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Recent advances in molecular genetics have highlighted the potential use of genetic testing to screen for adult-onset chronic diseases. Several issues must be addressed, however, before such tests can be recommended for population-based prevention programs. These issues include the adequacy of the scientific evidence, the balance of risks and benefits, the need for counseling and informed consent, and the costs and resources required. Ongoing assessment of the screening program and quality assurance of laboratory testing are also needed. This paper considers the application of general principles for mass screening to genetic testing for susceptibility to adult-onset chronic diseases. Evaluation of proposals for genetic screening in context of these principles reveals that needed evidence is often absent, particularly with respect to the predictive value of tests, efficacy of interventions, and social consequences of testing. The principles of population screening are developed into a framework for public health policy on genetic screening that has three stages: assessment of the screening test and interventions for those who test positive, including assessment of risks and costs, policy development, and program evaluation. Essential elements are identified, including evaluation of evidence and processes for consensus development and program evaluation. The proposed framework for public health policymaking outlined in this commentary, when combined with future efforts that involve an authoritative consensus process, may be useful for the evaluation and planning of genetic screening programs aimed at reducing morbidity and mortality from adult-onset chronic diseases.

Recent studies suggest that Asian and Pacific Islander women in the United States may underuse cancer screening tests. We examined the breast and cervical cancer screening practices of 6048 Asian and Pacific Islander women in 49 states from 1994 through 1997 using data from the Behavioral Risk Factor Surveillance System. About 71.7% [95% confidence interval (CI), 66.3-77.0%] of women in this sample aged > or =50 years had a mammogram in the past 2 years, and 69.5% (95% CI, 63.9-75.1%) had a clinical breast exam in the past 2 years. About 73.7% (95% CI, 71.3-76.0%) of women aged > or =18 years who had not undergone a hysterectomy had a Papanicolaou test in the past 3 years. Women with health insurance and those who had seen a physician in the past year were more likely to have been screened. These results underscore the need for continued efforts to ensure that Asian and Pacific Islander women who are medically underserved, including those without health insurance, have access to cancer screening services.

Purpose: Many new genetic tests for susceptibility to adult-onset diseases are developed on the basis of selected and high-risk groups. Before such tests can be used in medical practice, however, epidemiologic studies must be conducted to evaluate their clinical sensitivity, specificity, and positive predictive value in the general population. For many common adult-onset diseases, this process may take decades of follow-up., Method: We illustrate how clinical validation of new predictive genetic tests can be done retrospectively using case-control studies that are derived from population-based registries of diseases. We use the examples of birth defects and cancer registries to illustrate a hypothetical process by which such tests can be clinically validated., Results: We demonstrate how such epidemiologic studies can be successfully used to derive measures of a test's sensitivity, specificity, positive predictive value, negative predictive value, and of the population attributable fraction of disease due to the disease-susceptibility genes. Under certain assumptions, data derived from population-based case-control studies provide adequate estimates of lifetime risks for disease (penetrance) among people with specified genotypes., Conclusions: With adequate protections of human subjects, studies involving population-based registries of disease will increasingly become valuable in validating the numerous genetic tests that will emerge from advances in human genetic research and the Human Genome Project.

Background: Recent studies suggest that American Indian and Alaska Native women have important barriers to cancer screening and underuse cancer screening tests., Methods: We examined the breast and cervical cancer screening practices of 4,961 American Indian and Alaska Native women in 47 states from 1992 through 1997 by using data from the Behavioral Risk Factor Surveillance System., Results: About 65.1% [95% confidence interval (CI) 60.2 to 69.9%] of women in this sample aged 50 years or older had received a mammogram in the past 2 years. About 82.6% (95% CI 80.1 to 85.2%) of women aged 18 years or older who had not undergone a hysterectomy had received a Papanicolaou test in the past 3 years. Older women and those with less education were less likely to be screened. Women who had seen a physician in the past year were much more likely to have been screened., Conclusions: These results underscore the need for continued efforts to ensure that American Indian and Alaska Native women who are elderly or medically underserved have access to cancer screening services.

