Ceruloplasmin in Wilson's disease.

Ceruloplasmin was highly purified from one patient with Wilson's disease and partially purified from a second unrelated patient. The highly purified ceruloplasmin was indistinguishable from normal ceruloplasmin by electrophoresis, tryptic peptide map, oxidase activity, and copper, amino acid, and sugar composition. The partially purified ceruloplasmin was indistinguishable electrophoretically from normal ceruloplasmin. With penicillamine therapy, ceruloplasmin disappeared from the serum of the first patient; it reappeared after the drug was discontinued. The significance of this observation in regard to the basic defect in Wilson's disease is discussed.

Decision-making about breast cancer susceptibility testing: how similar are the attitudes of physicians, nurse practitioners, and at-risk women?

PURPOSE: To determine what consumers and providers would want to discuss about breast cancer susceptibility testing (BCST) and their preferred role in testing decisions. METHODS: We surveyed 426 at-risk women, 143 nurse practitioners, and 296 physicians in five specialties in Maryland. RESULTS: All groups believe it is important to discuss how the chance of breast cancer can be reduced and what the chances are of getting breast cancer if the test is positive. Both provider groups attributed more importance than consumers to discussing whether cancer can occur if the test is negative. Discussing the risk of depression and anxiety was more important to providers than consumers. Eighty-two percent of women would want their providers to make a recommendation about testing, but only 43% of nurse practitioners and 68% of physicians would do so. Eighteen percent of physicians underestimated the importance of informed consent for testing and 34% of discussing the risk of insurance discrimination. Fewer than 6% of women, if found to have a mutation, would be likely to undergo prophylactic mastectomy, whereas 12% of nurse practitioners and 34% of physicians would be likely to recommend such surgery. One third of respondents in all three groups supported testing a 13-year old daughter of a mutation-carrier. CONCLUSION: Physicians should place greater value on informed consent and discussing practical aspects of testing, and physicians and nurse practitioners should pay more attention to the limitations of testing children, insurance discrimination, and consumers' desire for provider recommendations. In light of the limited discordance between nurse practitioners and consumers, nurse practitioners can play an increasing role in education and counseling about BCST.

Genetic variation in nutritional requirements and susceptibility to disease: policy implications.

I have considered several questions that should be answered in order to develop rational public policy for preventing disability and premature death for common disorders for which genes play a role and for which nutritional modification within the normal range can be effective. The sensitivity and predictive value of screening tests, the increment in improved outcomes from screening compared with population-wide changes in diet; the benefit, if any, to be derived from diet modification for those not identified by screening; and the reliability of the laboratories performing the test are some of the factors to be considered. We must bear in mind that many of the common disorders for which we will soon have tests at the gene or gene-product level result from the interaction of multiple factors, both environmental and genetic. Genetic screening will detect only a small proportion of all those destined to manifest a specific disorder, such as coronary artery disease or colon cancer. Dietary modification will also be only one of several interventions that will be efficacious for certain disorders. In some of these cases, genetic screening will prove to be an effective adjunct to general nutritional changes whereas in others it will have little utility and in still others it could play the predominant role in preventing or reducing the severity of the disorder. If we are to reduce the burden of disease most effectively, we cannot ignore factors in our environment and social structure that limit people's ability to control their own health.

A successful city-wide smoke detector giveaway program.

Each year, 5,000 Americans die and 300,000 are hospitalized as a result of 2.8 million residential fires. Almost all house fires allow time for safe exit if an early warning is given. Smoke detectors are an effective, reliable, and inexpensive method of providing such warning. After an upsurge of deaths related to fires in 1982, Baltimore City gave away 3,720 smoke detectors to households that requested them. This study addressed two questions: (1) Did the households that received the smoke detectors install them? (2) Was the population reached by this giveaway program a population at high risk from fire? A survey of 231 randomly selected households among those requesting smoke detectors was conducted 8 to 10 months after the giveaway program. At that time, smoke detectors were installed in 92% (212/231) of the homes and 88% (187/212) of the installed smoke detectors were operational. Households requesting smoke detectors were in census tracts at higher risk from fire. The correlation coefficient between the rate of requesting a smoke detector and the risk of death or injury related to fires was r = .90, P less than .001. The 231 surveyed households had more personal fire risk factors than the general population. The success of this smoke detector giveaway program is notable in that it required the active participation of a high-risk population.

Effect of informed parental consent on mothers' knowledge of newborn screening.

