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Rational use of the PFA-100 device for screening of platelet function disorders and von Willebrand disease.

Two hundred and five patients referred for evaluation of platelet functions and 126 healthy controls were tested with the PFA-100 instrument. A cut-off value of 150 s for collagen/epinephrine (CEPI) closure time (CT) produced most acceptable sensitivity (90%), specificity (85.2%), and positive (82.6%) and negative (91.6%) predictivity values for screening of platelet function disorders and von Willebrand disease (vWD). All patients with vWD and Glanzmann thrombasthenia could be detected by PFA-100. Both CEPI and collagen/adenosine diphosphate (CADP) CTs were elevated in all of these cases. Sensitivity of the device was 81.6% for patients with platelet secretion defects. CADP CT was normal in 63.9% of the patients in this subgroup. Specificity (47%) and positive predictivity (57%) of the instrument were diminished in patients with low hemoglobin concentrations. Depending on the results, an algorithm was developed for screening of platelet function disorders and vWD with PFA-100.

Algorithms↗

Predictive value of cognition for different domains of outcome in recent-onset schizophrenia.

The aim of this study was to see whether and how cognition predicts outcome in recent-onset schizophrenia in a large range of domains such as course of illness, self-care, interpersonal functioning, vocational functioning and need for care. At inclusion, 115 recent-onset patients were tested on a cognitive battery and 103 patients participated in the follow-up 2 years after inclusion. Differences in outcome between cognitively normal and cognitively impaired patients were also analysed. Cognitive measures at inclusion did not predict number of relapses, activities of daily living and interpersonal functioning. Time in psychosis or in full remission, as well as need for care, were partly predicted by specific cognitive measures. Although statistically significant, the predictive value of cognition with regard to clinical outcome was limited. There was a significant difference between patients with and without cognitive deficits in competitive employment status and vocational functioning. The predictive value of cognition for different social outcome domains varies. It seems that cognition most strongly predicts work performance, where having a cognitive deficit, regardless of the nature of the deficit, acts as a rate-limiting factor.

Activities of Daily Living↗

[Predictive values of the usual biologic tests for the detection of human immunodeficiency virus infection. Consequences for screening].

This paper tries to review what is scientifically known about the predictive values of biological tests of HIV infection. The epidemiological situation for that infection is characterized by two facts: the very high values of sensitivity and specificity which are close to unity; the prevalence of seropositivity which is on average--at least in western countries--, very low (except for some small specific groups). Under those conditions, Negative Predictive Values are always very close to unity, and the percentage of false negative tests is extremely low. Things are quite different for Positive Predictive Value, which varies very rapidly with very small shifts or uncertainties about specificity and prevalence. In the case when prevalence is very low (general population screening) and at the same time specificity is not excellent (that means < 0.99 or even < 0.995), Positive Predictive Value is very poor and the proportion of false positive tests rather important. Indeed the analysis of scientific literature, using the method of "best synthesis evidence", reveals numerous discrepancies as to the value of specificity among different tests. Figures vary a lot from one study to another. It is not obvious which screening strategies are concerned by the results, which finally entail a strong statistical uncertainty. Finally, the figures published in the literature are given by high standard laboratories. One may fear the tests realized in routine laboratories are less reliable. As a conclusion, let us say that despite their very good quality, the biological tests, when used separately, should not be trusted without strong previous criticism when applied to samples of the general population. Any biological screening should be preceded by a clinical examination, including a precise inquiry, in order to detect people at risk, that means with a high prior probability. Clinical dialogue has moreover another great interest: it allows health consulting and education, and calls for personal responsibility for both seropositive and negative subjects. It is the best choice of method to reach a high preventive effectiveness.

HIV Infections↗

Modified National Institutes of Health Stroke Scale for use in stroke clinical trials: prospective reliability and validity.

