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Sensitivity, specificity, and predictive value of fecal occult blood testing (Hemoccult II) for colorectal neoplasia in symptomatic patients: a prospective study with total colonoscopy.

OBJECTIVES: To evaluate the specificity, sensitivity, and positive predictive value of fecal occult blood testing (FOBT) in symptomatic patients, with colonoscopy as the gold standard, and to assess the usefulness of FOBT as an ancillary examination in symptomatic patients for whom total colonoscopy is indicated. METHODS: We studied 439 consecutive patients who underwent Hemoccult II testing before total colonoscopy. RESULTS: The sensitivity, specificity, and positive predictive value for colorectal neoplasia (cancer and adenomatous polyps) was 76.5%, 56.7%, and 27.6%, respectively. The sensitivity, specificity, and positive predictive value for colorectal cancer were 69.2%, 73.2%, and 7.3%, respectively. CONCLUSIONS: The sensitivity, specificity, and positive predictive value of FOBT are difficult to estimate from screening programs, because Hemoccult-negative individuals do not undergo examination of the colon, and many of the Hemoccult-positive cases do not undergo total colonoscopy. With total colonoscopy serving as the gold standard, FOBT does not appear to be of much value as an ancillary examination in patients with symptoms potentially attributable to the lower gastrointestinal tract.

Adenomatous Polyps

[Sensitivity, specificity and predictive value of body mass index for the screening of juvenile arterial hypertension].

On the basis of various epidemiological studies, the specificity, sensitivity and predictive value of different indicators of obesity and overweight in relation to risk factor of juvenile hypertension are discussed. These screening tests, although highly specific, lack in sensitivity. The Authors suggest that such tests could be considered as useful tools in school preventive medicine for the identification of subjects not at risk.

Adolescent

Acute sensitivity vs. context-specific sensitization to cocaine as a function of genotype.

Individual variability in the acute and chronic effects of psychomotor stimulants is due, in part, to genetic factors. The purpose of this series of studies was to utilize a behavioral model of sensitization, namely increased locomotor activity, to assess individual variability in sensitization to the chronic effects of cocaine and its relationship to the acute stimulant effects of cocaine. Because the degree of sensitization is proportional to the training dose, genetic differences in acute sensitivity to cocaine were assessed and incorporated into the sensitization paradigm. Acute sensitivity and context-dependent sensitization were determined in six inbred mouse strains. Large quantitative and qualitative differences were found in the acute potency and efficacy of cocaine to stimulate locomotor activity. The ED50 was higher in the strains in which cocaine was most efficacious. Context-specific sensitization was determined via chronic administration of equiactive doses of cocaine (ED50) specifically paired with the test apparatus or with the home colony. Sensitization was time, environment, and genotype dependent. The differences in the number of trials required to show sensitization were unrelated to the acute locomotor stimulant effects of cocaine. These findings suggest that acute cocaine-induced locomotor activity and context-specific sensitization reflect different pharmacological properties of cocaine.

Animals

Post-vaccination tuberculin sensitivity for assessing BCG vaccination in areas with high prevalence of non-specific sensitivity.

The relationship of non-specific sensitivity to post-vaccination tuberculin sensitivity has been the subject of controversy. This relationship has an important bearing on the common practice of using post-vaccination tuberculin sensitivity for assessing BCG vaccination in areas with a high prevalence of non-specific sensitivity. If post-vaccination tuberculin sensitivity is found to be dependent on the amount of already existing, naturally acquired, non-specific sensitivity it could not be considered a reliable measure of the success of BCG vaccination. In a recent BCG trial in India a large number of persons were tested with PPD-S and PPD-B and also vaccinated with BCG vaccine or injected with placebo, by random allocation. Mutually exclusive random samples of the study population were retested with PPD-S at 2 1/2 months, 2 1/2 years and 4 years after vaccination. At each post-vaccination test the tuberculin sensitivity obtained among the placebo-injected controls provided a measure of the tuberculin sensitivity due to non-specific sensitivity that would have been present in the absence of BCG vaccination. The difference between the mean size of reactions to the post-vaccination test among the vaccinated and among the unvaccinated controls provided a measure of tuberculin sensitivity that was wholly due to BCG vaccination. Thus it was possible to separate and study the two components of post-vaccination tuberculin sensitivity. The results of the study indicate that post-vaccination tuberculin sensitivity can be used to assess BCG vaccination in areas with a high prevalence of non-specific sensitivity, provided the assessment is done in younger age groups and based on post-vaccination tuberculin sensitivity as measured at 2-3 months after vaccination and not later.

