No abstract

This pooled analysis of double-blind, randomized, placebo-controlled trials aimed to investigate the impact of DOxofylline compaRed tO THEOphylline (DOROTHEO 1 and DOROTHEO 2 studies) on functional and clinical outcomes in asthma. Asthmatic patients ≥16 years of age with forced expiratory volume in 1 s (FEV) ≥50% and <80% and with ≥15% post-bronchodilator increase in FEV were randomized in a 1:1:1:1 ratio in DOROTHEO 1 to receive doxofylline 200 mg, doxofylline 400 mg, theophylline 250 mg, or placebo; in DOROTHEO 2 patients were randomized in a 1:1:1 ratio to receive doxofylline 400 mg, theophylline 250 mg, or placebo. All double-blind treatments were taken orally with immediate release formulations and three times daily. Data evaluating the effect of doxofylline 400 mg, theophylline 250 mg and placebo on FEV, asthma events rate, use of salbutamol as rescue medication and adverse events (AEs) were pooled from both studies. The pooled-analysis of 483 patients demonstrated that both doxofylline 400 mg and theophylline 250 mg significantly increased FEV, reduced the rate of asthma events and use of salbutamol to relieve asthma symptoms compared to placebo (p< 0.01). No significant differences were detected between doxofylline 400 mg and theophylline 250 mg. Doxofylline 400 mg did not significantly (p > 0.05) increase the risk of AEs compared to placebo, conversely in patients treated with theophylline 250 mg the risk of AEs was significantly (p < 0.05) greater than in those that received placebo. We conclude that doxofylline seems to offer a promising alternative to theophylline with a superior efficacy/safety profile in the management of patients with asthma.

Between February and May 1984, we conducted a pilot study to examine the methods for a larger study of a previously reported relation between Reye's syndrome and medications. Thirty patients with Reye's syndrome, whose diagnosis was confirmed by an expert panel, and 145 controls were matched for age, race (black or not black), and antecedent illness (respiratory infection, chickenpox, or diarrhea) and selected from the same hospital, emergency room, or school, or identified by random digit dialing. Significantly more cases (93 per cent, 28 of 30) than members of each of the four control groups or all controls combined (46 per cent, 66 of 145) had received salicylates during matched antecedent illnesses (odds ratio of all 30 cases vs. all controls = 16.1; lower 95 per cent confidence limit = 4.6). The prevalence and mean severity score of signs, symptoms, and selected events during the antecedent illness tended to be lower among cases than controls. Thus, differences in the severity of this illness between cases and controls did not explain differences in medication exposures. This pilot study suggests an association between Reye's syndrome and the use of salicylates during an antecedent illness.

Summary A linear combination T of Student's t statistics is proposed as a practical method of obtaining confidence intervals for the common mean, and the distribution function of T is conveniently approximated for the general case. Exact percentage points of T are compared with those based on this approximation for two populations and various sample size configurations.

No abstract