Various forms of chemically induced liver injury and their detection by diagnostic procedures.
A large number of chemical agents, administered for therapeutic or diagnostic purposes, can produce various types of hepatic injury by several mechanisms. Some agents are intrinsically hepatotoxic, and others produce hepatic injury only in the rare, uniquely susceptible individual. Idiosyncrasy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberation of the host permitting the accumulation of hepatotoxic metabolites. The syndromes of hepatic disease produced by drugs have been classified hepatocellular, hepatocanalicular, mixed and canalicular. Measurement of serum enzyme activities has provided a powerful tool for studies of hepatotoxicity. Their measurement requires awareness of relative specificity, knowledge of the mechanisms involved, and knowledge of the relationship between known hepatotoxic states and elevated enzyme activities. (+info)
Use of ineffective or unsafe medications among members of a Medicare HMO compared to individuals in a Medicare fee-for-service program.
Adverse drug reactions and inappropriate prescribing practices are an important cause of hospitalization, morbidity, and mortality in the elderly. This study compares prescribing practices within a Medicare risk contract health maintenance organization (HMO) in 1993 and 1994 with prescribing practices for two nationally representative samples of elderly individuals predominantly receiving medical care within the Medicare fee-for-service sector. Information on prescriptions in the fee-for-service sector came from the 1987 National Medical Expenditures Survey (NMES) and the 1992 Medicare Current Beneficiary Survey (MCBS). A total of 20 drugs were studied; these drugs were deemed inappropriate for the elderly because their risk of causing adverse events exceeded their health benefits, according to a consensus panel of experts in geriatrics and pharmacology. One or more of the 20 potentially inappropriate drugs was prescribed to 11.53% of the Medicare HMO members in 1994. These medications were prescribed significantly less often to HMO members in 1994 than to individuals in the fee-for-service sector, based on information from both the 1987 NMES and the 1992 MCBS. Utilization of unsafe or ineffective medications actually decreased with increasing age in the HMO sample, with lowest rates in individuals over the age of 85. However, no relationship between age and medication use was seen in the NMES study, except for individuals over the age of 90 years. The study data support the conclusion that ineffective or unsafe medications were prescribed less often in the Medicare HMO than in national comparison groups. In fact, for the very old, who are most at risk, the use of these medications was much lower in the Medicare HMO than in the Medicare fee-for-service sector. Nevertheless, in 1994, approximately one of every nine members of this Medicare HMO received at least one such medication. Continued efforts and innovative strategies to further reduce the use of unsafe and ineffective drugs among elderly Medicare HMO members are needed. (+info)
Is reporting rate a good predictor of risks associated with drugs?
AIMS: Uncertainty as to relative under-reporting plagues the comparisons of spontaneous reporting rates as a tool for decision-making in pharmacovigilance. However, it is generally accepted that under-reporting should be reasonably similar for similar drugs sharing the same indication, country and period of marketing. To test this, we compared the adverse drug reaction reporting rates to the French regional pharmacovigilance centres for six pairs of identical drug marketed at the same time by different companies under different brand names (co-marketing). METHODS: All reaction reports were related to sales, to compute reporting rate; within each pair, the reporting rate ratio and its confidence interval were calculated. RESULTS: The rate ratios were all between 0.76 and 1.33. Two of them were significantly different from 1 (1.28; 95% C.I. [1.01; 1.60] and 1.33; 95% C.I. [1.06; 1.74]). CONCLUSIONS: These small differences in reporting rates would not warrant regulatory action and support the usual assumption of similar reporting for similar drugs. (+info)
Retrospective analysis of the frequency and recognition of adverse drug reactions by means of automatically recorded laboratory signals.
AIMS: To estimate the frequency of adverse drug reactions (ADRs) identified through the use of automatic signals generated from laboratory data (ALS) in hospitalised patients. To determine the frequency of spontaneous recognition of these ADRs by the attending physicians and to assess the potential value of ALS for detection of ADRs. METHODS: Laboratory results of patients hospitalised in a nine bed medical ward were automatically recorded over a period of 17 months. Values exceeding defined boundaries were used as ALS. Charts of every third patient were analysed retrospectively with regard to adverse drug related reactions and causality was evaluated as well as whether the ADR had been recognised during the period of hospitalisation. RESULTS: The charts and ALS of 98 patients were analysed. In 18 cases a drug-related adverse reaction was probable. Awareness to the reaction by the treating physicians was evident in 6 out of these 18 ADRs. Approximately 80% of the ADRs were considered predictable. Three ADRs were regarded as serious. CONCLUSIONS: Adverse drug reactions are common and often preventable. Only one third of ADRs which could have been detected through ALS were recognised by the attending physicians. An increased doctor's awareness of the frequency of drug related abnormal laboratory results by means of ALS is likely to increase the recognition rate of ADRs and might help to prevent them. (+info)
Use of dexfenfluramine, fenfluramine and phentermine and the risk of stroke.
