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At least 649 records · Page 36Linked to original sources
PubMed2000

Value of predictive genetic testing in management of hereditary non-polyposis colorectal cancer (HNPCC)

OBJECTIVE: To investigate the impact of predictive genetic testing on colonoscopic surveillance in an extended family with hereditary non-polyposis colorectal cancer (HNPCC). SETTING: Familial Bowel Cancer Service, The Royal Melbourne Hospital, Victoria. SUBJECTS: 96 people registered with the Service who were apparently unaffected members of an extended family that met the classic Amsterdam criteria for HNPCC and carried an MLH1 gene mutation (IVS9 + 3insT). INTERVENTION: Predictive genetic testing was offered in a cascade manner to at-risk family members; mutation-positive individuals were advised to have annual colonoscopic surveillance, while mutation-negative individuals were withdrawn from surveillance. MAIN OUTCOME MEASURES: Previous compliance with recommended colonoscopic surveillance; uptake and results of genetic testing; expected effect of genetic test results on number of colonoscopies over five years. RESULTS: 22 of the 96 family members (23%) were not complying with recommended surveillance. Of 48 individuals offered predictive genetic testing, 41 (85%) responded and 39 (81%) underwent testing. Seven of the 39 (18%) were positive for the family-specific mutation, and 32 (82%) were negative. The 39 tested individuals and 37 of their descendants who were registered with the screening program had undergone 70 colonoscopies in the five years before genetic testing. In the five years after testing, only 37 surveillance colonoscopies were planned (annual or two-yearly colonoscopies for the six mutation-positive individuals and five-yearly colonoscopies for four mutation-negative individuals with previously identified adenoma), an almost 50% reduction in colonoscopies. CONCLUSION: Predictive genetic testing in HNPCC families allows many individuals to be withdrawn from regular colonoscopic surveillance. It may therefore reduce costs, as well as have emotional benefits for many individuals.

Adult↗
PubMed1999

Comparison between creatine kinase brain isoenzyme (CKBB) activity and Sarnat score for prediction of adverse outcome following perinatal asphyxia.

AIM: To assess whether plasma creatine kinase brain isoenzyme (CKBB) levels or Sarnat scores are more accurate for prediction of poor neurological outcome in babies with suspected birth asphyxia. METHODS: In a retrospective study of 97 babies CKBB levels were compared to the presence of severe hypoxic ischaemic encephalopathy (HIE) as a predictive test for these outcomes: developmental delay, cerebral palsy, visual problems, deafness or death from perinatal asphyxia. The tests were compared using positive predictive values (PPV) and likelihood ratios (LR) with confidence intervals (CI). RESULTS: 3 babies had died from perinatal asphyxia and 14 survivors were found to have neurological or developmental problems. CKBB was elevated in babies with severe HIE (p = 0.0004). A receiver operator characteristic (ROC) curve showed the optimal discriminating value for CKBB to be 21 IU/L but the CKBB was a poor predictive test. For prediction of adverse outcome: CKBB > 21 sensitivity 76%, specificity 40%, PPV 21% and LR 1.3 (95% CI 0.8-1.7). Severe HIE sensitivity 53%, specificity 95%, PPV 69% and LR 10.6 (95% CI 3.8-29.2). CONCLUSION: CKBB is elevated following birth asphyxia but is a poor predictor of adverse neurological outcome.

Asphyxia Neonatorum↗
PubMed2004

Reliability and validity of a manual dexterity test to predict preclinical grades.

The University of California, San Francisco School of Dentistry wanted to determine if a predental school manual dexterity test predicts: 1) subsequent grades in preclinical restorative courses, and 2) faculty perceptions of satisfactory performance in these skills that would indicate the student is ready to advance to the clinic. The study population was comprised of all 244 applicants admitted to UCSF School of Dentistry's D.D.S. program from Classes of 2000 to 2002 and who matriculated into the program. The manual dexterity test (MDT) consisted of a two-hour block-carving test. Three preclinical faculty, three clinical faculty, and two basic science faculty graded the blocks. Even after instruction and calibration, faculty varied greatly in their grading (intra-rater reliability kappa statistics ranging from 0.34 to 1.00). Two of three preclinical raters gave No Passes for the MDT in 9.8 percent of the incoming, first-year dental students. Of these twenty-three students, only four (17 percent) were in the lower 10 percent of their classes according to their five preclinical restorative laboratory courses after two years, and four (33 percent) were among the twelve students the three preclinical laboratory directors identified as laboratory cautions. The MDT did not significantly (p=0.342) predict students in the bottom 10 percent after five restorative preclinical laboratory courses, above and beyond current admissions criteria. Among current admissions criteria, PAT score was the only item at least moderately correlated with preclinical average percentile class rank (Spearman correlation = 0.34). In conclusion, the MDT did not appear to add information to the current admissions criteria.

