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Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.

We consider how to combine several independent studies of the same diagnostic test, where each study reports an estimated false positive rate (FPR) and an estimated true positive rate (TPR). We propose constructing a summary receiver operating characteristic (ROC) curve by the following steps. (i) Convert each FPR to its logistic transform U and each TPR to its logistic transform V after increasing each observed frequency by adding 1/2. (ii) For each study calculate D = V - U, which is the log odds ratio of TPR and FPR, and S = V + U, an implied function of test threshold; then plot each study's point (Si, Di). (iii) Fit a robust-resistant regression line to these points (or an equally weighted least-squares regression line), with V - U as the dependent variable. (iv) Back-transform the line to ROC space. To avoid model-dependent extrapolation from irrelevant regions of ROC space we propose defining a priori a value of FPR so large that the test simply would not be used at that FPR, and a value of TPR so low that the test would not be used at that TPR. Then (a) only data points lying in the thus defined north-west rectangle of the unit square are used in the data analysis, and (b) the estimated summary ROC is depicted only within that subregion of the unit square. We illustrate the methods using simulated and real data sets, and we point to ways of comparing different tests and of taking into account the effects of covariates.

Carcinoma, Non-Small-Cell Lung↗

A data-analytic approach for estimating lead time and screening benefit based on survival curves in randomized cancer screening trials.

Screening tests are used frequently for control of diseases such as cancer. The increased survival time of screen-detected cases over those that are detected clinically may be due in part to 'lead time', or the length of time by which the disease is diagnosed earlier by screening in the presence or absence of any real extension in survival time. A realistic evaluation of screening needs to assess the true benefit of screening; that is, the length of time by which survival has been extended, beyond merely the time of the advanced diagnosis. The comparison of survival measured from time of entry between cases in a screening arm and in a control arm in randomized studies avoids the lead time bias. If the effects of average lead time and average benefit on survival are additive, these effects can be estimated by recognizing that (a) the difference in survival curves since time of diagnosis confounds benefit and lead time, but (b) the difference in survival curves since time of start of study involves benefit only. The method is evaluated on simulated data for its accuracy and may be used on data from randomized studies.

Bias↗

Evoked potential latencies as a function of contrast: a system analytical approach.

That the latency of the pattern evoked potential (EP) increases as the stimulus contrast decreases can be understood as the result of, first, a low-pass filtering process of the (contrast) signal followed by, second, and nonlinear 'threshold' stage. We show here that by using this simple concept it is possible to estimate the shape of the 'unit step' response of the low-pass filter with the latency vs. contrast data. We show also that the step responses calculated from several subjects are in reasonable agreement if they are normalized with using the subjects' own contrast thresholds. Within experimental error, the response of a filter consisting of four low-pass first-order stages with a 10.5 Hz cut-off frequency gives a reasonable fit to our own data and to that of one other study (Musselwhite and Jeffreys, 1982).

Differential Threshold↗

Biological monitoring of acrylonitrile exposure through a new analytical approach to hemoglobin and plasma protein adducts and urinary metabolites in rats and humans.

A new, simple and fast procedure of measuring acrylonitrile (ACN) in ACN derived mercapturic acids such as S-(2-cyanoethyl)-L-cysteine(CyEC), and in hemoglobin (Hb) and plasma protein adducts and urinary metabolites in rats and humans exposed to ACN was developed. ACN in mercapturic acids or proteins was analyzed by capillary gas chromatography (GC) by liberating ACN at a high-temperature in the injector port of GC with or without oxidizing sulfur atoms of the ACN-bound cysteines into sulfoxide form by hydrogen peroxide in vitro. At 350 degrees C, more than 90% of ACN in authentic CyEC was recovered by this method. Increasing a single ip dose of ACN from 5 to 50 mg/kg produced proportional increases in ACN bound to Hb 24 hr after the treatment. The alkylation of plasma protein with ACN was about 1/10 as low as that of Hb. After repeated daily ip doses of 1-10 mg/kg, ACN in Hb decreased with a half-life of about 9 days. ACN was also detected in the blood of workers exposed to ACN for 1 to 10 years at a Siberian synthetic rubber factory.

Acetylcysteine↗

Life-style and substance use among male African-American urban adolescents: a cluster analytic approach.

Cluster analyzed four variables: school attendance, employment, church attendance, and delinquency, to develop life-style profiles. Data from 218 African-American urban adolescents were used in the study. Five meaningful clusters were retained and subjected to criterion validity analyses using measures of spirituality, participation in a voluntary organization, self-esteem, and friend's substance use. The five clusters were then compared on cigarette, alcohol, marijuana, and hard drug use. The results suggest that a life-style that includes an adaptive compensatory behavior component may be more adaptive than a life-style that does not include compensatory behavior. For example, youths who left high school before graduation but were involved in church reported less alcohol and substance use than youths who left school and were not involved in any meaningful instrumental activity. Implications for intervention and future research on high-risk behaviors are discussed.

