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In a population-based birth cohort study of respiratory syncytial virus surveillance in the United States, 897/1,680 (53.4%) children were infected during infancy; 25/897 (2.8%) of those were hospitalized. Among symptomatic infants, 143/324 (44.1%) had lower respiratory tract infections. These data provide benchmarks to monitor effects of maternal vaccines and extended half-life monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Background: We investigated the individual and interaction effects of maternal plasma 훂‐ and ϒ‐tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8–9. Methods: Mother–child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second‐trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self‐reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother–child dyads) and tested for prespecified interaction terms. Results: Median cholesterol‐corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3–5.7) and 0.8 (0.7–0.9) (umol/mmol) for 훂‐ and ϒ‐tocopherol, respectively. Associations between 훂‐tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for ϒ‐tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal 훂‐tocopherol levels, whereas this trend was not observed among those without a history of asthma (p‐interaction =.05). Conclusion: We observed no associations for prenatal 훂‐ or ϒ‐tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between 훂‐tocopherol and child asthma. [ABSTRACT FROM AUTHOR]

Identifying child age of RSV infection associated with increased risk of asthma is important for developing asthma prevention strategies. Our systematic review aimed to comprehensively summarize studies of the association between age of RSV infection and childhood asthma risk. The study protocol was pre-registered, and our study report adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Inclusion criteria were prospective and retrospective cohort studies and case-control studies which assessed the association of age of RSV infection before age 2 years and risk of childhood asthma after age two years. Relevant studies were identified through MEDLINE, Embase, Cochrane and International Clinical Trials Registry Platform (ICTRP) from study inception through May 5, 2023. Studies were evaluated with the Quality In Prognosis Studies (QUIPS) tool. From 149 studies screened, five studies (two prospective cohort studies and three retrospective cohort studies) were included in our systematic review, including 47,603 participants. Available studies only assessed age of severe RSV infection and asthma risk. The included studies used different age categories and outcome definitions, and were rated as having high risk of bias. Two studies had sample sizes of less than 300 and did not provide conclusive results related to age of RSV hospitalization and asthma risk. The other three studies reported RSV hospitalization between age 6 months and 23 months compared with age 0–6 months being associated with a higher odds ratio, hazard ratio, or incidence rate ratio of asthma diagnosis/hospitalization. Due to the heterogeneous epidemiological designs, including exposures and outcome ascertainments of the included studies, we could not perform a meta-analysis, or calculate weighted averages of the effect estimates. Our systematic review highlights a major gap in our knowledge about the relationship between age of RSV infection and asthma risk. [ABSTRACT FROM AUTHOR]

Childhood wheeze, asthma, and allergic rhinitis are common and likely have prenatal origins. Oxidative stress is associated with respiratory disease, but the association of oxidative stress during the prenatal period with development of respiratory and atopic disease in childhood, particularly beyond the infancy period, is unknown. This study aims to investigate associations between prenatal oxidative stress, measured by maternal urinary F 2 -isoprostanes, and child respiratory outcomes, including effect modification by maternal race. We prospectively studied Black (n = 717) and White (n = 363) mother-child dyads. We measured F 2 -isoprostanes in 2nd-trimester urine (ng/mg-creatinine). At approximately age 4, we obtained parent report of provider-diagnosed asthma (ever), current wheeze, current asthma (diagnosis, symptoms and/or medication), and current allergic rhinitis (current defined as previous 12 months). We used multivariable logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) per interquartile range (IQR) increase in F 2 -isoprostane concentration, controlling for confounders. We examined modification by maternal race using interaction terms. The prevalence of provider-diagnosed asthma and current wheeze, asthma and allergic rhinitis was 14%, 19%, 15%, and 24%, respectively. Median (IQR) F 2- isoprostane levels were 2.1 (1.6, 2.9) ng/mg-creatinine. Associations between prenatal F 2 -isoprostanes and provider-diagnosed asthma, current wheeze, and current asthma were modified by maternal race. Results were strongest for current wheeze (aOR [95%CI]: 1.55 [1.16, 2.06] for White; 0.98 [0.78, 1.22] for Black; p-interaction = 0.01). We observed no association between F 2- isoprostanes and allergic rhinitis. Prenatal urinary F 2 -isoprostanes may be a marker associated with childhood wheeze/asthma in certain populations. Research is needed to understand underlying mechanisms and racial differences. [Display omitted] • Maternal race modified the association of the 2nd trimester urinary F 2 -isoprostanes and child asthma/wheeze. • Association with child wheeze at age 4–6 was significant for White, but not Black, dyads. • Creatinine-adjusted urinary F 2 -isoprostanes levels did not differ by maternal race. [ABSTRACT FROM AUTHOR]

Background: Childhood asthma is a common chronic disease that likely has prenatal origins. Gestational diabetes alters maternal physiology and may influence fetal risk for childhood‐onset disease. However, the association between gestational diabetes and child asthma is not well characterized. Objective: To investigate the association between gestational diabetes and wheeze/asthma at approximately 4 years of age in a racially diverse US cohort. Methods: We studied mother‐child dyads enrolled prenatally in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study. Gestational diabetes was determined by medical chart review. At approximately 4 years of age, we assessed child respiratory outcomes including parent report of physician‐diagnosed asthma (ever), current wheeze (symptoms within the past 12 months), and current asthma (physician diagnosis and/or medication or symptoms within the past 12 months). We used the modified Poisson regression to assess associations between gestational diabetes and child respiratory outcomes, adjusting for maternal age, race, prenatal smoking, pre‐pregnancy body mass index, parity, asthma history, socioeconomic status, and infant sex. Results: Among 1107 women, 66% were African American/Black. Six percent (n = 62) had gestational diabetes documented during pregnancy. Gestational diabetes was associated with increased risk of physician‐diagnosed asthma (adjusted risk ratio (RR) [95% Confidence Interval]: 2.13 [1.35, 3.38]; prevalence: 14%), current wheeze (RR: 1.85 [1.23, 2.78]; prevalence: 19%), and current asthma (RR: 2.01 [1.30, 3.10]; prevalence: 16%). Conclusions: Gestational diabetes was associated with increased risk of asthma and wheeze outcomes. Additional studies are needed to elucidate modifiable pathways underlying this association. [ABSTRACT FROM AUTHOR]

• 12% of HIV-infected or -exposed uninfected kids had bacteremia at hospitalization • For children found to have bacteremia, in-hospital mortality was 19% • Nearly 70% of Staphylococcus aureus isolates were methicillin resistant (MRSA) • ~50% of Klebsiella isolates had extended-spectrum beta-lactamase (ESBL) production • High MRSA and ESBL has implications for the empiric antibiotics used in Mozambique Bacteremia is a major cause of morbidity and mortality worldwide. Children infected with HIV present with patterns of bacteremia generally associated with poor prognosis. In Mozambique, data on bacteremia are sparce. We conducted an observational study of HIV-infected and HIV-exposed uninfected children, aged 0-59 months, hospitalized with fever between April 1, 2016 and February 28, 2019. A single bacterial culture was collected at admission. Descriptive statistics were used to summarize microorganisms detected and antibiotic susceptibility testing. A total of 808 HIV-infected (90%) and HIV-exposed uninfected (10%) children were enrolled. Blood culture positivity was 12% (95% CI: 9.9%-14.4%). Five organisms accounted for most cases: Staphylococcus Aureus (37%), Klebsiella spp (11%), Salmonella spp (11%), Escherichia Coli (9%) and Micrococcus (7%). Antibiotic resistance was common. Nearly 70% of Staphylococcus Aureus were methicillin-resistant and roughly 50% of Klebsiella had ESBL production. Community-acquired bacteremia was common in HIV-infected and HIV-exposed uninfected children hospitalized in Mozambique with a febrile illness. High rates of MRSA and ESBL producing organisms has implications for empiric antibiotics utilized in Mozambique. Longitudinal data on the prevalence and antimicrobial resistance patterns of important pathogens are badly needed to guide policy for drug formulary expansion and antibiotic prescription guidelines. [ABSTRACT FROM AUTHOR]