In the past decade, at least four sets of ethics guidelines for epidemiologists have been prepared by various national and international organizations. None, however, have been officially adopted by the American College of Epidemiology (ACE). Recently, the ACE asked its Ethics and Standards of Practice (ESOP) Committee to produce ethics guidelines. In this paper, we explain the context and rationale for this effort, describe the purpose and content of ethics guidelines in epidemiology, and discuss their strengths and weaknesses. Three issues that are central to the mission of ACE-education, policy, and advocacy-are inadequately addressed in existing ethics guidelines. In addition, ethics guidelines are not static documents; they should reflect the changing role of epidemiologists in society, including issues arising in emerging subspecialty areas. New, more dynamic, guidelines that emphasize core values, obligations, and virtues, may help to further define and legitimize the profession of epidemiology and will provide a foundation for the discussion of specific ethical issues in the classroom and in professional practice. Guidelines however, do not provide the final word on ethical issues. Specific decisions in particular cases require judgments made upon reflection of the core values, obligations, and virtues described in the guidelines. From our review, we conclude that a new set of guidelines is reasonable and warranted.

Objective: To determine whether HIV testing and posttest counseling may be associated with an increase in gonorrhea incidence among adolescents and young adults seen at a clinic for sexually transmitted diseases (STD)., Design: A historical cohort study with the collection of longitudinal data on the patients' HIV testing and counseling experience., Setting: Delgado STD clinic of New Orleans, Louisiana, a public ambulatory primary care center that serves mainly the economically disadvantaged Black population., Patients: A record-based inception cohort of 4031 patients aged 15-25 years diagnosed at the clinic between June 1989 and May 1991 with a first lifetime gonorrhea infection., Intervention: Routine confidential HIV tests and posttest counseling sessions experienced at the clinic during follow-up., Outcome Measure: Incidence rate of reported gonorrhea reinfection., Results: Of the patients, 51.5% were tested once for HIV antibodies and 25.9% twice or more. Formal posttest counseling occurred after 8.5% of the 4665 HIV-negative and 44.0% of the 49 HIV-positive tests. In the most pessimistic of several models controlling for history of gonorrhea, HIV testing and counseling history, and other potential confounding factors, a significantly lower rate of gonorrhea reinfection was observed after a first HIV-negative test than before [adjusted relative risk (RR), 0.66; 95% confidence interval (CI), 0.59-0.74; P < 0.00011. As compared with the pretest period, significantly higher rates of gonorrhea were observed after respectively a second (RR, 1.18; 95% CI, 1.01-1.37; P = 0.03) and a third (RR, 1.52; 95% CI, 1.22-1.88; P = 0.0001) HIV-negative test. No significant association was found between HIV-positive testing and any variation in gonorrhea rate (RR, 0.95; 95% CI, 0.56-1.62; P = 0.85). Posttest counseling for HIV-negative and HIV-positive results were followed respectively by a significantly higher rate of gonorrhea (RR; 1.27; 95% CI, 1.09-1.48; P = 0.002) and a non-significantly lower rate of gonorrhea (RR, 0.53; 95% CI, 0.17-1.60; P = 0.85)., Conclusion: Our results do not exclude the possibility of a modest increase in gonorrhea incidence after routine HIV testing and counseling in an STD clinic. Nevertheless, this conclusion holds only under the least favorable assumptions and applies solely to a minority of patients.

1. Breast cancer is a major health problem amenable to secondary prevention for reducing morbidity and mortality. 2. Given the large and increasing numbers of women in the workplace, breast cancer prevention and control measures should be included in workplace health promotion programs. However, despite the increasing prevalence of worksite health promotion programs in the United States, the prevalence of breast cancer programs in the workplace has been decreasing. 3. Despite the limited evaluative research of worksite breast cancer screening programs, a number of important conclusions conducted thus far. 4. Additional scientifically rigorous evaluation studies of worksite health programs for the early detection of breast cancer are needed, and additional innovative workplace programs aimed at increasing breast cancer screening need to be developed.

