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PubMed2006

What do we tell the children? Contrasting the disclosure choices of two HD families regarding risk status and predictive genetic testing.

Above all else, predictive genetic testing provides information. Gaining insight into the psychosocial effects of this information is a primary goal of genetic counseling. For individuals utilizing predictive genetic testing, the acquisition of genetic information requires choices regarding disclosure within the family. This study uses a phenomenological methodology to explore the contrasting choices of two sets of HD parents regarding the disclosure of genetic risk status to their children. Additionally, the children (now adults) discuss their lived experience growing up with contrasting disclosure dynamics, and their current views regarding the use of predictive genetic testing for themselves. The primary finding of this study is that all of the adult children now express preference for early disclosure of genetic risk and an open/supportive communication style regarding HD. This finding has value for clinicians working with HD families who must make decisions regarding disclosure issues related to predictive genetic testing.

Adaptation, Psychological↗
PubMed2001

Is there a case in favour of predictive genetic testing in young children?

Genetic testing has brought the ability to predict the onset of diseases many years before symptoms appear and the use of such predictive testing is now widespread. The medical fraternity has met the application of this practice to children with caution. The justification for their predominantly prohibitive stance has revolved around the lack of a readily identifiable medical benefit in the face of potential psychological harms to the child. We argue that predictive testing can have important psychosocial benefits and that the interests of the child have been construed too narrowly. Proponents of a prohibitive stance also argue that testing in childhood breaches the child's future right to make the same decision as an autonomous adult and to maintain this information as confidential. We argue that predictive genetic testing of children is not necessarily a violation of the child's future autonomy. Indeed, in some cases, such testing may facilitate the development of autonomy in the maturing child. We argue that parents are generally best placed to judge what is in their own child's overall interests, and that parental request for testing after appropriate genetic counselling should be respected unless there is clear evidence that the child will be harmed in an overall sense as a result of testing.

Adolescent↗
PubMed1991

Counselling patients with HIV infection about laboratory tests with predictive values.

Laboratory tests, including CD4 counts, p24 antigen, raised levels of B2 microglobulin, neopterin and CMV antibodies, have been established as important predictive markers of disease progression in patients with HIV infection. As HIV antibody testing becomes more accepted in medical practice, counselling about these laboratory predictors of progression can help patients and doctors plan together the patients' care and treatment. Addressing patients' main concerns at each stage of investigation and illness may help them to plan ahead of crises, reduce stress, and enhance communication between patients and health care providers.

Adult↗
PubMed2003

Predictive genetic testing for breast cancer and Huntington's disease: the opinions of midwives and nurses in Flanders.

OBJECTIVE: Investigate attitudes of midwives and nurses regarding predictive testing for hereditary breast cancer and Huntington's disease. METHODS: Mail questionnaires were sent to 119 midwives and 881 nurses. RESULTS: The response rate was 58% for midwives, but only 33% for nurses. The attitude toward predictive testing in an asymptomatic adult was more favourable in case of hereditary breast cancer than in case of Huntington's disease, mostly because prevention or therapy is unavailable for the latter condition. Prevention of breast cancer through prophylactic mastectomy elicited adverse reactions among 40% of the participants. Predictive testing for these diseases in an adolescent at the own request was also rated favourably while testing in children at the parents' request was less acceptable. For both diseases, concealing carrier status information from the employer or the insurance company was judged as acceptable by the majority. CONCLUSION: Our findings contribute to the understanding of nurses' and especially midwives' attitudes to predictive testing, which may in turn serve as a basis for genetic education for these groups of health care professionals.

Attitude of Health Personnel↗
PubMed2004

Ethical implications of predictive DNA testing for hereditary breast cancer.

Predictive medicine offers the possibility of detecting many common diseases that have a genetic basis, such as cancer; however, a genetic alteration might only indicate susceptibility to, not certainty of, disease. Whereas means for identifying a greater susceptibility to disease have been developed, effective interventions have progressed much more slowly. Awareness of one's susceptibility to disease without an actual possibility of intervention can lead to an unacceptable use of such information, or have a dramatic psychological impact on the person involved. Are the risks connected with the knowledge of susceptibility to genetic disease proportional to the benefits that such knowledge may provide? Does the knowledge of one's genetic condition constitute a service to the individual and society, or is this predominantly harmful for the person involved? The problem is vast, and involves medical, psychological, social, political and ethical dilemmas. These dilemmas, common to all predictive medicine, are most evident in predictive DNA testing for hereditary breast cancer. In our analysis, we will first examine the ethical values involved in genetic testing, highlighting the special ethical issues raised by predictive DNA testing for hereditary breast cancer. Next we will deal with genetic counseling, which, in our opinion, is the 'ethos' for ethically justifying predictive DNA testing.

