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PubMed2004

Improving measurement precision of test batteries using multidimensional item response models.

A conventional way to analyze item responses in multiple tests is to apply unidimensional item response models separately, one test at a time. This unidimensional approach, which ignores the correlations between latent traits, yields imprecise measures when tests are short. To resolve this problem, one can use multidimensional item response models that use correlations between latent traits to improve measurement precision of individual latent traits. The improvements are demonstrated using 2 empirical examples. It appears that the multidimensional approach improves measurement precision substantially, especially when tests are short and the number of tests is large. To achieve the same measurement precision, the multidimensional approach needs less than half of the comparable items required for the unidimensional approach.

Humans↗

PubMed1990

The multiple sleep latency test in the diagnosis of sleep disorders.

The multiple sleep latency test provides an objective measure of a patient's daytime sleepiness. Sixteen tests were performed at Groote Schuur Hospital in 1987 and 1988 according to a fixed protocol. In 8 patients the test was definitely abnormal (mean sleep latency less than 5 minutes) with 3 subjects diagnosed as having narcolepsy, 1 sleep apnoea syndrome, 1 idiopathic central nervous system hypersomnolence, 2 environment-related hypersomnolence and 1 psychophysiological hypersomnolence. In 2 patients the test results fell in the equivocal range (mean sleep latency 5-10 minutes), while in 5 the test revealed no evidence for a disorder of excessive sleep (mean sleep latency greater than 10 minutes). The test was uninterpretable for technical reasons in only 1 patient. In conclusion, the test--when performed in a standardised manner--is extremely helpful in the elucidation of possible disorders of excessive sleep.

Adult↗

PubMed1984

Interlist equivalencies for a numeral and a vowel/consonant multiple-choice monosyllabic test for severely/profoundly deaf young adults.

Conventional multiple-choice speech tests measuring discrimination of initial/final consonants, and the CID "Everyday" Sentences test are too difficult for many young adults whose hearing is severely/profoundly limited. Using the 6-choice closed-set paradigm, a new 12-item Numerals test was developed as well as a modification of the Pickett et al (Gallaudet) modified rhyme test of vowel and consonantal discrimination. This test, here called the Webster-Pickett (W/P) test, essentially expands the original 2 alternative lists to 6, with some further minor changes. Both these tests were administered to 35 students at the National Technical Institute for the Deaf (NTID). In combination, the new tests provided usable scores for the NTID population. Most of those who yielded scores of zero on the W-22, on the CID sentences tests and on the W/P test nevertheless scored above zero on Numerals, while those who scored 100% on Numerals scored between 0 and 100% on the W/P test. All 6 recorded lists of the Numerals test were equivalent. Slight corrections to those raw scores between 10 and 90% on the 6 lists of the W/P were proposed to yield interlist equivalence.

Deafness↗

PubMed2001

A study of anthropometric measures before and after external septoplasty in children: a preliminary study.

OBJECTIVE: To test the hypothesis that surgery on the growing nasal septum does not adversely affect nasal and midfacial dimensions. DESIGN: Paired study. SETTING: Tertiary care center. PARTICIPANTS: Children treated consecutively during a 4-year period; all had significant nasal obstruction and cosmetic disfigurement secondary to skeletal septal deformities. INTERVENTION: Nasal septal surgery (using an external approach), in which the quadrilateral cartilage was removed, remodeled, and reinserted as a free graft. OUTCOME MEASURES: Anthropometric linear measurements and indexes of the face and nose preoperatively and postoperatively; nasal dorsum length, nasal height, nasal dorsum index, nasal tip protrusion, columellar length, facial height, face width, upper face height, facial index, nose-upper face height index, and columellar length-nasal tip protrusion index. Continuous measurements were transformed into ordered categories with reference to normative data. Data were analyzed using Wilcoxon signed rank sum test (alpha level of.05) and by applying the Bonferroni adjustment for multiple testing. RESULTS: Twenty-six children were studied (12 females and 14 males); age at surgery ranged from 4.5 to 15.5 years (mean age, 9.5 years); average age at postoperative measurement, 12.5 years; mean follow-up, 3.1 years. Only nasal dorsum length (P =.007) and nasal tip protrusion (P =.04) were decreased by a statistically significant level before the Bonferroni adjustment. The change was not considered clinically significant. Thus, relative to age-appropriate norms, the dimensions of the nose and midface and their proportionality did not change after surgery. CONCLUSIONS: Appropriate nasal septal surgery involving excision and subsequent reinsertion of a remodeled segment of the quadrilateral cartilage has no deleterious effects on development of the nose and midface. We question the absolute dogma that nasal surgery in children must always be avoided.

