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At least 307 records · Page 17Linked to original sources

Extension of one-sided test to multiple treatment trials.

In a two-treatment clinical trial, a one-sided test is sometimes used in reaching a decision. Usually we are interested in doing a one-sided test because of the existence of an unequal preference between the two treatments. When a standard control is just as good or better than the new experimental treatment (which has more toxicity or cost), we will stay with the standard control. In this paper, we extend the concept of a one-sided test to the multiple treatment trial where three or more treatments are involved. We assume that there is an order of strictly decreasing preference among the treatments. We propose two multiple-step decision procedures that are similar to the bubble sorting algorithm and will guarantee a high probability of finally selecting the correct treatment. We also provide methods to calculate the sample size required to detect a specific difference. The derivation is based on normal data, and the extension to binomial or exponential data with random censoring is through large sample approximation.

Algorithms↗

The reproducibility of urinalysis using multiple reagent test strips.

Ninety urine samples were examined twice by 3 "observers" (two persons, using only visual observation, and one person using a spectrophotometric analyser) using multiple reagent teststrips. To determine reproducibility, inter- and intra-observer agreement were calculated and expressed as Cohen's kappa and as weighted kappa. The results show negligible intra-observer differences between the visual and spectrophotometric observation. The lack of agreement between inter- and intra-observer urinalysis results, using multiple reagent test strips was disappointing, considering the simplicity of the test procedure. Further improvement of reproducibility, e.g. by enhancing the discoloration of the test pads, is necessary. Reproducibility is not improved by using a spectrophotometric analyser instead of visual reading of the test strips.

Esterases↗

A blood test for multiple sclerosis based on the adherence of lymphocytes to measles-infected cells.

The increased capacity of lymphocytes from patients with multiple sclerosis to adhere to human epithelial cells persistently infected with measles virus has provided an accurate blood test for multiple sclerosis. When lymphocytes from affected patients were mixed with measles-infected human epithelial cells, the lymphocytes formed rosettes around a mean (+/-S.E.) of 69.2 +/-1.7% of the measles-infected cells. In contrast, lymphocytes from controls, either healthy or with other neurologic and non-neurologic diseases, formed rosettes around a mean of only 28.2+/-2.1% of the measles-infected cells. Of greater importance was the complete absence of overlap between multiple sclerosis and control values, thus indicating the diagnostic potential of the rosetting phenomenon. The severity, duration and activity of the disease had no effect on the degree of rosette formation.

Adult↗

The Preterm Prediction Study: toward a multiple-marker test for spontaneous preterm birth.

OBJECTIVE: The Preterm Prediction Study evaluated 28 potential biologic markers for spontaneous preterm birth in asymptomatic women at 23 to 24 weeks gestational age. This analysis compares those markers individually and in combination for an association with spontaneous preterm birth at <32 and <35 weeks gestational age. STUDY DESIGN: With the use of a nested case-control design from an original cohort study of 2929 women, results of tests from 50 women with a spontaneous preterm birth at <32 weeks and 127 women with a spontaneous preterm birth at <35 weeks were compared with results from matched-term control subjects. RESULTS: In the univariate analysis, the most potent markers that are associated with spontaneous preterm birth at <32 weeks by odds ratio were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and <10th percentile cervical length (odds ratio, 5.8), and in serum, >90th percentiles of alpha-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and >75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at <35 weeks were generally similar but not as strong. Univariate and multivariate logistic regression analyses demonstrated little interaction among the tests in their association with spontaneous preterm birth. Combinations of the 5 markers were evaluated for their association with <32 weeks spontaneous preterm birth. Ninety-three percent of case patients had at least 1 positive test result versus 34% of control subjects (odds ratio, 24.0; 95% CI, 6.4-93.4). Among the case patients, 59% had >or=2 positive test results versus 2.4% of control subjects (odds ratio, 56.5; 95% CI, 7.1-451.7). If a cutoff of 3 positive test results was used, 20% of case patients and none of the control subjects had positive test results (P < .002). With the use of only the 3 serum tests (alkaline phosphatase, alpha-fetoprotein, and granulocyte colony-stimulating factor), any positive test identified 81% of cases versus 22% of control subjects (odds ratio, 14.7; 95% CI, 5.0-42.7). For spontaneous preterm birth at <35 weeks gestation, any 2 positive tests identified 43% of cases and 6% of control subjects (odds ratio, 11.2; 95% CI, 4.8-26.2). CONCLUSION: Overlap among the strongest biologic markers for spontaneous preterm birth is small. This suggests that the use of tests such as maternal serum alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin test and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.

