Multicenter Randomized Controlled Trial of Withdrawal of Inhaled Corticosteroids in Cystic Fibrosis

Rationale: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.

Objectives: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.

Methods: Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age > 6.0 yr, FEV1 ? 40% predicted, and corticosteroid use > 3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.

Measurements and Main Results: Fluticasone group: n = 84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n = 87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23–1.48) fluticasone versus placebo.

Conclusions: In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.

An Extended Implementation of the Great Deluge Algorithm for Course Timetabling

Course Scheduling consists of assigning lecture events to a limited set of specific timeslots and rooms. The objective is to satisfy as many soft constraints as possible, while maintaining a feasible solution timetable. The most successful techniques to date require a compute-intensive examination of the solution neighbourhood to direct searches to an optimum solution. Although they may require fewer neighbourhood moves than more exhaustive techniques to gain comparable results, they can take considerably longer to achieve success. This paper introduces an extended version of the Great Deluge Algorithm for the Course Timetabling problem which, while avoiding the problem of getting trapped in local optima, uses simple Neighbourhood search heuristics to obtain solutions in a relatively short amount of time. The paper presents results based on a standard set of benchmark datasets, beating over half of the currently published best results with in some cases up to 60% of an improvement.

A longitudinal study of infant feeding and obesity throughout the life course

Background: The Centers for Disease Control and Prevention and the US Department of Health and Human Services promote breastfeeding as a strategy for reducing childhood overweight. We evaluated the relation between infant feeding and the development of overweight and obesity throughout life course. Methods: We investigated the association between infant feeding and obesity among 35 526 participants in the Nurses' Health Study II who were followed prospectively from 1989 to 2001. Mothers of participants provided information by mailed questionnaires on the duration of breast- and bottle-feeding, as well as the type of milk or milk substitute in the bottle. Information on body shape at ages 5 and 10, weight at age 18, current weight between 1989 and 2001, and height was reported by the participants. Results: The duration of breastfeeding, including exclusive breastfeeding, was not related to being overweight (25 body mass index (BMI)