Risk stratification of ambulatory patients suspected of Pneumocystis pneumonia.

To determine whether aspects of clinical history, physical examination, and laboratory studies improve the diagnostic accuracy of the chest roentgenogram in the diagnosis of Pneumocystis carinii pneumonia (PCP), we followed up 302 consecutive patients with respiratory symptoms and risk factors for human immunodeficiency virus. Of the 279 patients (92%) with follow-up information available, 31 (11%) were diagnosed with PCP. Only 68% of patients with PCP had typical chest roentgenograms. Regression analysis identified four independent predictors of PCP: diffuse or perihilar infiltrates, presence of mouth lesions, lactate dehydrogenase level more than 220 U/L, and erythrocyte sedimentation rate 50 mm/h or more. Using these four predictors, patients could be stratified into low-, intermediate-, and high-risk groups for PCP. We suggest that examination of the mouth, chest roentgenogram, lactate dehydrogenase level, and erythrocyte sedimentation rate be part of the evaluation of ambulatory patients with respiratory symptoms at risk for human immunodeficiency virus.

Effect of oral alanine loads on the serum triglycerides of oral contraceptive users and normal subjects.

The effect of orally administered L-alanine loads on serum triglycerides, and plasma insulin and glucose, was studied in 23 women using an estrogen-containing oral contraceptive and 13 healthy female controls. Oral contraceptive users had significantly higher fasting serum triglycerides than the controls. Serum triglycerides concentrations udnerwent little changes in the controls after alanine ingestion, whereas the oral contraceptive users showed increases which were maintained throughout the 3-hr sampling period. The two groups had similar elevations in plasma insulin after alanine loading; the glucose concentrations were unchanged. The changes in serum triglycerides may have resulted from increased metabolism of alanine to pyruvate, and its incorporation into lipids under the stimulus of elevated insulin levels.

PIP: 23 women using various combined oral contraceptive (OC) preparations were studied for the effect of oral L-alanine loads on serum triglycerides and plasma insulin and glucose levels. Fasting serum triglyceride levels were significantly (p less than .001) higher in women taking OCs than in the 13 control subjects. OC users also had significantly (p less than .001) higher serum triglyceride levels at all test times following alanine loading than controls. There were no marked differences between the preparations used. Increases in plasma insulin after alanine loading were similar for users and nonusers, while glucose concentrations were unchanged. It is suggested that the alteration in serum triglycerides may have been due to an increase metabolism of alanine to pyruvate, and its incorporation into lipids under insulin stimulus.

The effects of propranolol on cognitive function and quality of life: a randomized trial among patients with diastolic hypertension.

PURPOSE: We sought to determine whether propranolol has adverse effects on cognitive function, depressive symptoms, and sexual function in patients treated for diastolic hypertension. SUBJECTS AND METHODS: We performed a placebo-controlled trial among 312 men and women, 22 to 59 years of age, who had untreated diastolic hypertension (90 to 104 mm Hg). Patients were randomly assigned to treatment with propranolol (80 to 400 mg/day) or matching placebo tablets. Thirteen tests of cognitive function were assessed at baseline, 3 months, and 12 months. Five tests measured reaction time to, or accuracy in, interpreting visual stimuli; one test measured the ability to acquire, reproduce, and change a set of arbitrary stimulus-response sets; and seven tests measured memory or learning verbal information. Depressive symptoms and sexual function were assessed by questionnaires at baseline and 12 months. RESULTS: There were no significant differences by treatment assignment for 11 of the 13 tests of cognitive function at either 3 or 12 months of follow-up. Compared with placebo, participants treated with propranolol had slightly fewer correct responses at 3 months (33 +/- 3 [mean +/- SD] versus 34 +/- 2, P = 0.02) and slightly more errors of commission at 3 months (4 +/-5 versus 3 +/- 3, P = 0.04) and at 12 months (4 +/- 4 versus 3 +/- 3, P = 0.05). At 12 months, depressive symptoms and sexual function and desire did not differ by treatment assignment. CONCLUSIONS: Treatment of hypertension with propranolol had limited adverse effects on tests of cognitive function that were of questionable clinical relevance, and there were no documented adverse effects on depressive symptoms or sexual function. Selection of beta-blockers for treatment of hypertension should be based on other factors.