Adolescent

Comparison of seven kits for detection of rotavirus in fecal specimens with a sensitive, specific enzyme immunoassay.

A sensitive, specific enzyme immunoassay (SSEIA) was compared to four commercial, enzyme-linked immunosorbent assay (ELISA) kits and three latex agglutination assay (LAA) kits: (1) Rotavirus EIA, International Diagnostic Laboratories (IDL), (2) Pathfinder, Kallestadt (KAL), (3) Rotavirus Bio-EnzaBead, Litton (LIT), (4) Rotazyme II, Abbott (RTZII), (5) Slidex Rota-Kit, bioMerieux (SRK), (6) Meritec-Rotavirus, Meridian (MER), and (7) Rotalex, Medical Technology Corporation (RLX). The SSEIA was chosen as the reference method due to its greater sensitivity in comparison to immunoelectron microscopy and polyacrylamide gel electrophoreses of viral RNA segments. Upon evaluation of 136 specimens (of which 44 were positive by SSEIA), the ELISA kits (LIT, KAL, IDL, and RTZII) had sensitivities of 80%, 98%, 91% and 84%; specificities of 95%, 78%, 100%, and 88%; positive predictive values (PPV) of 88%, 68%, 100%, and 77%; and negative predictive values (NPV) of 91%, 99%, 96%, and 92%. When compared with SSEIA, the three LAA tests (SRK, MER, and RLX) had sensitivities of 73%, 75%, and 62%; specificities of 99%, 93%, and 95%; PPVs of 97%, 85%, and 84%; and NPVs of 88%, 89%, and 84%. LAA test results appeared to be reliable, if positive, but the sensitivities of these tests were less than those of the ELISA tests. The ELISA tests that employed specimen specific negative controls were superior in minimizing false positive reactions.

Evaluation Studies as Topic

Quantitation of cytokine mRNA levels utilizing the reverse transcriptase-polymerase chain reaction following primary antigen-specific sensitization in vivo--I. Verification of linearity, reproducibility and specificity.

The role of cytokines in vivo has been difficult to assess. This difficulty is due, in part, to the limited number of producer cells and the strict regulation of cytokine production. In order to address this situation, we have developed assays which allow us to quantitate both protein production and steady state mRNA levels from specific in vivo sites. In this report, we present data utilizing these assays on cells obtained from draining LN following specific sensitization with antigen in vivo. In order to determine the relative quantities of cytokine mRNA, we modified the reverse transcriptase-polymerase chain reaction which had been previously described. The modified assay is (1) linear over a large concn range of input template (2) demonstrates a high degree of reproducibility (SE approximately 13%) and (3) is very sensitive. Utilizing this assay, we have measured a constitutive mRNA (DHFR), quantitated both the presence of lymphokine mRNA (IL-2) and the induction of cytokine mRNA (TNF alpha). In this report we have examined the kinetics of TNF alpha mRNA expression and have demonstrated that following epicutaneous sensitization with picryl chloride, there is rapid induction (within 24 hr) of TNF alpha mRNA in the draining LN and that the levels of mRNA remain detectable through d7. In addition, we determined the time course of production of TNF protein by the draining LN cells and found that it was similar to that of the mRNA levels. A potential pathologic role for immune response generated TNF alpha is also discussed. We believe these experiments demonstrate that cytokine production following antigen-specific sensitization in vivo can be analyzed at both the cellular and molecular level. The data suggests that this approach can be used to study cytokine regulation in vivo.

Animals

Magnetic resonance imaging of the shoulder. Sensitivity, specificity, and predictive value.

