Preferences for Rectal Sexually Transmitted Infection Sample Collection and Sexual Behaviors Among Adolescent and Young Adult Women Accessing Primary Care Services.

BACKGROUND: High prevalence of asymptomatic rectal chlamydia and gonorrhea among women is increasingly recognized. Screening is controversial because of lack of natural history data. Barriers to screening may include reluctance to discuss anal sex and collect rectal samples. This study describes the prevalence of sexual contact exposing adolescent and young adult women to extragenital sexually transmitted infections and acceptability of self-collection and clinician collection of rectal samples, preference for self- versus clinician-collected rectal samples, and preference for home or doctor's office for sample collection. METHODS: Participants were recruited from a primary care office and completed structured interviews assessing types of sexual contact and attitudes about rectal sampling. Differences were tested using χ2 and 2-sided Fisher exact test. RESULTS: Of 110 cisgender women (aged 14-22 years) enrolled, the average age was 18.4 years (SD, 1.7 years), 83% reported a history of extragenital contact, 22% reported history of receptive anal intercourse. A majority of participants reported self- and clinician-collected rectal samples to be acceptable (86% and 73%, respectively), with preferences for self-collection (71%) over clinician collection (29%, P < 0.001) and collection at the doctor's office (85%) over home (15%, P < 0.001). CONCLUSIONS: Adolescent and young adult (AYA) women engage in behaviors that increase the risk of rectal sexually transmitted infection (STI). Self- and clinician-collected rectal samples were acceptable. A majority of AYA women preferred to collect rectal samples in the doctor's office rather than at home. This may reduce adolescents' access to direct-to-consumer STI services. Offering in-clinic, self-collected rectal samples may improve uptake of rectal STI screening in adolescent girls.

Impact of Screening and Co-located Parent Coaching Within Pediatric Primary Care on Child Health Care Use: A Stepped Wedge Design.

Childhood adversity and toxic stress have been associated with poor mental and physical health. This study examined if Parent Connext, a program that integrates adversity screening and parent coaching by co-located specialists within pediatric primary care, had an impact on health care utilization. This stepped wedge cluster randomized controlled trial evaluated Parent Connext across six pediatric primary care practices. All practices (clusters) were in the control period during year 1. Three practices were randomized to begin the Parent Connext intervention in year 2, and three practices were randomized to begin in year 3. Medical records of all patients under age 8 treated at these practices during these 3 years were queried retrospectively for participant-level primary outcomes (sick visits, emergency department visits, hospitalizations) and secondary outcomes (well-child and immunization adherence, referrals). The study sample included 27,419 patients followed for an average 1.39 (SD = 0.66) years in the control period and 1.07 (SD = 0.60) years in the intervention period. During the intervention period, patients had significantly fewer sick visits (IRR = 0.91, p < 0.001) which aligned with our hypothesis, decreased odds of well-child visit adherence (OR = 0.88, p < 0.001) which was unexpected, and increased odds of receiving a referral (OR = 1.45, p < 0.001). The odds of an emergency department visit, hospitalization, and 2-year immunization adherence did not differ between periods. Parent Connext resulted in a significant reduction in child sick visits, highlighting the potential benefit of two-generation approaches to pediatric care for child health.

Design and rationale for the supermarket and web-based intervention targeting nutrition (SuperWIN) for cardiovascular risk reduction trial.

