We have investigated the relation between lung function and dietary intake of the antioxidant vitamins C and E in the general population in a cross-sectional survey of a random sample of adults from the electoral register of an administrative area of Nottingham. In 2,633 subjects 18 to 70 yr of age, we measured FEV1 and FVC, allergen skin sensitivity to grass pollen, cat fur, and Dermatophagoides pteronyssinus, pack-years smoking exposure by personal recall, and usual dietary intake of vitamins C and E by semiquantitative food frequency questionnaire. After adjustment for the effects of age, sex, height, mean allergen skin wheal diameter, and pack-years smoking history, both FEV1 and FVC were significantly and independently related to mean daily intake of vitamin C, such that a standard deviation (40 mg/d) higher vitamin C intake was associated with a 25.0 (95% CI, 5.2 to 44.8; p = 0.01) ml higher FEV1 and a 23.3 (0.94 to 45.7, p = 0.04) ml higher FVC. There was also an association between vitamin E intake and lung function, such that a standard deviation (2.2 mg) higher intake of vitamin E was associated with a 20.1 (1.3 to 40.4, p = 0.04) ml higher FEV1 and a 23.1 (1.0 to 45, p = 0.04) ml higher FVC. However, vitamin C and vitamin E intakes were significantly correlated (r = 0.29, p < 0.001), and after allowing for the effects of vitamin C there was no additional independent effect of vitamin E on either FEV1 or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)

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In designing signal detection systems, careful consideration should be given to the criteria that are used to define an SDR. The choice of disproportionality statistic does not appreciably affect the achievable range of signal detection performance and so this can primarily be based on ease of implementation, interpretation and minimisation of computing resources. The changes in sensitivity and precision obtainable by replacing one algorithm with another are predictable. However, the absolute performance of a method is specific to the database and is best assessed directly on that database. New methods may be required to gain appreciable improvements.

Over a period of 5 years, the Innovative Medicines Initiative PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) project has addressed key research questions relevant to the science of safety signal detection. The results of studies conducted into quantitative signal detection in spontaneous reporting, clinical trial and electronic health records databases are summarised and 39 recommendations have been formulated, many based on comparative analyses across a range of databases (e.g. regulatory, pharmaceutical company). The recommendations point to pragmatic steps that those working in the pharmacovigilance community can take to improve signal detection practices, whether in a national or international agency or in a pharmaceutical company setting. PROTECT has also pointed to areas of potentially fruitful future research and some areas where further effort is likely to yield less.

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The time course of change in FEV1, bronchial reactivity, and daily measures of asthma control (peak expiratory flow, symptoms, and beta 2-agonist inhaler use) was determined during 6 wk of treatment with inhaled budesonide, 800 micrograms twice a day, and for 2 wk following cessation of treatment in 40 asthmatic subjects in a double-blind, placebo-controlled, parallel group study. Histamine reactivity, expressed as the provocative dose of histamine causing a 20% fall in FEV1 (PD20), was measured at intervals during the 8 wk of the study, with more frequent measurements after the first and last dose of drug to provide a detailed profile of change at the start and end of treatment. The first dose of budesonide caused a small increase in median values of FEV1 (0.2 L) and PD20 (1.0 doubling dose of histamine), which was maximum at 6 h. There was a further increase in FEV1 and PD20 over the 6 wk in the budesonide group relative to placebo, the maximum increases (0.53 L, 3.4 doubling doses of histamine) being recorded 6 h after the last dose on Day 42. Following cessation of treatment, FEV1 and PD20 declined and PD20 returned to placebo values at 1 wk. Median PEF increased by 40 and 30 L/min in the morning and evening, respectively, with budesonide treatment. Symptom scores and beta 2-agonist inhaler use were lower in the budesonide group than the placebo group during treatment but tended to be similar (symptom scores) or higher (beta 2-agonist) in the 2 wk following cessation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Subgroup analyses perform better than stratified analyses and should be considered over the latter in routine first-pass signal detection. Subgroup analyses are also clearly beneficial over crude analyses for larger databases, but further validation is required for smaller databases.