An observational study of isotretinoin recipients treated for acne in a health maintenance organization.

From September 1982 to June 1987, all members (N = 513) of the Group Health Cooperative of Puget Sound, Seattle, Wash, who were prescribed isotretinoin for acne were observed throughout the first 4- to 5-month course of therapy for effectiveness and adverse effects. The highest rates of use were among male subjects aged 15 to 24 years. Excluding 47 subjects whose prescriptions were stopped because of noncompliance or who left the care of Group Health Cooperative physicians, 39 (8.4%) of the remaining 466 discontinued taking the drug because of the following adverse effects: mucous/skin/musculoskeletal effects (17); elevated triglyceride levels (eight); headaches (five); increased liver enzyme levels (three); amenorrhea (two); and other (four). One subject, excluded from the 466 because of noncompliance, became pregnant while using medication from a previous prescription and had a therapeutic abortion; she was not under the care of a physician at the time of pregnancy. Most subjects (97%) developed a mucocutaneous symptom, and 42% developed musculoskeletal symptoms. Moderate elevations in liver enzyme levels developed in six (1.8%) of 341 subjects with normal baseline values. Of 389 subjects with normal baseline triglyceride values (less than 2.25 mmol/L), nine (2.3%) developed moderate elevations (4.5 to 9.0 mmol/L), and one (0.3%) developed a severe elevation (greater than or equal to 9.0 mmol/L). Of 24 subjects with elevated baseline triglyceride levels, three (12.5%) developed moderate elevations. Of an additional 53 subjects whose baseline serum triglyceride levels were not determined, two developed elevations during therapy, one up to 13.4 mmol/L. Subjects who were overweight or had elevated baseline serum triglyceride values had an increased risk of developing elevations in triglyceride levels during therapy (odds ratio, 6.0; 95% confidence interval, 1.6 to 22.0; and odds ratio, 4.35; 95% confidence interval, 0.9 to 20.2, respectively). Acne was improved for at least 94.0% of subjects.

Drug monitoring of surgical patients.

Intensive drug monitoring of surgical patients was carried out on selected wards in five hospitals in the United States, Scotland, and New Zealand from 1977 through 1981. This report describes the methods and some findings from the monitoring of 5,232 such patients. Patients received, on the average, nine drugs on the ward, and adverse reactions were associated with 2.2% of these drug orders. Of the 1,150 drug-attributed adverse reactions, only 62 were considered "major" by the attending physician, and 35 (affecting 20 patients) were termed "life threatening." There were no drug-attributed deaths.

Sedating drugs and automobile accidents leading to hospitalization.

The use of central nervous system depressant drugs among 244 people hospitalized for injuries suffered in an automobile accident was similar for drivers presumed at fault for the accident compared with other drivers and passengers. It was only slightly higher in the three groups than it was in the population at large. The absence of an important association in this population might be related to the warnings given to people filling prescriptions for these drugs.

Oral contraceptives and breast cancer.

The incidence of breast cancer among users and non-users of oral contraceptives (OCs) was determined at Group Health Cooperative of Puget Sound, Seattle, Washington, a health care organization which maintains computer files of diagnoses and outpatient drug use. In women 45 years of age or younger, the incidence was nearly identical in users and non-users. In premenopausal women over 45 years of age, there was a positive association between current OC use and breast cancer, the risk ratio estimates and 90% confidence intervals being 4.0 (1.8-9.0) in women 46-50 years of age and 15.5 (5.2-46) in women 51-55 years of age.

PIP: A study on the possible effect of (OCs) oral contraceptives on breast cancer risk was conducted at the Group Health Cooperative of Puget Sound in Seattle, Washington. Exposure and menopausal data were available on women and controls. Among the women aged 31-5, 20% used OCs during the period ending June 30, 1976 as compared with 13% 2 years later. For those women aged 51-5, user prevalence declined from 2% to 0.3%. 76 of 132 women with breast cancer were premenopausal and 4 were under 30 years of age. Estimates of breast cancer rates in the group of current OC users and nonusers were not adjusted for potential confounding by other risk factors; these were later assessed into a multiple logistic function. Those factors were: age, ponderal index, age at menarche, age at 1st pregnancy, history of benign breast disease, education, and race. Current OC use was entered into the risk function in the form of age-use interaction terms. 1 aspect of the case-control comparison which did not correspond to the population-based findings was the apparent protective effect of current OC use in the group ages 31-40. Among those currently using OCs, there is a preponderance of long-term users; no such trend exists among past users. Data from this study indicate that there may be a relation between OC use and breast cancer which is age dependent. Within the age group 31-45 years, the incidence in current users (0.71/1000 women-years) was nearly identical to nonusers (0.65/1000 women-years) however, current OC use was associated with a strong increase in breast cancer risk in premenopausal women 46-55 years. Other factors for which the breast cancer risk ratio may increase with age include pregnancy, and endocrine risk factor. Relationships previously noted which are included in these data include associations between risk and nulliparity, educational level, and slimness (for women who are premenopausal).

Replacement estrogens and breast cancer.

The relation between replacement estrogens and breast cancer in menopausal women (age 45-64 years) was evaluated in the Group Health Cooperative of Puget Sound, Washington State, a prepaid health care organization with fully computerized information on outpatient drug use and hospital diagnoses. Little association between current estrogen use and breast cancer was noted in women with a previous hysterectomy (relative risk (RR) = 1.1; 90% confidence interval (Cl), 0.7-1.8). In women with a natural menopause there was a positive association between current estrogen use and breast cancer (RR = 3.4; 90% Cl, 2.1-5.6). This association was strong in naturally menopausal women aged 45-54 years (RR = 10.2) and weaker in the older age group (RR = 1.9).

Replacement estrogens and endometrial cancer.

We examined the incidence of endometrial cancer in a large prepaid group practice in the Seattle area. From July, 1975, to July, 1977, there was a sharp downward trend in the incidence of endometrial cancer that paralleled a substantial reduction in prescriptions for replacement estrogens. Incidence rates were estimated for estrogen users and nonusers among women 50 to 64 years of age with intact uteri; current long-term users had an annual risk for endometrial cancer between 1 and 3 per cent, whereas nonusers had a risk less than 1/10th as great. These incidence rates remained fairly constant over time among users and nonusers; the drop in overall incidence soon after estrogen use declined suggests that the increased risk associated with estrogens falls quickly after discontinuation. The reduction in incidence of endometrial cancer in this group practice was part of a general decline in the United States after 1975.