Nonsteroidal anti-inflammatory drugs and neutropenia.

BACKGROUND: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and neutropenia is based primarily on case reports only. METHODS: A population-based, case-control study was performed with Medicaid claims data from six states. Cases were defined as patients hospitalized with neutropenia. Four controls per case were randomly chosen, matched for age, sex, state, and year. The frequency of exposure to NSAIDs in the 30 days before hospital admission in the cases was compared with the frequency in the identical period in the controls. The diagnosis of neutropenia was validated by review of medical records. RESULTS: The crude odds ratio for NSAIDs as a class was 3.3 (90% confidence interval, 1.6 to 6.6). The multivariate adjusted odds ratio was 4.2 (90% confidence interval, 2.0 to 8.7). No single class of NSAID, nor any individual NSAID, was associated with a unique risk, although the data on individual NSAIDs were sparse. Even excluding phenylbutazone and indomethacin, an increased risk was observed (3.5 [1.6 to 7.6]). CONCLUSIONS: Neutropenia is associated with the use of NSAIDs. However, given the low incidence of this disease, the additional number of cases of neutropenia caused by the use of NSAIDs is small. These data do not support the existence of a risk restricted to selected NSAIDs only.

A method of pharmacoepidemiologic analysis that uses computerized Medicaid.

A method of pharmacoepidemiologic data analysis that utilizes computerized Medicaid data is presented. A cohort design in which Medicaid enrollees receiving drugs that are normally used to treat similar underlying conditions is described. A period of time in which Medicaid service transactions are evident is required before an individual is eligible for selection into a cohort. Selection of study subjects and descriptions of cohorts are based on Medicaid service histories occurring during the preliminary, prerequisite period. Time at risk is considered to begin after a prescription for a study drug is dispensed and continues until either a refill is dispensed, a prescription for an alternative drug within the same therapeutic class is dispensed, or a predetermined number of days has passed. Subjects are followed forward in time and relevant health care transactions that are suggestive of suspected adverse drug reactions are noted. Incidence densities associated with sequentially ranked prescriptions within sequential courses of therapy are compared. Methods to increase the accuracy of case ascertainment are briefly discussed. Separate validation studies may be used to evaluate the validity of computerized case ascertainment methods and to compensate for misclassification of outcome. The proposed method is intended to provide timely estimates of risk for selected outcomes. For outcomes that cannot be accurately ascertained from computerized data, this method may be useful in determining the feasibility of more customized studies.

Relation of various epidemiologic factors to cervical cancer as determined by a screening program.

PIP: This study attempted to elucidate the etiology of cervical cancer by examining its association with a number of factors in a relatively unselected group of women. In 1963, a cytologic screening program was undertaken in Washington County, Maryland. The irrigation smear method was used. The final study group of 4341 was 46% of all white women aged 30-45 years enumerated in the census. Of the 4290 satisfactory smears, 46 were positive or suspicious. Subsequent investigation confirmed 31 cases of which 28 were at Stage 0 and 3 were invasive carcinoma of the cervix. Of 15 with suspicious cytologic findings 6 had confirmed findings, all of which were at Stage 0. Women who were never married had no confirmed cases. Currently-married women had lower rates than women whose marriages had been disrupted. Those who were married at age 16 or earlier had higher rates of cervical cancer as did those from lower socioeconomic levels. Having had multiple sex partners was associated with an increased risk of developing cervical cancer. Smokers had slightly higher rates than nonsmokers. Trichomonas vaginali s infestation was associated with higher rates. Findings indicate that trichomoniasis and cervical cancer are both associated with sexual activity.^ieng

Cervical cancer control: a study of morbidity and mortality trends over a twenty-one-year period.

Data from a 21-year period are presented to evaluate the effects of a mass cytologic screening program on uterine cancer morbidity and mortality in Louisville, Jefferson County, Kentucky. The success of screening was greatest in the younger age groups. There was a fall-off after age 45 years, especially in those age 60 years or older. Women at highest risk for cervical cancer, in the low socioeconomic quartile, had a better initial screening rate than the two middle-income quartiles, and had the highest rate of all women for subsequent rescreening. The greatest decrease in both morbidity and mortality was in women under the age of 50 years. Women age 30-39 and 50-59 years benefitted the most, as measured by mortality, with a decrease of 70.8 and 69.0%, respectively. There was no change in mortality rates for those age 70 years or older. Although the average annual age-adjusted rate increased from 13.2 to 15.3/100,000 women over the 21-year period.

Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease.

Despite the well-recognized association between oral contraceptives and deep venous thromboembolism, little is known about the risks associated with currently marketed formulations containing less than 50 micrograms of estrogen. To assess the venous thrombogenicity of low-estrogen oral contraceptives (those containing less than 50 micrograms of estrogen) relative to intermediate-dose (50 micrograms of estrogen) and high-dose (greater than 50 micrograms of estrogen) formulations, we conducted a cohort study of oral contraceptive users between the ages of 15 and 44 years in the Michigan Medicaid population. The period of the study was from 1980 through the third quarter of 1986. A total of 2,739,400 oral contraceptive prescriptions received by 234,218 women were analyzed. Using the low-estrogen cohort as the referent group, the age and calendar period adjusted relative risk of venous thromboembolism in users of intermediate-dose formulations was 1.5 (95% confidence interval (CI) 1.0-2.1, p = 0.04), and the relative risk in users of high-dose formulations was 1.7 (95% CI 0.9-3.0, p = 0.06). These data provide evidence that the dose-response relation between oral contraceptive estrogen and venous thromboembolism extends from 50 to 30 micrograms of estrogen, the dose range of currently marketed formulations.

Acute liver disease associated with erythromycins, sulfonamides, and tetracyclines.

OBJECTIVE: To determine whether erythromycins, sulfonamides, and tetracyclines are associated with an increased risk for acute hepatitis. DESIGN: Case-control study. SETTING: Medicaid billing data from Michigan and Florida between 1980 and 1987. PATIENTS: The 107 cases included patients hospitalized with acute symptomatic hepatitis without an identifiable cause of liver disease noted in the medical record. Four controls per case were randomly selected and were matched for age, sex, and state. RESULTS: Five cases (4.7%) and four controls (0.9%) were exposed to erythromycins, yielding an odds ratio of 5.2 (95% Cl, 1.1 to 26.6). No case or control was exposed to erythromycin estolate. Eight cases (7.5%) and three controls (0.7%) were exposed to oral sulfonamides, yielding an odds ratio of 11.4 (Cl, 2.7 to 67.8). All (except one control) had received trimethoprimsulfamethoxazole. Five cases (4.7%) and four controls (0.9%) were exposed to tetracyclines, yielding an odds ratio of 5.2 (Cl, 1.4 to 19.7). The results did not change substantively for erythromycin or sulfonamides after adjustment using multiple logistic regression for age, sex, state, and use of other hepatotoxic drugs. With tetracyclines, however, the odds ratio decreased to 3.6 (Cl, 0.9 to 14.3). Associations were also seen with isoniazid (P = 0.008) and rifampicin (P = 0.04). The number of patients developing acute symptomatic liver disease resulting in hospitalization for each million patients treated with a 10-day course of erythromycin was 2.28 cases; for sulfonamides, this figure was 4.8 cases; and for tetracycline, the figure was 1.56 cases. CONCLUSION: Erythromycin, sulfonamides, and tetracyclines are associated with acute symptomatic hepatitis resulting in hospitalization. Given the widespread use of these drugs, they will be among the more common drugs associated with hepatitis.