Background The potential for prenatal antibiotic exposure to influence asthma risk is not clear. We aimed to determine the effect of timing, dose, and spectrum of prenatal antibiotic exposure on the risk of childhood asthma. Methods We conducted a population-based cohort study of 84 214 mother–child dyads to examine the association of prenatal antibiotic exposure and childhood asthma using multivariable logistic regression models. Results Sixty-four percent of pregnant women received antibiotics. Prenatal antibiotic exposure was associated dose-dependently with increased odds of childhood asthma (adjusted odds ratio [aOR] for interquartile increase of 2 courses [interquartile range, 0–2], 1.26 [95% confidence interval {CI}, 1.20–1.33]). Among children exposed to at least 1 course in utero, the effect of timing at the first course was moderated by total maternal courses. Among pregnant women receiving a single antibiotic course, timing of exposure had no effect on childhood asthma risk. Among women receiving > 1 course, early exposure of the first course was associated with greater childhood asthma risk. Compared to narrow spectrum–only antibiotic use, broad spectrum–only antibiotic exposure was associated with increased odds of asthma (aOR, 1.14 [95% CI, 1.05–1.24]). There were effect modifications (P  < .001) by maternal asthma on total courses, and on timing of the first course, significant only among those without maternal asthma. Conclusions Increased cumulative dose, early pregnancy first course, and broad-spectrum antibiotic exposure were associated with childhood asthma risk. Our study provides important evidence supporting judicious prenatal antibiotic use, particularly timing of use and choice of antibiotics, in preventing subsequent childhood asthma. [ABSTRACT FROM AUTHOR]

Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n = 676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (poverall = .112, pnonlinear effect = .088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2018 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2018 article‐contains‐esm Yes article‐numbering‐style Unnumbered article‐registration‐date‐year 2018 article‐registration‐date‐month 6 article‐registration‐date‐day 4 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2018_Article_195.pdf pdf‐type Typeset target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> Childhood asthma is responsible for significant morbidity and health care expenditures in the United States. The incidence of asthma is greatest in early childhood, and the prevalence is projected to continue rising in the absence of prevention and intervention measures. The prevention of asthma will likely require a multifaceted intervention strategy; however, few randomized controlled trials have assessed such approaches. The purpose of this review was to use previous meta‐analyses to identify the most impactful risk factors for asthma development and evaluate the effect of risk factor reduction on future childhood asthma prevalence. Common and modifiable risk factors with large effects included acute viral respiratory infections, antibiotic use, birth by cesarean section, nutritional disorders (overweight, obesity), second hand smoke exposure, allergen sensitization, breastfeeding, and sufficient prenatal vitamin D level. Evaluation and estimates of risk factor modification on populations at risk should guide scientists and policymakers toward high impact areas that are apt for additional study and intervention. [ABSTRACT FROM AUTHOR]

Background Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission. Methods We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life. The primary outcome was severe RSV LRTI requiring ICU admission during the first year of life. We built a multivariable logistic regression model including demographic and clinical variables available at or shortly after birth to predict the primary outcome. Results In a population-based sample of 429 365 infants, 713 (0.2%) had severe RSV LRTI requiring ICU admission. The median age of admission was 66 days (interquartile range, 37–120). Our tool, including 19 variables, demonstrated good predictive accuracy (area under the curve, 0.78; 95% confidence interval, 0.77-0.80) and identified infants who did not qualify for palivizumab, based on American Academy of Pediatrics guidelines, but had higher predicted risk levels than infants who qualified (27% of noneligible infants with >0.16% predicted probabilities [lower quartile for eligible infants]). Conclusions We developed a personalized tool that identified infants at increased risk for severe RSV LRTI requiring ICU admission, expected to benefit most from immunoprophylaxis. [ABSTRACT FROM AUTHOR]

Objective: Nonadherence to controller and overuse of reliever asthma medications are associated with exacerbations. We aimed to determine patterns of seasonal asthma medication use and to identify time period(s) during which interventions to improve medication adherence could reduce asthma morbidity. Methods: We conducted a retrospective cohort study of asthmatics 4-50 years of age and enrolled in three diverse health insurance plans. Seasonal patterns of medications were reported by monthly prescription fill rates per 1000 individuals with asthma from 1998 to 2013, and stratified by healthcare plan, sex, and age. Results: There was a distinct and consistent seasonal fill pattern for all asthma medications. The lowest fill rate was observed in the month of July. Fills increased in the autumn and remained high throughout the winter and spring. Compared with the month of May with high medication fills, July represented a relative decrease of fills ranging from 13% (rate ratio, RR: 0.87, 95% confidence interval, 95%CI: 0.72-1.04) for the combination of inhaled corticosteroids (ICS) + long acting beta agonists (LABA) to 45% (RR: 0.55, 95%CI: 0.49-0.61) for oral corticosteroids. Such a seasonal pattern was observed each year across the 16-year study period, among healthcare plans, sexes, and ages. LABA containing control medication (ICS+LABA and LABA) fill rates were more prevalent in older asthmatics, while leukotriene receptor antagonists were more prevalent in the younger population. Conclusions: A seasonal pattern of asthma medication fill rates likely represents a reactive response to a loss of disease control and increased symptoms. Adherence to and consistent use of asthma medications among individuals who use medications in reaction to seasonal exacerbations might be a key component in reducing the risk of asthma exacerbations. [ABSTRACT FROM AUTHOR]

Background: The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations. More precise measurement approaches could improve testing of etiological theories of wheezing illness. Methods: We evaluated a continuous latent variable model of pediatric wheezing severity based on four ISAAC Wheezing Module items. Analyses included subgroups of children from three independent cohorts whose parents reported past wheezing: infants ages 0–2 in the INSPIRE birth cohort study (Cohort 1; n = 657), 6-7-year-old North American children from Phase One of the ISAAC study (Cohort 2; n = 2,765), and 5-6-year-old children in the EHAAS birth cohort study (Cohort 3; n = 102). Models were estimated using structural equation modeling. Results: In all cohorts, covariance patterns implied by the latent variable model were consistent with the observed data, as indicated by non-significant χ2 goodness of fit tests (no evidence of model misspecification). Cohort 1 analyses showed that the latent factor structure was stable across time points and child sexes. In both cohorts 1 and 3, the latent wheezing severity variable was prospectively associated with wheeze-related clinical outcomes, including physician asthma diagnosis, acute corticosteroid use, and wheeze-related outpatient medical visits when adjusting for confounders Conclusion: We developed an easily applicable continuous latent variable model of pediatric wheezing severity based on items from the well-validated ISAAC Wheezing Module. This model prospectively associates with asthma morbidity, as demonstrated in two ECHO birth cohort studies, and provides a more statistically powerful method of testing etiologic hypotheses of childhood wheezing illness and asthma. [ABSTRACT FROM AUTHOR]