Hypertension in women and the elderly. Some puzzling and some expected findings of treatment studies.

Almost 65% of the US population over age 60 has hypertension (systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg), which is strongly related to increased rates of coronary artery disease (CAD), stroke, and death. The need for treatment seems obvious. However, in young and middle-aged women, treatment is not straightforward, and trials have not specifically targeted this group. Data extrapolated from existing studies suggest that treatment of hypertension does not confer the same protection against CAD and stroke in women as it does in men. In fact, a trend toward harm in young and middle-aged white women receiving stepped care for hypertension has been reported. Therefore, for now, treatment of women in this age-group should be conservative; drugs should be prescribed only after a focused trial of lifestyle modification has failed. Until recently, elderly subjects were also excluded from treatment studies, despite the fact that they are at high risk for morbidity and death from hypertension-related diseases. Recent studies have established that treatment of hypertension in the elderly is extremely effective, that elderly women should be treated as aggressively as elderly men, and that low-dose diuretic or beta-blocker therapy should be initiated if lifestyle modifications are not effective.

Management of hypercholesterolemia. A primary care perspective.

We now have sufficient evidence to recommend an aggressive program of the detection and treatment of hypercholesterolemia. All adult patients should be screened and evaluated, and treatment decisions should be based on their LDL-cholesterol levels and the presence or absence of other risk factors. Diet therapy should be initiated in motivated patients for three to six months progressing from a qualitative to a quantitative approach. Patients with persistent elevations in their LDL-cholesterol levels who accept drug therapy can be begun on a regimen of nicotinic acid, gemfibrizol or bile acid-binding resins, and, when necessary, lovastatin.

Predictors of screening for hypercholesterolemia in a general internal medicine practice.

We compared current practice with the National Cholesterol Education Program (NCEP) guidelines for the detection and evaluation of hypercholesterolemia and analyzed the association of various patient and provider factors with screening. Using a retrospective medical records review of 1,000 randomly selected patients between the ages of 18 and 70 in a university-based general internal medicine practice--faculty, residents (categorical and primary care), and nurse practitioners--we found that 80% of patients were screened for hypercholesterolemia. Patients older than 35 were more likely to be screened than younger patients (87% versus 77%; P = .001), and, among younger patients, nonwhites were less likely to be screened than whites (58% versus 77%; P = .0001). Lipoprotein analysis was done in 60% of the 235 patients in whom it was indicated; older patients were significantly more likely to have these measurements. Among patients taking medications for hypercholesterolemia, 92% had lipoprotein analyses done beforehand. No differences were detected in screening by provider characteristics. We conclude that providers in our practice are appropriately aggressive in screening high-risk patients for hypercholesterolemia. The finding that young whites are screened much more often than nonwhites was surprising. Finally, although there is a high rate of screening overall, many patients with elevated cholesterol levels are not appropriately classified as to their low-density-lipoprotein levels.

Operational evaluation of treatment for tuberculosis. Results of 8- and 12-month regimens in Peru.

To measure the effectiveness of treatment for pulmonary tuberculosis in Peru we evaluated the fate of 2,669 patients who had tuberculosis diagnosed in 1981. Two regimens were used: (1) isoniazid, rifampin, pyrazinamide, and streptomycin daily for 2 months, then either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily for 6 months; and (2) isoniazid, streptomycin, and thiacetazone daily for 2 months, then either isoniazid and streptomycin twice weekly or isoniazid and thiacetazone daily for 10 months. Patients were not assigned at random to the 2 treatment regimens; thus, the results cannot be directly compared. In the 8-month group, 70% had a favorable outcome, 14% abandoned, 9% failed, 3% died, and 3% relapsed. In the 12-month group, 53% had a favorable outcome, 34% abandoned, 6% failed, 4% died, and 2% relapsed. In patients who did not abandon treatment, the results of both regimens were nearly identical. Patients in both groups who had been treated previously had significantly lower rates of cure than those not treated previously.

Training generalist physicians: structural elements of the curriculum.

