Biomedical subjects
L E Derby
Publications and source records attributed to L E Derby.
Flucloxacillin and cholestatic hepatitis.
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Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the role of risk factors.
BACKGROUND: Hospitalizations for acute liver injury in the absence of a viral infection or any other well-defined pathologic finding that could have caused it is rare. In this study, we included both outpatients and hospitalized patients with acute liver injury to estimate the risk of clinically important acute liver injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to study the role of certain risk factors. METHODS: This was a retrospective cohort study with secondary case-control analysis. The study included 536 general practitioners' practices in England and Wales for the period October 1987 through August 1991. A total of 625,307 persons who received more than 2 million prescriptions for one of 12 NSAIDs were followed up to estimate the risk of newly diagnosed acute liver injury. RESULTS: There were 23 cases of acute liver injury. The incidence of acute liver injury was 3.7 per 100,000 NSAID users or 1.1 per 100,000 NSAID prescriptions. None of the cases had a fatal outcome. Sulindac was the only NSAID with a substantially greater risk than that for the overall NSAID group. Users of NSAIDs who had rheumatoid arthritis had a 10-fold increased risk of acute liver injury compared with NSAID-treated patients with osteoarthritis. Concomitant exposure to other hepatotoxic medications also increased the risk. Transient minor increases in liver test values were not a useful predictor of diagnosed NSAID-associated acute liver injury. CONCLUSIONS: Although NSAIDs have been found to be associated with acute liver injury in a small number of persons, the risk is sufficiently small as to be of minimal concern for most NSAIDs.
Cholestatic hepatitis associated with flucloxacillin.
OBJECTIVE: To estimate the frequency of cholestatic hepatitis of uncertain origin occurring among persons who had recently received flucloxacillin, a drug which has recently been reported as causing cholestatic hepatitis, and to compare this frequency with that related to oxytetracycline, a drug which has seldom been reported as causing this disorder. DESIGN: A retrospective cohort study using data automatically recorded on general practitioners' office computers. SETTING: Some 600 general practices in the United Kingdom. SUBJECTS: 132,087 people who received flucloxacillin and 145,844 people who received oxytetracycline. MAIN OUTCOME MEASURE: Clinically documented cholestatic hepatitis of uncertain origin diagnosed 1-45 days after a prescription for flucloxacillin, 46-90 days after a prescription for flucloxacillin and, for comparison, 1-45 days after a prescription for oxytetracycline. RESULTS: There were 10 cases of cholestatic hepatitis of uncertain origin diagnosed within 45 days of receiving flucloxacillin that were either characteristic of or consistent with a syndrome recently described as being associated with this drug; there was one such case 46-90 days after a prescription for flucloxacillin; there were three such cases 1-45 days after a prescription for oxytetracycline. CONCLUSION: Flucloxacillin is a likely cause of cholestatic hepatitis. The risk is estimated to be in the range of 7.6 per 100,000 users (95% confidence interval, 3.6-13.9).
Erythromycin-associated cholestatic hepatitis.
OBJECTIVE: To estimate the risk of cholestatic hepatitis of uncertain origin in patients who had recently received erythromycin, a drug which is known to cause this disorder. DESIGN: A retrospective cohort study using data automatically recorded on general practitioners' office computers. SETTING: Some 600 general practices in the United Kingdom. SUBJECTS: 366,064 people who received erythromycin. MAIN OUTCOME MEASURE: Clinically documented cholestatic hepatitis of uncertain origin diagnosed 1-45 days after a prescription for erythromycin. RESULTS: There were 13 cases of cholestatic hepatitis of uncertain origin diagnosed within 45 days of receiving erythromycin which were either characteristic of or consistent with a syndrome previously described as being associated with this drug. CONCLUSION: The risk of cholestatic jaundice associated with erythromycin is estimated to be in the range of 3.6 per 100,000 users (95% confidence interval, 1.9-6.1).
Antidepressant drugs and suicide.