PURPOSE: The prevalence of chronic diseases is increasing largely due to suboptimal dietary habits. It is not known whether individualized, supermarket-based, nutrition education delivered by registered dietitians, utilizing the advantages of the in-store and online environments, and electronically collected purchasing data, can increase dietary quality. METHODS AND RESULTS: The supermarket and web-based intervention targeting nutrition (SuperWIN) for cardiovascular risk reduction trial is a randomized, controlled dietary intervention study. Adults identified from a primary care network with 1 or more risk factors were randomized at their preferred store to: (1) standard of care plus individualized, point- of-purchase nutrition education; (2) standard of care plus individualized, point- of-purchase nutrition education enhanced with online shopping technologies and training; or (3) standard of care alone. Educational sessions within each store's clinic and aisles, emphasized the dietary approaches to stop hypertension (DASH) diet. The primary assessment was an intention-to-treat comparison on the effects of the dietary interventions on mean change in DASH score (90-point range) from baseline to 3 months (post-intervention). Additional outcomes included blood pressure, lipids, weight, purchasing behavior, food literacy, and intervention feedback. Between April 2019 to February 2021, 267 participants were randomized (20 excluded due to coronavirus disease pandemic). Median age was 58 years, 69% were female, 64% had a college degree, 53% worked full-time, 64% were obese, 73% were treated with blood pressure and 42% with cholesterol medications, and most had low-to-moderate diet quality. CONCLUSION: The SuperWIN trial was designed to provide a rigorous evaluation of the efficacy of 2 novel, comprehensive, supermarket-based dietary intervention programs.

Prediction of adult class II/III obesity from childhood BMI: the i3C consortium.

BACKGROUND AND OBJECTIVES: Adult class II/III obesity (BMI ≥ 35 kg/m2) has significant adverse health outcomes. Early prevention and treatment are critical, but prospective childhood risk estimates are lacking. This study aimed to define the prospective risk of adult class II/III obesity, using childhood BMI. METHODS: Children ages 3-19 years enrolled in cohorts of the International Childhood Cardiovascular Cohort (i3C) consortium with measured BMI assessments in childhood and adulthood were included. Prospective risk of adult class II/III obesity was modeled based on childhood age, sex, race, and BMI. RESULTS: A total of 12,142 individuals (44% male, 85% white) were assessed at median age 14 [Interquartile range, IQR: 11, 16] and 33 [28, 39] years. Class II/III adult obesity developed in 6% of children with normal weight; 29% of children with overweight; 56% of children with obesity; and 80% of children with severe obesity. However, 38% of the 1440 adults with class II/III obesity (553/1440) were normal weight as children. Prospective risk of adult class II/III obesity varied by age, sex, and race within childhood weight status classifications, and is notably higher for girls, black participants, and those in the United States. The risk of class II/III obesity increased with older adult age. CONCLUSIONS: Children with obesity or severe obesity have a substantial risk of adult class II/III obesity, and observed prospective risk estimates are now presented by age, sex, race, and childhood BMI. Clinical monitoring of children's BMI for adult class II/III obesity risk may be especially important for females and black Americans.

Risk and outcomes of pulmonary fungal infection after pediatric lung transplantation.

BACKGROUND: Prospective studies to determine associated risk factors and related outcomes for pulmonary fungal infection (PFI) after pediatric lung transplant (PLT) are lacking. METHODS: NIH-sponsored Clinical Trials in Organ Transplantation in Children enrolled PLT candidates, collecting data prospectively for 2 years post-transplant. Demographics, signs/symptoms, radiology, pathology and microbiology were collected. Analyses evaluated for PFI-related risks and outcomes. RESULTS: In 59 PLT, pre-transplant fungal colonization occurred in 6 donors and 15 recipients. Cystic fibrosis (CF) was associated with pre-transplant colonization (P < .01). Twenty-five (42%) PLT had 26 post-transplant colonizations (median = 67 days, range = 0-750 days) with Candida (13), Aspergillus (4), mold (6) or yeast (3). Post-PLT colonization was not associated with CF, age, or pre-PLT colonization. Thirteen PFIs occurred in 10 (17%) patients, 3 proven (Candida species) and 10 probable (Candida [3], Aspergillus [3], Penicillium [3], and mold [1]). Pulmonary fungal infection was preceded by post-PLT colonization with the same organism in 4 of 13 PFI, but post-PLT colonization did not predict subsequent PFI (P = .87). Older age at transplant was a risk for PFI (P < .01). No mortality was attributed to PFI. Prophylaxis use was not associated with decreased post-PLT colonization (P = .60) or PFI (P = .48). CONCLUSION: In PLT, PFI and fungal colonization are common but without associated mortality. Post-PLT colonization did not predict PFI. Optimal prevention strategies require additional study.