BACKGROUND AND PURPOSE: To prospectively evaluate the reliability and validity of this previously developed stroke scale in an independently collected cohort. The National Institutes of Health Stroke Scale (NIHSS) has been criticized for its complexity and variability. Prior formal clinimetric analyses were used to obtain a modified version of NIHSS (mNIHSS), which retrospectively demonstrated improved reliability and validity. We sought to prospectively measure the reliability and validity of the mNIHSS. METHODS: Forty-five patients with a history of stroke or intracerebral hemorrhage were evaluated at the University of California, San Diego, Stroke Center from September 2000 through March 2001. Each patient was tested by 2 NIHSS-certified neurologists using the NIHSS, mNIHSS, Barthel Index, and Modified Rankin scales. RESULTS: There were a large percentage of high kappa values using the mNIHSS. Only 10 (66.67%) of 15 NIHSS kappa scores showed excellent agreement, whereas 10 (90.91%) of 11 mNIHSS kappa scores showed excellent agreement. As predicted, the mNIHSS was more reliable than the NIHSS because of the exclusion of items with low kappa values. With the use of correlation coefficient analysis, the mNIHSS was as valid as the NIHSS. CONCLUSIONS: This prospective study found high reliability and continued validity by using a previously developed mNIHSS. Items found to have low kappa values were consistent with the previously derived retrospective mNIHSS. The resulting mNIHSS scale has much higher kappa values. The mNIHSS showed improved agreement between examiners and was also easier to administer, having fewer and simpler items. Further prospective evaluation should assess whether the mNIHSS could be used in lieu of the NIHSS.

Academic Medical Centers↗

An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: II. Identification of genotoxicants, reprotoxicants, and carcinogens using in silico methods.

This study examined a novel method to identify carcinogens that employed expanded data sets composed of in silico data pooled with actual experimental genetic toxicity (genetox) and reproductive and developmental toxicity (reprotox) data. We constructed 21 modules using the MC4PC program including 13 of 14 (11 genetox and 3 reprotox) tests that we found correlated with results of rodent carcinogenicity bioassays (rcbioassays) [Matthews, E.J., Kruhlak, N.L., Cimino, M.C., Benz, R.D., Contrera, J.F., 2005b. An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. Regul. Toxicol. Pharmacol.]. Each of the 21 modules was evaluated by cross-validation experiments and those with high specificity (SP) and positive predictivity (PPV) were used to predict activities of the 1442 chemicals tested for carcinogenicity for which actual genetox or reprotox data were missing. The expanded data sets had approximately 70% in silico data pooled with approximately 30% experimental data. Based upon SP and PPV, the expanded data sets showed good correlation with carcinogenicity testing results and had correlation indicator (CI, the average of SP and PPV) values of 75.5-88.7%. Conversely, expanded data sets for 9 non-correlated test endpoints were shown not to correlate with carcinogenicity results (CI values <75%). Results also showed that when Salmonella mutagenic carcinogens were removed from the 12 correlated, expanded data sets, only 7 endpoints showed added value by detecting significantly more additional carcinogens than non-carcinogens.

Animals↗

Predictive values for cardiopulmonary exercise testing in sedentary Chinese adults.

OBJECTIVE: Normative data for cardiopulmonary exercise testing (CPET) may vary among subjects of different races. The objectives of the present study were to: (i) establish normal standards for cardiopulmonary responses during incremental cycle ergometer testing in order to derive predictive equations for clinically useful variables during CPET of Chinese subjects; and (ii) determine the validity of existing prediction equations of maximal exercise performance for use in our local Chinese population. METHODOLOGY: The maximal and submaximal cardiopulmonary responses were analysed for 95 healthy sedentary adult Chinese subjects (48 men and 47 women; aged 20-70 years) who underwent CPET using a cycle ergometer and an incremental work-rate protocol until symptom limitation. RESULTS: Measurements, at maximal exercise, of oxygen uptake (VO2(max)), power output and heart rate were regressed on age, height, weight and gender. The predictive equations for these exercise parameters performed better than those published previously in out-sample predictive accuracy. Comparison with previous studies also showed that prediction equations of VO2(max) derived from studies based predominantly or exclusively on Caucasian populations overestimated the actual values for our subjects. CONCLUSIONS: Previously established prediction equations for maximal exercise performance during CPET based on non-Chinese populations may not be applicable to Chinese subjects in our population.