Breast Neoplasms↗
PubMed1990

Using population-based serum drug concentration cutoff values to predict toxicity: test performance and limitations compared with Bayesian interpretation.

The use of population-based serum drug concentration cutoff values for several commonly monitored drugs as tests to distinguish toxicity from nontoxicity was studied. Serum drug concentration and response data published in studies of theophylline, digoxin, aminoglycosides, vancomycin, and procainamide were analyzed to determine the prevalence of toxicity in each group of patients. Serum drug concentration cutoff values were then varied, and the following performance characteristics of the cutoffs as tests for predicting toxicity were calculated for each value: sensitivity, specificity, likelihood ratio, predictive value, and ratio of net consequences. At commonly accepted cutoff values, sensitivity was lower than desirable, positive predictive values were less than negative values, and the ratio of net consequences indicated that false-negative errors are implicitly weighted as more risky than false-positive errors. As the cutoff for each drug was increased, specificity increased but sensitivity decreased, positive predictive values increased but negative predictive values decreased, and the ratio of net consequences increased. Therapeutic drug monitoring would improve if practitioners and laboratorians collaborated to (1) conduct prospective studies of the test performance characteristics of drug concentrations, (2) estimate the pretest probability of toxicity for each patient, (3) combine the pretest estimate with the test characteristics to make a posttest estimate, and (4) develop a more patient-specific, Bayesian approach.

Aminoglycosides↗
PubMed2002

[Analysis of 14 individuals who requested predictive genetic testing for hereditary neuromuscular diseases].

Predictive genetic testing for hereditary neuromuscular diseases is a delicate issue for individuals at risk and their families, as well as for medical staff because these diseases are often late-onset and intractable. Therefore careful pre- and post-test genetic counseling and psychosocial support should be provided along with such genetic testing. The Division of Clinical and Molecular Genetics was established at our hospital in May 1996 to provide skilled professional genetic counseling. Since its establishment, 14 individuals have visited our clinic to request predictive genetic testing for hereditary neuromuscular diseases (4 for myotonic dystrophy, 6 for spinocerebellar ataxia, 3 for Huntington's disease, and 1 for Alzheimer's disease). The main reasons for considering testing were to remove uncertainty about the genetic status and to plan for the future. Nine of 14 individuals requested testing for making decisions about a forthcoming marriage or pregnancy (family planning). Other reasons raised by the individuals included career or financial planning, planning for their own health care, and knowing the risk for their children. At the first genetic counseling session, all of the individuals expressed hopes of not being a gene carrier and of escaping from fear of disease, and seemed not to be mentally well prepared for an increased-risk result. To date, 7 of the 14 individuals have received genetic testing and only one, who underwent predictive genetic testing for spinocerebellar ataxia, was given an increased-risk result. The seven individuals including the one with an increased-risk result, have coped well with their new knowledge about their genetic status after the testing results were disclosed. None of them has expressed regret. In pre-test genetic counseling sessions, we consider it quite important not only to determine the psychological status of the individual, but also to make the individual try to anticipate the changes in his/her life upon receiving an increased-risk or a decreased-risk result. Sufficient time should be taken to build a good relationship between the individual and his/her family and the medical staff during pre-test counseling sessions. This will help the individuals feel satisfied with their own decisions for the future, whether they receive genetic testing or not.

Adult↗
PubMedDate not supplied

Testing 40 predictions from the transtheoretical model.

Sensitive measurement of behavior change requires dependent measures that are sensitive to the whole spectrum of change, not just a single aspect of change. Traditional outcome variables such as point prevalence for smoking cessation focus on a single discrete event and ignore all other progress. Alternatively, the criterion measurement model (CMM) is an approach that posits a three-construct outcome model (habit strength, positive evaluation strength, and negative evaluation strength), where different constructs are sensitive to change for different aspects of the temporal domain. In this article, a series of 40 differential a priori predictions were tested using a large representative sample of smokers. The focus was on the prediction of specific effect sizes rather than statistical significance. A series of comparisons involving stage transitions was examined using five variables representing the three CMM constructs. The predictions involved movement from one of three initial stages (precontemplation, contemplation, and preparation) to stage membership 12 months later. Thirty-six of the 40 predictions were confirmed, indicating that the outcome model has strong construct validity and accurately reflects movement between the stages of change.

Adolescent↗
PubMedDate not supplied

Public attitudes about genetic testing for Alzheimer's disease.

