The purpose of this study was to investigate the risk of transitional cell carcinoma among subjects with an intake of acetaminophen, aspirin, some other drugs and with some intercurrent diseases. The source person-time ('study base') included subjects living in Stockholm in 1985-1987. The study included 325 subjects with a transitional cell carcinoma of the urinary tract and 393 controls randomly selected from the source person-time. Data were obtained by a postal questionnaire supplemented by a telephone interview. A relative risk (with a 95% confidence interval) of 1.6 (1.1-2.3) was obtained after an intake of acetaminophen, adjusted for age, aspirin, gender and smoking. Conversely, a 30% decrease in risk was obtained after an intake of aspirin. No details in the exposure substantiated the finding for acetaminophen. The inherent validity problems of observational studies, and the weak evidence in this and previous studies of the association between acetaminophen and transitional cell carcinoma, makes available epidemiological evidence insufficient to regulate the use of this commonly ingested analgesic. Increased risks were, in addition, found for tetracyclines, nitrofurantoin and a history of allergic asthma and a decreased risk found for rheumatic symptoms. The findings stress the nonepidemiological data concerning the potential carcinogenicity of acetaminophen and may be a foundation for future research of some other drugs and diseases.
Eleven cases of acetazolamide-associated aplastic anaemia were reported in Sweden during a 17-year period. There were six women and five men with a median age of 71 years (range 63-85 years). The median dose of acetazolamide was 500 mg, and the median duration of treatment was 3 months (range 2-71 months). Ten of the eleven patients died, all within 8 weeks after detection of their aplastic anaemia. The relative risk of developing aplastic anaemia when taking acetazolamide was 13.3 (95% confidence limits (CL); 6.8-25.3). The estimated incidence of reported acetazolamide-associated aplastic anaemia is approximately one in 18,000 patient years. The results strongly indicate that acetazolamide treatment is associated with a substantial increase in the risk of developing aplastic anaemia.
Adverse experiences during licensed treatment with the antidepressant serotonin (5-HT) reuptake inhibitor zimeldine in Sweden are presented. Data were obtained from a written inquiry of 694 patients and 67 reports to the Medical Products Agency. The spectrum of adverse symptoms was in agreement with those reported in previous studies on zimeldine. The most frequent adverse experiences were headache, nausea, myalgia, signs of liver function disturbance, arthralgia, neurological symptoms, fever and insomnia. No new case of the Guillain-Barré syndrome was found. The estimated frequency of the zimeldine-induced hypersensitivity syndrome (HSS), comprising fever, myalgia and/or arthralgia and signs of liver function disturbance, ranged from 1.4% to 13% in the inquiry and from 0.63% to 3.4% in the report part of the study. Adverse experiences usually had a considerably higher incidence during the first 6 weeks of zimeldine treatment than thereafter. This is in agreement with the clinical experience that most of the adverse reactions occur early during zimeldine treatment. However, a number of adverse experiences did occur with a later onset. This may justify a prolongation of the compulsory 4 weeks' testing of liver function that is required during licensed treatment. There were significantly fewer patients who developed fever among the patients who had experienced previous zimeldine treatment than among those who had not. Otherwise there was no statistically significant difference in frequency of adverse symptoms between these two groups. Consequently zimeldine treatment per se does not seem to predispose to development of an HSS or other types of adverse reactions during subsequent therapy.
A retrospective analysis of the adverse reactions reported between 1979 and 1991, in the 139,000 children under six years of age vaccinated in Sweden with the Danish BCG vaccine, strain Copenhagen 1331, showed an incidence of 1.9 per 1000 vaccinated children. Regional lymphoglandular swellings and/or abscesses were most commonly reported in 1.4 per 1000. Serious, disseminated, BCG infections developed in four infants vaccinated neonatally. Three of the infants suffered from severe, combined, immunodeficiency syndrome, undiagnosed at the time of vaccination. The incidence of severe, combined, immunodeficiency syndrome was higher in the BCG-vaccinated population (4 per 100,000 infants vaccinated within a year of their births), compared with all newborns in Sweden (1 per 100,000). The mean age at the onset of symptoms was 2.4 months for the seven non-BCG-vaccinated infants versus 1.3 months for the four BCG-vaccinated ones, while the immunodeficiency syndrome was diagnosed at an average age of 7.6 months in those who were not vaccinated versus 5.3 months in those BCG-vaccinated. It is recommended that the selective BCG vaccination of infants at high risk of exposure to tuberculosis should be postponed to six months of age to reduce the risk of inoculating infants suffering from immunodeficiency syndromes.
OBJECTIVE: To examine the association between current alcohol consumption and major upper gastrointestinal bleeding. METHODS: In a case-control study in the United States, Sweden, and Hungary, 1004 incident cases with upper gastrointestinal bleeding without predisposing factors were compared with 2446 controls. Relative risks for categories of alcohol consumption (based on the number of drinks currently consumed/wk) were estimated using logistic regression; the potential confounding effects of cigarettes, nonsteroidal anti-inflammatory drugs, and other factors were controlled simultaneously. RESULTS: Compared with drinkers of or = 35 drinks; the trend was statistically significant (p or = 60 yr; and those who consumed beer, wine, liquor, or a combination of beverages. CONCLUSIONS: These findings provide evidence that consumption of alcohol increases the risk of major gastric and duodenal bleeding in nonpredisposed individuals.
