Relationship between breast cancer risk factors and mammographic breast density in the Fernald Community Cohort.

BACKGROUND: We investigated associations of known breast cancer risk factors with breast density, a well-established and very strong predictor of breast cancer risk. METHODS: This nested case-control study included breast cancer-free women, 265 with high and 860 with low breast density. Women were required to be 40-80 years old and should have a body mass index (BMI) <35 at the time of the index mammogram. Information on covariates was obtained from annual questionnaires. RESULTS: In the overall analysis, breast density was inversely associated with BMI at mammogram (P for trend<0.001), and parity (P for trend=0.02) and positively associated with alcohol consumption (ever vs never: odds ratio 2.0, 95% confidence interval 1.4-2.8). Alcohol consumption was positively associated with density, and the association was stronger in women with a family history of breast cancer (P<0.001) and in women with hormone replacement therapy (HRT) history (P<0.001). Parity was inversely associated with density in all subsets, except premenopausal women and women without a family history. The association of parity with density was stronger in women with HRT history (P<0.001). CONCLUSION: The associations of alcohol and parity with breast density appear to be in reverse direction, but stronger in women with a family history of breast cancer and women who ever used HRT.

Rewarding teaching faculty with a reimbursement plan.

OBJECTIVE: To develop a system for measuring the teaching effort of medical school faculty and to implement a payment system that is based on it. DESIGN: An interventional study with outcomes measured before and after the intervention. SETTING: A department of internal medicine with a university hospital and an affiliated Veterans Administration hospital. INTERVENTION: We assigned a value in teaching units to each teaching activity in proportion to the time expended by the faculty and the intensity of their effort. We then calculated total teaching units for each faculty member in the Division of General Internal Medicine and for combined faculty effort in each subspecialty division in the Department of Medicine. After determining the dollar value for a teaching unit, we distributed discretionary teaching dollars to each faculty member in the Division of General Internal Medicine and to each subspecialty division according to total teaching units. MEASUREMENTS AND MAIN RESULTS: The distribution of discretionary teaching dollars was determined. In the year after the intervention, there was a substantial redistribution of discretionary teaching dollars among divisions. Compared with an increase in total discretionary dollars of 11.4%, the change in allocation for individual divisions ranged from an increase of 78.2% to a decrease of -28.5%. Further changes in the second year after the intervention were modest. The distribution of teaching units among divisions was similar to the distribution of questions across subspecialties on the American College of Physicians In-Training Examination (r =.67) and the American Board of Internal Medicine Certifying Examination (r =.88). CONCLUSIONS: It is possible to measure the value of teaching effort by medical school faculty and to distribute discretionary teaching funds among divisions according to the value of teaching effort. When this intervention was used at our institution, there were substantial changes in the amounts received by some divisions. We believe that the new distribution more closely approximates the desired distribution because it reflects the desired emphasis on knowledge as measured by two of the most experienced professional groups in internal medicine. We also believe that our method is flexible and adaptable to the needs of most clinical teaching

Intercorrelations and sources of variability in three mutagenicity assays: a population-based study.

The purpose of this study was to evaluate the intercorrelation between three genetic assays in 112 subjects. The group was pooled from two originally separate but homogeneous subgroups of 56 persons each. Procedures included assays for hprt mutant frequencies, micronuclei in human lymphocytes, and mutations at the glycophorin A (gpa) loci. We found no statistically significant or biologically important intercorrelations among the three biomarkers. We did, however, observe significant correlations between log(e) hprt mutant frequency and cloning efficiency (inverse correlation for these 2 variables), age and log(e) hprt mutant frequency, an inverse relationship between cloning efficiency and age, and an important differential sex effect favoring a greater micronuclei frequency in females than males. No significant correlations between the covariates of interest and glycophorin A variant frequencies NN or NO were observed. Using multivariable linear regression, age was found to account for the majority of the variability in hprt mutant frequency (greater than sex and/or smoking); for micronuclei data, only sex contributed a statistically significant and biologically important proportion to the total variation. We conclude that despite observing no significant intercorrelations between the three assays performed simultaneously from the same individuals in a large population database, a significant correlation between age and hprt mutant frequency and an inverse association between cloning efficiency and hprt do exist; furthermore, we verified the strong differential sex-specific effect on micronucleus frequencies.