The current study provides estimated rates of suicide among users of antidepressant drugs. The data were derived from two population-based data resources: United Kingdom general practitioners using computers provided by Value Added Medical Products, Ltd., and Group Health Cooperative of Puget Sound. The results apply specifically to these populations. The overall rates of suicide in ever users of the study drugs usually used to treat depression were 6.5 x 10(-4) person-years in persons present in the U.K. resource and 5.1 x 10(-4) person-years in members of The Puget Sound group. Rates of suicide among users of particular antidepressant drugs varied somewhat, but the rates were consistent with biologic variability, with the possible exception of rates for mianserin (based on 4 exposed cases), which were higher than rates for other antidepressants. Consistent findings were (1) suicide rates are substantially higher in men than in women, and (2) the use of firearms as a mode of suicide is common in the northwest United States and uncommon in the United Kingdom.
Liver disease associated with diclofenac, naproxen, and piroxicam.
Based on information derived from computers used by general practitioners in the United Kingdom, we identified all patients with any recorded diagnosis of a liver disorder within 90 days of a prior prescription for diclofenac, naproxen, or piroxicam, three nonsteroidal antiinflammatory drugs (NSAIDs). The follow-up cohort consisted of 102,644 persons who used one or more of these drugs. A case history was requested from the physician to provide a description of the liver disorder and its relation to NSAID exposure. One case of clinically important liver disease was likely to have been caused by a study drug and another appeared to be caused by use of numerous NSAIDs. In 10 additional patients a causal connection between a study NSAID and the liver disorder seemed unlikely but could not be fully ruled out. We conclude that serious liver disease caused by diclofenac, naproxen, or piroxicam appears to be uncommon.
Large computer databases.
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Validation of information recorded on general practitioner based computerised data resource in the United Kingdom.
OBJECTIVE: To determine the extent of agreement between clinical information recorded on surgery computers of selected general practitioners and similar information in manual records of letters received from hospital consultants and kept in the general practitioners' files. DESIGN: Hospital consultants' letters in the manual records of selected general practitioners were photocopied and the consultants' clinical diagnoses were compared with diagnoses recorded on computer. SETTING: General practices in the United Kingdom using computers provided by VAMP Health for recording clinical information. SUBJECTS: 2491 patients who received one of three non-steroidal anti-inflammatory drugs and who attended 58 practices whose computer recorded data were considered after a preliminary review to be of satisfactory quality. RESULTS: Among 1191 patients for whom consultants' letters were forwarded a clinical diagnosis reflecting the diagnosis noted on a consultant letter was present on the computer record for 1038 (87%). CONCLUSION: Clinical information available on the computer records of the general practitioners who participated in this study is satisfactory for many clinical studies.
Renal parenchymal disease related to over-the-counter analgesic use.
The occurrence of parenchymal renal disease has been attributed in many case reports to heavy use of over-the-counter (OTC) analgesics. To quantify this putative relationship, we carried out a comprehensive case history review of newly diagnosed parenchymal renal disease requiring hospitalization among patients who ever used acetaminophen, aspirin, or ibuprofen, at Group Health Cooperative of Puget Sound. During the 6-year period 1984-1989, 17 cases of newly diagnosed, unexplained renal disease were identified among the 378,769 users of OTC analgesics, among whom 26,931 filled at least 20 prescriptions for the analgesics studied. Six of the 17 were possibly attributable to outpatient drug use. Of these, OTC analgesics were suspected clinically as a possible causal factor in two, but in both patients other causes seemed equally likely. We did not find any patients with anatomic or pathologic findings associated with analgesic nephropathy. We conclude that parenchymal renal disease attributable to OTC analgesic use and requiring hospitalization is a rare occurrence.
Ovulation induction and neural tube defects.
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A comparison of the risk of hypoglycemia between users of human and animal insulins. 1. Experience in the United Kingdom.
In a case-control study of 121 young insulin-dependent diabetics diagnosed as having an episode of hypoglycemia, the relative risk estimate comparing human with animal insulins was 0.8 (95% confidence interval 0.4, 1.6) controlling for age, general practice, and calendar time. We conclude that in this study population derived from general practices in the United Kingdom, the risk of hypoglycemia was no higher in users of human insulin than it was in users of animal insulins.
Hospitalizations because of hypoglycemia in users of animal and human insulins. 2. Experience in the United States.
In a 10-year (1979-1988) follow-up study of young insulin-dependent diabetics carried out at Group Health Cooperative of Puget Sound, the frequency of hospitalization for hypoglycemia remained constant. During the early years only animal insulins were available; during the latter years, human insulins were used in a majority of patients. The adjusted relative risk estimate for hospitalizations for hypoglycemia comparing users of human with users of animal insulins was 0.6 (95% confidence interval 0.2, 2.3). We conclude that the use of human insulins is not associated with an increased risk of hospitalization for hypoglycemia as compared with animal insulins in this population.