Aptitude Tests↗
PubMed1985

Limitations of failure of procainamide during electrophysiologic testing to predict response to other medical therapy.

To determine whether failure of procainamide to prevent initiation of ventricular tachyarrhythmias during electrophysiologic testing predicted failure of other antiarrhythmic regimens, 81 consecutive patients with coronary artery disease whose ventricular tachyarrhythmias remained inducible during procainamide administration were studied. Overall, 26 (12%) of 216 subsequent drug studies were successful and at least one effective drug regimen was identified in 22 (27%) of the 81 patients. Drug success was significantly related to the arrhythmia induced at baseline study; 7% of drug studies were successful in patients with sustained ventricular tachycardia, 24% in patients with ventricular fibrillation, and 29% in patients with nonsustained ventricular tachycardia. An effective drug regimen was found in 11 (19%) of 59 patients with sustained ventricular tachycardia, 4 (50%) of 8 patients with ventricular fibrillation and 7 (50%) of 14 patients with nonsustained ventricular tachycardia. In patients with sustained ventricular tachycardia, failure of procainamide to suppress the arrhythmia correlated with failure of other agents used singly but not in combination. This study supports the view that when procainamide fails to prevent initiation of the arrhythmia in patients with inducible sustained ventricular tachycardia it is unlikely that other individual standard agents will be effective. However, combination regimens may suppress the arrhythmia and should be evaluated. In patients with nonsustained ventricular tachycardia, all agents should be evaluated because failure to respond to procainamide does not predict subsequent responses to other agents either alone or in combination.

Adult↗
PubMed1997

Psychological distress in applicants for predictive DNA testing for autosomal dominant, heritable, late onset disorders. The Rotterdam/Leiden Genetics Workgroup.

In a comparative study on the effects of predictive DNA testing for late onset disorders, pre-test psychological distress was assessed in people at risk for Huntington's disease (HD, n = 41), cerebral haemorrhage (HCHWA-D, n = 9), breast and ovarian cancer (HBOC, n = 24), and polyposis coli (FAP, n = 45). Partners, if available, also participated in the study. Distress was measured with the subscales Intrusion and Avoidance of the Impact of Event Scale. People at risk for the neurodegenerative disorders reported more avoidance than those at risk for the cancer syndromes. People at risk for FAP and partners of those at risk for HBOC reported less intrusion than the others at risk and the other partners. Subjects who were more distressed reported more experiences with the disease in close relatives, the disease having a great impact on their lives, having considerations against predictive testing, expecting that being identified as a gene carrier would have adverse effects, and expecting relief after being identified as a non-carrier. Test candidates who expected an increase of personal problems showed higher avoidance, whereas those who could better anticipate future life as a carrier had higher intrusion levels. Generally, subjects with high distress levels are of more concern to the healthcare professional than those with low distress levels. However, high distress may reflect worrying as a mental preparation for the test result, whereas low distress may indicate denial-avoidance behaviour and poor anticipation of the test outcome. In pre-test counselling sessions, this should be acknowledged and addressed.

Adenomatous Polyposis Coli↗
PubMed1989

Isoinertial tests to predict lifting performance.

Previous research has found isoinertial strength testing to be superior to isometric and isokinetic strength testing for prediction of task performance. The purpose of this study was to investigate tests on an isoinertial lifting machine (ILM) and their ability to predict performance on actual lifting tasks. Sixteen male subjects performed two lifting tasks: maximum box lift to truck-bed height of 1.35 m; and 'speed lifts' of 60 concrete blocks (each 22.7 kg) to the same height. These performance tests were compared to three ILM tests: a maximal lift to 1.83 m, a second maximal lift to 1.52 m, and an endurance test that entailed 60 timed ILM lifts of 22.7 kg to 1.83 m. Pearson product-moment correlations between ILM tests and performance tasks varied from r = 0.55 to 0.71. Therefore, the isoinertial test protocols employed in this study were able to account for only 30% to 50% of the variance in the performance of maximal lifting and endurance tasks. In was concluded that prediction of maximal lifting ability or endurance ability using an ILM might be enhanced by closer approximation of specific task variables, or by inclusion of dynamic parameters to measure technique.