AIMS: To estimate the incidence of newly diagnosed idiopathic stroke among users of fenfluramine, dexfenfluramine and phentermine compared to obese nonusers. METHODS: We conducted a cohort study with nested case-control analysis utilizing data from the General Practice Research Database in the UK. Eight thousand four hundred and twenty-three subjects aged 69 years or less at the start of follow-up were exposed to at least one of the three study drugs and 17 225 similarly obese subjects were not exposed to any of the study drugs. RESULTS: We identified 45 incident cases of idiopathic CVA in this cohort of subjects. The incidence of CVA among all current users of a diet drug was 1.3/1000 person-years (95% CI 0.5, 3.5). The incidence for current fenfluramine users (n=2) was 2.6/1000 person-years (95% CI 0.7, 9.6), for current dexfenfluramine users (n=1) 1.1/1000 person-years (95% CI 0.3, 3.8), and for current phentermine users 0/1000 person-years (95% CI 0.0, 12.9). The incidence in obese nonusers was 0.6/1000 person-years (95% CI 0.4, 0. 9). The adjusted matched odds ratio (OR) for thrombotic stroke from the case-control analysis comparing current use of a diet drug to nonuse was 2.4 (95% CI 0.6, 9.1). There was only one exposed subject among seven who had haemorrhagic stroke. CONCLUSIONS: The incidence of CVA in generally young obese subjects during use of fenfluramine, dexfenfluramine or phentermine is low. Although we found an OR of 2. 4 comparing users of any of the anorexiants with nonusers, this is based on only three exposed cases and the confidence limits are wide. We conclude that our study does not support a substantial increased risk of stroke attributable to the use of fenfluramine, dexfenfluramine or phentermine. (+info)
Agranulocytosis in Bangkok, Thailand: a predominantly drug-induced disease with an unusually low incidence. Aplastic Anemia Study Group.
Agranulocytosis, a syndrome characterized by a marked reduction in circulating granulocytes, is strongly associated with medical drug use in Europe and the United States. Unregulated use of common pharmaceutical agents in developing countries has been suspected of causing large numbers of cases of agranulocytosis and deaths, especially among children. To elucidate the incidence and etiology of agranulocytosis in Thailand, a population-based case-control study of symptomatic agranulocytosis that resulted in hospital admission was conducted in Bangkok from 1990 to 1994. An attempt was also made to study the disease in Khonkaen (in northeastern Thailand) and Songkla (in southern Thailand), but there were insufficient cases in the latter regions, and the analysis was confined to subjects from Bangkok. In that region, the overall incidence of agranulocytosis was 0.8 per million per year; there were no deaths. As expected, the incidence was higher in females (0.9 per million), and it increased with age (4.3 per million beyond age 60). Among 25 cases and 529 controls the relative risk estimate for a combined category of all suspect drugs was 9.2 (95% confidence interval = 3.9-21), and the proportion of cases that could be attributed to drug use was 68%. For individual drugs and drug classes the data were sparse; within these limitations, the strongest association appeared to be with antithyroid drugs. One case and three controls were exposed to dipyrone, a drug known to cause agranulocytosis; with such scanty data the risk could not be evaluated. Exposure to pesticides or solvents was not associated with an increased risk. This is the first formal epidemiologic study of agranulocytosis in a developing country. As in the West, most cases are attributable to medical drug use. However, the incidence of agranulocytosis in Bangkok, and apparently, in Thailand as a whole, is unusually low, and the disease does not pose a public health risk. (+info)
The lung in the immunocompromised patient. Infectious complications part 2.
Pulmonary infections decisively contribute to morbidity and mortality in immunocompromised patients. Bacterial, mycobacterial and infections with Pneumocystis carinii have been reviewed in an article in the last issue of Respiration. In this review, viral and fungal pulmonary infections are discussed in HIV-positive patients and in patients treated with high-dose chemotherapy, stem cell or solid-organ transplantation. (+info)
A prospective study of adverse drug reactions in hospitalized children.
AIMS: There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. METHODS: An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. RESULTS: A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03-2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. CONCLUSIONS: Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. (+info)