Is Tachycardia at Discharge From the Pediatric Emergency Department a Cause for Concern? A Nonconcurrent Cohort Study.

STUDY OBJECTIVE: We evaluate the association between discharge tachycardia and (1) emergency department (ED) and urgent care revisit and (2) receipt of clinically important intervention at the revisit. METHODS: The study included a nonconcurrent cohort of children aged 0 to younger than 19 years, discharged from 2 pediatric EDs and 4 pediatric urgent care centers in 2013. The primary exposure was discharge tachycardia (last recorded pulse rate ≥99th percentile for age). The main outcome was ED or urgent care revisit within 72 hours of discharge. Additional outcomes included interventions received and disposition at the revisit, prevalence of discharge tachycardia at the index visit, and associations of pain, fever, and medications with discharge tachycardia. Multivariable logistic regression determined relative risk ratios for revisit and receipt of clinically important intervention at the revisit. RESULTS: Of eligible visits, 126,774 were included, of which 10,470 patients (8.3%) had discharge tachycardia. Discharge tachycardia was associated with an increased risk of revisit (adjusted RR 1.3; 95% confidence interval 1.2 to 1.5), increased risk of tachycardia at the revisit (relative risk 3.1; 95% confidence interval 2.6 to 3.7), and of the receipt of certain clinically important interventions (supplemental oxygen, respiratory medications and admission, antibiotics and admission, and peripheral intravenous line placement and admission). However, there was no increased risk for the composite outcome of receipt of any clinically important intervention or admission on revisit. CONCLUSION: Discharge tachycardia is associated with an increased risk of revisit. It is likely that tachycardia at discharge is not a critical factor associated with impending physiologic deterioration.

Epstein-Barr viral loads do not predict post-transplant lymphoproliferative disorder in pediatric lung transplant recipients: A multicenter prospective cohort study.

Prediction of PTLD after pediatric lung transplant remains difficult. Use of EBV VL in WB has been poorly predictive, while measurement of VL in BAL fluid has been suggested to have enhanced utility. The NIH-sponsored Clinical Trials in Organ Transplantation in Children (CTOTC-03) prospectively obtained serial quantitative measurements of EBV PCR in both WB and BAL fluid after pediatric lung transplantation. Descriptive statistics, contingency analyses, and Kaplan-Meier analyses evaluated possible association between EBV and PTLD. Of 61 patients, 34 (56%) had an EBV+PCR (at least once in WB or BAL). EBV donor (D)+patients more often had a positive PCR (D+/recipient (R)-: 13/18; D+/R+: 14/23) compared to EBV D- patients (6/17). Several D-/R- (5/12) patients developed EBV, but none developed PTLD. All four PTLD patients were D+/R- with EBV+PCR. Neither the time to first EBV+PCR nor the CT for PCR positivity in BAL or WB was statistically different between those with and without PTLD. Having an EBV-seropositive donor was associated with increased risk of EBV+PCR in WB. EBV load in BAL was not predictive of PTLD.

Sleep disordered breathing in young boys with Duchenne muscular dystrophy.

