A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide.

BACKGROUND: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide. METHODS: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial. RESULTS: The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo. CONCLUSIONS: The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.

Comparing the medical school curricula followed by students in an independent study program and a traditional one.

This 1988 retrospective study examined the medical school curricula followed by students from two classes using two curricular styles at one medical school. By consulting school records, the authors ascertained the courses actually taken, the number of weeks that students actually devoted to them, and the sequence of courses, both for those students following an independent-study curriculum and for those following a traditional one. These data were compared with the corresponding data concerning the traditional curriculum requirements to determine whether the curricula the students actually followed, in either style, showed any marked difference from the required curriculum. The findings showed that the curricula followed by the independent-study students deviated considerably from both the requirements of the traditional curriculum and also the actual curricula followed by the students using the traditional curriculum, who almost never chose to deviate from the requirements. The independent-study students showed considerable intragroup variation in the ways they organized their curricula, most commonly in eliminating selected formal clerkship or specialty medicine courses, or altering the duration of clerkships. Elective coursework was substituted for formal clerkship experiences in the majority of cases where clerkship courses were eliminated.

A biopsychosocial treatment approach to the management of diabetes mellitus.

The relationship among recent life stress, social support, a patient's locus of control, and the control of blood glucose is evaluated in persons with diabetes mellitus, using objective measures of these psychosocial variables. Short-term [fasting blood sugar (FBS)] and long-term [glycosylated hemoglobin (Hgb A-1C)] control measures are taken at two points in time in order to evaluate the effects of the psychosocial variables on change in diabetes control. For life events, a significant positive association was found between the number of recent life events and blood glucose control. Decrease in social support predicted a worsening of longer-term (Hgb A-1C) control over time. An external locus of control within the patient was associated both with poor short-term control at time one and prediction of poorer long-term control over time. The implications of these findings are discussed in support of a biopsychosocial approach to the management of diabetes mellitus.

A method to determine attitudes of faculty members toward use of laboratory tests.

Investigators have suggested that attitudes of faculty members toward diagnostic testing may encourage inappropriate laboratory use. In the present paper, the authors present a method for determining faculty attitudes on laboratory tests and the results of an analysis of such attitudes at one institution. The attitudes were determined from case simulations prepared by the faculty for senior medical student examinations. At the time the examination was being constructed, the faculty members weighted each laboratory test option following the case presentation for its appropriateness as positive, zero, or negative. The investigators subsequently categorized all of the laboratory tests according to their purpose and appropriateness with respect to the likelihood of diagnostic possibilities generated by the case. The results of the analysis showed that screening tests and tests to investigate unlikely diagnoses usually received weights close to zero and rarely received negative weights. This apparent indifference to tests with limited usefulness that generate some costs may be perceived by students as permission for their continued use.

Medical student training in the performance of diagnostic laboratory procedures.

A study was conducted to determine what diagnostic laboratory procedures medical students recalled being taught during pre-clerkship training, how well they felt they could perform these procedures on entrance to and exit from their clerkship year, and the estimate of frequency of personal performance during the clerkship year. Surveys were mailed to 223 graduating senior students of a medical school. They were asked to supply data regarding 15 pre-selected procedures. In only seven cases did a majority of students recall being taught a procedure. Higher percentages of students who trained at health science centres and a Veterans Administration hospital recalled being taught procedures compared to students who trained at community hospitals. In general, students who performed their pre-clerkship training at the health science centres rated their ability to perform procedures without assistance on entrance to the clerkship year higher than the other two groups. Students who performed at least one half of their clerkships at a health science centre rated their ability to perform procedures without assistance at the termination of their clerkship year higher than those who performed a majority of clerkships at community hospitals. The former group also reported a higher frequency of performance of the procedures than the community hospital group. Most of the procedures for all groups, however, were performed at a rate of less than one/month.