Adult↗
PubMed1997

Predictive genetic testing: psychological factors.

Advances in medical technology such as those linked to the human genome project are increasing the potential for predictive testing for a wide range of health threats. There have not been comparable advances in understanding of the psychological factors involved in such testing. These factors and issues relating to them are examined, and it is suggested that a cognitive-behavioral approach to the understanding and management of adverse reactions to testing is likely to be particularly fruitful. The use of such an approach should result in the development of effective pre- and posttest interventions to prevent, minimize, and manage distress associated with screening.

Adaptation, Psychological↗
PubMed2004

Genetics and genetic counseling: recommendations for Alzheimer's disease, frontotemporal dementia, and Creutzfeldt-Jakob disease.

In this paper we discuss the clinical genetics of three neurodegenerative diseases (Alzheimer's disease, frontotemporal dementia, and Creutzfeldt-Jakob disease), the current application of genetic testing for these diseases, and the role of genetic counseling in familial dementia. We review the literature addressing the clinical application of these genetic findings, including susceptibility testing and predictive testing. In addition, we share our own experience working with families with familial neurodegenerative disease, the genetic counseling process, and the major issues that need attention in the genetic counseling setting.

Aged↗
PubMed2000

Predictive genetic testing for hereditary non-polyposis colorectal cancer: uptake and long-term satisfaction.

The aim of this prospective study was to assess the uptake of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) and its associations with sociodemographic and other factors, and long-term satisfaction with taking the test. The test was offered to all high-risk members (n = 446) of 36 Finnish HNPCC families in which the mutation was known. The procedure comprised an educational counselling session, a period for reflection, and a test disclosure session. Data were collected by questionnaires sent before the educational counselling and 1 month and 1 year after the test disclosure. Of those eligible, 85% (n = 381) completed the first questionnaire study. Non-participation was more common among men living alone who had not participated in the clinical cancer surveillance programme. Of the 347 subjects who attended counselling, 334 (75% of all subjects) were actually tested. After logistic-regression analysis, the only significant factor predicting test acceptance proved to be employment status: those employed were more likely than others to accept the test (odds ratio = 2.25; 95% confidence intervals, 1.09 to 4.6 1). At follow-up, over 90% of the subjects were fully satisfied with the decision to take the test. In conclusion, acceptance of the test was considerably higher than in previously reported studies. We attribute this to our careful face-to-face individualized counselling, our health care system, and to attitudes of the Finnish population, which are generally favourable towards health care and disease prevention.

Adult↗
PubMed1993

On attitudes and appreciation 6 months after predictive DNA testing for Huntington disease in the Dutch program.

We have studied the 6-month follow-up attitudes of 63 individuals, after predictive testing for Huntington disease (HD). Reducing uncertainty (81%) and family planning (60%) were the major reasons for taking the test. Twenty-four individuals were diagnosed as having an increased risk (+/- 98%), and 39 a decreased risk (+/- 2%). Among those with an increased risk, denial or minimization of the ultimate impact of the increased risk result was observed. Most of them (84%) rated their current life situation, at the very least, as being good. Twenty-one percent of individuals with an increased risk who originally planned to have a family, decided to refrain from having children. Sixty percent of those with increased risk who still wished to have children, would choose to have prenatal testing. In most individuals with increased risk, the test result did not increase the previously expected control over their own future. Half of the partners of persons with increased risk acknowledged the burden of the future disease. Half had no one in whom they could confide. They showed loyalty to the denial and avoidance reactions of their spouses. Half of the individuals with decreased risk denied the impact of the result, as reflected by absence of relief, and emotional numbness. A third of persons with decreased risk experienced involvement with problems of affected relatives. We found that 20% of all participants were discontented with the support given by their general practitioner, who is normally regarded as being the most significant professional for aftercare. Our findings suggest that the perpetuation

Adult↗
PubMed2000

Huntington's disease: neurological assessment of potential gene carriers presenting for predictive DNA testing.

One hundred and fifty-six potential gene carriers who were 50% 'at risk' of inheriting the Huntington's disease (HD) mutation, and who presented for predictive testing, underwent neurological assessment before their gene status had been determined. The association between pre-gene result symptoms and minimal neurological signs (insufficient for diagnosis in their own right) and subsequent gene status was determined. Of these, 38% tested positive for the HD mutation. Fifty-one individuals had minor neurological signs. After exclusions, 61% of gene-positive patients had minor neurological signs, whereas only 8% testing gene negative had signs. Minimal chorea observed in the toes and feet with the subject supine, and the patient being stressed by a mental task carried 96% specificity and 86% positive predictive value for gene-positive status. Neurological symptoms did not distinguish gene status, but behavioural and cognitive symptoms were more often reported by the gene-positive group. Although an 'at-risk' individual may receive a gene-positive result, neurological examination remains the most accessible, reliable and cost effective means of determining clinical disease onset.