Adult↗

Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test.

OBJECTIVES: Transcatheter arterial chemoembolization (TACE) is the major treatment modality for patients with unresectable hepatocellular carcinoma (HCC). Hepatic failure after TACE is relatively common in patients with preexisting liver dysfunction. The purpose of this study was to evaluate whether the monoethylglycinexylidide test and other parameters might predict hepatic failure after TACE in HCC patients. METHODS: One hundred forty-two HCC patients undergoing TACE were enrolled into this study. Before TACE, their venous blood was collected 15 min after a bolus injection of lidocaine (1 mg/kg body weight). A fluorescence polarization immunoassay was used to measure monoethylglycinexylidide oncentrations in their sera. Univariate and multivariate analyses were performed on the monoethylglycinexylidide test and other parameters between patients with and without hepatic failure after TACE. RESULTS: Nineteen patients (13.4%) suffered hepatic failure after TACE. Univariate analysis revealed that the monoethylglycinexylidide concentration (17.7+/-5.8 vs 43.9+/-13.2 ng/ml), Child-Pugh score (6.9+/-0.6 vs 6.0+/-0.7), indocyanine green retention ratio at 15 min (32.4+/-6.5% vs 15.7+/-5.8%), prolonged PT, and serum total bilirubin and albumin showed significant differences between patients with and without hepatic failure after TACE. After a multiple logistic regression, only the monoethylglycinexylidide test was an independent predictor of hepatic failure (OR = 1.68, 95% CI = 1.07-2.65, p = 0.026). Among the 19 hepatic failure patients, three (15.8%) died of hepatic failure associated with TACE within 1 month after this procedure. CONCLUSIONS: As a predictor of hepatic failure after TACE, the monoethylglycinexylidide test is better than conventional liver function tests and clinical parameters. The monoethylglycinexylidide test may be used to select patients with relatively good liver reserves for safe TACE treatment.

Aged↗

Quantitative correlation of carcinogenic potency with four different classes of short-term test data.

The search for a short-term mutagenicity test to identify potential carcinogens has yielded over 100 assay systems, including the Ames test. This paper continues the investigation of Travis et al. into the prediction of carcinogenic potency of known mouse carcinogens using different classes of short-term toxicologic data. We used four classes of short-term test data (mutation, toxicity, reproduction and tumorigenicity) from the Registry of Toxic Effects of Chemical Substances (RTECS) database. We conclude that mutation data alone are poor predictors of carcinogenic potency, accounting for only 21% of the observed variability in experimentally-determined mouse TD50 values. We further conclude that batteries of toxicologic data containing varying types of short-term data are excellent predictors of the carcinogenic potency of known mouse carcinogens: four types of short-term data account for 82% of the observed variability in experimentally-obtained mouse TD50 values. By using all available toxicological data, we obtained a strong correlation between toxicologic assay results and carcinogenic potency of known mouse carcinogens.

Animals↗

[Predictive value of preoperative fasting glucose test of diabetic patients regarding surgical outcome in cataract surgery].

OBJECTIVE: To determinate the predictive value of preoperative glucose test of diabetic patients, with age above 40 years, for visual acuity outcome and clinical perioperative complications, in cataract surgery with local anesthesia, in an academical medical center. METHODS: Type 2 diabetic patients, above 40 years of age, indicated for cataract surgery between February 10, 2000 and January 10, 2001, at the State University of Campinas, São Paulo, Brazil. All patients had a preoperative medical assessment by a physician one week before surgery, and were submitted to serum fasting glucose test and 12-lead electrocardiogram. There was no delay in the surgeries of patients with abnormal serum glucose test results, so, the result of the test alone was not a reason to cancel the surgery. According to the glucose test, the patients were assigned to one of two groups: Normal Glucose Test Group (60-115 mg/dL) or Abnormal Glucose Test Group (>115 mg/dL). Postoperative best-corrected visual acuity and clinical perioperative complications were recorded on a standardized form. RESULTS: The sample consisted of 193 patients. 67 (34.7%) had a serum glucose test within normal limits (normal glucose test group) and 126 (65.3%) outside normal limits (abnormal glucose test group). The mean result of the "normal glucose test group" was 98.5+/-17.3 mg/dL and 166.5+/-48.9 mg/dL for the "abnormal glucose test group" (p<0.001). We observed perioperative complications in 21 (10.7%) patients, all arterial hypertension cases; 7 (10.5%) of these in patients with normal glucose test result and 14 (11.1%) in patients with abnormal result (p<0.888). The postoperative best-corrected visual acuity was similar in both groups. CONCLUSION: There was no influence of the preoperative serum glucose level on perioperative clinical complications or visual acuity outcome.