Do persons living near a uranium processing site have evidence of increased somatic cell gene mutations? A first study.

The objective of this study was to examine if individuals living near a uranium processing site have greater mutagenic damage, as measured by three mutagenicity assays, compared with subjects unexposed to any nuclear facilities. The design was a cross-sectional exploratory analysis of 112 subjects; 56 volunteer residents were from within a 5-mile radius of the Fernald Uranium Processing site and 56 'control' subjects were from a geographically separate area unexposed to any known uranium emissions. The groups were constrained to be similar in age and sex composition. The main outcome measures were three human somatic gene mutation assays consisting of the HPRT T-lymphocyte cloning assay to measure 6-thioguanine resistant lymphocytes; the glycophorin A assay to detect the loss of expression of the M or N allele; and the micronucleus assay as a marker of chromosomal damage. The results showed no statistically significant or quantitatively important differences between groups for all three mutagenicity assays; only the unselected cloning efficiency was statistically significantly different between groups (0.42 +/- 0.16 for the Fernald versus 0.35 +/- 0.12 for the comparison groups). In both groups, age was significantly related to HPRT mutant frequency, with a 1.25% rate of increase in mutant frequencies for each 1-year gain of age in the Fernald group and a 1.12% rate of increase in mutant frequencies for each 1-year gain of age in the comparison group. For the micronucleus data, females had a greater mean micronucleus frequency than males. In addition, smokers had an increased mean ln (natural logarithm) HPRT mutant frequency (3.06 +/- 0.14 for current smokers compared with a mean of 2.72 +/- 0.05 for non-current (i.e. never plus former) smokers). Our results are consistent with the previously reported association between sex type and micronucleus frequency, the known relationship between age and T-lymphocyte cloning efficiency and age and HPRT mutant frequency, and verify the wide inter-subject variability for the latter. Finally, we conclude that at a population level, the relationships between current cigarette use and HPRT mutant frequency, and sex type and micronucleus frequency, are stronger than is the association between geographic proximity to a uranium processing site and mutagenic abnormalities.

How an academic health center and a community health center found common ground.

Despite their divergent missions, academic health centers (AHCs) and community health centers (CHCs) are natural partners. This is becoming more obvious as national attention is focused on greatly increasing the number of primary care providers. AHCs are responding to this pressure and now need more sites to train primary care physicians, and CHCs need more primary care physicians (the AHCs' graduates) as staff. Thus these two types of institutions have a common interest. Other major themes of health care reform are also likely to drive AHCs and CHCs together, such as providing access to the uninsured, placing more emphasis on prevention and public health, and coordinating care in managed care systems to improve outcomes and control costs. Yet partnerships between these two kinds of institutions are still rare. This article describes a successful joint program begun in 1991 between the Lincoln Heights Health Center, which serves a poor, predominantly black community, and the University of Cincinnati Medical Center. All the program's activities are monitored by a policy committee made up of representatives from both institutions. For the first five years, the main hospital of the medical center is supporting the relationship with a $350,000 grant. Both parties retain their independent governance, yet collaborate closely and feel the relationship yields high value to each party and the community. For example, medical education in out-of-hospital settings has increased greatly, as have referrals to the AHC. The CHC has been able to recruit and retain high-quality physicians; its balance sheet has been favorably affected also.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of drinking water monochloramine on lipid and thyroid metabolism in healthy men.

The purpose of this study was to determine whether a 4-week consumption of 1.5L per day of drinking water containing monochloramine at a concentration of 2 ppm (ppm = mg/L) or 15 ppm under controlled conditions would alter parameters of lipid or thyroid metabolism in healthy men. Forty-eight men completed an 8-week protocol during which diet (600 mg cholesterol per day, 40% calories as fat) and other factors known to affect lipid metabolism were controlled. During the first 4 weeks of the protocol, all subjects consumed distilled water. During the second 4 weeks, one-third of the subjects were assigned randomly to drink 1.5 L per day of water containing 2 ppm of monochloramine, to drink 1.5 L per day of water containing 15 ppm monochloramine, or to continue drinking distilled water. Four blood samples were collected from each subject at the end of each 4-week study period. Subjects drinking monochloramine at a concentration of 2 ppm showed no significant changes in total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoproteins A1, A2, or B when compared to the distilled water group. Parameters of thyroid function also were unchanged by exposure to monochloramine at this concentration. However, subjects drinking monochloramine at a concentration of 15 ppm experienced an increase in the level of apolipoprotein B. Other parameters of lipid and thyroid metabolism did not change. We conclude that consumption of drinking water containing 2 ppm of monochloramine does not alter parameters of lipid and thyroid metabolism in healthy men. Consumption of water containing 15 ppm monochloramine may be associated with increased levels of plasma apolipoprotein B.