OBJECTIVE--To evaluate and describe the clinical course of angio-oedema reactions induced by angiotensin converting enzyme inhibitors. DESIGN AND METHODS--All reports of angio-oedema reactions associated with angiotensin converting enzyme inhibitors submitted to Swedish Adverse Reactions Advisory Committee were reviewed and the clinical courses summarised. Numbers of cases judged to be induced by angiotensin converting enzyme inhibitors were related to their annual usage, estimated from total sales of defined daily doses, as well as to the estimated number of new patients. All cases of angio-oedema associated with angiotensin converting enzyme inhibitors reported to the World Health Organisation's international drug information system were also summarised. RESULTS--36 of the 38 reported cases in Sweden between 1981 and 1990 were judged to be related to angiotensin converting enzyme inhibitors. During 1981 through 1990, altogether 1309 cases of angio-oedema associated with angiotensin converting enzyme inhibitors were registered with the international drug information system. The incidence of reported cases of angio-oedema increased largely in parallel with the increased sales (usage) of angiotensin converting enzyme inhibitors. Of the 36 Swedish patients, 77% experienced the reaction within the first three weeks after starting treatment. 10 patients needed hospitalisation, two of whom had life threatening laryngeal obstruction. With one exception all 36 patients were free of symptoms within one week after discontinuing the drug. CONCLUSIONS--Angio-oedema induced by angiotensin converting enzyme inhibitors is a rare but potentially life threatening reaction, which in most instances occurs shortly after the start of treatment. Any patient in whom the reaction is suspected should have the treatment interrupted and, if necessary, be admitted for observation.
Comment In: BMJ. 1992 Jul 18;305(6846):1831515849
Comment In: BMJ. 1992 May 30;304(6839):14431628033
The utilisation of hypnotics, sedatives, and minor tranquillisers (HSmT) was studied by means of drug-delivery and hospital occupancy statistics for 1975-1977 in a Swedish university hospital. A total of 0.53 so-called defined daily doses (DDD)/bed-day were delivered in 1975, implying that every second patient might have regularly been prescribed HSmT. The benzodiazepines were predominant with 71% of the deliveries. Five major drugs accounted for 88%. The drug pattern and the range of DDD/day-bed (0.09-1.18) differed considerably between the departments. Drugs not recommended by the hospital's Pharmacy and Therapeutics Committe accounted only for 3% of deliveries. In a drug surveillance study performed in two medical wards, HSmT were prescribed for 43% of 274 patients. Drug delivery and prescription data were in broad agreement. Drug information activities in the hospital had a clearly discernable influence on the delivered DDD/bed-day. This measure is an inexpensive indicator of drug utilisation in a hospital and a suitable basis for therapeutic audit.
A comparison has been made of risk estimates for agranulocytosis connected with sulphasalazine and trimethoprim-sulphamethoxazole (T-SM) therapy calculated from data in the Swedish Drug Monitoring System ("spontaneous" reports, sales and prescription information) and a population based case-control study (the IAAAS). The relative risk for agranulocytosis during sulphasalazine treatment was calculated to be 107 and 123 by the spontaneous reporting system and the case-control study, respectively. The corresponding excess risk in both systems was 1.8. For T-SM the relative risk was 17 in the spontaneous reporting system and 12 in the case-control study, while the excess risk calculated for 3 days of treatment was 0.9 in the spontaneous reporting system, and 1.6 for 3 or more days of treatment in the case-control study. It is concluded that the Swedish Drug Monitoring System gives an appropriate estimate of the risk of developing agranulocytosis in association with the two drugs studied.
Drug-related blood dyscrasias as reported in Sweden during a 10-yr period have been analysed in relation to sales and prescription data. The number of cases reported were as follows: agranulocytosis 390, thrombocytopenia 391, pancytopenia 50 and aplastic anaemia 36. The annual incidence rates per 10(6) inhabitants were: agranulocytosis 4.8, thrombocytopenia 5.6, pancytopenia 1.1 and aplastic anaemia 0.5. Incidences in the elderly were higher for all dyscrasias except aplastic anaemia. The most commonly reported drugs for all dyscrasias were sulphonamides and diuretics, but when related to sales data the risk of agranulocytosis was high for clozapine, dapsone, mianserin and sulphasalazine, while the risk did not seem to be increased for furosemide. For thrombocytopenia, furosemide, co-trimoxazole and the measles, mumps and rubella vaccine were most commonly reported. The risk for pancytopenia and aplastic anaemia was increased for acetazolamide and co-trimoxazole. As spontaneous reporting systems are primarily set up for signalling purposes, such data must always be interpreted with utmost care.