record. Internal prices were the amounts paid by insurers for the ACO's services; external paid prices were the amounts paid by insurers for the same services when delivered by unaffiliated providers. MAIN MEASURES: Ordering rates (orders per 100 face-to-face encounters with adult patients): overall, designated to be completed internally within the ACO, considered "inappropriate" (e.g., MRI for simple headache), and thought to be "appropriate" (e.g., screening colonoscopy). KEY RESULTS: We found no significant difference in overall ordering rates across the Control, Single Median Price, or Paired Internal/External Median Prices study arms. For every 100 encounters, clinicians in the Control arm ordered 15.0 (SD 31.1) tests, those in the Single Median Price arm ordered 15.0 (SD 16.2) tests, and those in the Paired Prices arms ordered 15.7 (SD 20.5) tests (one-way ANOVA p-value 0.88). There was no difference in ordering rates for tests designated to be completed internally or considered to be inappropriate or appropriate. CONCLUSIONS: Displaying paid-price information did not alter how frequently primary care and specialist clinicians ordered imaging studies and procedures within an ACO. Those with a particular interest in removing waste from the health care system may want to consider a variety of contextual factors that can affect physician-targeted price transparency.