Lack of effect of drinking water chlorine on lipid and thyroid metabolism in healthy humans.

Animal studies and a single human epidemiological study have suggested that chlorine in drinking water may raise the level of blood cholesterol. The purpose of this study was to determine whether a 4-week exposure to drinking water chlorine (1.5 L per day) at a concentration of 20 ppm (ppm = mg/L) under controlled conditions would alter circulating parameters of lipid metabolism in healthy humans. Thirty men and thirty women each completed an 8-week protocol during which diet (600 mg cholesterol per day, 40% calories as fat) and other factors known to affect lipid metabolism were controlled. For the first 4 weeks of the protocol, all subjects consumed distilled water. For the second 4 weeks, half of the subjects were assigned randomly to drink 1.5 L per day of chlorinated water (20 ppm), while the others continued drinking distilled water. Four blood samples were collected from each subject at the end of each 4-week study period. Compared to the control group, those subjects given chlorine showed no significant changes in total plasma cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, or apolipoproteins A1, A2, or B. There was a trend toward low serum thyroxine and triiodothyronine levels in men given chlorine, though thyroid-stimulating hormone levels were unchanged. This trend, if real, was not clinically significant. Thus, short-term exposure to chlorinated drinking water at 20 ppm appears to have no significant impact on parameters of lipid or thyroid metabolism in healthy humans.

Lack of effect of drinking water barium on cardiovascular risk factors.

Higher cardiovascular mortality has been associated in a single epidemiological study with higher levels of barium in drinking water. The purpose of this study was to determine whether drinking water barium at levels found in some U.S. communities alters the known risk factors for cardiovascular disease. Eleven healthy men completed a 10-week dose-response protocol in which diet was controlled (600 mg cholesterol; 40% fat, 40% carbohydrate, 20% protein; sodium and potassium controlled at the subject's pre-protocol estimated intake). Other aspects of the subjects' lifestyles known to affect cardiac risk factors were controlled, and the barium content (as barium chloride) of the drinking water (1.5 L/day) was varied from 0 (first 2 weeks), to 5 ppm (next 4 weeks), to 10 ppm (last 4 weeks). Multiple blood and urine samples, morning and evening blood pressure measurements, and 48-hr electrocardiographic monitoring were performed at each dose of barium. There were no changes in morning or evening systolic or diastolic blood pressures, plasma cholesterol or lipoprotein or apolipoprotein levels, serum potassium or glucose levels, or urine catecholamine levels. There were no arrhythmias related to barium exposure detected on continuous electrocardiographic monitoring. A trend was seen toward increased total serum calcium levels with exposure to barium, which was of borderline statistical significance and of doubtful clinical significance. In summary, drinking water barium at levels of 5 and 10 ppm did not appear to affect any of the known modifiable cardiovascular risk factors.

Addressing unanswered questions about population cholesterol screenings: the Model Systems for Blood Cholesterol Screening Program.

Elevated blood cholesterol is one of the three major modifiable risk factors for heart disease. Almost 60% of adults in the United States have an elevated blood cholesterol level, yet most adults are unaware of their level. The National Heart, Lung and Blood Institute (NHLBI) and other organizations have now recommended that all adults be tested to assess their blood cholesterol level. New portable blood cholesterol analyzers have recently been designed and are being promoted widely for cholesterol screening. However, there are many unanswered questions about the reliability of these devices and about the usefulness of mass cholesterol screening programs. The Model Systems for Blood Cholesterol Screening Program, an NHLBI-funded effort consisting of three research projects designed to provide a systematic evaluation of these devices and of mass cholesterol screening, is described. This research will contribute to a data base from which recommendations regarding public cholesterol screening will be made.