In a general population survey (N = 314), 79 percent of respondents stated that they would take a hypothetical genetic test to predict whether they will eventually develop Alzheimer's disease. The proportion fell to 45 percent for a "partially predictive" test (which had a one in ten chance of being incorrect). Inclination to obtain testing was similar across age groups. Respondents were willing to pay $324 for the completely predictive test. Respondents stated that if they tested positive, they would sign advance directives (84 percent), get their finances in order (74 percent), and purchase long-term care insurance (69 percent). Only a third of respondents expressed concern about confidentiality. The results suggest that people value genetic testingfor personal and financial reasons, but they also underscore the need to counsel potential recipients carefully about the accuracy and implications of test information.

Adult↗
PubMed1998

The critical power function is dependent on the duration of the predictive exercise tests chosen.

The linear relationship between work accomplished (W(lim)) and time to exhaustion (t(lim)) can be described by the equation: W(lim) = a + CP x t(lim). Critical power (CP) is the slope of this line and is thought to represent a maximum rate of ATP synthesis without exhaustion, presumably an inherent characteristic of the aerobic energy system. The present investigation determined whether the choice of predictive tests would elicit significant differences in the estimated CP. Ten female physical education students completed, in random order and on consecutive days, five all-out predictive tests at preselected constant-power outputs. Predictive tests were performed on an electrically-braked cycle ergometer and power loadings were individually chosen so as to induce fatigue within approximately 1-10 mins. CP was derived by fitting the linear W(lim)-t(lim) regression and calculated three ways: 1) using the first, third and fifth W(lim)-t(lim) coordinates (I135), 2) using coordinates from the three highest power outputs (I123; mean t(lim) = 68-193 s) and 3) using coordinates from the lowest power outputs (I345; mean t(lim) = 193-485 s). Repeated measures ANOVA revealed that CPI123 (201.0+/-37.9W) > CPI135 (176.1+/-27.6W) > CPI345 (164.0+/-22.8W) (P<0.05). When the three sets of data were used to fit the hyperbolic Power-t(lim) regression, statistically significant differences between each CP were also found (P<0.05). The shorter the predictive trials, the greater the slope of the W(lim)-t(lim) regression; possibly because of the greater influence of 'aerobic inertia' on these trials. This may explain why CP has failed to represent a maximal, sustainable work rate. The present findings suggest that if CP is to represent the highest power output that an individual can maintain "for a very long time without fatigue" then CP should be calculated over a range of predictive tests in which the influence of aerobic inertia is minimised.

Adenosine Triphosphate↗
PubMed1988

Reliability of brightness comparison testing in predicting afferent pupillary defects.

We tested the reliability of brightness comparison testing in predicting relative afferent pupillary defects (RAPDs) in 206 patients. For unselected patients, brightness comparison testing correctly predicted the RAPD in 62% of patients. For subgroups of patients with glaucoma and optic nerve lesions, correct predictions were made in 92% and 83% of patients, respectively. Sensitivity and specificity of brightness comparison testing with a 6-V test light were 85% and 49%, respectively. In subgroups of patients who are strongly suspected of having an RAPD but in whom pupillary testing is not possible, brightness comparison testing can reliably predict presence or absence of an RAPD.

Amblyopia↗
PubMed2001

Postgenomic medicine. Presymptomatic testing for prediction and prevention.

Significant changes are occurring in genetic screening paradigms. Genetic screening is moving from traditional analytes, such as small molecules and proteins, to molecular genetic testing involving DNA and RNA. There are significant consequences to these changes, involving issues for the family unit, such as misattribution of parentage, and concerns regarding discrimination, confidentiality, and privacy. Although these latter issues have broader concerns for medicine and medical information, in the context of genetic testing, information derived from one individual can have a significant impact on others within their family. Screening is also changing from mendelian disease ascertainment to predictive testing. Issues that arise involve appropriate age at testing for adult-onset disorders, the clinical validity and clinical use of genetic testing for complex diseases, and the efficacy of interventions following genetic testing. We are also learning that the phenotypes of even simple mendelian disorders are influenced by complex genetic and environmental factors. The observations that genotypes rarely predict phenotypes absolutely have significant ramifications for counseling based on mutation analysis, for example in neonates who have not yet manifested symptoms and in older children and in adults undergoing predictive testing. Molecular genetic testing often proceeds rapidly from the research laboratory to the clinical setting. We must recognize that for single-gene disorders with high penetrance, the information derived from such testing may be relatively easy to interpret and apply. For complex diseases, however, the populations studied and their demographic characteristics are extremely important for extrapolation to counseling of individual patients. The value of population-based predictive testing is exemplified by newborn screening. It is clear that the Human Genome Project, and the information and technologies from it, will have a much broader impact on public health by presymptomatic prediction and prevention of disease.

