Public cholesterol screening in the previously diagnosed: misuse of resources or beneficial function?

The attendance of individuals with a previous diagnosis of hyperlipidemia at public cholesterol screenings is often criticized as a misuse of such programs. This study explored the post-screening actions of 811 participants in a cholesterol screening program who had previously been diagnosed with cholesterol elevations and whose blood levels at this screening required further medical referral. We also studied the responses of physicians from whom these subjects sought care. Within five months, 559 of 753 participants completing the survey (74.0%) sought medical follow-up. Physicians retested the blood cholesterol levels of 75.0% of these 559; high-risk screenees were more likely to be retested and to be informed that their levels were elevated than moderate-risk subjects (P < .0001). Physicians increased cholesterol-lowering dietary advice for high-risk subjects (P < .0001) and medication prescriptions for both risk groups (P < .0001). Participants seeking medical care after the screening program had better cholesterol-lowering dietary practices and reported increased regimen compliance (moderate-risk: P = .01; high-risk: P < .0001) than those individuals not obtaining medical follow-up. One year after screening, blood cholesterol levels were 4.5% lower (P = .001) in those complying with referral but were virtually unchanged in noncompliers. Screening program confirmation of high blood cholesterol levels combined with referral appeared to have a positive impact on previously diagnosed screenees. We conclude that there may be merit in including previously diagnosed individuals in cholesterol screening programs.

Fitting the Armitage-Doll model to radiation-exposed cohorts and implications for population cancer risks.

The Armitage-Doll model of carcinogenesis is fitted to Japanese bomb survivors with the DS86 dosimetry and to three other radiation-exposed cohorts. The model is found to provide an adequate description of solid cancer incidence and also, to a lesser extent, of that of leukemia as a function of radiation dose when up to two radiation-affected stages are assumed. For non-leukemias the optimal model is one in which there are two radiation-affected stages separated by two additional stages. In the case of leukemia one radiation-affected stage or two adjacent stages provide suitable fits. There appear to be significant differences between the optimal models fitted to each cohort, although there is no heterogeneity within the Japanese data set by sex, by cancer type, or by age at exposure. Low-dose and low-dose-rate population risks for a population having the cancer and overall mortality rates of the current UK population are calculated on the basis of the optimal models fitted to the Japanese data to be about 8.3 x 10(-2) excess cancer deaths person-1 Sv-1, 10.1 x 10(-2) radiation-induced cancer deaths person-1 Sv-1, or 1.40 years of life lost person-1 Sv-1. Risks for a population having the mortality rates of the current Japanese population are about 6.5 x 10(-2) excess cancer deaths person-1 Sv-1, 7.8 x 10(-2) radiation-induced cancer deaths person-1 Sv-1, or 0.89 years of life lost person-1 Sv-1. It is a feature of the Armitage-Doll model, and other multistage models of carcinogenesis, that if radiation acts at more than one stage then (inverse) dose-rate effects may arise as a result of interactions between the effects of a protracted dose at the various radiation-affected stages. However, it is shown in this paper that these three measures of cancer risk in general display fairly slight dependence on administered dose in the range 0.001 to 1.0 Sv and on the length of the time over which the dose is administered in the range 1 to 100 years. Dose-rate effects resulting from the protraction of a radiation exposure over many years acting on (the same) cells at various stages of a multistep process of carcinogenesis are therefore expected to be slight. Dose-rate effects which have been observed in epidemiological studies and cellular radiobiology may thus find their explanation in other phenomena such as short-term intracellular repair.

Improving referral compliance after public cholesterol screening.