Adult↗

A longitudinal assessment of predictive value of a caries activity test in young children.

A longitudinal study was conducted in Okayama, Japan to investigate the predictive value of a caries activity test (Cariostat). The subjects were 100 children who participated in routine dental examinations at 18, 24 and 36 months. Results indicated caries prevalence of 9% at 18 months, 21 percent at 24 months and 70 percent at 36 months. Cariostat scores at each age were correlated with dmft at 36 months and with whether or not child was caries-free at 36 months. Cariostat scores at each age showed good validity (sensitivity + specificity) for whether or not child was caries-free at 36 months. These results indicated that caries activity test, Cariostat, was effective for predicting caries occurrence in young children.

Child, Preschool↗

Predicting stimulant medication response in ADHD: evidence from an integrated profile of neuropsychological, psychophysiological and clinical factors.

There have been significant advances in understanding the neurobiology of Attention-Deficit/Hyperactivity Disorder (ADHD) and it is timely to examine the ability of biological and psychological markers to predict medication response in this disorder. We evaluated prediction of medication response in adolescent ADHD using neuropsychological testing and psychophysiological measures of central and autonomic function. Fifty ADHD adolescents participated in pre- and post-stimulant medication testing. Separately ranked performance in auditory oddball and visual Working Memory (WM) tasks determined 20 "responders" and 20 "non-responders" with 10 "neutrals" excluded from the discriminant function analyses (DFA). For both oddball and WM performance rankings, the two groups did not differ in age, sex, or handedness. However, responders did have higher levels of symptomatology than non-responders at baseline. Pre-stimulant medication psychophysiology variables were used as predictors in each DFA. Oddball performance correctly classified 85.0% of responders and 95.0% of non-responders. Better response was associated with increased resting beta power (left posteriorly), delayed oddball target N1 (frontally), decreased oddball target P2 (left posteriorly) and decreased WM distractor P3 (right frontally). Working memory performance classified 80.0% of responders and 90.0% of non-responders, with a broadly similar profile of psychophysiological predictors. These finding indicate the value of integrating neuropsychological and psychophysiological data in predicting medication response in ADHD.

Adolescent↗

Neuropsychological markers of progression from mild cognitive impairment to Alzheimer's disease.

To find early clinical markers that may predict a likely progression to Alzheimer's disease (AD), the authors performed neuropsychological tests on 82 mild cognitive impairment (MCI) subjects. After 3 years, 38 patients developed AD while 44 retained the diagnosis of MCI. The cognitive differences between the groups were studied. Patients who developed AD showed significantly lower values than did MCI subjects in some neuropsychological scores (P = .02-.001), with sensitivities and specificities higher than 84% and 64%, respectively, for detecting early-onset AD, with a 7.9-fold increased risk of converting to AD (P < .001). Regarding the logistic regression model, the CAMCOG Memory and Perception cognitive screening items were the optimum independent tools to classify the patients who will progress to AD, showing a relative risk of progression of 10.5 (P = .002), 5.5 (P = .008), and 3.9 times (P = .05), respectively, with a sensibility of of 92.1% and a specificity 72.7%.

Aged↗

Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. Sensitivity, specificity and relative predictivity.