Adolescent↗

Heart rate variability in diabetic patients during orthostatic load--a spectral analytic approach.

Spectral analysis of heart rate variability (HRV) was used to assess the autonomic nervous control of cardiac function during orthostatic load in insulin-dependent diabetic patients and healthy subjects. The diabetic patients were divided into three groups: diabetics without neuropathy (group 1), diabetics with peripheral neuropathy (group 2), and diabetics with peripheral and autonomic neuropathy (group 3). Resting mid-frequency (MF, 0.05-0.15 Hz) and respiration-related (RF, power around respiration rate) HRV were significantly lower in group 2 and 3 diabetics than in controls, indicating a reduced parasympathetic nervous system influence on the heart. Standing MF and RF spectral power data were significantly lower in all diabetic groups than in controls, suggesting marked alterations in the autonomic cardiovascular control during a mild physical load not only in symptomatic diabetics but also in patients with no signs and symptoms of neuropathy. The difference between supine and standing MF power, an estimate of beta-adrenergic influence on the heart, was significantly lower in all diabetic subject groups studied than in controls. This suggests a reduced sympathetic nervous system influence on the heart in diabetic patients. Our data suggest that computerized spectral analysis of HRV during orthostatic load seems to be a very sensitive method of evaluating of the autonomic nervous systems influence on the heart in patients suffering from diabetes mellitus.

Adult↗

Analytical approach to mathematical modelling of the isometric contraction of the hypertrophied myocardium.

It is attempted on the basis of the Hill two-element model to simulate mathematically the rising phase of the isometric mechanogram in the pressure-hypertrophied rat myocardium (Goldblatt II). The evaluation is based on the experimentally determined force-velocity relation as well as on the characteristic of the series-elastic stiffness. The changes in the isometric mechanogram of the hypertrophied heart muscle observed in the experiment can be mathematically predicted solely by means of the alterations in the force-velocity relationships induced by the hypertrophy, whereby the characteristic of the series-elastic stiffness is considered to be unchanged.

Cardiomegaly↗

A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients. A re-evaluation of the North American risperidone study.

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R2 = 0.50-0.51, p < 0.001). Only depressive symptoms did not contribute significantly to these results (p > 0.10). Path analysis showed that the greater mean change (p < 0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.

Antipsychotic Agents↗

Early attack and subsequent changes produced in an industrial lignin by a fungal laccase and a laccase-mediator system: an analytical approach.

An industrial kraft pine lignin (Indulin AT, KL) was characterized and treated in both aqueous-buffered media and dioxane to water, either with a partially purified laccase from Fusarium proliferatum or with the laccase plus 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic-acid (ABTS) as mediator. The changes in the lignin after different incubation periods were analyzed through the application of high performance liquid chromatography (HPLC), UV-visible (Vis) spectroscopy and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). At the onset of incubation, laccase-treated samples showed a slight polymerization and strong modifications in UV-Vis spectra. Through Py-GC/MS, a decrease in phenolic and methoxy-bearing pyrolysis products was observed, in contrast to an increase in the more oxidized products. After longer incubation periods (48 h) a substantial polymerization was detected by HPLC, along with a decrease in the guaiacyl (G) units. In contrast, the analysis by HPLC of the samples recovered from the laccase-ABTS system (LMS) showed an intense depolymerization, accompanied by a sizeable loss in G units and a decrease in the methyl and ethyl side-chain phenolic compounds. These results provide conclusive evidence of a rapid initial attack of the industrial lignin by laccase and notable modifications in the KL after longer incubation periods with laccase or LMS.

Benzothiazoles↗

Ivemark's renal-hepatic-pancreatic dysplasia: analytic approach to a perinatal autopsy.

A case of Ivemark's renal-hepatic dysplasia syndrome is presented. The findings are suggestive of a ductal obstructive process anatomically located at the junction of ducts with the parenchyma. The differential diagnosis includes Meckel syndrome, short rib polydactyly syndromes, and glutaric aciduria type 2. The molecular basis for this syndrome remains unknown.

Abnormalities, Multiple↗

Changing analytical approaches in European epidemiology -- a short comment on a recent article.

Multilevel analysis is today considered a more appropriate way to monitor health care performance, as it allows a less biased estimation of uncertainty, and can also separate and quantify contextual (as opposed to individual) effects. Multilevel analysis should be applied as the standard methodology for hospital comparisons. A greater awareness of this question in future Journal articles may be in order.

Adult↗