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Traversa G, Walker AM, Menniti Ippolito F, Caffari B, Capurso L, Dezzi A, Koch M, Maggini M, Spila Alegiani S, Raschetti R. Gastroduodenal toxicity of different NSAIDs: a case-control study in the Province of Rome. Epidemiology 1995;6:49-54.
Andrade SE, Walker AM, Platt R, Hollenberg NK, Testa MA, Saperia GM, Gottlieb LK. Discontinuation of antihyperlipidemic drugs: Do rates reported in clinical trials predict rates in primary care settings? N Engl J Med 1995;332:1125-1131.
Avorn J, Bohn RL, Mogun H, Gurwitz GH, Monane M, Everitt D, Walker AM. Neuroleptic drug exposure and treatment of parkinsonism in the elderly. Am J Med 1995;99:48-54.
Oliveria SA, Felson DT, Reed JI, Cirillo PA, Walker AM. The incidence of symptomatic hand, hip and knee osteoarthritis in a health maintenance organization. Arthritis Rheum 1995;38:1134-1141.
Hayashi K, Walker AM. Japanese and American reports of randomized trials: Differences in the reporting of adverse effects. Contr Clin Trials 1995; (in press).
Donahue JG, Choo PW, Manson JE, Platt R. The incidence of herpes zoster. Arch Intern Med 1995;155:1605-1609.
Choo PW, Donahue JG, Manson JE, Platt R. The epidemiology of varicella and its complications. Journal of Infectious Diseases 1995;172:706-712.
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 = 3.4-28.1).
Recent and past use of NSAIDs does not increase the risk of ulcer. The
use of ketorolac appears to carry a greater gastrotoxicity than other NSAIDs.
(Epidemiology 1995;6:49-54)
Background: Discontinuation rates for drugs used to treat chronic conditions may affect the success of therapy. However, the discontinuation rates reported in clinical trials may not reflect those in primary care settings.
Methods: We conducted a cohort study using computerized research files and medical records on 2369 new users of antihyperlipidemic therapy at two health maintenance organizations (HMOs) from 1988 through 1990. The rates of drug discontinuation in these primary care settings were compared with the rates reported in clinical trials published from 1975 through 1993, located with the Medline data base.
Results: In the HMOs, the one-year probability of drug discontinuation was 41 percent for bile acid sequestrants (95 percent confidence interval, 38 to 44 percent), 46 percent for niacin (95 percent confidence interval, 42 to 51 percent), 15 percent for lovastatin (95 percent confidence interval, 11 to 19 percent), and 37 percent for gemfibrozil (95 percent confidence interval, 31 to 43 percent). For the bile acid sequestrants, niacin, and gemfibrozil, the risks of discontinuation were substantially higher in the HMOs than in randomized clinical trials, in which the summary estimates of this risk were 31 percent, 4 percent, and 15 percent, respectively, for trials of one year or longer. The rates of discontinuation in open-label studies were similar to those in the HMOs.
Conclusions: The discontinuation rates reported in randomized
clinical trials may not reflect the rates actually observed in primary
care settings. The effectiveness and tolerability of antihyperlipidemic
medications should be studied further in populations that typically use
the agents. (N Engl J Med 1995;332:1125-31.)
Purpose: Despite the widespread use of neuroleptic medications for the elderly, little is known about the frequency of treatment for drug-induced parkinsonian syndromes in this age group, particularly with L-dopa-type drugs, which are more appropriate for the treatment of true idiopathic Parkinson's disease.
Patients and Methods: We identified 3,512 patients aged 65 to 99 enrolled in a large state Medicaid program who were newly prescribed a drug to treat parkinsonian symptoms. Controls were comparable program enrollees of similar age who had not been prescribed an antiparkinsonian drug. In a case-control study, we evaluated the use of neuroleptic drugs in the 90 days before initiation of antiparkinsonian therapy.
Results: Patients taking neuroleptics were 5.4 times more likely to begin antiparkinsonian medication than were nonusers (95% confidence interval [CI] 4.8 to 6.1). They also had a greater than two-fold increase in risk of beginning therapy with a dopaminergic drug specific for idiopathic Parkinson's disease, not generally indicated for treatment of drug-induced parkinsonism (adjusted odds ratio 2.2, 95% CI 1.9 to 2.7). Clear dose-response relationships were demonstrated, as were differences among neuroleptics. Among all patients started on dopaminergic drugs in this population, 37% of such therapy was attributable to prior neuroleptic use. Continuation of the neuroleptic persisted in 71% of patients so treated.
Conclusion: Neuroleptic use is a common cause of extrapyramidal
dysfunction in the elderly, and the side effect is frequently treated by
adding an anticholinergic or dopaminergic drug to the regimen. The use
of anticholinergic drugs presents risks of additional drug side effects;
the use of dopaminergic drugs, generally not appropriate for drug-induced
parkinsonian syndrome, suggests that extrapyramidal neuroleptic side effects
may often be mistaken for idiopathic Parkinson's disease in older patients.
(Am J Med 1995;99:48-54)
Objective: To quantify the incidence of symptomatic hand, hip, and knee osteoarthritis (OA) among members of the Fallon Community Health Plan, a health maintenance organization located in central Massachusetts.