The sensitivity, specificity, and predictive value of magnetic resonance imaging in the diagnosis of lesions of the rotator cuff, glenohumeral capsule, and glenoid labrum were evaluated in ninety-one patients and fifteen asymptomatic volunteers. Magnetic resonance imaging demonstrated 100 per cent sensitivity and 95 per cent specificity in the diagnosis of complete tears, and it consistently predicted the size of the tear of the rotator cuff. There was a definite correlation between atrophy of the supraspinatus muscle and the size of a complete, chronic tear of the rotator cuff. The sensitivity and specificity of magnetic resonance imaging in the differentiation of tendinitis from degeneration of the cuff were 82 and 85 per cent, and in the differentiation of a normal tendon from one affected by tendinitis with signs of impingement the sensitivity and specificity were 93 and 87 per cent. The formation of spurs around the acromion and acromiocalvicular joint correlated highly with increased age of the patient and with chronic disease of the rotator cuff. The sensitivity and specificity of magnetic resonance imaging in the diagnosis of labral tears associated with glenohumeral instability were 88 and 93 per cent. The study showed that high-resolution magnetic-resonance imaging is an excellent non-invasive tool in the diagnosis of lesions of the rotator cuff and glenohumeral instability.

Acromioclavicular Joint

Specificity, sensitivity, and prevalence in the design of randomized trials: a univariate analysis.

The number of cases needed to conduct a randomized trial is related to the sensitivity and specificity of a measurement indicative of a condition, to the prevalence of the condition, to the expected benefit of therapy (or other basis for change), and to the statistical precision desired. Sample size calculations frequently ignore sensitivity and specificity (at least qualitatively) probably because no simple formula is provided in the literature. Such a formula is included here. As an example, the number of patients required for a randomized clinical trial was calculated for a clinical outcome (nonfatal myocardial infarction or coronary artery disease death) used to detect atherosclerotic heart disease and is compared to the sample sizes required for each of three noninvasive diagnostic studies (exercise ECG ST depression, exercise LVEF reduction, and thallium myocardial imaging) performed for the detection of atherosclerotic heart disease. We calculated that the sample size should be much smaller when these diagnostic studies are employed compared to the clinical outcome, thereby offering the potential for reduced cost and complexity of a randomized clinical trial.

Adult

HLA-DRB1*01 subtyping by allele-specific PCR amplification: a sensitive, specific and rapid technique.

The two DR1-associated cellular specificities Dw1 and Dw20, as well as DR'Br' (Dw'BON'), cannot be unequivocally assigned by serological typing or restriction fragment length polymorphism (RFLP) analysis. We have developed and compared two polymerase chain reaction-based (PCR) typing methods for distinguishing these DRB1 alleles; allele-specific amplification of DRB1*01 alleles followed by an agarose gel electrophoresis detection step and group-specific DRB1*01 amplification followed by hybridization with sequence-specific oligonucleotide probes. The two typing strategies gave completely concordant results in the 33 DRB1*01-positive and the 46 DRB1*01-negative individuals and cell lines studied. No false-negative or false-positive typing results were obtained. All possible heterozygous combinations of the DRB1*0101-0103 alleles could be distinguished by both typing methods. DRB1*01 subtyping by allele-specific PCR amplification was performed in less than 3 hours, including PCR amplification, detection and interpretation steps. The technique will be a valuable complement to DR typing by serology and RFLP analysis. Allele-specific DRB1 amplifications or group-specific amplifications followed by directed allele-specific amplifications of DRB1 alleles, typing based on the absence or presence of amplified products, may well prove to be the technical innovation that will firmly establish PCR-based DR typing in routine clinical tissue typing.

Alleles

Sensitivity, specificity, and cost-effectiveness of the sensitive thyrotropin assay in the diagnosis of thyroid disease in ambulatory patients.

The sensitivity and specificity of two sensitive thyrotropin assays were compared with those of other standard thyroid function tests in 544 ambulatory subjects who were clinically euthyroid, thyrotoxic, or hypothyroid. Both sensitive thyrotropin assays had the highest sensitivity and specificity (95%/89% and 92%/95%), following by estimated free thyroxine (T4) level (82% and 94%), calculated free T4 index (78% and 93%), and free triiodothyronine index (86% and 88%). Sensitivity of the two thyrotropin assay kits in the diagnosis of thyrotoxicosis was 86% and 95%, and that in the diagnosis of hypothyroidism was 92% and 94%. Other tests were nearly as sensitive in the diagnosis of thyrotoxicosis but not hypothyroidism. A cost analysis of a testing strategy that used either total T4, free T4 index, or sensitive thyrotropin assay alone as the first-line thyroid test disclosed that to establish the patient's thyroid metabolic status would have cost $11,093, $14,536, and $24,902, respectively, using each test first. We suggest that, at current prices, routine use of the thyrotropin assay as a first-line test in ambulatory patients is not as cost-effective as the free T4 index.