Alkaline Phosphatase↗

Statistical errors and their effect on electrodiagnostic medicine.

Failure to demonstrate abnormalities on diagnostic tests in patients felt certain to have a disease is all too common, especially when symptoms are mild to moderate. One strategy used in such cases is to perform multiple tests hoping that one will confirm the clinical suspicion. An example of this strategy is found in carpal tunnel syndrome where multiple tests are often used to confirm the diagnosis. Unfortunately, this approach is often erroneous. Since no diagnostic test can perfectly discriminate between normal and abnormal, critical values are set at levels where most subjects are correctly classified. Using this methodology, approximately 2.5% of patients who are normal will be mistakenly called abnormal. This type I error, is additive when additional independent tests are performed. Since no two tests for a single condition are completely independent, the total error is less than the sum of the individual errors for each test. Even after accounting for interdependency, the total error of combined tests may be unacceptably high. If a single, highly discriminating, test is not available and multiple tests are used, abnormalities in more than a single test are needed to distinguish between normals and abnormals.

Carpal Tunnel Syndrome↗

Electrostatic endothelial cell seeding technique for small-diameter (<6 mm) vascular prostheses: feasibility testing.

Multiple studies have indicated the importance of surface charge in the adhesion of multiple cardiovascular cell lines including platelets and endothelial cells on the substrate materials (1,4,7-10,12-15). It is the purpose of this article to report a feasibility study conducted using an electrostatic endothelial cell seeding technique. The feasibility study was conducted using human umbilical vein endothelial cells (HUVEC), a static pool apparatus, a voltage source, and a parallel plate capacitor. The HUVEC concentration and seeding times were constant at 560,000 HUVEC/ml and 30 min, respectively. Scanning electron microscopy examination of the endothelial cell adhesion indicated that an induced temporary positive surface charge on e-PTFE graft material enhances the number and the maturation (flattening) of HUVECs adhered. The results indicated that the total number of endothelial cells adhered (70.9 mm2) was increased from 9198 +/- 1194 HUVECs on the control (no induced surface charge) e-PTFE to 22,482 +/- 4814 HUVECs (2.4 x control) on the maximum induced positive surface charge. The total number of cells in the flattened phase of adhesion increased from 837 +/- 275 to 6785 +/- 1012 HUVECs (8.1x) under identical conditions. Thus, the results of the feasibility study support the premise that electrostatic interaction is an important factor in both the endothelial cell adhesion and spreading processes and suggest that the electrostatic seeding technique may lead to an increased patency of small diameter (<6 mm) vascular prostheses.

Blood Vessel Prosthesis↗

The predictive ability of the allied health professions admission test.

Multiple regression models are formulated which analyze the usefulness of AHPAT as a predictor of success in allied health programs. The models are estimated by using data from the four baccalaureate programs in the School of Allied Health Professions at the State University of New York at Stony Brook. We attempt to reconcile differences in the usefulness of AHPAT that have been noted in the literature. Estimation results indicate that AHPAT is indeed a useful predictor, but the new explanatory power of the models suggests that other factors need to be considered.

Allied Health Personnel↗

[Abdominal infect--what does radiologic diagnosis contribute? Required and superfluous tests].

Multiple radiological techniques can be employed to search for the source of abdominal sepsis. Plain abdominal film can give important direct or indirect information about the origin of sepsis. Computer tomography plays the most important role. Abscesses with their typical signs (gas within encapsuled extraluminal fluid, enhancement of membrane), as well as embolism and thrombosis, can be reliably detected as sources of sepsis. Magnet resonance imaging is an alternative for patients who would otherwise be regularly exposed to X-rays (e.g. in Crohn's disease). Dependent on the clinical setting studies of the gastrointestinal tract with water-soluble contrast media are indicated (e.g. for detection of fistulas or insufficiency of an anastomosis). Angiography and scintigraphic studies are not helpful in the search for the source of abdominal sepsis.

Abdominal Abscess↗

Dividing attention within and between hemispheres: testing a multiple resources approach to limited-capacity information processing.