To determine whether knowledge was improved as a result of obtaining informed consent from parents for newborn screening of their infants for phenylketonuria (PKU) and other hereditary metabolic disorders, new mothers in seven Maryland hospitals were interviewed either before receiving a standard disclosure (n = 210) or after giving consent (n = 418). The mean knowledge score of the women interviewed after giving consent was significantly higher (P less than .001). Receiving the disclosure was a more powerful predictor of knowledge score, accounting for 40% of the variance, than demographic factors, which accounted for 9%. Women whose consent was obtained just prior to discharge tended to have lower knowledge scores than women whose consent was obtained earlier (P = .03). Women with higher knowledge scores were somewhat less likely to favor consent than women with lower scores. Although consent may not be appropriate for some low-risk procedures, informing parents can be easily and inexpensively accomplished.

Discharging patients with prescriptions instead of medications: sequelae in a teaching hospital.

OBJECTIVE: This study measures the incidence of discrepancies among written prescriptions, medication regimens transcribed onto patient discharge instruction sheets (DCIs), and labels on medications dispensed by community pharmacies after discharge of patients from an academic medical center. METHODS: During a 2-month study period, we collected copies of prescriptions and DCIs. We also called care givers after discharge and asked them to read the medication labels that were filled from discharge prescriptions. Care givers were also asked whether they received instruction from community pharmacies. RESULTS: Data were collected on 335 prescriptions for 192 patients. Differences among the prescriptions, DCIs, and medication labels were found for 40 (12%) of the medications prescribed at discharge, representing 19% of the patients studied. Nineteen prescriptions had prescriber errors in dosing frequencies or dosage formulations. Three prescriptions were filled with different medication concentrations or strengths than requested. Prescriptions were altered by the community pharmacists for unexplained reasons in 6 cases, whereas the DCIs and original prescriptions differed in 12 cases. Only 44% of families were counseled about proper medication administration by their pharmacists. CONCLUSIONS: A potential for medication errors exists when pediatric patients are discharged with unfilled prescriptions. The potential may be worsened when discharge instructions are created from a prescription rather than from the label of a dispensed medication. Educational and risk-management efforts should emphasize the importance of writing complete, legible prescriptions and consulting appropriate reference materials to ensure that dose formulations and guidelines are accurate. Whenever possible, prescriptions should be filled before patients are discharged, so that the dispensed medications can be reviewed, and health care providers can provide accurate discharge instructions.

Medical and ethical issues in genetic screening--an academic view.

This article is intended to acquaint those whose principal concerns are the health and safety of workers with genetic screening and some of the medical and ethical issues it raises. Population-based genetic screening increasingly is being considered for predicting future disease in the person being screened. A major problem in screening for alleles that contribute to the development of common, multifactorial disorders is low sensitivity and positive predictive value. In many instances, no demonstrably effective prophylaxis or treatment is available to help those with positive test results. This creates ethical problems of assuring that testing is in the person's best interest and raises in turn issues of autonomy, discrimination, and privacy. Instead of screening for genetic predispositions to harm from workplace exposures, other means of improving the health of workers may bring greater benefits to a higher proportion of workers. The current state of genetic tests for chronic beryllium disease are considered. None are suitable for screening.

The impact of the federal cutback on genetic services.

A survey of directors of federally supported genetics, sickle cell and hemophilia programs was undertaken to determine the effect of reduced federal awards for fiscal year 1983 (FY83). Most states deemed ineligible for federal genetics and sickle cell grants for FY83 were unable to make up federal losses with funds from other sources. In FY82, per capita allocations to genetics and sickle cell programs were not significantly different between states that remained eligible in FY83 and those that became ineligible. In FY83, however, per capita allocations were significantly lower in the ineligible states. If cutbacks were to curtail operations, most program directors would give their highest priority to preserving newborn screening and follow-up services. Of the 23 states that do not currently charge for newborn screening, 8 are contemplating imposition of a charge. The findings suggest that continued or expanded availability of genetic services depends, in part, on federal support.

Primary care physicians' perceptions of barriers to genetic testing and their willingness to participate in research.

Our objective was to explore the barriers and motivations to: 1) appropriate diffusion of genetic services into primary care practice; and 2) primary care physicians' (PCPs) willingness to participate in clinical studies to assess the safety and effectiveness of emerging genetic technologies. A random sample (n = 994) of PCPs was invited to be interviewed. Of the 80 who agreed, 60 were interviewed, 52 by telephone. A semi-structured guide was used. A questionnaire mailed to 752 of the PCPs was used to elicit information from physicians who did not want to be interviewed. Among interviewees, uncertainty as to the clinical utility and clinical validity of predictive genetic testing were the leading barriers to incorporation of this technology into practice, being mentioned by 60 and 43% of subjects, respectively. Of the 100 (13. 3%) physicians returning the questionnaire who declined to be interviewed, 30% said they would be willing to participate in research on the safety and effectiveness of predictive genetic tests. Of those who were interviewed, 92% were willing to participate in such research. Most physicians do not see genetics as important in their practice today; many anticipate greater importance in the future. The proportion of physicians interested in participating in research to assess the safety and effectiveness of genetic tests is sufficient to make large scale, collaborative, practice-based evaluation feasible. Additionally, participation in research may serve as an effective medium for physician education in genetics.