OBJECTIVES: To describe sleep-disordered breathing (SDB) in young boys with Duchenne muscular dystrophy (DMD) and its relationship with pulmonary function tests (PFTs). STUDY DESIGN: This retrospective study examined diagnostic polysomnogram and PFT data of boys younger than 18 years with DMD and treated with steroids. Spirometry, respiratory muscle strength, body mass index (BMI), sleep architecture variables, and indices of SDB were analyzed. We examined the effect of PFT measures on the risk of each type of respiratory event using logistic regression and have reported results as OR (95% CI). RESULTS: Subjects included 110 boys with DMD, mean age 11.5 (5.6-17.9) years. Mean (±SD) percent forced vital capacity predicted was 79.5% ± 29.1%. Mean BMI for all subjects was 21.9 ± 7.0 kg/m(2), and mean BMI z-score was 0.65 ± 1.93. Seventy (63.6%) subjects had obstructive sleep apnea; 37 (33.6%) subjects had central sleep apnea; 18 (17%) subjects had hypoventilation. Median (IQR) Apnea Hypopnea Index was 2.9 (1.6-6.9) and median Obstructive Index was 1.5 (0.5-3.8). Obstructive Index during rapid eye movement sleep positively correlated with BMI (r = 0.33, P = .002), BMI z-score (r = 0.22, P = .04), and age (r = 0.31, P = .004). Lower forced vital capacity was associated with increased risk of hypoventilation (OR 0.8, P = .001). CONCLUSION: SDB is common in young boys with DMD treated with steroids. It is manifest with rapid eye movement-obstructive sleep apnea, often severe, and strongly influenced by BMI.

Obstructive lung disease in children with idiopathic scoliosis.

OBJECTIVE: To measure the prevalence of obstructive lung disease (OLD) among patients undergoing preoperative pulmonary assessment for idiopathic scoliosis. STUDY DESIGN: This was a retrospective, descriptive review from clinical data in a tertiary care pediatric hospital in the US. Patients (n = 176) with idiopathic scoliosis with Cobb angles of ≥ 40 degrees who performed acceptable and repeatable preoperative pulmonary function testing were included. The primary outcome measure was the forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio. RESULTS: The prevalence of OLD (low FEV1/FVC ratio) was 39% (68/176 patients). In multivariate modeling, radiographic measures were poor predictors of pulmonary function outcomes of FVC (r(2) 0.06), FEV1 (r(2) 0.05), FEV1/FVC ratio (r(2) 0.08), and total lung capacity (r(2) 0.06). CONCLUSIONS: OLD is common in patients with idiopathic scoliosis. We recommend preoperative pulmonary function testing for patients with idiopathic scoliosis under consideration for spinal fusion surgery.

Hemoglobin concentration and body mass index are determinants of plasma von Willebrand factor and factor VIII levels.

BACKGROUND: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. VWD is characterized by an abnormal quantity or quality of von Willebrand Factor (VWF). Anemia is often found at presentation for a bleeding disorder evaluation due to chronic blood loss. OBJECTIVES/HYPOTHESIS: We hypothesized that anemia is associated with elevations in both VWF and factor VIII (FVIII) over baseline. We also hypothesized that obesity would be associated with increased levels of VWF. METHODS: We conducted a single-center review of the electronic health record for patients that had proximal von Willebrand profiles and Hb data. RESULTS: We identified 4552 unique subjects with VWF studies and a CBC within 24 h. We found that decreasing hemoglobin inversely correlated with VWF antigen, VWF ristocetin cofactor activity, and FVIII activity. We also found that obesity and Black race were independently associated with increased VWF antigen, activity, and FVIII activity. Hb, race, and body mass index (BMI) continued to be determinants of VWF and FVIII levels in multivariable analysis. CONCLUSION: Our study demonstrates that anemia, race, and BMI were found to be associated with elevation of VWF antigen, VWF activity, and FVIII levels. As many individuals with anemia present for evaluation for a bleeding disorder, these variables need to be considered. KEY POINTS: - Anemia was found to be associated with elevation of VWF antigen, VWF activity and FVIII levels. - Testing von Willebrand factor at times of anemia may mask a diagnosis of von Willebrand Disease.

Perioperative exposure to volatile organic compounds in neonates undergoing cardiac surgery.