BACKGROUND: Noncompliance with referral to a physician for retesting and diagnosis is a concern in public cholesterol screening. METHODS: Participants (n = 2109) were referred by a health professional or lay communicator and randomly assigned to a coupon offer, referral reminder letter, or control group. A questionnaire was completed at screening, and a telephone interview was conducted 5 months later. RESULTS: Physician visit rates showed no professional or lay differences. For "no history" subjects, the behavioral interventions were effective compared with controls (coupon = 60.7% and reminder = 57.7% vs control = 46.1%). With professional counseling, only the coupon was effective; for lay counseling, both coupon and reminder yielded higher visit rates. Adjusted for sociodemographics, heart disease risk factors, and health perceptions, the intervention effects remained (professional-coupon offer: odds ratio [OR] = 1.94, 95% confidence interval [CI] = 1.21, 3.09; professional-reminder letter: OR = 1.04, 95% CI = 0.67, 1.63; lay-coupon offer: OR = 2.52, 95% CI = 1.52, 4.18; and lay-reminder letter: OR = 3.10, 95% CI = 1.83, 5.22). CONCLUSIONS: For unaware participants, lay counselors and referral follow-up efforts tailored to specific cholesterol risk groups are indicated.

Attendance patterns and characteristics of participants in public cholesterol screening.

We conducted free, voluntary, public cholesterol screenings in supermarkets in the Rochester, New York, area during a four-month period for demonstration and research purposes. We assessed demographic characteristics and attendance patterns of the 8,583 participants. Compared with 1980 census data for the same census tracts, our participants were likelier to be white, older, female, and better educated than the general population in the area. Most screenees knew about the screenings in advance, and 79% came to the store just for screening. Weekend and weeknight screenings attracted more men and more younger people, in comparison to weekday screenings. However, referral rates based on high cholesterol (HC) test results were similar during all screening times. Overall, 22% of screenees reported a previous diagnosis of HC, but in the highest cholesterol-level group, 45% of screenees reported a history of HC. Previous awareness of HC did not vary according to screening time. These findings indicate that, like other screenings, cholesterol screenings in a public setting do not attract a representative sample of the whole population. The screenings did, however, attract a large number of high-risk individuals, many of whom had no prior awareness of HC. These results should be valuable in planning and targeting future cholesterol screenings.

Patterns of physicians' treatments for referral patients from public cholesterol screening.

Current interest in high blood cholesterol and attendance at public cholesterol screening programs has raised the issue of whether physicians are responding to referrals according to existing national assessment and treatment recommendations. This study assessed the relationship of characteristics of referrals from a series of public blood cholesterol screenings to physicians' treatment practices. For this analysis, the sample was restricted to 1,324 subjects, from the 2,109 referred, who reported seeking physician care. At five months after screening, 75% of subjects reported their physician prescribed a diet; 16% of physicians prescribed medication. Multiple logistic regression, adjusted for sociodemographic characteristics and other coronary heart disease (CHD) risk factors, indicated that screening cholesterol risk level, prior history of high blood cholesterol levels, and type of medical contact were consistently related to receipt of diet and medication treatment, but other CHD risk factors were underutilized. "Moderate" risk subjects with no history of high blood cholesterol were less likely to have received dietary advice, but a screening-risk level interaction did not occur for medication. The results imply that current treatment guidelines may not be working and suggest the need for continued physician education in the management of hypercholesterolemia.

Time variations in the risk of cancer following irradiation in childhood.

The Japanese atomic bomb survivors and three other cohorts of children exposed to radiation are analyzed, and evidence is found for a reduction in the radiation-induced relative risk of cancers other than leukemia with time following exposure. Multiplicative adjustments to the excess risk either of the form exp[-delta.(time since exposure)] or of the form [time since exposure] gamma give equivalent goodness of fit. Using the former type of adjustment an annual overall reduction of 6.9-8.6% in excess relative risk is indicated (depending on the year after which this reduction might take effect). Using the second type of multiplier an adjustment to the excess relative risk varying between [time after exposure]-2.0 and [time after exposure]-3.2 fits best overall. All these reductions are statistically significant at the 5% level. There is no significant variation by cohort, by sex, by cancer type, or by age at exposure group in the degree of annual reduction in excess relative risk. Although time-adjusted relative and absolute risk models give equivalently good fits within each cohort, there is significant variation between cohorts in the degree of increase of risk with time in the absolute risk formulation, in contrast to the lack of such heterogeneity for the relative risk formulation. It is shown that if the range of observed reductions in relative risk is assumed to operate 40 or more years after exposure in the youngest age groups, the calculated UK population risks would be reduced by 30-45% compared to those based on a constant relative risk model.

Chromosome aberrations in relation to radiation dose following partial-body exposures in three populations.