Two experiments tested the limiting case of a multiple resources approach to resource allocation in information processing. In this framework, the left and right hemispheres are assumed to have separate, limited-capacity pools of undifferentiated resources that are not mutually accessible, so that tasks can overlap in their demand for these resources either completely, partially, or not at all. We tested all three degrees of overlap in demand for left hemisphere supplies, using dual-task methodology in which subjects were induced to pay different amounts of attention to each task. Experiment 1 compared complete and partial overlap by combining a verbal memory load with a task in which subjects named nonsense syllables briefly presented to either the left or right visual field (LVF and RVF, respectively). Experiment 2 compared complete versus no overlap by using the same verbal memory load combined with a laterally presented same-different judgment task that did not require a spoken response. Decrements from single-task performance were always more severe when the visual field task stimulus was presented to the RVF. Further, subjects in Experiment 1 were able to trade performance between tasks on both LVF and RVF trials because there was always at least some overlap in left hemisphere demand. In Experiment 2, performance trade-offs were observed on RVF (complete overlap) trials, but not on LVF trials, where no overlap in demand existed. These results contradict a single-capacity model, but they support the idea that the hemispheres' resource supplies are independent and have implications for both cerebral specialization and divided attention issues.

Attention↗

The role of computer-aided assessment in health professional education: a comparison of student performance in computer-based and paper-and-pen multiple-choice tests.

There is a lack of empirical research in the use of computers in assessment. A study was conducted to compare student performance in computerized and paper-and-pen multiple-choice tests and assess the extent and effect of 'computer anxiety'. The LXR.TEST 5.1 software was used for the computerized test. A validated rating scale was used to assess computer anxiety. Most students had little computer experience other than in word processing. Only about a third of the students had moderate to mild computer anxiety. Neither computer experience nor anxiety correlated significantly with performance in the computer test. Whereas students performed significantly better in the paper test than in the computer test, there was no statistical difference in ranking in the two assessments formats. This suggests that computer-based assessment could be used with confidence for the purposes of ranking students, but care should be taken in using it for grading.

Journal Article↗

The leukocyte adherence-inhibition assay as a diagnostic test for multiple sclerosis: study of a substance found in MS blood.

We have modified and adapted two well-accepted cancer immunology research techniques to study blood leukocyte phenomena of MS patients. The LAI test of Halliday and Miller and the 3 molar potassium chloride (3M KCl) tumor antigen extraction technique of Dean and McCoy were adapted to extract from pooled MS whole blood an MSRM. The LAI test results of 53 of 58 MS patients (91%) were considered positive, but only three of 75 control subjects (4%) were positive when tested against the MSRM. This indicates that patients with MS had a greater specific reactivity to the MSRM than did the control subjects (healthy individuals and patients with disease other than MS). The specificity and reproducibility of this reaction were tested with materials prepared from various malignant diseases. Sensitized leukocytes showed consistently higher reactivity to antigen extracts prepared from corresponding types of tumors than to extracts prepared from tumors of other histological types. Our results indicate that (1) the LAI test is able to corroborate the neurological diagnosis of MS and (2) there is a blood constituent found only in the MS patient.

Antibody Specificity↗

Differences unrelated to clinical competence in the results of repeated multiple-station tests of clinical skills.

PURPOSE: To determine the extent to which systematic differences not related to group differences in clinical competence could be observed in the results of six administrations of the same multiple-station test of clinical skills. METHOD: The same 16 stations were administered as part of the Ontario International Medical Graduates Program clinical skills screening examination on three different occasions, and on each occasion in two sessions. The interval between the first (fall 1986) and second (March 1990) administrations was four years, and that between the second and third (July 1990) administrations, four months. International medical graduates were the candidates in the first two administrations; the third administration was to a combined sample of fourth-year clinical clerks and interns. A different item functioning (DIF) approach with sessions within administration as the grouping variable was used to describe the extent of differences unrelated to clinical competence in the results of the different test administrations. For the generalizability and DIF calculations the designs were balanced by sampling down to 33 cases in each session. RESULTS: Station DIF values varied considerably from station to station. DIF effects between sessions with administrations were less than those between administrations, and were less between the two administrations separated by four months than between the two administrations separated by four years. CONCLUSION: Hypotheses concerning the relative magnitudes of station DIF and total-test aggregated values of DIF, as a function of the time intervals between test occasions, were substantiated, demonstrating that the greater the time interval between test administrations, the greater the magnitude of DIF.

Clinical Competence↗

Multiple hypothesis testing strategies for genetic case-control association studies.