Adolescent↗

PubMed1975

Delayed cutaneous hypersensitivity and peripheral lymphocyte counts in patients with advanced cancer.

One hundred eighty-three patients with advanced solid neoplasms were tested for their ability to react to four common skin test antigens (tuberculin PPD, streptokinase-streptodornase, mumps, and Monilia) and their ability to develop delayed cutaneous hypersensitivity (DCH) to 2, 4 dinitrochlorobenzene (DNCB). All patients were followed for at least 6 months or until death. Histologic tumor types studied were: melanoma (65), sarcoma (28), squamous cell carcinoma (23), and adenocarcinoma (67). The rate of progression of disease within 6 months of testing was lower in patients who had a positive response to a challenging dose of 50 mug of DNCB. Reactivity to recall antigens had no prognostic value except in patients with adenocarcinomas. Among patients with adenocarcinoma, those who reacted strongly to DNCB and one or more skin test antigens had the best prognosis, while those who were nonreactive to all had the worst prognosis (progression rate: 18% vs. 78%). Peripheral lymphocyte counts were related to the results of DCH to DNCB and skin tests. The preseence or absence of lymphocytopenia (count less than 1000/mm3) had prognostic value in patients who had positive skin test(s). In such patients, the disease progression rate was much higher in patients who were anergic to DNCB and who were lymphocytopenic (90% vs. 40%). These data suggest that DCH to DNCB, recall antigens, and peripheral lymphocyte counts are useful immunologic measurements in patients with advanced cancer. Although the prognostic value of each individual test is relatively limited, the predictive worth can be increased when multiple tests are employed. Pertinent findings reported in the literature are reviewed.

Adenocarcinoma↗

PubMed1983

A modification of the (75Se) selenomethionine assay for the detection of complement-dependent antibody in human tumor systems.

A modification of Brook's prelabeling (75SE) selenomethionine assay was developed and evaluated for detection of complement-dependent antibody (CDA) in a human tumor system. CDA was indeed detected in some breast cancer patients' sera. To determine whether the assay was reliable and reproducible, xenoantibodies were raised in rabbits by immunization with a human breast cancer line, Sk-Br-3, and tested against that line and five other unrelated human cancer lines. Multiple tests were performed on separate days. It can be concluded from the data that the assay is reliable and reproducible. The assay has wide application in investigating the biologic role of complement-dependent antibody activity in human and experimental animal tumor systems.

Adenocarcinoma↗

PubMed2026

Vegan multinutrient supplementation significantly increases Omega-3 index and 25-OH-vitamin D status: a randomized, double-blind, placebo-controlled trial in healthy young vegans.