Structural chromosome aberrations were evaluated in peripheral blood samples obtained from three populations exposed to partial-body irradiation. These included 143 persons who received radiotherapy for enlarged thymus glands during infancy and 50 sibling controls; 79 persons irradiated for enlarged tonsils and 81 persons surgically treated for the same condition during childhood; and 77 women frequently exposed as young adults to fluoroscopic chest X rays during lung collapse treatment for tuberculosis (TB) and 66 women of similar ages treated for TB with other therapies. Radiation exposures occurred 30 and more years before blood was drawn. Doses to active bone marrow averaged over the entire body were 21, 6, and 14 cGy for the exposed thymic, tonsil, and TB subjects, respectively. Two hundred metaphases were scored for each subject, and the frequencies of symmetrical (stable) and asymmetrical (unstable) chromosome aberrations were quantified in 97,200 metaphases. Cells with stable aberrations were detected with greater frequency in the irradiated subjects compared with nonirradiated subjects in all three populations, and an overall test for an association between stable aberrations and partial-body ionizing radiation was highly significant (P less than 0.001). We found no evidence that radiation-induced aberrations varied by age at exposure. These data show that exposure of children or young adults to partial-body fractionated radiation can result in detectable increased frequencies of stable chromosome aberrations in circulating lymphocytes 30 years later, and that these aberrations appear to be informative as biological markers of population exposure.

The risk of breast cancer after irradiation of the thymus in infancy.

It is well established that exposure to ionizing radiation during or after puberty increases a woman's risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose-response relation was linear (P less than 0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 10(4) person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life.

A comparative study between individuals receiving thymic irradiation in infancy and their nontreated siblings: clinical and laboratory thyroid abnormalities.

While impairment of thyroid function has been demonstrated for high-dose external radiation (e.g., for Hodgkin's disease), the long-term functional effects of low-dose external radiation have not been fully explored. One hundred fifty-three subjects with a past history of thymic irradiation during infancy were stratified into three dose levels and compared with 51 nonirradiated subjects from a sibling cohort with respect to previously undiagnosed clinical and laboratory thyroidal abnormalities. There was no apparent association between previous thymic irradiation and mean serum levels of T4, free T4, TSH, or antithyroid antibodies, nor was the prevalence of undetected hypothyroidism or hyperthyroidism significantly altered in the irradiated group. Serum thyroglobulin levels were elevated in subjects with palpable thyroid nodules, all of which occurred in thymic-irradiated subjects. Thus persons who have received low-level external thymic irradiation in infancy should continue to have periodic thyroid examinations, but routine serial measurement of other serum thyroidal parameters does not appear to be indicated.

Lymphocyte subclasses and immunoglobulins in adults receiving radiation treatment in infancy for thymic enlargement.

One-hundred and fifty-three subjects who were irradiated in infancy for an alleged enlarged thymus and 51 controls were studied to quantify the phenotypically different subpopulations of peripheral blood lymphocytes and immunoglobulins. These subjects were selected from a larger cohort which has been followed prospectively since the early 1950s. Previous studies of this cohort have shown a radiation dose-related increased risk of thyroid carcinomas and adenomas in the irradiated group as well as a recent excess of various extrathyroid neoplasms. In this substudy, no significant differences in lymphocyte subpopulations or immunoglobulin levels were observed between the irradiated and control groups. These findings support a hypothesis that the radiation-related excess of neoplasms in this cohort may have resulted from direct cellular damage with subsequent mutations rather than impaired immune function.

The influence of potential biases on the risk of breast tumors among women who received radiotherapy for acute postpartum mastitis.