Methods: Incident OA was defined as the first evidence of OA by radiography (grade of greater or equal to 2 on the Kellgren-Lawrence scale of 0-4) plus joint symptoms at the time the radiograph was obtained or up to 1 year before the radiograph was obtained.
Results: The age- and sex-standardized incidence rate for hand OA was 100/100,000 person-years (95% confidence interval [95% CI] 86, 115), for hip OA 88/100,000 person-years (95% CI 75, 101), and for knee OA 240/100,000 person-years (95% CI 218, 262). The incidence of hand, hip, and knee OA increased with age, and women had higher rates than men, especially after age 50. A leveling off or decline occurred for both groups around the age of 80.
Conclusion: In a large study of symptomatic OA we observed incidence
rates that increased with age. In women ages 70-89, the incidence of knee
OA approached 1% per year. (Arthritis Rheum 1995;38:1134-1141)
Background: We sought to identify differences in the description of adverse drug experiences in reports of randomized clinical trials (RCTs) from the United States and Japan, using diclofenac and simvastatin as test drugs.
Methods: Reports were identified in MEDLINE (Index Medicus 1966-1990), EMBASE (Excerpta Medica, 1974-1990), JAPICDOC (1979-1990), and JOIS-III (JMEDICINE, 1980-1990). In each search keywords describing study design were paired with the drugs' generic names, chemical names, and development numbers. Twenty-seven U.S. reports (18 for diclofenac and 9 for simvastatin) and 22 Japanese reports (17 for diclofenac and five for simvastatin) identified in these four databases were selected for review. For each paper we identified the relation of the article to the data (preliminary, primary, and secondary reports, reviews), the means of identifying adverse reactions, the principal outcomes of the trials, and a variety of descriptive measures relating to study design, authorship, and elements of presentation.
Results: With few exceptions, Japanese reports were not indexed in English-language databases, and studies from the United States were not carried in the Japanese databases. The Japanese literature consisted exclusively of primary reports of clinical trials, whereas the United States literature was dominated by review articles and secondary reports of data from trials not fully published elsewhere. Japanese reports contained more detail on adverse experiences but reported principally those attributed to the drugs by attending clinicians. U.S. reports by contrast offered little detail, but tended to include all adverse experiences, whether or not clinically attributed to drugs. A preponderance of U.S. articles reported significant differences between drugs in safety or treatment efficacy, whereas only one third of the Japanese articles did so for the same agents. Reports from both countries offered few details of the methods used to gather information on adverse drug experiences, and as a result the reported absolute frequencies of such events are difficult to compare between trials or to generalize to other settings.
Conclusions: The reporting of adverse reactions in clinical trials
is inadequate in both the United States and Japanese literature. The shortcomings
are complementary, in that reports of U.S. trials contain insufficient
detail and Japanese reports do not interpret or synthesize experience.
Clinical research into drug safety in both countries could be improved
through the adoption of simple standards of clarity and consistency in
the monitoring and reporting of drug adverse effects. (Contr Clin Trials
1995; in press)
Background: There are few population-based studies of the natural history and epidemiology of herpes zoster. Although a relatively common cause of morbidity, especially among the elderly, contemporary estimates of herpes zoster incidence are lacking. Herein we describe a population-based investigation of incident and recurrent herpes zoster from 1990 through 1992 in a health maintenance organization.
Methods: The health maintenance organization's automated medical records contain clinical and administrative information about care rendered to patients in ambulatory settings, emergency departments, and hospitals. Cases of herpes zoster were ascertained by screening the medical record for coded diagnoses. The predictive value of a herpes zoster diagnosis code was determined by review of a sample of patient records. Records from all patients with potential recurrences were also reviewed.
Results: The overall incidence, based on 1075 cases in 500,408 person-years, was 215 per 100,000 person-years (95% confidence interval, 192 to 240 per 100,000) and did not vary by gender. Although the rate increased sharply with age, approximately 5% of the cases occurred among children younger than 15 years. Infection with human immunodeficiency virus was documented in 5% of the persons with incident herpes zoster and cancer in 6%. Four persons had confirmed recurrences of herpes zoster (744 per 100,000 person-years; 95% confidence interval, 203 to 1907); three of these persons were infected with the human immunodeficiency virus.
Conclusions: The recorded incidence of herpes zoster was 64%
higher than that reported 30 years ago; the age-standardized rate was more
than twofold higher. Immunosuppressive conditions had little impact on
overall incidence, although they were strongly associated with early recurrences.
(Arch Intern Med 1995;155:1605-1609)
The automated records of over 250,000 members of a health maintenance organization were analyzed to assess the epidemiology of varicella and its complications between 1 July 1990 and 30 June 1992. All complications were verified by review of full-text medical records. The incidence rates of varicella in persons <15 years of age were 20%-50% lower than published figures, probably reflecting underreporting. The rates in those greater than or equal to 15 years old, however, were greater than those reported for 1972-1978 (607 vs. 291/100,000 years, 15-19 years old; 175 vs. 33/100,000 years, greater than or equal to 20 years old). The rates of hospitalization for uncomplicated varicella, skin superinfections, and pneumonia in children were, respectively, 15, 11, and 4 times higher than previous estimates. Hospitalization rates for adults with pneumonia and uncomplicated varicella were >5 times higher than prior figures. Thus, varicella in adults and varicella complications in general may be more frequent than previously estimated. (Journal of Infectious Diseases 1995;172:706-712)