In this randomized, double-blind, placebo-controlled trial, 72 healthy vegan adults (aged 19-57 years) received a multinutrient supplement consisting of a vitamin and mineral supplement (providing 26 µg vitamin D) and an omega-3 supplement administered in either a single dose (EPA 98.7 mg, DHA 171.0 mg, additional vitamin D 36 µg, vitamin E 3.7 mg) or a double dose (EPA 197.4 mg, DHA 342.0 mg, additional vitamin D 72 µg, vitamin E 7.4 mg) or placebo capsules for 4 months. Nutrient biomarkers were assessed at baseline and at the end of the intervention after 4 months. An analysis of covariance was employed to test for between-group differences (p < 0.05) and adjusted for multiple testing using the Bonferroni-Holm method. Compared to the control group, which showed on average a significant decline in both the omega-3-index and 25-hydroxyvitamin D, participants in both intervention groups demonstrated significant increase in these parameters (p < 0.001). Although the double dose group exhibited numerically greater increases in omega-3 index and vitamin D compared to the simple dose group, the differences between these dosing regimens were not statistically significant. As expected, vitamin E levels remained unchanged, reflecting its inclusion solely for antioxidative protection in the omega-3 supplement rather than as a critical nutrient in vegan diets. In conclusion, supplementation significantly improved omega-3 and vitamin D status in healthy vegans, with no significant benefit from doubling the dose. Although clinical endpoints were not evaluated, improved nutrient status may have potential implications for health. The study has been registered at the German Clinical Trials Register (DRKS00028151).

Humans↗

PubMed2006

ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research.

The product of the ABCB1 gene, P-glycoprotein (PGP), is a transmembrane active efflux pump for a variety of drugs. It is a putative mechanism of multidrug resistance in a range of diseases. It is postulated that ABCB1 polymorphisms contribute to variability in PGP function, and that therefore multidrug resistance is, at least in part, genetically determined. However, studies of ABCB1 genotype or haplotype and PGP expression, activity or drug response have produced inconsistent results. This critical review of ABCB1 genotype and PGP function, including mRNA expression, PGP-substrate drug pharmacokinetics and drug response, highlights methodological limitations of existing studies, including inadequate power, potential confounding by co-morbidity and co-medication, multiple testing, poor definition of disease phenotype and outcomes, and analysis of multiple drugs that might not be PGP substrates. We have produced recommendations for future research that will aid clarification of the association between ABCB1 genotypes and factors related to PGP activity.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2004

Linkage disequilibrium mapping via cladistic analysis of single-nucleotide polymorphism haplotypes.

We present a novel approach to disease-gene mapping via cladistic analysis of single-nucleotide polymorphism (SNP) haplotypes obtained from large-scale, population-based association studies, applicable to whole-genome screens, candidate-gene studies, or fine-scale mapping. Clades of haplotypes are tested for association with disease, exploiting the expected similarity of chromosomes with recent shared ancestry in the region flanking the disease gene. The method is developed in a logistic-regression framework and can easily incorporate covariates such as environmental risk factors or additional unlinked loci to allow for population structure. To evaluate the power of this approach to detect disease-marker association, we have developed a simulation algorithm to generate high-density SNP data with short-range linkage disequilibrium based on empirical patterns of haplotype diversity. The results of the simulation study highlight substantial gains in power over single-locus tests for a wide range of disease models, despite overcorrection for multiple testing.

Chromosome Mapping↗

PubMed1976

Results of the Center for Disease Control Proficiency Testing Program for the detection of hepatitis B surface antigen.

The changes in the types and numbers of tests used by participants in the Center for Disease Control Proficiency Testing Program for the detection of hepatitis B surface antigen from the beginning of the program in 1971 until October 1975 are analyzed; the implications of these changes are discussed. Changes in the use of agar gel diffusion, rheophoresis, counterelectrophoresis, complement fixation, reverse passive latex agglutination, radioimmunoassay, and reverse passive hemagglutination tests are reviewed. The performance of the participants for 1975 is reported, and factors related to performance (type or combinations of tests used, procedures used to confirm specificity, etc.) are discussed. The increase in the use of third-generation tests in place of tests with lower sensitivity and the decrease in the use of multiple tests undoubtedly represent increased efficiency and effectiveness.

Blood Donors↗

PubMed2005

Identifying genetic variation affecting a complex trait in simulated data: a comparison of meta-analysis with pooled data analysis.