Rates of Sudden Unexplained Infant Death (SUID), bronchiolitis, and central apnea increase in winter in temperate climates. Though associations between these three conditions are suggested, more work is required to establish if there is a causal pathway linking bronchiolitis to SUID through inducing central apnea. Utilizing a large population-based cohort of infants studied over a 20-year period (n = 834,595, from birth years 1989–2009)), we analyzed ecological associations between timing of SUID cases, bronchiolitis, and apnea healthcare visits. Data were analyzed between 2013 and 2015. We used a Cox Proportional Hazards model to analyze possible interactions between maternal smoking and maternal asthma with infant bronchiolitis on time to SUID. SUID and bronchiolitis both occurred more frequently in winter. An increase in bronchiolitis clinical visits occurred within a few days prior to apnea visits. We found a temporal relationship between infant bronchiolitis and apnea. In contrast, no peak in SUID cases was seen during peaks of bronchiolitis. Among those without any bronchiolitis visits, maternal smoking was associated with an increased risk of SUID: Hazard Ratio (HR) of 2.38 (95% CI: 2.11, 2.67, p-value <0.001). Maternal asthma was associated with an increased risk of SUID among infants with at least one bronchiolitis visit: HR of 2.40 (95% CI: 1.04, 5.54, p-value = 0.04). Consistent trends between bronchiolitis, apnea, and SUID were not established due to small numbers of SUID cases. However, interaction analysis revealed potential differential associations of bronchiolitis and SUID by maternal smoking, maternal asthma status. [ABSTRACT FROM AUTHOR]

Background: Infants with lower respiratory tract infections (LRTIs) are at an increased risk of developing childhood wheezing illnesses (including asthma), but it is not currently possible to predict those at risk for these long-term outcomes. The current objective was to examine whether urine levels of club cell 16-kDa secretory protein (CC16) at the time of an infant LRTI are associated with the development of childhood wheezing illnesses. Methods: Prospective study of 133 previously healthy infants enrolled during a healthcare visit for a LRTI and followed longitudinally for childhood wheezing illnesses. Urine levels of CC16 at the time of enrollment were measured after validating a commercially available enzyme-linked immunosorbent assay kit for serum. The outcome of interest was parental report of subsequent childhood wheeze (defined as ≥1 episode of wheezing following the initial LRTI) at the 1-year follow-up visit. Logistic regression was used for the main analysis. Results: The median (interquartile range) urine levels of CC16 (ng/mg of creatinine) at the time of an infant LRTI were 11.1 (7.7-20.1) for infants with subsequent childhood wheeze and 13.4 (8.3-61.1) for those without ( p = 0.11). In the main multivariate analysis using a logarithmic transformation of the urine levels of CC16, a twofold increase in urine levels of CC16 was associated with ∼30% decreased odds (OR = 0.74 [95% confidence interval (CI) 0.56-0.98], p = 0.04) of subsequent childhood wheeze after adjustment for potential confounders. Conclusions: An inverse association was found between urine levels of CC16 at the time of an infant LRTI and the odds of subsequent childhood wheeze. Urine CC16 may be a useful biomarker of the development of childhood wheezing illnesses after LRTIs in infancy. [ABSTRACT FROM AUTHOR]

Viral bronchiolitis affects 20%–30% of infants; because there is no known effective treatment, it is important to identify risk factors that contribute to its pathogenesis. Although adequate folate intake during the periconceptional period prevents neural tube defects, animal data suggest that higher supplementation may be a risk factor for child respiratory diseases. Using a population-based retrospective cohort of 167,333 women and infants, born in 1995–2007 and enrolled in the Tennessee Medicaid program, we investigated the association between the filling of folic acid–containing prescriptions and infant bronchiolitis. We categorized women into the following 4 groups in relation to the first trimester: “none” (no prescription filled), “first trimester only,” “after first trimester,” and “both” (prescriptions filled both during and after the first trimester). Overall, 21% of infants had a bronchiolitis diagnosis, and 5% were hospitalized. Most women filled their first prescriptions after the fifth to sixth weeks of pregnancy, and most prescriptions contained 1,000 µg of folic acid. Compared with infants born to women in the “none” group, infants born to women in the “first trimester only” group had higher relative odds of bronchiolitis diagnosis (adjusted odds ratio = 1.17, 95% confidence interval: 1.11, 1.22) and greater severity (adjusted odds ratio = 1.16, 95% confidence interval: 1.11, 1.22). This study's findings contribute to an understanding of the implications of prenatal nutritional supplement recommendations for infant bronchiolitis. [ABSTRACT FROM PUBLISHER]

A correction is presented to the article "Dose, Timing, and Spectrum of Prenatal Antibiotic Exposure and Risk of Childhood Asthma" which appeared in the February 1, 2021 issue.

Background Immunoprophylaxis is the only pharmaceutical intervention for mitigating respiratory syncytial virus (RSV) infection. Patient level data on adherence to American Academy of Pediatrics (AAP) immunoprophylaxis recommendations are limited. This study characterizes adherence to AAP guidelines in privately insured and Medicaid populations. Methods We performed a retrospective birth cohort study of 211 174 privately insured children in Northern California; and 458 837 publicly insured children in Tennessee born between January 1, 1996 and December 31, 2008. Adherence to the AAP guideline was defined for eligible infants as the number of doses of RSV immunoprophylaxis administered over the number recommended for 4 mutually exclusive eligibility groups: chronic lung disease, prematurity <29 weeks, prematurity <32 weeks, and other eligibility. Results We identified 3456 California (Kaiser Permanente Northern California [KPNC]) and 12 251 Tennessee (Tennessee Medicaid [TennCare]) infants meeting AAP eligibility criteria. Immunoprophylaxis administration increased over the study period, from 15% for all eligible groups in 1998 to 54% in 2007. Adherence was highest among babies with chronic lung disease (KPNC 67% and TennCare 55%). Nonadherence (0% adherence) was greatest among infants of African American mothers (adjusted odds ratio [AOR] = 1.32; 95% confidence interval [CI] = .98–1.78); those with mothers with less than a high school education (AOR = 1.58; CI = 1.09–2.30) in KPNC; and in infants of Hispanic mothers in TennCare (AOR = 1.65; CI = 1.24–2.20). In KPNC, 0.11% of ineligible term infants and 5% of ineligible premature infants received immunoprophylaxis; the corresponding proportions in TennCare were 1% and 11%. Conclusions Overall adherence with AAP guidelines has increased over time. Considerable overuse and underuse of immunoprophylaxis are evident with identifiable risk groups to target for improvement. [ABSTRACT FROM PUBLISHER]

Aims To determine pharmacokinetic and pharmacogenomic correlates of efavirenz central nervous system ( CNS) side effects following a single dose. Methods Thirty-four healthy HIV-negative African Americans were administered a 600 mg dose of efavirenz. Blood samples for pharmacokinetics were drawn serially from 0 to 12 h post-dose. Neuropsychometric testing with drowsiness visual analogue scale, grooved pegboard and letter digit substitution tests was done the day prior to dosing and at 1, 2, 3, 4 and 6 h post-dose. Subjective CNS symptoms were assessed at 6 h post-dose. Composite CYP2 B6 516/983 genotype was determined. Results Pharmacokinetic indices reflecting increased plasma efavirenz exposure were associated with slower non-dominant hand grooved pegboard task completion ( Cmax, P1 h = 0.01, P2 h = 0.05, P3 h = 0.03, P4 h = 0.01; AUC, P1 h = 0.04; clearance P1 h = 0.05, P2 h = 0.02, P6 h = 0.01). In a repeated measures model analysis that adjusted timing of neuropsychometric testing for timing of peak drug concentration, clearance ( P < 0.001), AUC(0.312 h) ( P = 0.001) and Cmax ( P = 0.008) were associated with non-dominant grooved pegboard test performance. CYP2B6 genotype trended to correlate with non-dominant hand grooved pegboard at 4 and 6 h ( P = 0.07 and 0.06). Decreased drowsiness at 6 h was associated with higher Cmax ( P = 0.02). Conclusions Following a single dose of efavirenz, an association between pharmacokinetics and neuropsychometric performance was discernable. A weaker association between genotype and neurocognitive test performance is likely mediated by effect of genotype on plasma clearance. Strategies that lower Cmax during initial dosing may decrease CNS side effects. [ABSTRACT FROM AUTHOR]