Although cardiac transplantation offers prolonged survival and improved quality of life to patients with end-stage heart failure, many patients with idiopathic dilated cardiomyopathy do not undergo this procedure. Possible barriers to cardiac transplantation were examined among 138 patients with idiopathic dilated cardiomyopathy from five hospitals in Washington, DC. Patients underwent follow-up for approximately 5 years. The patients or a close family member were interviewed at baseline about socioeconomic factors and medical history. The patients or their next-of-kin were recontacted at 1-year intervals to determine patients' vital status and to obtain information about cardiac transplantation. Overall, the cumulative survival at 12 and 60 months was 75.8% and 37.3%, respectively. Only 3.6% (5 of 138) of the patients underwent cardiac transplantation, and 19 (13.8%) patients had been placed on a waiting list for a heart transplant. Black race and nonmarried status were inversely associated with cardiac transplantation. Factors associated with not having been placed on a waiting list included older age, lower income, and lack of private health insurance. Black race was found to be significantly, but inversely associated with cardiac transplantation while older age was inversely associated with having been placed on a waiting list after adjusting for sex, race, education, and private insurance. These findings suggest that black patients with idiopathic dilated cardiomyopathy are less likely to undergo cardiac transplantation.

This paper provides an overview of the ethical and cultural issues that were taken into account in planning a cross-cultural study of barriers to breast and cervical cancer screening among Houma Indian women who reside in Terrebonne Parish, Louisiana. In such cross-cultural studies, the investigators and members of the target population are from different cultural backgrounds. In planning the study, ethical principles and cultural norms were carefully specified to ensure that the welfare of the participants would be protected and potential benefits maximized. This experience with the Houma Indian Nation illustrates the need for greater participation of research subjects in the planning and implementation of studies on their behalf. An ethical, culturally sensitive approach to cancer control research is needed to address the health concerns of Native American populations.

Background: The authors examined predictors of mortality from kidney cancer in 332,547 men who were screened as part of the Multiple Risk Factor Intervention Trial., Methods: The vital status of each member of this cohort was ascertained through 1990. Death certificates were obtained from state health departments and coded by a trained nosologist. Three hundred ninety-eight deaths due to kidney cancer occurred among the cohort of 332,547 men after an average of 16 years of follow-up. The authors used the Cox proportional hazards model to study the joint associations of age, race, income, blood pressure, cigarette smoking, and use of medication for diabetes with risk of death from kidney cancer., Results: The authors observed independent associations with age, cigarette smoking status (relative risk [RR] = 2.02; 95% confidence interval [CI], 1.65-2.48), and systolic blood pressure (relative risk [RR] = 1.12 for systolic blood pressure level 10 millimeters of mercury higher; 95% CI, 1.06-1.18). The authors obtained similar results when deaths that occurred during the first 5 years were excluded., Conclusions: These findings add to the increasing body of evidence that cigarette smoking and blood pressure level are modifiable risk factors for kidney cancer in men.

The present study was designed to help learn more about the ethical interests and concerns of public health nurses employed in state and local health departments. Self-administered postal questionnaires were mailed to 41 public health nurses employed at health units in Region I of the Louisiana Office of Public Health. Basic demographic information was obtained along with information about the workers' previous instruction or training in ethics and the nature of ethical conflicts encountered in their public health practice. Only 38% (15 of 39) of the surveyed nurses had had formal instruction in ethics. Even fewer (7.3%) had received continuing education on ethics. Most of the nurses felt confident in their ability to recognize an ethical conflict or dilemma in the workplace; fewer felt confident in their ability to resolve an ethical conflict or dilemma. A high proportion of the nurses agreed that there is a need for continuing education courses on ethics for public health workers. Nurses who had received formal ethics instruction were more likely to feel confident in their ability to recognize an ethical conflict in their public health practice. Continuing education programs on ethics are needed that are designed to meet the specific needs of front-line public health workers.

A survey was undertaken to learn about cancer screening practices of adult women residing in Houma, Louisiana, many of whom are of Cajun descent. The women were identified using a telephone sampling procedure and interviewed about their use of screening mammography, clinical breast examinations, Pap smears, and other factors. Interviews were completed for 50 women aged 50 to 75 years. Forty-eight percent (24 of 50) were self-identified Cajuns, 34% were non-Cajun white, 14% were black, and 4% were of other races. Only 42% of the Cajun women and 41% of non-Cajun white women reported having had a mammogram in the last year. The Cajun women were less educated on average (P < .05) and were less likely to use cancer screening tests and more likely to smoke, although the latter differences were not significant (P > .05). In view of their geographical isolation and unique culture, more research is needed to identify barriers to preventive health services in Cajun communities.