Adolescent↗
PubMed2004

Sensitivity, specificity, positive predictive value, and negative predictive value of the dipyridamole sestamibi stress test in predicting graft occlusion or > or = 50% new native coronary artery disease in men versus women and in patients aged > or = 65 years versus < 65 years who had prior coronary artery bypass grafting.

The sensitivity, specificity, positive predictive value, and negative predictive value of the dipyridamole sestamibi stress test (DSST) in predicting graft obstruction or > or = 50% new native coronary artery disease (CAD) in 88 men compared with 56 women with prior coronary artery bypass surgery were 96% and 94% (p = NS), 30% and 67% (p = NS), 91% and 96 % (p = NS), 50% and 57% (p = NS), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the DSST in predicting graft obstruction or > or = 50% new native CAD in 92 patients aged < 65 years were 95% and 95% (p = NS), 50% and 40% (p = NS), 96% and 87% (p = NS), and 43% and 67% (p = NS), respectively.

Adult↗
PubMed2002

General practitioners and predictive genetic testing for late-onset diseases in Flanders: what are their opinions and do they want to be involved?

OBJECTIVE: Investigate the attitudes of general practitioners (GPs) concerning predictive testing for late-onset diseases, as well as the perception of their own role in this context. METHODS: 356 GPs received mail questionnaires with telephone pre-notifications and reminders. RESULTS: The questionnaire was returned by 60% (n=215). The GPs' attitudes toward predictive testing for breast cancer, thyroid cancer, Alzheimer disease and Huntington's disease were influenced by the availability and the type of preventive and therapeutic options, the age of onset of the disease as well as by ethical concerns. Regarding a possible tasks for GPs, most of the GPs focussed on gate-keeping aspects, such as providing information and making referrals. CONCLUSION: The GPs were supportive of a limited role for general practice in predictive testing. Genetic education for GPs is needed, with attention to non-directiveness and the characteristic psychosocial and ethical implications of this particular type of genetic testing.

Adolescent↗
PubMed2004

Methodology in longitudinal studies on psychological effects of predictive DNA testing: a review.

In the last two decades predictive testing programs have become available for various hereditary diseases, often accompanied by follow-up studies on the psychological effects of test outcomes. The aim of this systematic literature review is to describe and evaluate the statistical methods that were used in these follow-up studies. A literature search revealed 40 longitudinal quantitative studies that met the selection criteria for the review. Fifteen studies (38%) applied adequate statistical methods. The majority, 25 studies, applied less suitable statistical techniques. Nine studies (23%) did not report on dropout rate, and 18 studies provided no characteristics of the dropouts. Thirteen out of 22 studies that should have provided data on missing values, actually reported on the missing values. It is concluded that many studies could have yielded more and better results if more appropriate methodology had been used.

DNA↗
PubMed2000

Predictive genetic testing in diabetes: a case study of multiple perspectives.

Genetic testing is now possible in maturity onset diabetes of the young (MODY), an unusual genetic subtype of diabetes. To date, there has been no research into the implications of genetic testing for MODY families. The case study of the first known instance of predictive genetic testing for diabetes described in this article focuses on the perspectives of the family and the health care professionals involved in the decision-making process. Open-ended interviews were conducted before and after the predictive test. Content analysis highlighted four key areas: autobiographical experiences, motivations for testing, competing priorities in genetic counseling, and differing attitudes to predictive testing for children. Reactions to the predictive test result are presented. The implications of these findings for the provision of predictive genetic testing in diabetes are considered.

Adult↗
PubMed2003

Role of coagulation testing in predicting bleeding risk.

Coagulation testing is employed widely prior to open surgery and invasive procedures. This is based on the assumption that such testing is of clinical value in the prediction of bleeding. In order to improve the clinical understanding of the potential limitations of first-line coagulation tests used in this way, we have systematically reviewed the literature that addresses the value of routine coagulation testing in helping to predict bleeding risk. We conclude unreservedly that indiscriminate coagulation testing is not useful in a surgical or a medical setting. This is due to the limited sensitivity and specificity of the tests, coupled with the low prevalence of bleeding disorders resulting in a high number of false positives, poor positive predictive value for bleeding and numerous false negatives resulting in false reassurance. Since most abnormal results can be predicted and most cases of significant bleeding disorder identified from a complete clinical assessment, the employment of selective laboratory testing is more cost-effective and represents evidence-based clinical practice.

Adult↗