Objectives. To examine the time-dependent changes of spirometry (percent-predicted forced expiratory volume in 1 second [%FEV1]) and the Pediatric Respiratory Assessment Measure (PRAM) during the treatment of acute asthma exacerbations. Study design . We conducted a prospective study of participants aged 5-17 years with acute asthma exacerbations managed in a Pediatric Emergency Department. %FEV1 and the PRAM were recorded pretreatment and at 2 and 4 hours. We examined responses at 2 and 4 hours following treatment and assessed whether the changes of %FEV1 and of the PRAM differed during the first and the second 2-hour treatment periods. Results . Among 503 participants, median [interquartile range, IQR] age was 8.8 [6.9, 11.4], 61% were male, and 63% were African-American. There was significant mean change of %FEV1 during the first (+15.4%; 95% CI 13.7 to 17.1; p < .0001), but not during the second (+1.5%; 95% CI −0.8 to 3.8; p = .21), 2-hour period and of the PRAM during the first (-2.1 points; 95% CI −2.3 to −1.9; p < .0001) and the second (-1.0 point; 95% CI −1.3 to −0.7; p < .0001) 2-hour periods. Conclusions . Most improvement of lung function and clinical severity occur in the first 2 hours of treatment. Among pediatric patients with acute asthma exacerbations, the PRAM detects significant and clinically meaningful change of severity during the second 2-hour treatment, whereas spirometry does not. This suggests that spirometry and clinical severity scores do not have similar trajectories and that clinical severity scores may be more sensitive to clinical change of acute asthma severity than spirometry. [ABSTRACT FROM AUTHOR]

Early-life severe respiratory syncytial virus (RSV) infection has been associated with the onset of childhood wheezing illnesses. However, the relationship between RSV infection during infancy and the development of childhood asthma is unclear. We aimed to assess the association between RSV infection during infancy and childhood asthma. INSPIRE is a large, population-based, birth cohort of healthy infants with non-low birthweight born at term between June and December, 2012, or between June and December, 2013. Infants were recruited from 11 paediatric practices across middle Tennessee, USA. We ascertained RSV infection status (no infection vs infection) in the first year of life using a combination of passive and active surveillance with viral identification through molecular and serological techniques. Children were then followed up prospectively for the primary outcome of 5-year current asthma, which we analysed in all participants who completed 5-year follow-up. Statistical models, which were done for children with available data, were adjusted for child's sex, race and ethnicity, any breastfeeding, day-care attendance during infancy, exposure to second-hand smoke in utero or during early infancy, and maternal asthma. Of 1946 eligible children who were enrolled in the study, 1741 (89%) had available data to assess RSV infection status in the first year of life. The proportion of children with RSV infection during infancy was 944 (54%; 95% CI 52–57) of 1741 children. The proportion of children with 5-year current asthma was lower among those without RSV infection during infancy (91 [16%] of 587) than those with RSV infection during infancy (139 [21%] of 670; p=0·016). Not being infected with RSV during infancy was associated with a 26% lower risk of 5-year current asthma than being infected with RSV during infancy (adjusted RR 0·74, 95% CI 0·58–0·94, p=0·014). The estimated proportion of 5-year current asthma cases that could be prevented by avoiding RSV infection during infancy was 15% (95% CI 2·2–26·8). Among healthy children born at term, not being infected with RSV in the first year of life was associated with a substantially reduced risk of developing childhood asthma. Our findings show an age-dependent association between RSV infection during infancy and childhood asthma. However, to definitively establish causality, the effect of interventions that prevent, delay, or decrease the severity of the initial RSV infection on childhood asthma will need to be studied. US National Institutes of Health. [ABSTRACT FROM AUTHOR]

Objective. There is limited information on performance rates for tests of lung function and inflammation in pediatric patients with acute asthma exacerbations. We sought to examine how frequently pediatric patients with acute asthma exacerbations could perform noninvasive lung function and exhaled nitric oxide (FENO) testing and participant characteristics associated with successful performance . Methods. We studied a prospective convenience sample aged 5-17 years with acute asthma exacerbations in a pediatric emergency department. Participants attempted spirometry for percent predicted forced expiratory volume in 1 second (%FEV1), airway resistance (Rint), and FENO testing before treatment. We examined overall performance rates and the associations of age, gender, race, and baseline acute asthma severity score with successful test performance. Results. Among 573 participants, age was (median [interquartile range]) 8.8 [6.8, 11.5] years, 60% were male, 57% were African-American, and 58% had Medicaid insurance. Tests were performed successfully by the following [ n (%)]: full American Thoracic Society-European Respiratory Society criteria spirometry, 331 (58%); Rint, 561 (98%); and FENO, 354 (70% of 505 attempted test). Sixty percent with mild-moderate exacerbations performed spirometry compared to 17% with severe exacerbations (p = .0001). Participants aged 8-12 years (67%) were more likely to perform spirometry than those aged 5-7 years (48%) (OR = 2.23, 95% CI: 1.45-3.11) or 13-17 years (58%) (OR = 1.61, 95% CI: 1.00-2.59). Conclusions. There is clinically important variability in performance of these tests during acute asthma exacerbations. The proportion of patients with severe exacerbations able to perform spirometry (17%) limits its utility. Almost all children with acute asthma can perform Rint testing, and further development and validation of this technology is warranted. [ABSTRACT FROM AUTHOR]

Background: The ability to measure 25-hydroxyvitamin D (25OHD) levels from blood spot cards can simplify sample collection versus samples obtained by venipuncture, particularly in populations in whom it is difficult to draw blood. We sought to validate the use of blood spot samples for the measurement of 25OHD compared to serum or whole blood samples and correlate the measured levels with intake estimated from dietary recall. Methods: Utilizing 109 biological mothers of infants enrolled in the Tennessee Children's Respiratory Initiative cohort, we measured 25OHD levels through highly selective liquid chromatography-tandem mass spectrometry on samples from blood spot cards, serum, and whole blood collected at enrollment. Dietary questionnaires (n = 65) were used to assess 25OHD intake by dietary recall. Sample collection measures were assessed for agreement and 25OHD levels for association with dietary 25OHD intake. Results: The mean absolute differences (95%CI) in 25OHD levels measured between whole blood and blood spot (n = 50 pairs) or serum and blood spot (n = 20) were 3.2 (95%CI:1.6, 4.8) ng/ml and 1.5 (95%CI:20.5,3.4) ng/mL. Intake by dietary recall was marginally associated with 25OHD levels after adjustment for current smoking and race in linear regression. Discussion: 25OHD levels determined by mass spectrometry from blood spot cards, serum and whole blood show relatively good agreement, although 25OHD levels are slightly lower when measured by blood spot cards. Blood spot samples are a less invasive means of obtaining 25OHD measurements, particularly in large population-based samples, or among children when venipuncture may decrease study participation. [ABSTRACT FROM AUTHOR]

