Inhaled tobramycin effectively reduces FEV1 decline in cystic fibrosis. An instrumental variables analysis.

RATIONALE: The efficacy of inhaled tobramycin on chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) has been established in clinical trials. However, little is known about its clinical effectiveness on lung function outside randomized controlled trial settings; conventional analysis of existing registry data has heretofore been confounded by treatment selection bias. OBJECTIVE: To determine effectiveness of inhaled tobramycin on FEV1 decline in patients with chronic P. aeruginosa infections using observational data from the Cystic Fibrosis Foundation Patient Registry. METHODS: Patient-level tobramycin use was measured at first chronic P. aeruginosa infection (n = 13,686 patients; age, 6-21 yr). Decline in FEV1 2 years after infection was estimated for patients treated with tobramycin and compared with untreated patients. Multiple linear regressions with confounder adjustment and propensity scores were used to estimate mean FEV1 decline for each group. Because care is organized by centers, we used center-specific prescription rates as an instrument to reduce treatment-by-condition bias. MEASUREMENTS AND MAIN RESULTS: Using center-level prescribing rates, instrumental variables analysis showed less FEV1 decline for patients who received tobramycin when first eligible compared with those who did not receive tobramycin (difference, 2.55% predicted; 95% confidence interval, 0.16-4.94; P = 0.0366). CONCLUSIONS: Inhaled tobramycin is effective in reducing lung function decline among patients 6 to 21 years of age with CF. Because CF care is organized by center, using center-specific prescription rates as an instrumental variable is a feasible approach to using the Cystic Fibrosis Foundation Patient Registry to determine treatment effectiveness. More generally, this approach can correct for treatment-by-condition bias arising from observational studies.

Baroreflex sensitivity after adenotonsillectomy in children with obstructive sleep apnea during wakefulness and sleep.

STUDY OBJECTIVES: Children with obstructive sleep apnea have blunted baroreflex sensitivity and increased blood pressure variability. The aim of the study was to test the hypothesis that treatment of sleep apnea by adenotonsillectomy results in significant improvement of baroreflex sensitivity, lowering of blood pressure and blood pressure variability and increase vagal heart rate modulation. STUDY DESIGN: One hundred ninety-four children aged 9.6 ± 2.3 years were enrolled; 133 had obstructive sleep apnea and 61 were healthy controls. For children with sleep apnea, polysomnography with 3-lead electrocardiography and continuous blood pressure was performed before adenotonsillectomy, then 6 weeks and 6 months postoperatively. Controls underwent the same assessment at study entry and 6 months later. Spontaneous baroreflex sensitivity was measured in the time and frequency domains. Data analyses were performed for available and complete cases. RESULTS: Children with sleep apnea experienced postoperatively an increase in baroreflex sensitivity and decrease in blood pressure variability during wakefulness and sleep. A decrease in blood pressure during sleep and in heart rate during wakefulness was also measured. The improvement in baroreflex sensitivity was predicted by the change in the apnea-hypopnea and arousal indices. A normal pattern of rising baroreflex sensitivity during the night was restored in children with severe apnea after surgery. However, baroreceptor sensitivity did not completely normalize after treatment. CONCLUSION: Treatment of obstructive sleep apnea in children by adenotonsillectomy is associated with gradual improvement in known risk factors for cardiovascular disease. Complete normalization of baroreceptor sensitivity was not achieved 6 months postoperatively.

Effect of chronic sleep restriction on sleepiness and working memory in adolescents and young adults.

OBJECTIVES: To test the feasibility of using a home-based sleep restriction protocol in adolescents and young adults; and to examine the different effects of chronic sleep restriction on a subjective sleepiness scale and working memory task in adolescents and young adults. METHOD: Twenty adolescents (ages 13-16 years) and 20 young adults (ages 18-20 years) underwent a 2-week home-based sleep manipulation protocol consisting of a week of 5 school days with 8 hr spent in bed per night and another week of 5 school days with 6 hr spent in bed per night. The protocol used a counterbalanced crossover experimental design. Subjective sleepiness was scored by the participant each morning, and working memory tests were administered during the weekend corresponding to each experimental week. RESULTS: Adherence to the prescribed protocol was similar in the two groups, and both groups achieved the desired differences in total sleep duration across the two sleep conditions. Subjective sleepiness scores significantly increased in young adults after sleep restriction, but were not accompanied by significant changes in working memory. However, reaction times during simple verbal and arithmetic working memory tasks increased among adolescents after sleep restriction, without affecting accuracy on task, and without eliciting increases in subjective sleepiness scores. CONCLUSION: Mild sleep restriction for 5 days impairs reaction times during working memory tasks in adolescents in the absence of increased perception of sleepiness.