We have found race to be an independent predictor of mortality in a preliminary analysis of data from an ongoing study of patients with idiopathic dilated cardiomyopathy. Our previous, analyses, however, were based on only 12 to 24 months of follow-up. In the present analysis, which is based on up to 5 years of follow-up, we extended our earlier observations and examined whether other socioeconomic factors account for the association with race. A total of 128 patients from five Washington, DC, area hospitals were included in the analysis. One hundred three (80.5%) of the patients were black and 25 (19.5%) were white. The black patients were less likely to have private health insurance, less educated on average, and more likely to have a household income < or = $15,000. No racial differences were found in cardiac medication usage, with the exception of beta blockers and antiarrhythmics. The cumulated survival among black patients at 12 and 60 months was 71.5% and 39.1%, respectively, compared with 92% and 31.4% among whites. Age, ventricular arrhythmias, and ejection fraction were significant predictors of survival in univariate analysis. The univariate association with black race was of borderline significance. In multivariable analysis using the proportional hazards model, age and ejection fraction were significant independent predictors of survival. The association with ventricular arrhythmias was of borderline significance. The association with black race, which was statistically nonsignificant, was diminished even further by adjustment for income and type of health insurance. Thus, the previously reported association with black race may be accounted for by socioeconomic factors related to access to health care.

Marital status and other socioeconomic and clinical factors were examined as predictors of survival in idiopathic dilated cardiomyopathy using data from a hospital-based study in Washington, DC. Twenty-five (18.1%) of the cases (n = 138) were single, 66 (47.8%) were married, 25 (18.1%) were divorced or separated, and 22 (15.9%) were widowed. Married patients were more likely to be male, to have an annual household income greater than $15,000, and to live with another person (p < or = 0.01) as compared with those who were single, widowed, divorced or separated. Widowed patients were older on average and more likely to abstain from drinking alcohol. The cumulative survival among widowed patients at 12 and 24 months was 54.6 and 48.5%, respectively, as compared with 75.8 and 59.0% among single patients and 80.0 and 71.2% among married patients. The survival of divorced or separated patients was relatively good with a cumulative survival of 84.0% at both 12 and 24 months. Older age, lower ejection fraction, ventricular arrhythmias, bundle branch block, and marital status were significant predictors of survival in univariate analysis using the proportional hazards model. In multivariable analysis, age, race, ejection fraction, and marital status were statistically significant independent predictors of survival, with single patients with idiopathic dilated cardiomyopathy having a poorer survival than those who were married (adjusted RR = 2.5, 95% CI 1.1-6.2, p < 0.05). The observed association with marital status may be explained by psychosocial factors not examined in the present study such as quality of social network or psychological stress.

Although bronchial asthma and emphysema have been associated with idiopathic dilated cardiomyopathy in case-control studies, little is known about the prognostic importance of chronic respiratory disease in idiopathic dilated cardiomyopathy. To study this, we examined history of bronchial asthma, emphysema and chronic bronchitis, and respiratory medication use as possible predictors of survival in idiopathic dilated cardiomyopathy using data from a Washington, DC, population-based study (n = 129). The cumulative survival rates among patients with a history of emphysema or chronic bronchitis were 60% and 48% at 12 and 36 months, respectively, compared with 81.8% and 67.2% among patients without emphysema or chronic bronchitis. The survival rates of idiopathic dilated cardiomyopathy patients with and without a history of bronchial asthma at the time of idiopathic dilated cardiomyopathy diagnosis were similar. In multivariate analysis using the proportional hazards model, only ventricular arrhythmias and ejection fraction were found to be statistically significant predictors of survival in idiopathic dilated cardiomyopathy. The adjusted relative risk estimate for emphysema and chronic bronchitis was close to one. Thus, the results of this population-based study do not suggest that history of chronic respiratory illness is an independent predictor of survival in idiopathic dilated cardiomyopathy.