Background. Polymorphisms in CYP2B6 affect the steady-state plasma concentrations of nevirapine and efavirenz. In many resource-limited countries, a single dose of nevirapine has been widely prescribed to pregnant women at delivery, to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). We characterized associations between genetic polymorphisms and the pharmacokinetics of single doses of nevirapine and efavirenz. Methods. Plasma drug concentrations were determined over the 13-day period after administration of a 200-mg oral dose of nevirapine to nonpregnant, HIV-negative African Americans. A 600-mg oral dose of efavirenz was subsequently administered, and pharmacokinetic sampling was repeated. Pharmacokinetic parameters were estimated using a noncompartmental approach. Primary analyses involved 2 CYP2B6 polymorphisms (516G→T and 983T→C) known to predict increased steady-state plasma nevirapine and efavirenz exposure. Exploratory analyses involved another 51 polymorphisms in CYP2B6, ABCB1, CYP3A4, and CYP3A5. Results. On the basis of the composite CYP2B6 516/983 genotype, the 34 participants comprised 10 extensive, 17 intermediate, and 7 slow metabolizer genotypes. The composite CYP2B6 516/983 genotype was significantly associated with plasma drug exposure and clearance for efavirenz but not nevirapine. Exploratory analyses suggested possible associations between additional CYP2B6 polymorphisms and the pharmacokinetics of nevirapine and efavirenz. Conclusions. Selective pressure for drug-resistant HIV-1 after administration of single-dose nevirapine may not differ substantially according to CYP2B6 516/983 genotype. Additional polymorphisms, genes, and populations warrant further study. [ABSTRACT FROM AUTHOR]

OBJECTIVES. The goals were to estimate the year-round burden of health care visits attributable to bronchiolitis and to identify risk factors for bronchiolitis in term healthy infants. METHODS. We conducted a population-based, retrospective cohort study of 103 670 term, non-low birth weight infants enrolled in Tennessee Medicaid in 1995-2003. We monitored infants through the first year of life. Risk factors for bronchiolitis during infancy and rates of inpatient, emergency department, and outpatient visits during the study period were calculated by using claims data. RESULTS. Over the 9 study years, rates of bronchiolitis visits were 238 outpatient visits per 1000 infant-years, 77 emergency department visits per 1000 infant-years, and 71 hospitalizations per 1000 infant-years. Average annual rates of bronchiolitis visits increased 41%, from 188 visits per 1000 infant-years to 265 visits per 1000 infant-years, from 1996-1997 to 2002-2003. Analysis of the linear trend in 500-g increments demonstrated a negative association between increasing birth weight and bronchiolitis diagnosis. There was a significant negative trend between maternal age and infant bronchiolitis diagnosis. Compared with infants of mothers 20 to 29 years of age, infants of mothers 15 to 19 years of age had a small increase in risk of having a bronchiolitis visit, whereas infants of older mothers (30-39 or 40-44 years of age) were less likely to have a visit. CONCLUSIONS. The disease burden of bronchiolitis is substantial, with increasing rates of all types of visits among term, otherwise-healthy infants enrolled in Tennessee Medicaid between 1995 and 2003. Protective factors in this cohort of term infants included higher birth weight and older maternal age. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Our goal was to determine whether maternal asthma and maternal smoking during pregnancy are associated with the incidence and severity of clinically significant bronchiolitis in term, otherwise healthy infants without the confounding factors of small lung size or underlying cardiac or pulmonary disease. PATIENTS AND METHODS. We conducted a population-based retrospective cohort study of term, non-low birth weight infants enrolled in the Tennessee Medicaid Program from 1995 to 2003. The cohort of infants was followed through the first year of life to determine the incidence and severity of bronchiolitis as determined by health care visits and prolonged hospitalization. RESULTS. A total of 101 245 infants were included. Overall, 20% of infants had ≥1 health care visit for bronchiolitis. Compared with infants with neither factor, the risk of bronchiolitis was increased in infants with maternal smoking only, maternal asthma only, or both. Infants with maternal asthma only or with both maternal smoking and asthma had the highest risks for emergency department visits and hospitalizations. Infants with a mother with asthma had the highest risk of a hospitalization >3 days, followed by infants with both maternal asthma and smoking, and maternal smoking only. CONCLUSIONS. Maternal asthma and maternal smoking during pregnancy are independently associated with the development of bronchiolitis in term, non-low birth weight infants without preexisting cardiac or pulmonary disease. The risk of bronchiolitis among infants with mothers who both have asthma and smoke during pregnancy is ∼50% greater than that of infants with neither risk factor. Efforts to decrease the illness associated with these 2 risk factors will lead to decreased morbidity from bronchiolitis, the leading cause of hospitalization for severe lower respiratory tract infections during infancy. [ABSTRACT FROM AUTHOR]

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) Study is a prospective, multicity, 6-month incidence study conducted from May 2020 to February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other National Institutes of Health–funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics, and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5598 individuals, including 1913 principal participants (children), 1913 primary caregivers, 729 secondary caregivers, and 1043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research. Trial registration: ClinicalTrials.gov. Identifier: NCT04375761 [ABSTRACT FROM AUTHOR]

Pregnant women with asthma have increased frequency of respiratory viral infections and exacerbations. Because of these risks, women with asthma may be subject to increased surveillance during pregnancy and may, therefore, be at increased risk of antibiotic receipt. The objective of this study was to assess the relationship between maternal asthma and outpatient prenatal antibiotic prescription fills to inform antibiotic stewardship. We included women who delivered a singleton, term, non-low birthweight, and otherwise healthy infant enrolled in the Tennessee Medicaid Program. Maternal asthma and prenatal antibiotic fills were ascertained from healthcare encounters and outpatient pharmacy claims. We examined the association between maternal asthma and prenatal antibiotic fills using modified Poisson regression. Our study population included 168354 pregnant women, 4% of whom had asthma. Women with asthma had an increased risk of filling at least one prenatal antibiotic prescription (adjusted risk ratio [aRR] 1.27, 95% confidence interval [CI] 1.25-1.28) and had an increased number of fills during pregnancy (aRR 1.54, 95% CI 1.51-1.57) compared to women without asthma. Among those who filled at least one antibiotic prescription, women with asthma had earlier first prenatal antibiotic prescription fill and increased likelihood of filling at least one course of broad-spectrum antibiotics during pregnancy (versus narrow-spectrum). Pregnant women with asthma had more outpatient antibiotic prescription fills than pregnant women without asthma. These findings highlight that pregnant women with asthma disproportionately fill more antibiotic prescriptions during pregnancy, providing data that may inform antibiotic stewardship. [ABSTRACT FROM AUTHOR]

In this cohort study of hospitalized patients with linked medical record data, we developed International Classification of Diseases (ICD) criteria that accurately identified laboratory‐confirmed, severe influenza hospitalizations (positive predictive value [PPV] 80%, 95% confidence interval [CI] 71–87%), which we validated through medical record documentation. These criteria identify patients with clinically important influenza illness outcomes to inform evaluation of preventive and therapeutic interventions and public health policy recommendations. [ABSTRACT FROM AUTHOR]