We explored the power and consistency to detect linkage and association with meta-analysis and pooled data analysis using Genetic Analysis Workshop 14 simulated data. The first 10 replicates from Aipotu population were used. Significant linkage and association was found at all 4 regions containing the major loci for Kofendrerd Personality Disorder (KPD) using both combined analyses although no significant linkage and association was found at all these regions in a single replicate. The linkage results from both analyses are consistent in terms of the significance level of linkage test and the estimate of locus location. After correction for multiple-testing, significant associations were detected for the same 8 single-nucleotide polymorphisms (SNP) in both analyses. There were another 2 SNPs for which significant associations with KPD were found only by pooled data analysis. Our study showed that, under homogeneous condition, the results from meta-analysis and pooled data analysis are similar in both linkage and association studies and the loss of power is limited using meta-analysis. Thus, meta-analysis can provide an overall evaluation of linkage and association when the original raw data is not available for combining.

Computer Simulation↗

PubMed1987

The epidemiology of depression in medical care.

Major depression may be the most common medical or psychiatric disorder seen in primary medical care clinics, occurring in approximately 6 to 10 percent of the clinic populations. Despite this high prevalence rate, patients with depression often go undiagnosed or are misdiagnosed. The evidence suggests a multifactorial etiology for this problem. Many patients with depression selectively focus on the somatic components of their depressive syndrome and minimize or even deny affective and cognitive symptoms. Depression and medical disorders also often occur concomitantly with depression causing amplification of somatic complaints. Due to the unidimensional focus on the biomedical model many physicians only evaluate and treat the physical illness and do not diagnose the depression. This often leads to aggressive medical testing and treatment that carries the risk of iatrogenic injury (polysurgery, multiple tests and procedures, prescription of opiates and benzodiazepines). Several interventions are suggested to improve the diagnostic acumen of primary care physicians.

Depressive Disorder↗

PubMed1983

Noninvasive assessment of carotid artery disease.

Noninvasive methods of detecting carotid disease were developed to avoid the morbidity and occasional mortality associated with cerebral angiography. The tests developed are of the following two types: direct, which uses imaging or the detection of flow disturbances to identify disease at the bifurcation, and indirect, which infers the presence of bifurcation disease by detecting changes at a remote site. The initial goal of only detecting disease has now been broadened, with this technology being used to address important clinical and epidemiologic questions such as the natural history of carotid bifurcation disease. The recognition of these important contributions has been compounded, however, by the large number of tests that are available, producing the problem of deciding which test or tests should be used for a particular patient. The use of multiple tests avoids the deficiencies of single tests but compounds medical costs. For a cost-effective single form of testing for all circumstances, duplex scanning methods offer the greatest possibility of detecting all degrees of disease.

Angiography↗

PubMed1993

[An applied study on the method of multi-factorial quantitative-risk assessment (MFQRA) for mass screening of colorectal cancer].

This paper reported an actual effectiveness evaluation for MFQRA, as a primary screening procedure, applied in a mass screening for colorectal cancer since 1989 to 1990 among a general population with the age of 30 and above in Jia-shan county where is a high incidence area of colorectal cancer in this nation. Results of this paper demonstrated that (1) attributable degree (AD) can identify subpopulations or subgroups with different incidence risks from a general population, and provide evidence for decision-making of advanced screening procedures and even for prevention of colorectal cancer; (2) Sensitivity of MFQRA was much higher, compared to conventional fecal occult blood test (FOBT) and symptomatic screening methods (65.89% vs 34%-50%); (3) Multiple tests with FOBT by reverse passive hemagglutination (RPHA) were effective and practical method for mass screening of colorectal cancer.

Adult↗

PubMed1997

Nonparametric analysis of clustered ROC curve data.

