Gastroduodenal toxicity of different nonsteroidal antiinflammatory drugs.

Although the etiologic relation between nonsteroidal antiinflammatory drug (NSAID) use and gastrointestinal lesions is well documented, newly introduced NSAIDs deserve a fresh examination for their risk/benefit ratio. To estimate the association between consumption of ketorolac and the occurrence of gastroduodenal lesions, we conducted a case-control study. The study population comprised 600 outpatients with a confirmed endoscopic diagnosis of ulcer and erosion in 1991 and 1992 and 6,000 community controls matched by age and sex. We retrieved the prescription history through a computerized prescription monitoring system. We defined exposure to each study drug as "current" (month of endoscopy and preceding month), "recent" (second or third month preceding endoscopy). and "past" (fourth to sixth month preceding endoscopy). Current users of NSAIDs showed a 30% increase in the incidence of gastroduodenal lesions [odds ratio (OR) = 1.3; 95% confidence interval (CI) = 0.98 - 1.8] after adjustment for recent or past use of any NSAID, recent or past gastrotoxic therapy, recent or past use of gastroprotective drugs, and recent or past use of any other drug. Among NSAIDs, ketorolac was the only one showing a distinctly elevated risk of gastroduodenal lesions (OR = 4.2; 95% CI = 1.9-9.4). Current use of any NSAID was associated with almost a doubling of risk for ulcer alone (OR = 1.9; 95% CI = 1.3-3.0); no elevation in risk was found for erosions. The adjusted relative risk for ulcer associated with current use of ketorolac was 9.8 (95% CI = 3.4-28.10. Recent and past use of NSAIDs does not increase the risk of ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer mortality in ethylene oxide workers.

A cohort of 1971 chemical workers licensed to handle ethylene oxide was followed up retrospectively from 1940 to 1984 and the vital status of each subject was ascertained. No quantitative information on exposure was available and therefore cohort members were considered as presumably exposed to ethylene oxide. The cohort comprised 637 subjects allowed to handle only ethylene oxide and 1334 subjects who obtained a licence valid for ethylene oxide as well as other toxic gases. Potential confounding arising from the exposure to these other chemical agents was taken into consideration. Causes of death were found from death certificates and comparisons of mortality were made with the general population of the region where cohort members were resident. Seventy six deaths were reported whereas 98.8 were expected; the difference was statistically significant. The number of malignancies for any site exceeded the expected number (standardised mortality ratio (SMR) = 130; 43 observed deaths; 95% confidence interval (95% CI) 94-175) and approached statistical significance. For all considered cancer sites the SMRs were higher than 100 but the excess was only significant (p < 0.05, two sided test) for lymphosarcoma and reticulosarcoma (International Classification of Diseases--9th revision (ICD-9) = 200; SMR = 682; four observed deaths; 95% CI 186-1745). The excess of cases for all cancers of haematopoietic tissue (ICD-9 = 200-208) also approached statistical significance (SMR = 250; six observed deaths; 95% CI 91-544). Focusing the analysis on the subcohort of the ethylene oxide only licensed workers, who are likely to have experienced a more severe exposure to this gas, it became evident that all but one of the observed cases of haematopoietic tissue cancers in the cohort were confined to this subgroup, enhancing the relevant SMR to 700 (95% CI 237-1637) and the SMR of lymphosarcoma and reticulosarcoma to 1693 (95% CI 349-4953).

Epidemiological use of drug prescriptions as markers of disease frequency: an Italian experience.

All Italian citizens are covered by the National Health Service (NHS) and medical records of individual drug prescriptions are routinely collected and processed. A procedure entitled EPIFAR has been developed which, on the basis of a computer routine, makes it possible to trace back the prescription history of each individual included in the NHS. The validity of information gathered through the EPIFAR procedure to provide estimates of tuberculosis (TB) prevalence has been evaluated. A comparison with routine surveillance data has been made. The EPIFAR procedure identified a total figure of TB patients seven times higher than that from official notifications. A sample survey was conducted among the prescribing physicians in order to quantify the proportion of TB cases among subjects receiving prescriptions of anti-TB drugs. According to general practitioner recall 66.4% of the patients were treated because of TB diagnosis, TB prophylaxis and TB relapse.