Educational material about genetic tests: does it provide key information for patients and practitioners?

Genetic testing for common conditions will be used increasingly in primary care, but resources for patient counseling are decreasing. It is also necessary that primary care practitioners be better equipped to do basic genetic counseling. Therefore, the quality of informational materials for practitioners and patients is important. It was unknown how often key elements recommended by policy groups were actually included in such material. It was our aim to determine the content of printed informational material for practitioners and patients on genetic testing. We performed (1) a telephone survey of organizations in the United States that developed genetic tests or services and (2) a content analysis of pamphlets obtained from these organizations to determine the presence of 10 critical elements necessary to evaluate the appropriateness and performance of the tests. Almost 95% (169/178) of organizations responded to our survey; 131/169 (78%) reported using informational materials. We analyzed 115 pamphlets collected from 125/131 (95%) organizations. Elements least frequently included in the pamphlets were risks and benefits, patient rights, and intended use or purpose of the test. Most frequently included were descriptions of the conditions detected by the test, and the appropriate patients for testing. Nearly one half of the pamphlets included some statement about the accuracy of the test, but most of these did not specify whether their statements referred to sensitivity, specificity, or predictive value. Overall, pamphlets tended to contain information that would aid in determining a patient's eligibility for a genetic test, but did not contain sufficient information about the tests themselves. Our results suggest that several critical elements need to be added to enhance informed choices by patients and physicians.

Attitudes of physicians and genetics professionals toward cystic fibrosis carrier screening.

With the identification of the cystic fibrosis (CF) gene and its major mutations in 1989, there has been considerable debate among health professionals as to whether population-based carrier testing should be instituted. This paper presents the results of a survey to determine the attitudes of physicians and genetics professionals toward CF carrier testing. Factors associated with differences in attitudes also were examined. A questionnaire was mailed to primary care physicians and psychiatrists in 10 states who graduated from medical school between 1950 and 1985. For comparison, medical geneticists and genetic counselors in the same states also received the questionnaire. A total of 1,140 primary care physicians and psychiatrists (64.8%) and 280 medical geneticists and genetic counselors (79.1%) responded. Although 92% of respondents believed that a couple should be tested after asking about a test that detected 80% of carriers, only 43.9% of respondents believed such a test should be offered routinely. Those specialists most likely to have been involved in genetic services were most opposed to routine screening. The most important reason reported for opposition to routine screening was the consequences of an 80% detection rate. When presented with a hypothetical "error-free" test, 75.9% of respondents favored routine testing. Our findings suggest that there was little support for routinely offering the CF carrier test available at the time of this study among the physicians and professionals most involved in the provision of genetic services.

Problems with the report of the Expert Panel on blood cholesterol levels in children and adolescents.

An Expert Panel convened by the National Cholesterol Education Program has recommended selective screening and treatment of children for high blood cholesterol levels, based on family history of cardiovascular disease or high blood cholesterol. This recommendation is problematic for several reasons. First, the recommended diets are likely to cause only a slight decrease in low-density lipoprotein cholesterol levels, the projected benefits of which will be offset by a similar decrease in high-density lipoprotein cholesterol levels. Lack of efficacy of the recommended diets could lead to use of more restrictive diets or to cholesterol lowering drugs. Second, even under optimistic assumptions, beneficial effects of cholesterol intervention will be small and delayed for many decades. As a result, childhood cholesterol-lowering efforts will not be cost-effective. Third, the Expert Panel's recommendations do not address important gender differences. Girls have higher average cholesterol levels than boys. They will therefore qualify for more dietary and drug treatment despite their lower age-adjusted risk of heart disease and the lack of association between cholesterol levels and cardiovascular mortality in women. Finally, recent evidence from randomized trials, cohort studies, and animal experiments suggests that cholesterol lowering may have serious adverse effects. This evidence was not discussed in the Expert Panel's report. Given current evidence, any screening and treatment of children for high blood cholesterol levels is, at best, premature.

Prenatal genetic testing: content of discussions between obstetric providers and pregnant women.