The genetic case-control association study of unrelated subjects is a leading method to identify single nucleotide polymorphisms (SNPs) and SNP haplotypes that modulate the risk of complex diseases. Association studies often genotype several SNPs in a number of candidate genes; we propose a two-stage approach to address the inherent statistical multiple comparisons problem. In the first stage, each gene's association with disease is summarized by a single p-value that controls a familywise error rate. In the second stage, summary p-values are adjusted for multiplicity using a false discovery rate (FDR) controlling procedure. For the first stage, we consider marginal and joint tests of SNPs and haplotypes within genes, and we construct an omnibus test that combines SNP and haplotype analysis. Simulation studies show that when disease susceptibility is conferred by a SNP, and all common SNPs in a gene are genotyped, marginal analysis of SNPs using the Simes test has similar or higher power than marginal or joint haplotype analysis. Conversely, haplotype analysis can be more powerful when disease susceptibility is conferred by a haplotype. The omnibus test tracks the more powerful of the two approaches, which is generally unknown. Multiple testing balances the desire for statistical power against the implicit costs of false positive results, which up to now appear to be common in the literature.

Case-Control Studies↗

Fine mapping by linkage and association in nuclear family and case-control designs.

This report summarizes the Genetic Analysis Workshop 14 contributions related to fine-mapping strategies, in which examining smaller regions by association with single-nucleotide polymorphisms (SNPs) can yield savings in genotyping and multiple-testing penalties. The aim of the analyses conducted in Group 7 contributions was to localize disease susceptibility loci from either the simulated or the Collaborative Study on the Genetics of Alcoholism (COGA) data within identified regions of linkage. Among the 10 contributions, most groups analyzed the simulated data, one group analyzed the COGA data only, and one group analyzed both data sets. The research questions included evaluation of new methods of analysis, as well as comparisons among alternative methods, analytic strategies, and study designs. Methods of interest included an algorithm for SNP marker ordering, a locally weighted transmission disequilibrium test statistic, a likelihood-ratio test statistic for family-based association in nuclear families, a robust test statistic for case-control association studies, and Bayesian spatial modeling methods for haplotype clustering and association. Evaluations included comparisons among confidence intervals for loci detected via linkage, effects of multiple testing adjustments and trade-offs between type I error and power, comparisons among haplotype-based (multilocus) and genotype-based (multilocus and single-locus) association analyses, and design of fine-mapping and replication studies. While several promising new approaches were identified, further development and evaluation of methods for multiple testing, regression modeling of association with multiple markers and haplotypes, and combined treatment of linkage and association data are necessary if we are to identify many of the genes that contribute to complex traits.

Alcoholism↗

Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard.

Excessive daytime sleepiness (EDS) is an important symptom that needs to be quantified, but there is confusion over the best way to do this. Three of the most commonly used tests: the multiple sleep latency test (MSLT), the maintenance of wakefulness test (MWT) and the Epworth sleepiness scale (ESS) give results that are significantly correlated in a statistical sense, but are not closely related. The purpose of this investigation was to help clarify this problem. Previously published data from several investigations were used to calculate the reference range of normal values for each test, defined by the mean+/-2 SD or by the 2.5 and 97.5 percentiles. The 'rule of thumb' that many people rely on to interpret MSLT results is shown here to be misleading. Previously published results from each test were also available for narcoleptic patients who were drug-free at the time and who by definition had EDS. This enabled the sensitivity and specificity of the three tests to be compared for the first time, in their ability to distinguish the EDS of narcolepsy from the daytime sleepiness of normal subjects. The receiver operator characteristic curves clearly showed that the ESS is the most discriminating test, the MWT is next best and the MSLT the least discriminating test of daytime sleepiness. The MSLT can no longer be considered the gold standard for such tests.

Adolescent↗

The Brief Repeatable Battery of Neuropsychological Tests for Multiple Sclerosis: a preliminary serial study.

The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for MS consisting of the selective reminding, 10/36 spatial recall, symbol digit modalities, paced auditory serial addition (PASAT) and word list generation tests is a sensitive measure of early cognitive impairment in MS patients. We administered it to 19 chronic stable MS patients every 60 days for 120 days to examine variability. The mean coefficient of variation for the tests ranged from 18% to 22%. A significant practice effect was seen in the PASAT results (P < 0.05) using the Wilcoxon signed rank test. These results suggest that cognitive fluctuations analogous to motor fluctuations may occur in MS patients and that the BRB-N may be useful in clinical trials of agents expected to alter cognitive function in MS patients if test-retest variability and practice effects are taken into account. Further study is warranted.

Adult↗