Background: Altered mental status (AMS) is a priority presenting sign that must be assessed in HIV-infected, febrile children, yet diagnosis is difficult in areas with limited diagnostic capacity. Malaria and bacterial meningitis have been reported as the most common causes of AMS in febrile children presenting to the hospital in sub-Saharan Africa. However, in an HIV-infected child, central nervous system manifestations are diverse.Methods: We conducted a clinical observational study of HIV-infected febrile children, aged 0-59 months, hospitalized in Mozambique and prospectively followed. Within this cohort, a nested study was designed to characterize children admitted with AMS and to assess factors associated with mortality. Univariate and multivariable analysis were performed comparing characteristics of the cohort by AMS status and evaluated demographic and clinical factors by in-hospital mortality outcome.Results: In total, 727 children were enrolled between April 2016 and February 2019, 16% had AMS at admission. HIV-infected, febrile children, who presented with AMS and who had a diagnosis of bacteremia, had a 4-fold increased relative odds of in-hospital mortality, and children who presented with neurologic symptoms on admission had a roughly 8-fold higher odds of in-hospital mortality relative to children without presenting neurologic findings.Conclusions: Mozambique has a pressing need to expand local diagnostic capacity. Our results highlight the critical need for clinicians to incorporate a broader differential into their potential causes of AMS, and to develop a Ministry of Health approved diagnostic and management algorithm, which is standardly used, to manage patients for whom reliable and relevant diagnostic services are not available. [ABSTRACT FROM AUTHOR]

Childhood asthma is responsible for significant morbidity and health care expenditures in the United States. The incidence of asthma is greatest in early childhood, and the prevalence is projected to continue rising in the absence of prevention and intervention measures. The prevention of asthma will likely require a multifaceted intervention strategy; however, few randomized controlled trials have assessed such approaches. The purpose of this review was to use previous meta-analyses to identify the most impactful risk factors for asthma development and evaluate the effect of risk factor reduction on future childhood asthma prevalence. Common and modifiable risk factors with large effects included acute viral respiratory infections, antibiotic use, birth by cesarean section, nutritional disorders (overweight, obesity), second hand smoke exposure, allergen sensitization, breastfeeding, and sufficient prenatal vitamin D level. Evaluation and estimates of risk factor modification on populations at risk should guide scientists and policymakers toward high impact areas that are apt for additional study and intervention. [ABSTRACT FROM AUTHOR]

Background: Maternal vitamin D status during pregnancy may influence lung development and risk of childhood wheeze and asthma. We investigated the relationship between prenatal vitamin D and child asthma in a racially diverse cohort with a high burden of vitamin D insufficiency and child asthma.Materials and methods: We included mother-child dyads in the prenatal Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort (2006-2011, Shelby County, Tennessee). Maternal plasma vitamin D [25(OH)D] was measured from second trimester (n = 1091) and delivery specimens (n = 907). At age 4-6 years, we obtained parent report of current child wheeze (symptoms within the past 12 months) and asthma (physician diagnosis and/or medication or symptoms within the past 12 months). We used multivariable logistic regression to assess associations of 25(OH)D and child wheeze/asthma, including an interaction term for maternal race.Results: Median second trimester 25(OH)D levels were 25.1 and 19.1 ng/ml in White (n = 366) and Black women (N = 725), respectively. We detected significant interactions by maternal race for second-trimester plasma 25(OH)D and child current wheeze (p = .014) and asthma (p = .011). Odds of current wheeze and asthma decreased with increasing 25(OH)D in dyads with White mothers and increased in dyads with Black mothers, e.g. adjusted odds ratio (95% confidence interval) for asthma: 0.63 (0.36-1.09) and 1.41 (1.01-1.97) per interquartile range (15-27 ng/ml 25[OH]D) increase, respectively. At delivery, protective associations in White dyads were attenuated.Conclusion: We detected effect modification by maternal race in associations between prenatal 25(OH)D and child wheeze/asthma. Further research in racially diverse populations is needed. [ABSTRACT FROM AUTHOR]

Background: Viral bronchiolitis is a common respiratory infection that often affects term, otherwise healthy infants. A small literature suggests maternal stress during pregnancy is associated with bronchiolitis. However, the association between maternal exposure to lifetime traumatic stress, including traumatic events occurring in childhood or throughout the life course, and bronchiolitis has not been studied previously.Objectives: To investigate the association between maternal exposure to total lifetime and childhood traumatic stress events and infant bronchiolitis.Methods: We studied mother-infant dyads enrolled in a prospective prenatal cohort, recruited 2006-2011, and Tennessee Medicaid. During pregnancy, we assessed maternal lifetime exposure to types of traumatic events by questionnaire. We captured bronchiolitis diagnoses in term, non-low birthweight infants' first 12 months using linked Medicaid data. In separate models, we assessed the association of maternal lifetime traumatic events (0 to 20 types) and a subset of traumatic events that occurred during childhood (0 to 3: family violence, sexual, and physical abuse) and infant bronchiolitis using multivariable log-binomial models.Results: Of 629 women, 85% were African American. The median count (interquartile range) of lifetime traumatic events was 3 (2, 5); 42% reported ≥1 childhood traumatic event. Among infants, 22% had a bronchiolitis diagnosis (0 to 2 lifetime traumatic events: 24%; 3 events: 20%; 4 to 5 events: 18%; 6 or more events: 24%). Total maternal lifetime traumatic events were not associated with bronchiolitis in multivariable analyses. For maternal childhood traumatic events, the risk of infant bronchiolitis increased with number of event types reported: adjusted Risk ratios were 1.12 (95% confidence interval [CI] 0.80, 1.59), 1.31 (95% CI 0.83, 2.07), and 2.65 (95% CI 1.45, 4.85) for 1, 2, and 3 events, respectively, vs none.Conclusions: Infants born to women reporting multiple types of childhood trauma were at higher risk for bronchiolitis. Further research is needed to explore intergenerational effects of traumatic experiences. [ABSTRACT FROM AUTHOR]

Prior research suggests that women diagnosed and treated for gestational diabetes mellitus (GDM) gain less total gestational weight than normoglycemic women. Our study finds that race/ethnicity modifies this association. Relative to normoglycemic women, non-Hispanic white women with GDM gain less weight but non-Hispanic black and Hispanic women gain more weight. [ABSTRACT FROM AUTHOR]

We sought to determine the real-world effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis in a population-based cohort to inform policy. The study population included infants born during 1996-2008 and enrolled in the Kaiser Permanente Northern California integrated health-care delivery system. During the RSV season (November-March), the date of RSV immunoprophylaxis administration and the following 30 days were defined as RSV immunoprophylaxis protected period(s), and all other days were defined as unprotected period(s). Numbers of bronchiolitis hospitalizations were determined using International Classification of Diseases, Ninth Revision, codes during RSV season. We used a proportional hazards model to estimate risk of bronchiolitis hospitalization when comparing infants' protected period(s) with unprotected period(s). Infants who had ever received RSV immunoprophylaxis had a 32% decreased risk of bronchiolitis hospitalization (adjusted hazard ratio = 0.68, 95% confidence interval: 0.46, 1.00) when protected periods were compared with unprotected periods. Infants with chronic lung disease (CLD) had a 52% decreased risk of bronchiolitis hospitalization (adjusted hazard ratio = 0.48, 95% confidence interval: 0.25, 0.94) when protected periods were compared with unprotected periods. Under the new 2014 American Academy of Pediatrics (AAP) guidelines, 48% of infants eligible for RSV immunoprophylaxis on the basis of AAP guidelines in place at birth would no longer be eligible, but nearly all infants with CLD would remain eligible. RSV immunoprophylaxis is effective in decreasing hospitalization. This association is greatest for infants with CLD, a group still recommended for receipt of RSV immunoprophylaxis under the new AAP guidelines. [ABSTRACT FROM AUTHOR]

The article discusses a study on how the MEssaging for Diabetes, or MED intervention improves short-term medication adherence among low-income adults with type 2 diabetes. Study highlights include assessment of demographic and clinical attributes at baseline, examination of the relationship between text message engagement and changes in medication adherence using a Spearman's rank correlation coefficient, and a table that outlines patient characteristics by condition.