To train more generalist physicians, structural changes must be made along the continuum of medical education. Future generalists require in-depth exposure to primary care practice, with substantive experience in the longitudinal management of patient panels and the opportunity to work with successful generalist role models. Clinical training and course work must incorporate a wide range of skills and disciplines, including areas now under-emphasized, such as epidemiology, health services, and psychosocial medicine. Recommendations for structural changes to increase the generalist focus of medical education include: 1) the development within institutions of central authorities, involving departments of internal medicine, family medicine, and pediatrics, in joint efforts to foster all aspects of generalist training, including recruitment, curriculum development, community linkages, innovative approaches to training, and recognition and support for successful generalist teachers; 2) commitment of a minimum of 50% of clinical training to ambulatory care settings at both medical school and residency levels; 3) required longitudinal care experiences for all medical students and a 20% or greater time commitment to longitudinal care for internal medicine, pediatrics, and family medicine residents; and 4) increased numbers of generalist faculty and enhanced teaching skills among faculty in the outpatient environment, to guarantee increased exposure of medical students and residents to generalist role models.

Operational evaluation of treatment for tuberculosis. Results of a "standard" 12-month regimen in Peru.

To measure the operational effectiveness of treatment for tuberculosis in Peru was evaluated the outcome of a 12-month treatment regimen in 2,510 patients who had tuberculosis diagnosed in 1980. All patients had acid-fast bacilli detected by sputum microscopy and were to be treated with isoniazid, streptomycin, and thiacetazone daily for 2 months followed by either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily. Only 47% had a favorable outcome, 41% abandoned treatment, 6% failed treatment, 4% died, and 2% relapsed. Of 1,483 patients who completed treatment, 79% had a favorable outcome, whereas 21% had an unfavorable result (treatment failure, relapse, or death). These data indicate that failure to complete treatment is the major reason for the low rate of success but that, in addition, the effectiveness of the regimen in patients who complete treatment is not optimal.

Evaluation of two food frequency methods of measuring dietary calcium intake.

To assess the ability of food frequency methods to measure current dietary calcium intake in elderly women, the authors administered two types of food frequency instruments to 37 randomly selected women who attended two senior citizens centers in San Francisco, and they compared those responses to seven-day food records. A 34-item food frequency instrument (with portion sizes rated as small, medium, or large) correlated well (r = 0.76) with the estimated calcium intake from seven-day records. Limiting the instrument to the top 15, 10, or five foods that contribute to dietary calcium intake had little effect on this correlation (r = 076, 0.75, and 0.67, respectively). Rating all portions as "medium" reduced these correlations somewhat. An 18-item instrument, which asks respondents to rate portion sizes in ounces or cups, did not correlate as well with the seven-day records (r = 0.49). The authors conclude that brief food frequency instruments which rate portion sizes on a simple qualitative scale may be suitable for many clinical uses and adequate for some types of epidemiologic studies of calcium intake in elderly women.

Physician management of hypercholesterolemia. A randomized trial of continuing medical education.

To determine the effect of continuing medical education (CME) on compliance with the recommendations of the National Cholesterol Education Program Expert Panel on high serum cholesterol levels in adults, we randomly assigned primary physicians in 174 practices to 3 groups, 2 that underwent either standard or intensive CME and a control group. The standard CME group was offered a free 3-hour seminar on high serum cholesterol levels; the intensive CME group was offered in addition follow-up seminars and free office materials. After 18 months, we audited 13,099 medical records from the 140 practices that remained in the study. There were no significant differences (P > .15) in screening for high serum cholesterol or compliance with guidelines between the groups receiving continuing medical education (51% screening; 33% compliance) and the control group (57% screening; 37% compliance). In the prespecified subgroup of patients with hypercholesterolemia, there was a trend toward a modest benefit from the continuing medical education interventions: compliance was 21% in the control group, 23% in the standard CME group, and 27% in the intensive CME group (P = .07 overall). These results emphasize the need for better ways to change behavior in practicing physicians and the importance of studying the implementation of preventive health recommendations.

Should we be measuring blood cholesterol levels in young adults?