Adult

Context-specific sensitization to naloxone-precipitated withdrawal in hamsters: effect of pimozide.

Three experiments were conducted to investigate the development of context-specific sensitization to naloxone-precipitated withdrawal in hamsters. In Experiment 1, animals in group M/S were given morphine (15 mg/kg) injections in a distinctive environment and saline in the home cage. Animals in group S/M were given saline in the distinctive environment and morphine in the home cage, and animals in group S/S were given saline in both environments. All groups were challenged subsequently with naloxone (0.4 mg/kg) in the distinctive environment and then observed for signs of opiate withdrawal. The results showed that group M/S gave more naloxone-precipitated withdrawal signs than each of the other groups, which did not differ from one another. Experiment 2 was designed to test the effect of pimozide on context-specific sensitization to naloxone-precipitated withdrawal. The design was similar to that of Experiment 1 but group P/M/S, which received an injection of pimozide (0.5 mg/kg) 4 h prior to morphine, was added. The results indicated that context-specific sensitization developed as in Experiment 1, except among animals treated with pimozide. Experiment 3 was designed to determine whether pimozide interferes with the development or the expression of context-specific sensitization. Six groups, differing in the frequency and timing of the pimozide injection, were employed. The results indicated that pimozide interfered with context-specific sensitization, whenever it was given. It is concluded that pimozide interferes with the expression of context-specific sensitization, although a separate effect on the development of sensitization is not ruled out.

Animals

Beyond sensitivity, specificity and statistical independence.

Sensitivity and specificity have clear definitions when there is a single test for one disease, and the test is either positive or negative. This paper presents a unified approach for obtaining posterior probabilities (predictive values) when there are more than two test outcomes and/or more than one disease state. In these cases, sensitivity and specificity do not have clear definitions. Three examples from the literature demonstrate how this approach simplifies the presentation of Bayesian revision of prior probabilities. Use of proper care in data collection for the purpose of estimating conditional probabilities can avoid assumptions of statistical independence.

Decision Support Techniques

[Histochemical characteristics of experimental candidiasis with specific sensitization].

The authors studied histochemically the significance of specific sensitization in the pathogenesis of specific moniliasis. The activity of various enzymes of the fungus and of the cells of the inflammatory infiltrate with the subsequent quantitative assessment was determined. In visceral moniliasis tissue changes were in a definite correlation with the changes of the active agents in the cells of the fungus and in the cells of the inflammatory inflitrate. An increase in the activity of the fungus enzymes was noted at the early periods of parasitic infestation; this was later replaced by its reduction, coinciding with the reduction of the amount of the vegetative forms. Preliminary administration of the moniliasis allergen induced an increase of the sensitivity to the subsequent infection. Changes in the specifically sensitized rats developed against the background of marked vascular disturbances and coursed by the hyperergic type.

Animals

Ambulatory 24-h esophageal pH monitoring: normal values, optimal thresholds, specificity, sensitivity, and reproducibility.

Ambulatory 24-h esophageal pH monitoring is increasing in popularity as the means to measure esophageal exposure to gastric juice and document the presence of gastroesophageal reflux disease, particularly before surgical therapy. Normal values for pH exposure were obtained from 50 asymptomatic healthy subjects. Receiver operating characteristic curves constructed from another 25 asymptomatic healthy subjects and 25 selected patients with other markers of increased esophageal acid exposure showed that a composite score and the percent total time pH less than 4 provide the most efficient interpretation of the test with a sensitivity of 96%, a specificity of 100% and an accuracy of 98% for the composite score, and a sensitivity, specificity, and accuracy of 96% for the percent total time pH less than 4. Repeat monitoring of healthy volunteers and symptomatic subjects in the inpatient and outpatient environment showed no significant difference, with the exception that the number of reflux episodes was significantly greater during the outpatient recording in volunteers. This did not affect the clinical accuracy of the test. Esophageal pH probes were well tolerated, but caused belching and coughing during the early part of the monitored period. We conclude that computerized ambulatory 24-h esophageal pH monitoring in the outpatient setting provides accurate and reproducible results.

Adult

Detection of P-glycoprotein with a rapid flow cytometric functional assay using Fluo-3: evaluation of sensitivity, specificity and feasibility in multiparametric analysis.