OBJECTIVE: Volatile organic compounds (VOCs) are used in the sterilization and manufacture of medical equipment. These compounds have high vapor pressures with low water solubility and are emitted as gases from solids or liquids. They can be mutagenic, neurotoxic, genotoxic, and/or carcinogenic. Safe limits of exposure are not known for neonates. This study examined determinants of exposure in newborns undergoing cardiac surgery. METHODS: Twenty metabolites of 16 VOCs (eg, xylene, cyanide, acrolein, acrylonitrile, N, N-dimethylformamide, 1,3-butadiene, styrene, and benzene) were measured as metabolites in daily urine samples collected from 10 neonates undergoing cardiac operations (n = 150 samples). Metabolites were quantified using reversed-phase ultra-high performance liquid chromatography and electrospray ionization tandem mass spectrometry. Repeated measures analysis of covariance was performed for each metabolite to examine associations with use of medical devices. RESULTS: At least 3 metabolites were detected in every sample. The median number of metabolites detected in each sample was 14 (range, 3-15). In a model controlling for other factors, the use of extracorporeal membrane oxygenation was associated with significantly (P ≤ .05) greater metabolite levels of acrolein, acrylonitrile, ethylene oxide, propylene oxide, styrene, and ethylbenzene. Patients breathing ambient air had greater levels of metabolites of acrolein, xylene, N,N-dimethylformamide, methyl isocyanate, cyanide, 1,3-butadiene (all P ≤ .05). CONCLUSIONS: Exposure to volatile organic compounds is pervasive in newborns undergoing cardiac surgery. Sources of exposure likely include medical devices and inhalation from the air in the intensive care unit. The contribution of VOC exposure during cardiac surgery in newborns to adverse outcomes warrants further evaluation.

Pediatric Hospitalists' Performance of Recommended Minor Procedures: A Multicenter Study.

BACKGROUND AND OBJECTIVES: Performance of minor procedures is highly variable among pediatric hospitalists. Our objective was to describe procedural frequency and measure self-assessed competence in recommended minor procedures among practicing hospitalists. METHODS: An electronic survey was administered across 20 US institutions. An individual survey assessed training, frequency, independence, and success in performing 11 minor procedures. The site survey described practice settings at participating study sites. The primary outcome was respondents' self-assessed competence (SAC), derived by averaging self-assessed independence and success scores (each on a 5-point Likert scale) across all 11 minor procedures. Associations between predictor variables and SAC were determined through analysis of variance for categorical variables and fitted regression models for continuous variables. RESULTS: Of the 360 survey respondents, the majority were female (70%), not fellowship trained (78%), and had 10 years or fewer experience as a hospitalist (72%). Lumbar puncture and bag mask ventilation were most frequently performed. Greater procedural frequency and time since graduation from training were associated with higher SAC scores among respondents. Practice characteristics, including comanagement of patients and reserved time for practicing procedures, were associated with higher SAC scores. The presence of a simulation center and fellowship program was not associated with higher SAC scores. CONCLUSIONS: Pediatric hospitalists that performed procedures more frequently had higher self-assessed procedural competence. Tailored opportunities with increased hands-on experience in performing minor procedures may be important to develop and maintain procedural skills.

Pharmacokinetic parameters over time during sepsis and the association of target attainment and outcomes in critically ill children and young adults receiving ceftriaxone.