Adult↗
PubMed2004

Attitudes to predictive DNA testing for myocilin glaucoma: experience with a large Australian family.

PURPOSE: Glaucoma is a major cause of visual impairment and blindness in developed countries. Half of those with glaucoma are unaware that they have the disease. Mutations in the myocilin (MYOC) gene are responsible for 3 to 5% of primary open angle glaucoma, thus predictive DNA testing in family members of some glaucoma pedigrees is possible. We wished to determine the attitudes of affected and unaffected family members to the use of predictive DNA testing in glaucoma. SUBJECTS AND METHODS: We surveyed the attitudes of family members from one such pedigree to determine the acceptability of predictive DNA testing. We studied 72 members of a large family in which the MYOC mutation, THR377MET, segregates. Family members were examined over an 8-year period as part of research initiated to identify the gene. Once the mutation was identified, we offered participants the result of their DNA test after a genetic counseling session. Family members were subsequently given a questionnaire about the counseling and DNA result. RESULTS: Most wished to know their result after counseling; 26 of 27 (96%) felt the genetic counseling session was necessary, but participants' attitudes varied as to whether they preferred this in person, by phone, or letter. Forty three patients were resurveyed 5 years after their initial counseling session. No adverse problems relating to the predictive testing were reported, though two had been asked about DNA testing by insurance companies; 5 of 24 (21%) individuals who had been informed they did not carry the mutation were unsure if they carried the mutation 5 years after counseling, while all 19 mutation carriers (who were being examined annually) correctly recalled their mutation status. CONCLUSIONS: This study suggests that predictive glaucoma testing in appropriate circumstances is acceptable to patients and their families.

Attitude to Health↗
PubMed2005

Posttreatment 13C-urea breath test is predictive of antimicrobial resistance to H. pylori after failed therapy.

OBJECTIVE: We tested whether a 13C-urea breath test can predict antimicrobial resistance of Helicobacter pylori (H. pylori). METHODS: Seventy patients who had failed triple eradication therapy and 108 untreated H. pylori-infected patients were given a 13C-urea breath test, endoscopy for culture of H. pylori, and assessment of clarithromycin resistance. The patients who had failed triple therapy then received 1 week of quadruple therapy to eradicate residual H. pylori. RESULTS: The posttreatment value of the 13C-urea breath test expressed as excessive delta13CO2 per ml (ECR) was higher in patients with residual H. pylori with clarithromycin resistance than in those without (23.8 vs 10.6; P<.0001). With a cutoff of ECR >or< or =15, the 13C-urea breath test was 88.6% sensitive and 88.9% specific in predicting clarithromycin resistance of residual H. pylori. The H. pylori eradication rate of the rescue regimen was higher for patients with a posttreatment ECR of the 13C-urea breath test < or =15 than for those with a value >15 (93.8% vs 73.3%; P<.05). In contrast, in treatment-naive H. pylori-infected patients, the pretreatment value of the 13C-urea breath test did not differ between patients infected with clarithromycin-resistant or-sensitive isolates (P>.05). CONCLUSION: The posttreatment value of the 13C-urea breath test is predictive of clarithromycin resistance in residual H. pylori after failed triple therapy and predicts efficacy of the rescue regimen. The value of the noninvasive test is promising for primary care physicians who need to select a rescue regimen without invasive H. pylori culture.

Adult↗
PubMed1991

Predictive patch testing of "Medigloves" on humans using the repeated insult technique.

The predictive patch tests using the repeated insult technique with pieces of ETO sterilized "Medigloves" on 200 human subjects showed negative allergic reactions in all cases. Therefore, the sensitizing potential of "Medigloves" is quite low, if any. Mild to severe forms of miliaria rubra were occasionally observed in about one fourth of the subjects during the induction and challenge periods since the weather was quite warm and humid. However, three subjects who developed more pronounced miliaria rubra on the skin underneath rubber-glove squares were selected for provocative use tests. The results were negative in all cases. A subject who showed a false-positive allergic reaction also showed negative results in a provocative use test and in patch tests with standard rubber chemicals and pieces of "Medigloves" from various batches. Occlusive patch tests for 72 hours with Mediglove pieces from the same batch used in the initial test challenge phase were repeatedly negative when performed during the cool time of the year. In tropical countries, predictive closed patch tests employing solid occlusive materials should be done during cool weather in order to prevent or minimize the occurrence of miliaria. In hot weather, this is a common source of false positive reactions.