Hospital admission for xanthine toxicity.
A follow-up study of 35,909 outpatients who filled more than 220,000 prescriptions for theophylline over 9 years revealed 30 hospitalizations for xanthine toxicity. The overall estimated incidence rate of 7.8/10,000 person-years at risk indicates that in this population, hospitalization for xanthine toxicity is a relatively rare event.
A large population-based follow-up study of trimethoprim-sulfamethoxazole, trimethoprim, and cephalexin for uncommon serious drug toxicity.
We conducted a population-based 45-day follow-up study of 232,390 people who were prescribed trimethoprim-sulfamethoxazole (TMP-SMZ), 266,951 prescribed trimethoprim alone, and 196,397 prescribed cephalexin, to estimate the risk of serious liver, blood, skin, and renal disorders resulting in referral or hospitalization associated with these drugs. The results were based on information recorded on office computers by selected general practitioners in the United Kingdom, together with a review of clinical records. The risk of clinically important idiopathic liver disease was similar for persons prescribed TMP-SMZ (5.2/100,000) and those prescribed trimethoprim alone (3.8/100,000). The risk for those prescribed cephalexin was somewhat lower (2.0/100,000). Only five patients experienced blood disorders, one of whom was exposed to TMP-SMZ; of seven with erythema multiforme and Stevens-Johnson syndrome, four were exposed to TMP-SMZ. The one case of toxic epidermal necrolysis occurred in a patient who took cephalexin. Finally, only five cases of acute parenchymal renal disease occurred, none likely to be caused by a study drug. We conclude that the risk of the serious diseases studied is small for the three agents, and compares reasonably with the risk for many other antibiotics.
Nonsteroidal antiinflammatory drugs and certain rare, serious adverse events: a cohort study.
We performed a population-based study of over 100,000 users of diclofenac, naproxen, or piroxicam to identify cases of important blood, skin, central nervous system, kidney, pancreas, or pulmonary disorders caused by these drugs. In three cases a causal relation seemed likely; one of hemolytic anemia attributed to diclofenac, one of neutropenia attributed to naproxen, and one of pancreatitis attributed to piroxicam. In 13 additional cases a causal connection seemed unlikely but could not be fully ruled out. We conclude that such illnesses are uncommonly caused by the three agents studied.
Liver disorders in patients receiving chlorpromazine or isoniazid.
Based on information derived from computers and clinical records obtained from general practitioners in the United Kingdom, we estimated the frequency of liver toxicity associated with two known hepatotoxins, chlorpromazine and isoniazid. Among the cohort of 10,502 users of chlorpromazine, 14 had illnesses compatible with drug-induced liver disease, a frequency of 1.3/1000 users (95% Cl 0.8, 2.2). Four presumed cases of the disorder occurred among 921 users of isoniazid, for a frequency of 4/1000 users (95% Cl 1.7, 11.1). This study provides population-based quantification of the frequency of liver disorders associated with the use of these two agents.
The risk of myocardial infarction associated with antihypertensive drug treatment in persons with uncomplicated essential hypertension.
We conducted a case-control study based on computer-recorded information accrued in the United Kingdom General Practice Research Database to assess and compare the relation between different antihypertensive drug therapies and myocardial infarction in patients with no known clinical or laboratory risk factors for myocardial infarction other than hypertension. Cases were treated hypertensive patients with no other known risk factors who developed a first acute myocardial infarction between January 1, 1993, and October 31, 1994. They were ascertained from a review of the clinical record together with a questionnaire filled out by the attending general practitioner. Controls were matched to each case for age, sex, general practice, and index date. Antihypertensive therapy was derived from the computerized patient record. The study consisted of 210 cases and 793 controls. Compared with users of beta-blockers alone, the adjusted relative risk (RR) estimates for all other treatment regimens were close to 1.0. A comparison of users of calcium channel blockers alone with users of beta-blockers alone yielded a RR estimate of 0.9 (95% CI 0.5, 1.7). We conclude that the risk of acute myocardial infarction in otherwise healthy, treated hypertensive patients is not materially associated with the particular drug they receive.