INTRODUCTION: Early sepsis results in pharmacokinetic (PK) changes due to physiologic alterations. PK changes can lead to suboptimal drug target attainment, risking inadequate coverage from antibiotics like ceftriaxone. Little is known about how ceftriaxone PK and target attainment quantitatively change over time in patients with sepsis or the association between target attainment and outcomes in critically ill children and young adults. METHODS: A retrospective analysis of a prospective study was conducted in a single-center pediatric intensive care unit. Septic patients given at least one ceftriaxone dose (commonly as 50 mg/kg every 12 h) and who had blood obtained in both the first 48 h of therapy (early) and afterwards (late) were included. Normalized clearance and central volume were estimated and compared in both sepsis phases. We evaluated target attainment, defined as concentrations above 1× or 4× the minimum inhibitory concentration (MIC) for 100% of dosing intervals, and investigated the association between target attainment and clinical outcomes. RESULTS: Fifty-five septic patients (median age: 7.5 years) were included. Normalized clearance and central volume were similar in both phases (6.18 ± 1.48 L/h/70 kg early vs. 6.10 ± 1.61 L/h/70 kg late, p = 0.60; 26.6 [IQR 22.3, 31.3] L/70 kg early vs. 24.5 [IQR 22.0, 29.4] L/70 kg late, p = 0.18). Individual percent differences in normalized clearance and central volume between sepsis phases ranged from -39% to 276% and -51% to 212% (reference, late sepsis), respectively. Fewer patients attained the 1× MIC target in late sepsis (82% late vs. 96% early, p = 0.013), which was associated with transition to once daily dosing, typically done due to transfer from the pediatric intensive care unit (PICU) to a lower acuity unit. Failure to attain either target in late sepsis was associated with antibiotic broadening. CONCLUSION: Ceftriaxone PK parameters were similar between early and late sepsis, but there were large individual differences. Fewer patients attained MIC targets in late sepsis and all who did not attain the less stringent target received once daily dosing during this period. The failure to attain targets in late sepsis was associated with antibiotic broadening and could be an area for antibiotic stewardship intervention.

Comparison of technical errors in pediatric bitewing radiographs acquired with round vs rectangular collimation.

OBJECTIVE: To compare technical errors in bitewing radiographs acquired with round vs rectangular collimation in a hospital-based pediatric dentistry training program. STUDY DESIGN: A retrospective chart review was conducted of 176 digital bitewing radiographs exposed with round collimation and 106 exposed with rectangular collimation. The number of re-exposures was calculated, and errors in central ray entry (CRE; "cone cuts"), horizontal and vertical positioning, and angulation were measured. RESULTS: There were no greater re-exposures but significantly more CRE errors with rectangular collimation (21.7%; n = 23; 95% confidence interval [CI], 13.9%-30.0%) than with round collimation (3.4%; n = 6; 95% CI, 0.7%-6.1%). CRE error location, horizontal positioning errors, and size of horizontal overlapped contacts were statistically different but not clinically important. CONCLUSIONS: Use of rectangular collimation resulted in increased CRE errors but no other clinically significant problems. This technique should be used to reduce radiation exposure to patients.

Diagnosis Code and Health Care Utilization Patterns Associated With Diagnostic Uncertainty.

BACKGROUND AND OBJECTIVES: Diagnostic uncertainty is challenging to identify and study in clinical practice. This study compares differences in diagnosis code and health care utilization between a unique cohort of hospitalized children with uncertain diagnoses (UD) and matched controls. PATIENTS AND METHODS: This case-control study was conducted at Cincinnati Children's Hospital Medical Center. Cases were defined as patients admitted to the pediatric hospital medicine service and having UDs during their hospitalization. Control patients were matched on age strata, biological sex, and time of year. Outcomes included type of diagnosis codes used (ie, disease- or nondisease-based) and change in code from admission to discharge. Differences in diagnosis codes were evaluated using conditional logistic regression. Health care utilization outcomes included hospital length of stay (LOS), hospital transfer, consulting service utilization, rapid response team activations, escalation to intensive care, and 30-day health care reutilization. Differences in health care utilization were assessed using bivariate statistics. RESULTS: Our final cohort included 240 UD cases and 911 matched controls. Compared with matched controls, UD cases were 8 times more likely to receive a nondisease-based diagnosis code (odds ratio [OR], 8.0; 95% confidence interval [CI], 5.7-11.2) and 2.5 times more likely to have a change in their primary International Classification of Disease, 10th revision, diagnosis code between admission and discharge (OR, 2.5; 95% CI, 1.9-3.4). UD cases had a longer average LOS and higher transfer rates to our main hospital campus, consulting service use, and 30-day readmission rates. CONCLUSIONS: Hospitalized children with UDs have meaningfully different patterns of diagnosis code use and increased health care utilization compared with matched controls.