Current methods for estimating the accuracy of diagnostic tests require independence of the test results in the sample. However, cases in which there are multiple test results from the same patient are quite common. In such cases, estimation and inference of the accuracy of diagnostic tests must account for intracluster correlation. In the present paper, the structural components method of DeLong, DeLong, and Clarke-Pearson (1988, Biometrics 44, 837-844) is extended to the estimation of the Receiver Operating Characteristics (ROC) curve area for clustered data, incorporating the concepts of design effect and effective sample size used by Rao and Scott (1992, Biometrics 48, 577-585) for clustered binary data. Results of a Monte Carlo simulation study indicate that the size of statistical tests that assume independence is inflated in the presence of intracluster correlation. The proposed method, on the other hand, appropriately handles a wide variety of intracluster correlations, e.g., correlations between true disease statuses and between test results. In addition, the method can be applied to both continuous and ordinal test results. A strategy for estimating sample size requirements for future studies using clustered data is discussed.

Angiography, Digital Subtraction↗

PubMed2002

A comprehensive method for genome scans.

In applications involving the use of genome scans the problem of correcting for multiple testing figures prominently. A frequently used approach is the Bonferroni adjustment, but this is known to be often severely conservative. As an alternative we use the method of importance sampling to accurately and efficiently obtain required exceedance probabilities. This method is comprehensive in the sense that it has application to exceedance probabilities for other classes of test statistics, such as those for linkage disequilibrium or Hardy-Weinberg equilibrium at multiple loci. We illustrate the importance sampling technique by focusing on affected sib pair tests done at a large number of fully informative markers. We demonstrate how our approach can be used to obtain exceedance probabilities for arbitrary marker spacings, and we compare our approach with that of Feingold et al. [1993], which uses the method of large deviations and does not provide the means for adjusting for unequal marker spacing.

Genetic Linkage↗

PubMed2001

A confidence-set approach for finding tightly linked genomic regions.

As more studies adopt the approach of whole-genome screening, geneticists are faced with the challenge of having to interpret results from traditional approaches that were not designed for genome-scan data. Frequently, two-point analysis by the LOD method is performed to search for signals of linkage throughout the genome, for each of hundreds or even thousands of markers. This practice has raised the question of how to adjust the significance level for the fact that multiple tests are being performed. Various recommendations have been made, but no consensus has emerged. In this article, we propose a new method, the confidence-set approach, that circumvents the need to correct for the level of significance according to the number of markers tested. In the search for the gene location of a monogenic disorder, multiplicity adjustment is not needed in order to maintain the desired level of confidence. For complex diseases involving multiple genes, one needs only to adjust the level of significance according to the number of disease genes--a much smaller number than the number of markers in a genome screen-to ensure a predetermined genomewide confidence level. Furthermore, our formulation of the tests enables us to localize disease genes to small genomic regions, an extremely desirable feature that the traditional LOD method lacks. Our simulation study shows that, for sib-pair data, even when the coverage probability of the confidence set is chosen to be as high as 99%, our approach is able to implicate only the markers that are closely linked to the disease genes.

Chromosome Mapping↗

PubMed1991

Progression of coronary atherosclerosis: is coronary spasm related to progression?

A total of 239 patients undergoing serial coronary angiography with a concomitant ergonovine provocation test were studied between July 1974 and June 1987. The progression of coronary artery disease was evaluated in relation to risk factors, especially coronary artery spasm. Patients were classified into three groups: 1) new myocardial infarction group (39 patients); 2) progression without infarction group (90 patients); and 3) nonprogression group (110 patients). To assess how risk factors and coronary spasm are related to the occurrence of new myocardial infarction and progression without infarction, 11 variables in the three groups were examined: age, gender, the time interval between the studies, fasting blood sugar, systolic blood pressure, diastolic blood pressure, smoking, serum cholesterol, triglyceride, uric acid and a positive response to the ergonovine provocation test. Multiple regression analysis selected three independent predictors of progression without infarction: cholesterol (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). Multiple regression analysis also selected three independent predictors of the occurrence of new myocardial infarction: fasting blood sugar (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). A positive response to the ergonovine provocation test was the strongest factor for occurrence of both new myocardial infarction and progression without infarction. To evaluate segmental arterial changes, 3,275 coronary artery segments were analyzed in the 239 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