Recent studies have suggested that patients with idiopathic dilated cardiomyopathy (IDCM) who smoke have an improved prognosis as compared with nonsmokers. We examined this paradoxical finding using data from a population-based study in Washington, D.C. (n = 127). Current smokers were more likely to have a left-ventricular ejection fraction (LVEF) of 25% or greater as compared with IDCM patients who were past smokers or lifelong nonsmokers (p < or = 0.02). The cumulative survival among current smokers at 12 and 24 months was 88.1 and 81.4%, respectively, as compared with 77.9 and 71.6% among past smokers and 74.0 and 64.3% among patients who had never smoked. In a univariate analysis using the proportional hazards model, lifelong nonsmokers and former smokers were about twice as likely to die as compared with smokers, although the association was not significant (p > 0.10). In multivariable analysis, older age, LVEF, and ventricular arrhythmias - but not cigarette smoking-were found to be statistically significant independent predictors of survival (p < or = 0.05).

The ethical problems that surrounded the Tuskegee Syphilis Study prompted widespread public criticism when they first surfaced in 1972; the Tuskegee Study remains an important case in bioethics. We recently examined public health student knowledge of the ethical significance of the Tuskegee Study as part of an ethics curriculum needs assessment at Tulane University. A brief questionnaire was administered to 236 graduate students currently enrolled in seven epidemiology courses. Basic demographic information was obtained along with information about degree program. A series of questions was then asked to assess student knowledge of bioethics including the ethical significance of the Tuskegee Study. Only 19% (46 of 236) of the students demonstrated knowledge of the ethical significance of the Tuskegee Study. Knowledge of the Tuskegee Study's ethical significance was higher among students who were from the United States and those who were enrolled in the epidemiology program (P < .05). The ethical problems that surrounded the Tuskegee Study have rarely been encountered in public health. However, this important case stands as an exemplar of the potential for ethical abuses in human subjects research. Such cases ought to be highlighted in public health curricula. Medical Subject Headings (MeSH): blacks, African Americans, educational curriculum, epidemiology, ethics, public health, racism.

Racial, socioeconomic, and clinical factors were examined as predictors of survival in idiopathic dilated cardiomyopathy using cases from five Washington, DC-area hospitals. One hundred three (80.5%) of the patients were black and 25 (19.5%) were white. The black patients were less likely to have private health insurance, less educated on average, and more likely to have a household income of $15,000 or less (P < or = .05). No racial differences were found in cardiac medication usage, with the exception of beta blockers and antiarrhythmics. The cumulative survival among black patients at 12 and 24 months was 71.5% and 63.6%, respectively, as compared with 92.0% and 86.3% among whites. The 12-month survival of black patients with ventricular arrhythmias or an ejection fraction of less than 25% was particularly poor. Age, ventricular arrhythmias, ejection fraction, and cigarette usage were significant predictors of survival in univariate analysis using the proportional hazards model. The univariate association with black race was of borderline significance (P < or = .07). In multivariate analysis, age and race were statistically significant independent predictors of survival. A strong association with black race was observed with an estimated relative risk of mortality of 5.41 (P < or = .02) after adjustment for age, ejection fraction, ventricular arrhythmias, and educational attainment. Poorer survival among blacks may be caused by a greater severity of disease at the time of diagnosis or by racial differences in cardiac care, comorbid conditions, or biologic factors affecting survival.

Use of desmopressin acetate (DDAVP) for patients having cardiac surgery is controversial. We did a double-blind, randomized study of 83 patients having cardiac operations at Georgetown University Hospital. The effect of DDAVP on bleeding as compared to placebo was evaluated by blood loss, replacement volume, and laboratory tests. There were no significant differences in baseline and intraoperative data between the DDAVP (n = 40) and placebo (n = 43) groups. Total drainage for the first 24 postoperative hours was 1,214 mL (+/- 78) for the DDAVP group and 1,386 mL (+/- 116) for the placebo group (not significant). There were no significant differences in replacement therapy. In this study, administration of DDAVP did not decrease bleeding.