Background Respiratory syncytial virus (RSV) is associated with acute respiratory infection. We sought to identify RSV variants associated with prolonged infection. Methods Among healthy term infants we identified those with prolonged RSV infection and conducted (1) a human genome-wide association study (GWAS) to test the dependence of infection risk on host genotype, (2) a viral GWAS for association with prolonged RSV infection using RSV whole-genome sequencing, (3) an analysis of all viral public sequences, (4) an assessment of immunological responses, and (5) a summary of all major functional data. Analyses were adjusted for viral/human population structure and host factors associated with infection risk. Results We identified p.E123K/D and p.P218T/S/L in G protein that were associated with prolonged infection (P adj =.01). We found no evidence of host genetic risk for infection. The RSV variant positions approximate sequences that could bind a putative viral receptor, heparan sulfate. Conclusions Using analysis of both viral and host genetics we identified a novel RSV variant associated with prolonged infection in otherwise healthy infants and no evidence supporting host genetic susceptibility to infection. As the capacity of RSV for chronicity and its viral reservoir are not defined, these findings are important for understanding the impact of RSV on chronic disease and endemicity. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory infections are ubiquitous and may have long-term implications on respiratory health. There are many scoring systems used to objectively measure severity of respiratory infections in clinical and research settings. A respiratory severity score derived exclusively from physical exam components (RSS-HR) was studied as an objective measure of disease severity and was compared to a previously described score that uses pulse oximetry as a component of its score (RSS-SO). Findings: A score was derived from 497 infants. The RSS-HR median score was higher in infants that were hospitalized (8.0) versus outpatient (4.0, p < 0.001), and those with lower respiratory tract infections (LRTI) (6.5) versus upper respiratory infections (URI) (1.0, p < 0.001). When discriminating upper versus LRTIs the concordance index of regression for RSS-HR was 0.91 and RSS-SO was 0.93. Conclusions: RSS-HR distinguishes disease severity based on level of care, as well as LRTI versus URI. [ABSTRACT FROM AUTHOR]

Background and objective: The ‘attack rate’ of asthma following viral lower respiratory tract infections (LRTI) is about 3–4 fold higher than that of the general population; however, the majority of children who develop viral LRTI during infancy do not develop asthma, and asthma incidence has been observed to continuously decrease with age. Thus, we do not understand how viral LRTI either predispose or serve as a marker of children to develop asthma. The Tennessee Children's Respiratory Initiative has been established as a longitudinal prospective investigation of infants and their biological mothers. The primary goals are to investigate both the acute and the long-term health consequences of varying severity and aetiology of clinically significant viral respiratory tract infections on early childhood outcomes. Methods: Over four respiratory viral seasons, 2004–2008, term, non-low birth weight previously healthy infants and their biological mothers were enrolled during an infant's acute viral respiratory illness. Longitudinal follow up to age 6 years is ongoing. Results: This report describes the study objectives, design and recruitment results of the over 650 families enrolled in this longitudinal investigation. The Tennessee Children's Respiratory Initiative is additionally unique because it is designed in parallel with a large retrospective birth cohort of over 95 000 mother–infant dyads with similar objectives to investigate the role of respiratory viral infection severity and aetiology in the development of asthma. Conclusions: Future reports from this cohort will help to clarify the complex relationship between infant respiratory viral infection severity, aetiology, atopic predisposition and the subsequent development of early childhood asthma and atopic diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Diabetic patients with lower literacy or numeracy skills are at greater risk for poor diabetes outcomes. This study evaluated the impact of providing literacy- and numeracy-sensitive diabetes care within an enhanced diabetes care program on A1C and other diabetes outcomes. RESEARCH DESIGN AND METHODS -- In two randomized controlled trials, we enrolled 198 adult diabetic patients with most recent A1C ≥7.0%, referred for participation in an enhanced diabetes care program. For 3 months, control patients received care from existing enhanced diabetes care programs, whereas intervention patients received enhanced programs that also addressed literacy and numeracy at each institution. Intervention providers received health communication training and used the interactive Diabetes Literacy and Numeracy Education Toolkit with patients. A1C was measured at 3 and 6 months follow-up. Secondary outcomes included self-efficacy, self-management behaviors, and treatment satisfaction. RESULTS -- At 3 months, both intervention and control patients had significant improvements in A1C from baseline (intervention - 1.50 [95% CI - 1.80 to - 1.02]; control -0.80 [-1.10 to -0.30]). In adjusted analysis, there was greater improvement in A1C in the intervention group than in the control group (P = 0.03). At 6 months, there were no differences in A1C between intervention and control groups. Self-efficacy improved from baseline for both groups. No significant differences were found for self-management behaviors or satisfaction. CONCLUSIONS -- A literacy- and numeracy-focused diabetes care program modestly improved self-efficacy and glycemic control compared with standard enhanced diabetes care, but the difference attenuated after conclusion of the intervention. [ABSTRACT FROM AUTHOR]

Genetic variants in the β2-adrenergic receptor ( ADRB2) coding block have been associated with different parameters of asthma severity, but there is no consensus on which variants are most important. Our objective was to determine whether the genetic variants in the 5′- or 3′-flanking regions of ADRB2 impact the response to therapy. DNA was obtained initially from 72 adults hospitalized for an asthma exacerbation. We sequenced a 5,000 bp region of the ADRB2 gene that spanned the flanking regions and identified 31 single nucleotide polymorphisms (SNPs). Nonresponders to asthma therapy were defined as patients whose forced expiratory volume in 1 second (FEV1) worsened by >10% at 24 hours after admission. We then evaluated the relationship between the 19 common SNPs and response to asthma-specific therapy during acute disease exacerbations. Our results showed a significant association between nonresponders and a haplotype of five promoter SNPs in a nearly complete linkage disequilibrium. An analysis of the promoter and coding block polymorphisms in an extended cohort of 99 patients confirmed that promoter haplotype was the genetic component most strongly associated with asthmatic nonresponders, which was statistically significant among whites ( p < 0.05). An identification of this promoter haplotype may provide an alternate explanation for the variation in the asthma responses observed with ADRB2 coding block polymorphisms. [ABSTRACT FROM AUTHOR]

Objective: Little is known about racial differences in asthma outcomes during pregnancy. We performed a cohort study to estimate racial differences in maternal asthma outcomes in a low-income population of pregnant women in which blacks and whites have similar medical care access and benefits. Methods: We conducted a population-based cohort study of asthma-related morbidity in black and white pregnant women enrolled in Tennessee's Medicaid Program, TennCare. Pregnant women were identified through TennCare enrollment files linked to birth certificates, 1995–2001. Prepregnancy, women with asthma were identified using International Classification of Diseases, 9th Revision, codes for health care visits and pharmacy files for asthma medication. Adjusted relative rates (RR) of rescue cortico-steroid prescriptions, emergency department (ED) visits, and hospitalizations during pregnancy were compared by race using Poisson regression. Results: We identified 4,315 women with asthma (4%) from a population of 112,171 pregnant women of black or white race with at least 180 days of continuous enrollment in TennCare before pregnancy. Blacks were more likely to receive a course of rescue corticosteroids than whites (14.6% versus 11.9%, adjusted RR 1.35, 95% confidence interval [CI] 1.14–1.61), have an emergency department visit (16.7% versus 8.7%, adjusted RR 1.89, 95% CI 1.57–2.27), or be hospitalized for asthma (9.0% versus 5.2%, adjusted RR 1.73, 95% Cl 1.34–2.24). Conclusion: Pregnant women with asthma had high asthma-related morbidity. Black women had clinically significantly more morbidity than whites. There is a need to improve the medical care of low-income women with asthma, particularly black women. [ABSTRACT FROM AUTHOR]