Data from a 30-year follow-up study of 606 women given radiotherapy for acute postpartum mastitis and two non-irradiated control groups were reanalyzed to determine whether bias could account for the reported increased risk of benign and malignant breast tumors in the irradiated population. The biases examined were comparison group selection (i.e. selection bias); differential medical verification of breast tumors between exposed and unexposed groups; differential detection of breast tumors; and confounding. Overall age-adjusted relative risk (RR) estimates for breast cancer (RR = 2.0; 95% CL:1.3-3.1) and for benign neoplastic (RR = 3.5; 95% CL:1.8-6.8) and non-neoplastic breast tumors (RR = 1.5; 95% CL: 1.2-2.1) were compared to those obtained after adjustment for the above biases. The increased risk for breast cancer among the irradiated women could not be accounted for by any of the biases examined, supporting previous reports based on this cohort. However, the suggested association of radiation with benign breast tumors may represent a selection bias since the RR estimate for non-neoplastic breast tumors was no longer statistically significant (RR = 1.2; 95% CL:0.8-1.6) while that for neoplastic breast lesions declined to 2.0 (95% CL:1.1-1-4.0) when non-irradiated women with acute postpartum mastitis were used as the comparison group instead of the non-irradiated female siblings of the exposed. This finding suggests that acute postpartum mastitis may predispose a woman to later developing a benign breast tumor irrespective of whether or not radiotherapy was used to treat this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of extrathyroid tumors following radiation treatment in infancy for thymic enlargement.

Two thousand eight hundred and fifty-six individuals who received X-ray treatments in infancy for an enlarged thymus gland and their 5053 nonirradiated siblings have been followed prospectively since 1953 to evaluate the risk of radiation-induced neoplastic disease. The health status of the entire cohort has been ascertained periodically by mail questionnaire survey. Based on the cumulative experience of five surveys of this cohort, the irradiated group has a statistically significant increased risk for both benign and malignant extrathyroid tumors, the age-adjusted relative risks being 2.0 and 2.2, respectively. Benign tumors of the bone, nervous system, salivary gland, skin, and breast (females only) and malignant tumors of the skin and breast (females only) account for the excess incidence of extrathyroid tumors among the thymic-irradiated individuals. Although a radiation-induced excess of extrathyroid tumors was suggested in an earlier survey of this cohort, small numbers restricted attribution of this excess to specific sites. The implications of these findings are discussed. Thyroid tumors are addressed in a separate paper.

Exogenous hormone use and fibrocystic breast disease by histopathologic component.

In a hospital-based case-control study of 590 women with biopsy-proven fibrocystic breast disease and 1,018 control women with other surgical conditions, no linear relationship was evident between the use of oral contraceptives or of estrogen replacement therapy and the degree of epithelial atypia of the fibrocystic lesions. Case-control and intracase comparisons suggested that oral contraceptive use might be associated with an increased occurrence of sclerosing adenosis among the premenopausal women and of gross cysts among the postmenopausal women. Estrogen replacement therapy, which was positively associated with fibrocystic breast disease as a whole among the post-menopausal women, was most frequently used among the cases whose biopsy specimens exhibited gross cysts, papillomatosis or papillary hyperplasia.

Differences in breast cancer risk factors according to the estrogen receptor level of the tumor.

One hundred and forty-eight postmenopausal breast cancer cases and 585 postmenopausal controls were included in an investigation of whether various risk factors for breast cancer are associated with the level of estrogen (E) receptor (ER) protein in the tumor. In an intracase analysis, the tumor ER level was positively associated with nulliparity, late age at first live birth, a history of benign breast disease, and having breast-fed at least 1 child and was negatively associated with previous use of E replacement therapy. A case-control analysis suggested that the first three variables, established risk factors for breast cancer, are associated with an increased risk for malignant breast tumors that are ER-positive but not for those that are ER-negative. This analysis did not provide a clear interpretation of the findings in the intracase comparisons with regard to prior breast-feeding and the use of E replacement therapy.

An epidemiologic study of epithelial carcinoma of the ovary.

A case-control study to identify risk factors for epithelial ovarian cancer was undertaken among women in the age group 45-74 years who had been admitted to seven hospitals in Connecticut between July, 1977, and March, 1979. Characteristics that were found to increase the risk of epithelial ovarian cancer included being white, never having been pregnant, having a late age at menopause, having a family history of cancer of the ovary or endometrium, and having a long estimated number of years of ovulation. Prior use of post-menopausal estrogens did not alter the risk for epithelial ovarian cancer, but there was some indication that oral contraceptives protect against ovarian cancer. Women with ovarian cancer were somewhat more likely to have had a history of an underactive thyroid and were somewhat less likely to have had a history of an overactive thyroid than controls, although these trends were not statistically significant.