Objective-To compare the relative risks of serious gastrointestinal complications reported with individual non-steroidal anti-inflammatory drugs.Design-Systematic review of controlled epidemiological studies that found a relation between use of the drugs and admission to hospital for haemorrhage or perforation.Setting-Hospital and community based casecontrol and cohort studies.Main outcome measures-(a) Estimated relative risks of gastrointestinal complications with use of individual drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the studies.

The last decade has seen a surge in the use of computerized health care data for pharmacoepidemiology. Of all European databases, the General Practice Research Database (GPRD) in the UK, has been the most widely used for pharmacoepidemiological research. Since 1994, this database has belonged to the UK Department of Health, and is maintained by the Office of National Statistics (ONS). Currently, around 1500 general practitioners with a population coverage in excess of 3 million, systematically provide their computerized medical data anonymously to ONS. Validation studies of the GPRD have documented the recording of medical data into general practitioners’ computers to be near to complete. The GPRD collects truly population‐based data, has a size that makes it possible to follow‐up large cohorts of users of specific drugs, and includes both outpatient and inpatient clinical information. The access to original medical records is excellent. Desirable improvements to the GPRD would be additional computerized information on certain variables and linkage to other health care databases. Most published studies to date have been in the area of drug safety. The General Practice Research Database has proved that valuable data can be collected in a general practice setting. The full potential of this rich computerized database has yet to come. This experience should serve to encourage others to develop similar population‐based data in other countries.

We conducted a nested case-control study of 1,377 cases of upper gastrointestinal bleeding or perforation (UGIB) and 10,000 controls to evaluate the association of individual nonsteroidal antiinflammatory drugs (NSAIDs), utilization characteristics, and other risk factors for these conditions. Age was the strongest risk factor for UGIB. Male gender, history of complicated peptide ulcer disease, and current use of steroids were also risk factors for UGIB. The adjusted odds ratio (OR) for current NSAID use was 4.3 [95% confidence interval (CI) = 3.7-5.0]. The ORs for current NSAID use were similar for fatal cases and for the gastric, duodenal, prepyloric, and multiple sites of lesion, but the OR was substantially increased for perforations (OR = 16.9;95% CI = 9.1-31.5). Women age 80 years and older experienced the greater effect of NSAID use. Current users of multiple NSAIDs and recent switchers showed ORs of 9.0 and 6.2, respectively. Ibuprofen showed the lowest OR and diflunisal, the highest. ORs for low, medium, and high NSAID daily dose were 2.9, 4.2, and 5.8, respectively. This trend was present among new, short-term, and long-term users. Simultaneous use of multiple NSAIDs as well as use of a single individual NSAID at high doses greatly increases the risk of complicated peptic ulcer disease.

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Current use of hormone replacement therapy was associated with a higher risk of venous thromboembolism, although the risk seemed to be restricted to the first year of use.