Adult↗
PubMed1995

Ability of visual tests to predict underlying cervical neoplasia. Colposcopy and speculoscopy.

OBJECTIVE: To describe the attributes of colposcopy and a low-power, magnified examination that utilizes chemiluminescent illumination (speculoscopy) in the visualization of cervical epithelium in a predefined, high-risk population and to compare how the two tests predict cervical histology. STUDY DESIGN: During this multicenter, prospective study, 395 women who were referred to our colposcopy clinic underwent a repeat cervical smear and speculoscopy followed immediately by colposcopy. Abnormal colposcopic lesions were biopsied and endocervical curettage performed when indicated. Histologic diagnoses were compared with cytology, speculoscopy and colposcopy results. RESULTS: Colposcopy was more sensitive than speculoscopy in the detection of cervical neoplasia (97% vs. 82%) (P < .001) and was superior in visualizing focal lesions and vascular patterns. An antecedent acetowhite abnormality detected during speculoscopy was highly predictive of subsequent abnormal colposcopy (97% positive predictive value). The "overall" rate of acetowhite lesions during speculoscopy was nearly half the rate during colposcopy (P < .001). CONCLUSION: Colposcopy is better suited than speculoscopy to the follow-up of patients with abnormal cervical cytology because it facilitates lesion grading and assists in directing biopsies. Speculoscopy is best utilized as a dichotomous screening test based on the presence or absence of at least one well-demarcated acetowhite lesion and may be more suitable than colposcopy as an adjunct to cervical cancer screening due to its lower overcall rate. The biophysical properties of blue-white chemiluminescent light as it relates to the diagnosis of cervical neoplasia are discussed.

Adult↗
PubMed2004

Predictive genetic testing in young people: when is it appropriate?

Predictive genetic testing is currently offered to adults for a range of conditions, even when there is no possibility of prophylaxis or treatment. However, similar testing in children and adolescents is advised against in international guidelines. Despite this, several authors have argued against the existing guidelines. Given the lack of empirical evidence, it is important that clinicians are aware not only of the guidelines, but also of the arguments in favour of such testing.

Adolescent↗
PubMed1982

Prediction of remission in adult acute leukemia: development and testing of predictive models.

Logistic regression methods were applied to derive a set of models relating achievement of CR to prognostic characteristics in a group of 300 adult acute leukemia patients treated with cytosine arabinoside, vincristine, and prednisone combined with adriamycin (ADOAP) or rubidazone (ROAP). These models were tested prospectively in an independent group of 107 subsequent patients treated with ADOAP or ROAP therapy, by comparing observed outcomes to predictions of response based on the models. Several models were able to identify subgroups of patients with good, intermediate, and poor prognoses. A model regarded as clinically useful and which provided a good fit to both the population from which it was derived and the test population included the pretreatment factors age, history of an antecedent hematologic disorder, temperature, blood urea nitrogen, hemoglobin, and liver size.

Acute Disease↗
PubMed2003

Potential use of the alkaline comet assay as a predictor of bladder tumour response to radiation.

Bladder tumours show a variable response to radiotherapy with only about 50% showing good local control; currently there is no test to predict outcome prior to treatment. We have used five bladder tumour cell lines (T24, UM-UC-3, TCC-SUP, RT112, HT1376) to investigate the potential of the alkaline comet assay (ACA) to predict radiosensitivity. Radiation-induced DNA damage and repair were compared to clonogenic survival. When the five cell lines were irradiated and initial DNA damage was plotted against cell survival, at all doses (0-6 Gy), a significant correlation was found (r2=0.9514). Following 4 Gy X-irradiation, all cell lines, except T24, showed a correlation between SF2 vs half-time for repair and SF2 vs residual damage at 5, 10, 20 and 30 min. The T24 cell line showed radioresistance at low doses (0-2 Gy) and radiosensitivity at higher doses (4-6 Gy) using both cell survival and ACA end points, explaining the lack of correlation observed for this cell line. These data indicate that initial DNA damage and residual damage can be used to predict for radiosensitivity. Our data suggest that predictive tests of radiosensitivity, appropriate to the clinical situation, may require the use of test doses in the clinical range.

Carcinoma, Transitional Cell↗