Efficacy of supermarket and web-based interventions for improving dietary quality: a randomized, controlled trial.

Dietary interventions may best be delivered at supermarkets, which offer convenience, accessibility, full food inventories and, increasingly, in-store registered dietitians, online shopping and delivery services. In collaboration with a large retail supermarket chain, we conducted a multisite supermarket and web-based intervention targeting nutrition trial (no. NCT03895580), randomizing participants (n = 247 (139 women and 108 men)) 2:2:1 to two levels of dietary education (Strategy 1 and Strategy 2) or an enhanced control group that included educational components beyond the routine standard of care. Both Strategies 1 and 2 included individualized, in-person, dietitian-led, purchasing data-guided interventions. Strategy 2 also included online tools for shopping, home delivery, selection of healthier purchases, meal planning and healthy recipes. The primary endpoint was change in dietary approaches to stop hypertension (DASH) score (a measure of adherence to the DASH diet) from baseline to 3 months. The primary endpoint was met because, at 3 months, the DASH score increased by 4.7 more for the combined Strategy 1 and Strategy 2 groups than for the control group (95% confidence interval (CI) (0.9, 8.5), P = 0.02). In a prespecified hierarchical test, at 3 months, DASH score increased by 3.8 more for the Strategy 2 group than for the Strategy 1 group (95% CI (0.8, 6.)9, P = 0.01). This trial demonstrates the efficacy of data-guided, supermarket-based, dietary interventions and modern online shopping tools in improving dietary quality in a free-living, community-based population. The trial also demonstrates the opportunity for academic investigators to collaborate with retailers to design and rigorously test comprehensive healthcare interventions.

Inhibition of PI3K by PX-866 prevents transforming growth factor-alpha-induced pulmonary fibrosis.

Transforming growth factor-alpha (TGFalpha) is a ligand for the epidermal growth factor receptor (EGFR). EGFR activation is associated with fibroproliferative processes in human lung disease and animal models of pulmonary fibrosis. EGFR signaling activates several intracellular signaling pathways including phosphatidylinositol 3'-kinase (PI3K). We previously showed that induction of lung-specific TGFalpha expression in transgenic mice caused progressive pulmonary fibrosis over a 4-week period. The increase in levels of phosphorylated Akt, detected after 1 day of doxycycline-induced TGFalpha expression, was blocked by treatment with the PI3K inhibitor, PX-866. Daily administration of PX-866 during TGFalpha induction prevented increases in lung collagen and airway resistance as well as decreases in lung compliance. Treatment of mice with oral PX-866 4 weeks after the induction of TGFalpha prevented additional weight loss and further increases in total collagen, and attenuated changes in pulmonary mechanics. These data show that PI3K is activated in TGFalpha/EGFR-mediated pulmonary fibrosis and support further studies to determine the role of PI3K activation in human lung fibrotic disease, which could be amenable to targeted therapy.

Morbidity and cost burden of prenatal myelomeningocele repair.