An epidemiologic study was carried out to examine the possible role of diabetes mellitus and other factors in the development of idiopathic dilated cardiomyopathy. Possible associations with diabetes and other factors were examined by comparing newly diagnosed case patients (n = 129) ascertained from five Washington, DC area hospitals with neighborhood control subjects (n = 258) identified using a random-digit dialing technique. The case patients and control subjects were matched by sex and 5-year age intervals and were compared in the analysis using conditional logistic regression methods. A statistically significant association was observed between idiopathic dilated cardiomyopathy and history of diabetes (relative odds = 2.2; 95% confidence interval: 1.5 to 3.3). The association with diabetes was not explained by race, income, cigarette usage, or hypertension. A total of 28.7% (37/129) of the case patients had a reported history of diabetes, as compared with 13.6% (35/258) of the control subjects (P < 0.05). A possible interactive effect was also observed between diabetes and history of hypertension (P > 0.05). These findings support the view that diabetics, particularly those with a history of hypertension, may be at increased risk of idiopathic dilated cardiomyopathy.

In this study, we have confirmed the ability of liposome-encapsulated doxorubicin to modulate drug resistance, as previously observed in CH LZ cells (Thierry et al., Cancer Commun. 1, 311-316, 1989), in two human multidrug-resistant (MDR) cell lines, the breast cancer MCF-7/ADR cell line, and the ovarian carcinoma SKVLB cell line. This effect was specific to MDR cells, as liposomally encapsulated doxorubicin did not enhance cell sensitivity to the drug in the parental cell lines. Cytotoxicity assays demonstrated that empty liposomes in the presence of free doxorubicin (Dox) reversed resistance to the drug at a level that may be higher than that observed when liposome-encapsulated Dox is used. This effect seems to be due to the high affinity of Dox for cardiolipin, one of the liposome components, which leads to the association of the drug and the cardiolipin-containing liposomes in the culture medium before entry into the cells. Neither pretreatment of empty liposomes before drug treatment nor combined incubation of vincristine and empty liposomes alter MDR in CH LZ cells, suggesting that the drug must be encapsulated or complexed to the liposomes to overcome MDR. Because MDR in CH LZ cells does not seem to be related to GSH level, MDR modulation by liposome-encapsulated Dox apparently may not be effected by altering the GSH function. These results suggest that the enhancement of sensitivity of MDR cells using Dox encapsulated in liposomes or complexed with liposomes may be explained by an increase in cell drug incorporation and by an intracellular drug redistribution. Fluorescence confocal microscopy study indicated that Dox is transported and distributed mainly in intracytoplasmic vesicles in SKVLB and MCF-7/ADR cells, whereas in parental cells the drug is located mainly in the nucleus. In addition, presentation of Dox in liposomes modifies the drug distribution pattern in MDR cells by partially shifting the drug to nuclear compartments. Thus, liposome-associated Dox may bypass the vesicular drug transport in MDR cells, resulting in the enhancement of the drug biological activity.

Objective: To determine the knowledge, beliefs, attitudes, and practices of obstetricians-gynecologists regarding human immunodeficiency virus (HIV) prevention., Methods: Office-based obstetricians-gynecologists in the Washington, DC metropolitan area who reported providing primary care were interviewed by telephone. The survey response rate was 62% (N = 268)., Results: The percentages of obstetricians-gynecologists who reported regularly assessing the HIV risk of new adolescent and adult patients were 67 and 40%, respectively. Seventy-two percent reported regularly counseling patients at risk to use condoms for vaginal intercourse, and 60% regularly counseled patients at risk to limit their number of sexual partners. The level of general risk-factor assessment and confidence in the ability to reduce patients' HIV risk were the strongest correlates of the frequency and thoroughness of HIV risk assessment and counseling., Conclusions: The percentage of obstetricians-gynecologists who assess and counsel patients about HIV risks is below the 75% goal for the year 2000 established by the United States Department of Health and Human Services. Continuing medical education for obstetricians-gynecologists is needed to improve their knowledge and skills in HIV prevention.

Ethical conflicts between moral principles and methodologic standards sometimes occur in epidemiologic research. When dilemmas are discerned, they may be analyzed using the ethical principles of beneficence, nonmaleficence, justice, and respect for the autonomy of persons. We argue that, in addition to scientific validity, the welfare and rights of research subjects should be taken into account in making decisions regarding all aspects of the design and conduct of epidemiologic studies, and that the commitment of epidemiologists to the advancement of scientific knowledge should not outweigh or override all other considerations.