This study identified a genotype of respiratory syncytial virus (RSV) associated with increased acute respiratory disease severity in a cohort of previously healthy term infants. The genotype (2stop+A4G) consists of two components. The A4G component is a prevalent point mutation in the 4th position of the gene end transcription termination signal of the G gene of currently circulating RSV strains. The 2stop component is two tandem stop codons at the G gene terminus, preceding the gene end transcription termination signal. To investigate the biological role of these RSV G gene mutations, recombinant RSV strains harboring either a wildtype A2 strain G gene (one stop codon preceding a wild-type gene end signal), an A4G gene end signal preceded by one stop codon, or the 2stop+A4G virulenceassociated combination were generated and characterized. Infection with the recombinant A4G (rA4G) RSV mutant resulted in transcriptional readthrough and lower G and fusion (F) protein levels than for the wild type. Addition of a second stop codon preceding the A4G point mutation (2stop+A4G) restored G protein expression but retained lower F protein levels. These data suggest that RSV G and F glycoprotein expression is regulated by transcriptional and translational readthrough. Notably, while rA4G and r2stop+A4G RSV were attenuated in cells and in naive BALB/c mice compared to that for wild-type RSV, the r2stop+A4G RSV was better able to infect BALB/c mice in the presence of preexisting immunity than rA4G RSV. Together, these factors may contribute to the maintenance and virulence of the 2stop+A4G genotype in currently circulating RSV-A strains. [ABSTRACT FROM AUTHOR]

Infant respiratory syncytial virus (RSV) bronchiolitis in the first 6 months of life was associated with increased odds of pneumonia, otitis media, and antibiotic prescription fills in the second 6 months of life. These data suggest a potential value of future RSV vaccination programs on subsequent respiratory health. [ABSTRACT FROM AUTHOR]

Background Aspects of infant antibiotic exposure and its association with asthma development have been variably explored. We aimed to evaluate comprehensively and simultaneously the impact of dose, timing, and type of infant antibiotic use on the risk of childhood asthma. Methods Singleton, term-birth, non–low-birth-weight, and otherwise healthy children enrolled in the Tennessee Medicaid Program were included. Infant antibiotic use and childhood asthma diagnosis were ascertained from prescription fills and healthcare encounter claims. We examined the association using multivariable logistic regression models. Results Among 152 622 children, 79% had at least 1 antibiotic prescription fill during infancy. Infant antibiotic use was associated with increased odds of childhood asthma in a dose-dependent manner, with a 20% increase in odds (adjusted odds ratio [aOR], 1.20 [95% confidence interval {CI}, 1.19–1.20]) for each additional antibiotic prescription filled. This significant dose-dependent relationship persisted after additionally controlling for timing and type of the antibiotics. Infants who had broad-spectrum-only antibiotic fills had increased odds of developing asthma compared with infants who had narrow-spectrum-only fills (aOR, 1.10 [95% CI, 1.05–1.19]). There was no significant association between timing, formulation, anaerobic coverage, and class of antibiotics and childhood asthma. Conclusions We found a consistent dose-dependent association between antibiotic prescription fills during infancy and subsequent development of childhood asthma. Our study adds important insights into specific aspects of infant antibiotic exposure. Clinical decision making regarding antibiotic stewardship and prevention of adverse effects should be critically assessed prior to use during infancy. [ABSTRACT FROM AUTHOR]

• An analysis of mtDNA mutation pathogenicity was performed in persons with HIV. • Multi-domain neurocognitive performance outcomes were assessed. • Greater predicted pathogenicity was associated with less motor impairment. • Results were independent of ancestry and estimated mtDNA quantity. Mitochondrial DNA (mtDNA) genetic variation is associated with neurocognitive (NC) impairment (NCI) in people with HIV (PWH). Other approaches use sequence conservation and protein structure to predict the impact of mtDNA variants on protein function. We examined predicted mtDNA variant pathogenicity in the CHARTER study using MutPred scores, hypothesizing that persons with higher scores (greater predicted pathogenicity) have more NCI. CHARTER included NC testing in PWH from 2003 to 2007. MutPred scores were assigned to CHARTER participants with mtDNA sequence; any score > 0.5 was considered potentially deleterious. Outcomes at cohort entry were NCI, defined by global and seven NC domain deficit scores, and by mean global and domain NC performance T-scores. Univariate and multivariable regression analyses assessed associations between having a deleterious variant and NCI. Additional models included estimated peripheral blood cell mtDNA copy number. Data were available for 744 PWH (357 African ancestry; 317 European; 70 Hispanic). In the overall cohort, PWH having any potentially deleterious variant were less likely to have motor impairment (16 vs. 25 %, p = 0.001). In multivariable analysis, having a deleterious variant remained associated with lower likelihood of motor impairment (adjusted odds ratio 0.59 [95 % CI 0.41–0.88]; p = 0.009), and better motor performance by T-score (β 1.71 [0.31–3.10], p = 0.02). Associations persisted after adjustment for estimated mtDNA quantity. In these PWH, having a potentially deleterious mtDNA variant was associated with less motor impairment. These unexpected findings suggest that potentially deleterious mtDNA variations may confer protection against impaired motor function by as yet unknown mechanisms. [ABSTRACT FROM AUTHOR]

The article discusses the systematic review of the safety and effectiveness of palivizumab for treatment of cystic fibrosis in children, conducted by Kua and Lee, which highlights the lack of data and the critical need for additional studies. The authors agree with the conclusion by Kua and Lee on the potential role of respiratory synctial virus (RSV) immunoprophylaxis in reducing RSV hospitalization in children, but stresses extreme caution in interpreting the literature.

RSV bronchiolitis (an acute lower respiratory tract viral infection in infants) is the most common cause of infant hospitalizations in the United States (US). The only preventive intervention currently available is monthly injections of immunoprophylaxis. However, this treatment is expensive and needs to be administered simultaneously with seasonal bronchiolitis cycles in order to be effective. To increase our understanding of bronchiolitis timing, this research focuses on identifying seasonal bronchiolitis cycles (start times, peaks, and declinations) throughout the continental US using data on infant bronchiolitis cases from the US Military Health System Data Repository. Because this data involved highly personal information, the bronchiolitis dates in the dataset were "jittered" in the sense that the recorded dates were randomized within a time window of the true date. Hence, we develop a statistical change point model that estimates spatially varying seasonal bronchiolitis cycles while accounting for the purposefully introduced jittering in the data. Additionally, by including temperature and humidity data as regressors, we identify a relationship between bronchiolitis seasonality and climate. We found that, in general, bronchiolitis seasons begin earlier and are longer in the southeastern states compared to the western states with peak times lasting approximately 1 month nationwide. [ABSTRACT FROM AUTHOR]