OBJECTIVE: This study compared the morbidities and financial burden associated with prenatal open myelomeningocele repair versus postnatal repair. MATERIALS AND METHODS: The retrospective study cohort included 23 mother-infant dyads undergoing prenatal repair and 30 with postnatal repair. Financial, demographic, and medical information were obtained for mother-infant dyads from each infant's birth through the first year of life. RESULTS: Infants in the prenatal repair group were significantly affected by sequelae of prematurity, including apnea, bronchopulmonary dysplasia, and retinopathy of prematurity. Importantly, fewer of these infants required ventriculoperitoneal shunt procedures and the overall improved composite outcome of shunting or death. Infants in the postnatal repair group required more hospital readmissions in the first year of life. Financial costs for mother-infant dyads in the prenatal repair group were higher, driven by the length of stay in the neonatal intensive care unit and maternal hospital admissions. Kaplan-Meier curves analyzing the relative contributions of the length of stay and total charges in the population were constructed. The maternal contribution was markedly different between groups due to postoperative hospitalization, readmission, and close fetal surveillance required. Though these differences did not reach statistical significance, it highlights an important burden on families and the medical system. CONCLUSIONS: This is the first study to report the contributions of prematurity in relation to maternal and infant morbidity and financial costs. The benefits of prenatal myelomeningocele repair include lower risk for ventriculoperitoneal shunting and fewer hospital readmissions. The risk of preterm birth and its neonatal sequelae continue to be a significant burden.

Baroreflex gain in children with obstructive sleep apnea.

RATIONALE: We previously demonstrated that children with obstructive sleep apnea have increased blood pressure associated with changes in left ventricular mass index. Others have shown in adults that blood pressure variability is an important predictor of changes in left ventricular mass. The baroreflex system buffers blood pressure changes by varying heart rate. We have thus hypothesized that (1) baroreflex system gain is increased during sleep, improving blood pressure buffering; (2) children with obstructive sleep apnea lack this baroreflex gain increase; and (3) reduced blood pressure buffering results in exaggerated blood pressure variability that is associated with end-organ damage. OBJECTIVES: Compare measures of left ventricular mass index and nighttime baroreflex gain of healthy children to those of children with obstructive sleep apnea. METHODS: A total of 169 children (50 control subjects, 63 with mild obstructive sleep apnea, and 56 with severe obstructive sleep apnea) with a mean age of 9.9 years (+/-2.2) underwent echocardiography followed by polysomnography with continuous blood pressure measurement. Baroreflex gain was calculated in time and frequency domains. MEASUREMENTS AND MAIN RESULTS: Healthy children demonstrated a nighttime pattern of increasing baroreflex gain. Children with obstructive sleep apnea had decreased nighttime baroreflex gain compared with control subjects. Nighttime blood pressure and blood pressure variability were significantly correlated with left ventricular mass index. CONCLUSIONS: Obstructive sleep apnea is associated with a decrease in nighttime baroreflex gain and an increase in blood pressure variability. This increase is correlated with changes in left ventricular mass index.

Growth velocity predicts recurrence of sleep-disordered breathing 1 year after adenotonsillectomy.

RATIONALE: Adenotonsillectomy, the first line of treatment of sleep-disordered breathing (SDB), is the most commonly performed pediatric surgery. Predictors of the recurrence of SDB after adenotonsillectomy and its impact on cardiovascular risk factors have not been identified. OBJECTIVES: Demonstrate that gain velocity in body mass index (BMI) defined as unit increase in BMI/year confers an independent risk for the recurrence of SDB 1 year after adenotonsillectomy. METHODS: Children with SDB and hypertrophy of the tonsils and a comparison group of healthy children were followed prospectively for 1 year. MEASUREMENTS AND MAIN RESULTS: Serial polysomnographies, BMI, and blood pressure were obtained before adenotonsillectomy and 6 weeks, 6 months, and 1 year postoperatively. Gain velocity in BMI, BMI and being African American (odds ratios, 4-6/unit change/yr; 1.4/unit and 15, respectively) provided equal amounts of predictive power to the risk of recurrence of SDB. In the group that experienced recurrence, systolic blood pressure at 1 year was higher than at baseline and higher than in children who did not experience recurrence. CONCLUSIONS: Three clinical parameters confer independent increased risk for high recurrence of SDB after adenotonsillectomy: gain velocity in BMI, obesity, and being African American. A long-term follow-up of children with SDB and monitoring of gain velocity in BMI are essential to identifying children at risk for recurrence of SDB and in turn at risk for hypertension.