The performance of a battery of three of the most commonly used in vitro genotoxicity tests--Ames+mouse lymphoma assay (MLA)+in vitro micronucleus (MN) or chromosomal aberrations (CA) test--has been evaluated for its ability to discriminate rodent carcinogens and non-carcinogens, from a large database of over 700 chemicals compiled from the CPDB ("Gold"), NTP, IARC and other publications. We re-evaluated many (113 MLA and 30 CA) previously published genotoxicity results in order to categorise the performance of these assays using the response categories we established. The sensitivity of the three-test battery was high. Of the 553 carcinogens for which there were valid genotoxicity data, 93% of the rodent carcinogens evaluated in at least one assay gave positive results in at least one of the three tests. Combinations of two and three test systems had greater sensitivity than individual tests resulting in sensitivities of around 90% or more, depending on test combination. Only 19 carcinogens (out of 206 tested in all three tests, considering CA and MN as alternatives) gave consistently negative results in a full three-test battery. Most were either carcinogenic via a non-genotoxic mechanism (liver enzyme inducers, peroxisome proliferators, hormonal carcinogens) considered not necessarily relevant for humans, or were extremely weak (presumed) genotoxic carcinogens (e.g. N-nitrosodiphenylamine). Two carcinogens (5-chloro-o-toluidine, 1,1,2,2-tetrachloroethane) may have a genotoxic element to their carcinogenicity and may have been expected to produce positive results somewhere in the battery. We identified 183 chemicals that were non-carcinogenic after testing in both male and female rats and mice. There were genotoxicity data on 177 of these. The specificity of the Ames test was reasonable (73.9%), but all mammalian cell tests had very low specificity (i.e. below 45%), and this declined to extremely low levels in combinations of two and three test systems. When all three tests were performed, 75-95% of non-carcinogens gave positive (i.e. false positive) results in at least one test in the battery. The extremely low specificity highlights the importance of understanding the mechanism by which genotoxicity may be induced (whether it is relevant for the whole animal or human) and using weight of evidence approaches to assess the carcinogenic risk from a positive genotoxicity signal. It also highlights deficiencies in the current prediction from and understanding of such in vitro results for the in vivo situation. It may even signal the need for either a reassessment of the conditions and criteria for positive results (cytotoxicity, solubility, etc.) or the development and use of a completely new set of in vitro tests (e.g. mutation in transgenic cell lines, systems with inherent metabolic activity avoiding the use of S9, measurement of genetic changes in more cancer-relevant genes or hotspots of genes, etc.). It was very difficult to assess the performance of the in vitro MN test, particularly in combination with other assays, because the published database for this assay is relatively small at this time. The specificity values for the in vitro MN assay may improve if data from a larger proportion of the known non-carcinogens becomes available, and a larger published database of results with the MN assay is urgently needed if this test is to be appreciated for regulatory use. However, specificity levels of <50% will still be unacceptable. Despite these issues, by adopting a relative predictivity (RP) measure (ratio of real:false results), it was possible to establish that positive results in all three tests indicate the chemical is greater than three times more likely to be a rodent carcinogen than a non-carcinogen. Likewise, negative results in all three tests indicate the chemical is greater than two times more likely to be a rodent non-carcinogen than a carcinogen. This RP measure is considered a useful tool for industry to assess the likelihood of a chemical possessing carcinogenic potential from batteries of positive or negative results.

Animals↗

Koilocytotic atypia in Papanicolaou smears. Reproducibility and biopsy correlations.

BACKGROUND: It would be useful if cervical smears containing koilocytes alone could be reliably separated from those containing other forms of nuclear atypia within the spectrum of low grade squamous intraepithelial lesions (LSIL) and that this separation was predictive of differences in biopsy follow-up. In this article, the authors sought to test this possibility. METHODS: Consecutive smears diagnosed as LSIL from 140 patients who had follow-up colposcopic biopsies were reviewed independently by three observers. The inter- and intraobserver reproducibility in diagnosing smears with koilocytes alone was assessed by the kappa statistic. Comparison of each reviewer's cytologic diagnosis with a reviewed biopsy diagnosis was assessed using chi-square analysis. The quantity of abnormal cells was compared with the presence or absence of a lesion on biopsy. RESULTS: Kappa values for any 2 observers agreeing on koilocytosis as a separate category ranged from 0.22-0.47 (poor to good). Intraobserver reproducibility across all cytologic categories ranged from 0.35-0.62 (poor to good). A cytologic diagnosis of koilocytosis predicted a lower rate of high grade SIL (HSIL) on initial biopsy for one of the observers, but not for the other two. Koilocytosis did not predict a lower rate of LSIL on initial biopsy or HSIL in follow-up biopsies for any observer. The quantity of cells on the initial smear did not correlate with a lesion on biopsy. CONCLUSIONS: Separation of LSIL into two diagnostic categories is not feasible because of its poor cytologic reproducibility and inability to predict differences in biopsy diagnosis. The quantity of abnormal cells in LSIL is not predictive of the detection of a lesion on biopsy.