Comparisons of referral criteria for public screening of blood cholesterol levels.

Total and high-density lipoprotein (HDL) cholesterol levels of 2,387 adults were screened at a worksite and a bloodbank. Hypothetical referral decisions were made according to three sets of guidelines: the 1984 National Institutes of Health Consensus Conference guidelines (NIHCC), a single referral cutpoint of 5.2 millimoles per liter (mmol per L), and the current National Cholesterol Education Program (NCEP) guidelines for screening in physicians' office. Under the NIHCC guidelines, 31 percent of the participants would have been referred to their physicians, 32 percent under the NCEP guidelines, and 56 percent would have been referred had the 5.2 mmol per L cutpoint been used. Twenty-four percent of the participants would have been referred under both the NIHCC and NCEP guidelines; 7 percent would have been referred under the NIHCC guidelines, but not the NCEP's. Eight percent would have been referred under the NCEP guidelines, but not the NIHCC's. Those who would have been referred were older, and more likely to be male and to have low levels of HDL cholesterol than the 7 percent who would have been referred under NIHCC guidelines only. All of the 8 percent had coronary heart disease, or two or more other coronary risk factors, whereas none of the 7 percent did. If low HDL had been used as a risk factor under NCEP guidelines, the number of persons referred would have increased slightly (to 34 percent) and low HDL levels would have become one of the most prevalent risk factors. The researchers concluded that public cholesterol screening programs should use the NCEP guidelines (with or without HDL), rather than the NIHCC guidelines, or a single 5.2 mmol per L cutpoint.

Screening, diagnosis, and treatment of hypercholesterolemia.

All adults should be screened for high blood cholesterol. Those found to be high should undergo a diagnostic process to confirm and classify their disorder. Diet is recommended for all and drug therapy should be considered for those who do not meet treatment goals on diet.

Should physicians perform their own quality assurance audits?

Quality assurance is required of all hospital outpatient clinics although there is little evidence documenting its value. The purposes of this study were to assess the impact of quality assurance audits on physicians' ordering behavior and to learn whether doctors who actually performed audits behaved differently from physicians who passively received audit results. Baseline influenza vaccination and screening mammography ordering rates were established for the authors' residents' clinic in 1985. In 1986, residents were assigned randomly to three groups. Residents in one group audited their own charts for 1985 influenza vaccination ordering; the second group audited its own charts for 1985 screening mammography ordering; and the third group performed no audit but received the other groups' results. Passive receipt of results improved ordering of vaccination from 40% to 59% and ordering of mammography from 8% to 16%. Actual performance of audits improved ordering of mammography from 16% to 26% but did not improve vaccination ordering. These quality assurance audits were effective in improving the performance of selected preventive health measures in a residents' clinic.

An ambulatory medical education program for internal medicine residents.

Teaching the fundamentals of ambulatory medicine has many well known difficulties. An education program with specific topics covered and modeled after continuing medical education programs for practicing physicians was instituted for residents in a university hospital clinic and was evaluated. The program was effective in improving the residents' knowledge, in enhancing their attitudes toward the clinic, and in improving their performance of influenza vaccinations. No adverse effects of the program were found. This approach, in which a curriculum is carefully defined and participation of the house staff is required, makes the ambulatory medical education process more accountable for what is taught.

Effects of chlorinated drinking water on human lipid metabolism.

Atherosclerosis with its complications is the most important health problem affecting American adults. The levels of serum cholesterol, of high and low density lipoproteins, and of apolipoproteins A1, A2, and B are major risk factors for the development of atherosclerotic lesions. Animal studies suggest that chlorinated drinking water may elevate the serum cholesterol. Studies are too limited to confirm or refute this effect in humans. Since millions of humans have and have had daily exposure to chlorinated drinking water, it is essential to study the effects of such exposure on human lipid metabolism. We have begun a protocol to discover whether consuming chlorinated drinking water elevates serum cholesterol and the other lipid components of blood known to be associated with atherosclerosis. This protocol has been designed to improve the chance of observing an effect while preserving the ability to generalize the data.