Should we measure blood cholesterol levels in all adults, or only in those at high risk of coronary heart disease (CHD)? Most men under the age of 35 years and women under the age of 45 years--roughly half the adult population--are at very low short-term risk of CHD. One consequence is that drug treatment to lower high blood cholesterol levels in the average young adult is an extremely expensive means of prolonging life; the estimated $1 million to $10 million per year of life is 100 to 1000 times the cost of other approaches. Individualized dietary treatment is somewhat cheaper but relatively ineffective. Another consequence of the low CHD risk in young adults is the greater likelihood that intervention may have harmful effects that outweight the benefits. Meta-analysis of primary prevention trials in middle-aged men reveal an increase in non-CHD deaths among those randomized to cholesterol interventions, an unexpected finding that is more substantial than the decrease in CHD deaths. This raises the possibility that one or more of the cholesterol interventions could have very serious adverse effects among young adults, whose risk of non-CHD death is normally 100 times their risk of CHD death. We conclude that the policy of screening and treating high blood cholesterol levels in young adults is neither cost-effective, nor does it satisfy ethical standards requiring strong evidence that preventive interventions do more good than harm. Fortunately, cholesterol screening in young adults is also not necessary: most CHD events associated with high blood cholesterol levels in this population will not occur for decades and can be prevented by treatment that is begun in middle age. Cholesterol screening and treatment in young adults should be limited to individuals with known coronary disease or other unusual factors that place them at high short-term risk of CHD death.

Comparison of a lifestyle modification program with propranolol use in the management of diastolic hypertension.

OBJECTIVE: To compare the management of mild diastolic hypertension (90 to 104 mm Hg) using a nonpharmacologic intervention with that using propranolol or placebo. DESIGN: Randomized, placebo-controlled trial with a 2 x 2 factorial design. SETTING: University-based ambulatory care center. PARTICIPANTS: Two hundred seven men and 105 women, 22 to 59 years of age, 73% white, who had mild diastolic hypertension untreated for at least eight weeks. INTERVENTIONS: 1) a multicomponent lifestyle modification intervention (lifestyle focus group, or LFG) administered in eight weekly meetings + placebo, 2) LFG + propranolol, 3) propranolol alone, and 4) placebo alone, followed for 12 months. MEASUREMENTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and self-reported adverse effects at each of nine follow-up visits; fasting total cholesterol, triglycerides, and glucose at baseline and 12 months; 24-hour urine sodium (Na+) and potassium (K+), three-day food records and physical activity questionnaire at three and 12 months; and a quality of life questionnaire at 12 months. MAIN RESULTS: The mean decreases in DBP at 12 months were: 8.5 mm Hg in the LFG + propranolol group; 7.7 mm Hg in the propranolol-only group; 5.9 mm Hg in the placebo-only group; and 5.4 mm Hg in the LFG + placebo group. Repeated-measures analysis of covariance showed that level of baseline DBP (p < 0.0001), time of follow-up (p < 0.0001), and propranolol use (p < 0.0001) were significantly associated with a decrease in DBP at 12 months. Despite reductions in urinary Na+ (-35 mEq; 95% CI = -50, -19), dietary Na+ (-521 mg; 95% CI = -710, -332), total calories ingested (-238; 95% CI = -335, -140), and weight (-1.4 lb; 95% CI = -3.7, +0.8), and significant increases in dietary K+ (+294 mg; 95% CI = +107, +480) and in mets-minutes of exercise (+43; 95% CI = +20, +67) at three months, assignment to the LFG intervention had no effect on DBP at three or 12 months. The subjects assigned to take propranolol more frequently reported fatigue during ordinary activities, sleep disturbance, decrease in sexual activity, and depressed feelings, when compared with the subjects taking placebo, but the numbers of study withdrawals did not differ by drug assignment. No significant difference in total cholesterol and glucose levels was observed by group assignment. Triglycerides increased significantly in the subjects assigned to propranolol (mean difference = +20 mg/dL; 95% CI of difference +1.5, +39). There was no difference in the responses to 21 quality of life items between the subjects assigned to propranolol and those assigned to placebo. CONCLUSIONS: This multicomponent lifestyle modification intervention was unable to promote persistent behavior changes and thus was inferior to propranolol therapy for the treatment for mild diastolic hypertension. Future research should focus on single modifiable factors to lower blood pressure.