Background-Recent trends in physician diagnosed chronic obstructive pulmonary disease (COPD) in the UK were estimated, with a particular focus on women. Methods-A retrospective cohort of British patients with COPD was constructed from the General Practice Research Database (GPRD), a large automated database of UK general practice data. Prevalence and all-cause mortality rates by sex, calendar year, and severity of COPD, based on treatment only, were estimated from January 1990 to December 1997. Results-A total of 50 714 incident COPD patients were studied, 23 277 (45.9%) of whom were women. From 1990 to 1997 the annual prevalence rates of physician diagnosed COPD in women rose continuously from 0.80% (95% CI 0.75 to 0.83) to 1.36% (95% CI 1.34 to 1.39), (p for trend <0.01), rising to the rate observed in men in 1990. Increases in the prevalence of COPD were observed in women of all ages; in contrast, a plateau was observed in the prevalence of COPD in men from the mid 1990s. Allcause mortality rates were higher in men than in women (106.8 versus 82.2 per 1000 person-years), with a consistently increased relative risk in men of 1.3 even after controlling for the severity of COPD. Significantly increased mortality rates were also observed in adults aged less than 65 years. The mean age at death was 76.5 years; patients with severe COPD died an average of three years before those with mild disease (p<0.01) and four years before the age and sex matched reference population. Conclusions-While prevalence rates of COPD in the UK seem to have peaked in men, they are continuing to rise in women. This trend, together with the ageing of the population and the long term cumulative eVect of pack-years of smoking in women, is likely to increase the present burden of COPD in the UK. (Thorax 2000;55:789-794)

After reports from Japan of neuropsychiatric adverse events (NPAEs) in children taking oseltamivir phosphate (hereafter referred to as oseltamivir [Tamiflu; F. Hoffmann-La Roche Ltd, Basel, Switzerland]) during and after the 2004--5 influenza season, Roche explored possible reasons for the increase in reporting rate and presented regular updates to the US FDA and other regulatory authorities. This review summarizes the results of a comprehensive assessment of the company's own preclinical and clinical studies, post-marketing spontaneous adverse event reporting, epidemiological investigations utilizing health claims and medical records databases and an extensive review of the literature, with the aim of answering the following questions: (i) what the types and rates of neuropsychiatric abnormalities reported in patients with influenza are, and whether these differ in patients who have received oseltamivir compared with those who have not; (ii) what levels of oseltamivir and its active metabolite, oseltamivir carboxylate are achieved in the CNS; (iii) whether oseltamivir and oseltamivir carboxylate have pharmacological activity in the CNS; and (iv) whether there are genetic differences between Japanese and Caucasian patients that result in different levels of oseltamivir and/or oseltamivir carboxylate in the CNS, differences in their metabolism or differences in their pharmacological activity in the CNS. In total, 3051 spontaneous reports of NPAEs were received by Roche, involving 2466 patients who received oseltamivir between 1999 and 15 September 2007; 2772 (90.9%) events originated from Japan, 190 (6.2%) from the US and 89 (2.9%) from other countries. During this period, oseltamivir was prescribed to around 48 million people worldwide. Crude NPAE reporting rates (per 1,000,000 prescriptions) in children (aged < or =16 years) and adults, respectively, were 99 and 28 events in Japan and 19 and 8 in the US. NPAEs were more commonly reported in children (2218 events in 1808 children aged < or =16 years vs 833 in 658 adults) and generally occurred within 48 hours of the onset of influenza illness and initiation of treatment. After categorizing the reported events according to International Classification of Diseases (9th edition) codes, abnormal behaviour (1160 events, 38.0%) and delusions/perceptual disturbances (661 events, 21.7%) were the largest categories of events, and delirium or delirium-like events (as defined by the American Psychiatric Association) were very common in most categories. No difference in NPAE reporting rates between oseltamivir and placebo was found in phase III treatment studies (0.5% vs 0.6%). Analyses of US healthcare claims databases showed the risk of NPAEs in oseltamivir-treated patients (n = 159,386) was no higher than those not receiving antivirals (n = 159,386). Analysis of medical records in the UK General Practice Research Database showed that the adjusted relative risk of NPAEs in influenza patients was significantly higher (1.75-fold) than in the general population. Based on lite...

Summary Studies of underground miners occupationally exposed to radon have consistently demonstrated an increased risk of lung cancer in both smokers and non-smokers. Radon exposure also occurs elsewhere. especially in houses. and estimates based on the findings for miners suggest that residential radon is responsible for about one in 20 lung cancers in the UK, most being caused in combination with smoking. These calculations depend. however, on several assumptions and more direct evidence on the magnitude of the risk is needed. To obtain such evidence, a case-control study was carried out in south-west England in which 982 subjects with lung cancer and 3185 control subjects were interviewed. In addition, radon concentrations were measured at the addresses at which subjects had lived during the 30-year period ending 5 years before the interview. Lung cancer risk was examined in relation to residential radon concentration after taking into account the length of time that subjects had lived at each address and adjusting for age. sex, smoking status, county of residence and social class. The relative risk of lung cancer increased by 0.08 (95% Cl -0.03, 0.20) per 100 Bq m-3 increase in the observed time-weighted residential radon concentration. When the analysis was restricted to the 484 subjects with lung cancer and the 1637 control subjects with radon measurements available for the entire 30-year period of interest, the corresponding increase was somewhat higher at 0.14 per 100 Bq m-3 (95% Cl 0.01. 0.29), although the difference between this group and the remaining subjects was not statistically significant. When the analysis was repeated taking into account uncertainties in the assessment of radon exposure, the estimated increases in relative risk per 100 Bq m-3 were larger, at 0.12 (95% Cl -0.05. 0.33) when all subjects were included and 0.24 (95% Cl -0.01, 0.56) when limited to subjects with radon measurements available for all 30 years. These results are consistent with those from studies of residential radon carried out in other countries in which data on individual subjects have been collected. The combined evidence suggests that the risk of lung cancer associated with residential radon exposure is about the size that has been postulated on the basis of the studies of miners exposed to radon.

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.