The specificity and sensitivity of a flow cytometric assay simultaneously measuring expression and transport function of the multidrug resistance associated P-glycoprotein (Pgp) was evaluated. The monoclonal antibody (mAb), MRK16 was used to detect phenotypic Pgp expression while Fluo-3-AM was used as a fluorescent substrate in a Pgp functional transport assay. The specificity of the functional assay was examined in two vinblastine selected human leukemic cell lines (K562/VLB2.5 and CCRF-CEM/VLB50) with acquired Pgp overexpression. Downmodulation of Pgp function in these cell lines could be demonstrated with different substances (verapamil, vinblastine, trifluoperazine, cyclosporin A, progesterone and quinidine) and was proven to be consistently higher in the vinblastine selected cells than in their non-selected drug sensitive counterparts. Unexpectedly, modulator activity was also observed in drug sensitive K562 and CCRF-CEM cell lines despite the inability to detect Pgp in those cells by MRK16 flow cytometrically. Low level expression of the MDR1 gene encoding Pgp in sensitive K562 cells was however demonstrated with a sensitive RT-PCR procedure. The small effect of Pgp modulators in non-drug selected cells could therefore be attributed to low level basal expression of Pgp and illustrates the sensitivity of the functional assay. Also, the effect of various Pgp modulators on Pgp function was more pronounced in a subpopulation of Pgp expressing lymphocytes than in lymphocytes which did not express Pgp. Finally, a correlation was found between discrete variations in Pgp expression and Pgp function of CD4+ lymphocytes, underscoring the feasibility of the functional assay in a triple parametric procedure. The triple parametric assay holds promise to detect Pgp expression and function in clinical samples containing mixtures of malignant and non-malignant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem

The logistic modeling of sensitivity, specificity, and predictive value of a diagnostic test.

A method is described for modeling the sensitivity, specificity, and positive and negative predictive values of a diagnostic test. To model sensitivity and specificity, the dependent variable (Y) is defined to be the dichotomous results of the screening test, and the presence or absence of disease, as defined by the "gold standard", is included as a binary explanatory variable (X1), along with variables used to define the subgroups of interest. The sensitivity of the screening test may then be estimated using logistic regression procedures. Modeled estimates of the specificity and predictive values of the screening test may be similarly derived. Using data from a population-based study of peripheral arterial disease, the authors demonstrated empirically that this method may be useful for obtaining smoothed estimates of sensitivity, specificity, and predictive values. As an extension of this method, an approach to the modeling of the relative sensitivity of two screening tests is described, using data from a study of screening procedures for colorectal disease as an example.

Arterial Occlusive Diseases

Mite allergen exposure is a risk for the incidence of specific sensitization.

BACKGROUND: Mite allergen exposure is essential for the process of specific allergic sensitization. However, it is not clear whether incidence of specific sensitization at school age depends on the level of mite antigen exposure. Therefore the relationship between mite allergen exposure and incidence of specific sensitization was investigated. METHODS: Eighteen hundred twelve primary school children were enrolled in a population-based 2-year follow-up study. In three consecutive skin prick tests (SPTs), each 12 months apart, sensitization to Dermatophagoides pteronyssinus (Dpt) and six non-Dpt allergens was ascertained. To assess exposure to Der p I between the first and second SPTs (period I) and the second and third SPTs (period II), the amount of antigen per gram of dust (taken from the children's mattresses was measured. By using the SPT reactions to Dpt as a basis, conversions after "no wheal" were classified as doubtful incidence (average yearly incidence = 6.7%) or definite incidence (average yearly incidence = 3.2%). Then, with the use of multiple logistic regression, the risk of exposure to Der p I (medians: 1.4 micrograms/gm in period I, 1.6 micrograms/gm in period II) was analyzed with adjustment being made for gender, low gestational age, parental atopy, and initial sensitization to non-Dpt allergens. RESULTS: Regarding doubtful incidence, the analysis failed to identify a reliable cutoff point of exposure. For definite incidence, the Der p I exposure represents a significant risk in the total population, starting from a concentration of 9 micrograms/gm. This effect is modified by an initial sensitization to non-Dpt allergens: for these children exposure to concentrations above 2 micrograms/gm poses a significant risk, whereas for the population without other initial sensitizations, only an extremely high cutoff limit (> 80 micrograms/gm) gains significance. CONCLUSION: Our data suggest that a concentration limit of 2 micrograms Der p I antigen per gram of dust should be regarded as minimal avoidance level for primary prevention in children with sensitization to other inhalant allergens.

Animals