Following a needs assessment, the American Lung Association of the District of Columbia (ALADC) began a 3-year pilot program (1986 to 1989) to improve the health status of 5- to 10-year-old urban black asthmatic children. The authors hypothesized that participation in a 1-day asthma camp curriculum, using a collaborative multidisciplinary team approach between university and community-based staff, would provide an effective educational intervention to teach children and their families daily management strategies for asthma. The 84 participants (mean age: 9.6 years) were predominantly black (93%), male (73%), and from single-parent or single-guardian homes (52.7%). Follow-up interviews suggested that a high percentage of the children were using new techniques such as aerosol/inhalers (78%) and breathing/warm-up exercises (55%). Overall, participation in this novel program was associated with a clinically significant, 36% to 69% reduction in school absences, emergency room visits, and hospitalizations.

A method is described for modeling the sensitivity, specificity, and positive and negative predictive values of a diagnostic test. To model sensitivity and specificity, the dependent variable (Y) is defined to be the dichotomous results of the screening test, and the presence or absence of disease, as defined by the "gold standard", is included as a binary explanatory variable (X1), along with variables used to define the subgroups of interest. The sensitivity of the screening test may then be estimated using logistic regression procedures. Modeled estimates of the specificity and predictive values of the screening test may be similarly derived. Using data from a population-based study of peripheral arterial disease, the authors demonstrated empirically that this method may be useful for obtaining smoothed estimates of sensitivity, specificity, and predictive values. As an extension of this method, an approach to the modeling of the relative sensitivity of two screening tests is described, using data from a study of screening procedures for colorectal disease as an example.

This national survey examined the knowledge and use of the living will among 494 family physicians of the American Academy of Family Physicians in 39 jurisdictions with living will statutes. The findings revealed a positive relationship between physician knowledge of the living will and its clinical use. Additionally, a positive relationship between physician knowledge and willingness to initiate discussions on the document with patients was found. The implications of these findings, as related to disclosure of the living will in the informed consent process, is discussed.

Ten patients with Parkinson's disease (PD) with motor fluctuations that responded to a protein redistribution diet were studied. All 10 patients were receiving standard Sinemet (levodopa/carbidopa). Five randomly selected patients were changed from standard Sinemet to a controlled-release form of Sinemet. The other five patients continued to receive standard Sinemet. To maintain the same degree of control of PD in the five patients switched to the controlled-release form of Sinemet, the daily levodopa intake increased. While receiving optimal therapy (standard Sinemet or controlled-release Sinemet) and a protein redistribution diet, all 10 patients then underwent hourly videotaping and blood sampling (for plasma levodopa levels) during 2 consecutive days. Videotapes were blindly reviewed for PD disability, dyskinesia, and the time required to walk a measured distance. Comparing the two groups, standard Sinemet with controlled-release Sinemet, respectively, mean levodopa requirements were 505 and 1895 mg, plasma levodopa levels were 6.1 and 17.6 mumol/L, and abnormal involuntary movement scale scores were 14 and 26. Their mean PD disability scores did not differ statistically or clinically. Also no statistically significant differences were noted in either their mean walking times or their mean daily dose frequencies.

In summary, job-exposure matrices consist of a number of related methods for the assessment of occupational exposures that have been adapted to a variety of research settings. The potential advantages of job-exposure matrices include the avoidance of some forms of bias and enhanced statistical power to detect associations. However, misclassification of exposures may be problematic, and the sensitivity of this approach has not been consistently shown to be greater than that of conventional methods of exposure assessment based upon interviews of subjects. The job-exposure matrix approach may be especially useful for studies involving the historical reconstruction of exposures at industrial sites. More attention needs to be given to improving the completeness and accuracy of employment history information and to the validity of exposure estimates over time. Future developments may include the increased availability and utilization of quantitative exposure estimates such as environmental air sampling and personal monitoring data. Although job-exposure matrices are generally associated with case-control study designs, they may also be useful in prospective studies. Thus, job-exposure matrices are a potentially valuable addition to epidemiologic research methods which, if applied judiciously, may contribute to etiologic research and to the identification and control of hazardous exposures in the workplace.