Biopsy↗

[Results of prenatal amniotic fluid diagnosis in suspected hemolytic disease of newborn].

759 amniotic fluid samples have been examined spectrophotometrically according to Liley and chemically for bilirubin from 286 patients with suspicion of morbus haemolyticus fetalis. The results obtained, gave the following findings for the procedure of Liley: sensitivity 75.0 per cent, specivity 96.5 per cent, accuracy 85.3 per cent, predictive value of positive test 95.6 per cent and predictive value of negative test 79.1 per cent and for the chemical test respectively: 88.2 per cent, 81.7 per cent, 85.0 per cent, 83.0 per cent and 87.2 per cent. A pathological delta E value is suspect of a serious erythroblastosis. But a serious morbus haemolyticus fetalis may be excluded with higher likelihood by concentration of bilirubin chemically determined below the pathological range then by correlated values of delta E. Finally we conclude that two different methods for amniotic fluid diagnostic are of higher predictability.

Amniocentesis↗

Low yield for extended reading of patch tests with topical corticosteroids.

BACKGROUND: On the basis of reports that up to 30% of patch test reactions are missed if an extended reading is not performed, we required that patients who were being patch tested with the corticosteroid series return for a reading at least 1 week after placement of the allergens. OBJECTIVE: To report our institutional experience with extended readings (day 7 or beyond) of patch test reactions to the corticosteroid series. METHODS: We retrospectively reviewed patch test reactions to corticosteroids since extended readings were implemented (April 2001 to June 2004). RESULTS: A total of 135 patients were patch tested with 1,656 corticosteroid allergens. On day 5, five patients had five positive patch test reactions; by the time of the extended reading, no new reactions had developed in these patients. Of the patients with no reactions on day 5, two had a positive result at the extended reading: each had a relevant reaction to budesonide 0.1%, one on day 7 and the other on day 9. CONCLUSIONS: Only 2 reactions (to 1,656 corticosteroids) became apparent at the extended reading. Extended readings were of limited value in our experience.

Administration, Topical↗

Predictive value of hypo-osmotic swelling test to identify viable non-motile sperm.

AIM: To determine the predictive value of the hypo-osmotic swelling (HOS) test to identify viable, non-motile sperm. METHODS: Semen samples from 20 men with severe asthenozoospermia underwent traditional seminal analysis, eosin-nigrosin (EN) staining and the HOS test. A further EN stain was then performed on a HOS pre-treated aliquot and a total of 2000 further sperm examined. RESULTS: The median sperm density was 5.1 million/mL (IQR 4.3 approximately 13.1) and the median motility was 3.0% (IQR 0 approximately 7). Seven samples showed complete asthenozoospermia. Initial EN staining showed 59% viability (range 48 approximately 69) despite the poor standard parameters and 47% (range 33 approximately 61) in the complete asthenozoospermia subgroup. The HOS test showed 49.9% reacted overall (range 40 approximately 59) and 41.7% (range 22 approximately 61) in the complete asthenozoospermia subgroup. The combined HOS/EN stain showed the positive predictive value of the HOS test to identify viable sperm was 84.2 % overall and 79.7% in the complete asthenozoospermia subgroup. CONCLUSION: The HOS test can effectively predict sperm viability in patients with severe and complete asthenozoospermia.

Adult↗