OBJECTIVE: To document the content and accuracy of discussions about prenatal genetic testing between obstetric providers and pregnant women. METHODS: The first prenatal visits of 169 pregnant women with 21 obstetricians and 19 certified nurse-midwives were audiotaped and analyzed for whether a discussion of family history or genetic testing took place and if so, its length, content, and accuracy. RESULTS: Family history was discussed in 60% of visits, maternal serum marker screening in 60%, second-trimester ultrasonography for fetal anomalies in 34%, and for women at least 35 years old, amniocentesis or chorionic villus sampling (CVS) in 98%. The length of discussions of genetic testing averaged 2.5 minutes for women younger than 35 years of age and 6.9 minutes for older women. Topics discussed most often were the practical details of testing, the purpose of testing, and the fact that testing is voluntary. Discussions seldom were comprehensive. Obstetricians were more likely to make a recommendation about testing than were nurse-midwives and were less likely to indicate that testing is voluntary. Most women were satisfied with the amount of information, and the majority of women of advanced maternal age had made a decision about amniocentesis or CVS by the end of the visit. CONCLUSION: The information about genetic testing provided in the first prenatal visit is inadequate for ensuring informed autonomous decision-making. Guidelines addressing the content of these discussions should be developed with input from obstetricians, nurse-midwives, genetic counselors, and pregnant women.

Genetics and social class.

OBJECTIVE: To assess claims that genes are a major determinant of social class. DESIGN: Using genetic epidemiological principles, five claims on the role of genes in determining social class are examined: (1) traits that run in families are usually inherited; (2) complex traits can be explained by alleles at a single gene locus; (3) complex traits are transmitted intact from one generation to the next; (4) natural selection explains social advantage. (5) Heritability estimates provide a valid estimate of the importance of genes in explaining complex human traits or behaviour. RESULTS: (1) Traits that run in families can result from environmental exposures that differ by social class. (2) The protein encoded by any single gene has too narrow a range of biological activity to explain traits as complex as social status. (3) Because alleles at different gene loci are transmitted independently, genetic inheritance cannot explain why offspring display the same complex traits as their parents. (4) The propagation of mutations that might result in a selective advantage takes much longer than the time for which any social class has achieved or maintained dominance. (5) Heritability measures are accurate only when environment is maintained constant. This is impossible in evaluating human traits. CONCLUSIONS: The roots of social class differences do not lie in our genes. Consequently, genetics cannot be used as a justification for maintaining a ruling class, limiting procreation among the poor, or minimising social support programmes.

Physicians' knowledge of genetics and genetic tests.

PURPOSE: To assess primary care physicians' and psychiatrists' knowledge of genetics and genetic tests and the factors associated with differences in these physicians' knowledge. METHOD: Questionnaires were mailed in 1991 to 1,795 primary care physicians (family physicians, internists, pediatricians, obstetrician-gynecologists) and psychiatrists who had graduated from medical school between 1950 and 1985 (67.6% of the sample had graduated after 1970) and who were members of professional societies. The questions elicited demographic and practice characteristics as well as knowledge of genetics concepts and facts and awareness of the availability of genetic tests. To validate the questionnaire, 360 medical geneticists and genetic counselors received questionnaires. Statistical analysis involved arc-sine function transformation, t-tests, analyses of variance, F-tests, Tukey's HSD, and stepwise multiple regression. RESULTS: A total of 1,140 (64.8%) of the non-geneticist physicians responded. They correctly answered an average of 73.9%, SD, 13.9%, of the knowledge items, compared with 94.6%, SD, 4.2%, for the genetics professionals (p < .001). The most significant predictors of knowledge were recency of graduation from medical school and practicing in primary care specialties in which exposure to genetics problems is likely. Other significant predictors (from most to least important) were graduation from a U.S. medical school, willingness to adopt a new predictive test before it becomes standard practice, not using pharmaceutical companies as a source of information about new medical practices, and taking a required genetics course in medical school. CONCLUSIONS: The results suggest that knowledge of genetics and genetic tests is increasing among physicians, particularly among more recent graduates and physicians who are exposed to genetics problems in their practices, but deficiencies remain. Although a medical school course in genetics may improve knowledge, it is not sufficient. Greater emphasis is needed at all levels of medical education to reduce the chance of physician error as more genetic tests become available.

Are we ready to screen for inherited susceptibility to cancer?

The discovery of inherited gene mutations that increase the risk of certain cancers could greatly expand the use of predictive genetic testing in healthy individuals. In families with hereditary forms of cancer, the use of genetic tests to determine whether family members have inherited susceptibility mutations (ISMs) may improve outcome. Even within high-risk families, questions remain about the role of other genetic, nutritional, and environmental factors in the development of cancer, the value of monitoring people with ISMs, and the safety and efficacy of preemptive interventions. Before screening is undertaken in the general population, these questions must be addressed. Also, the frequency and penetrance of ISMs in the population at large must be determined, as well as the safety and effectiveness of screening. Lastly, mechanisms need to be established to ensure that those offered screening give full, informed, autonomous consent and that laboratories involved in testing meet quality standards.