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O Gefeller

Publications and source records attributed to O Gefeller.

At least 109 records · Page 6Linked to original sources
PubMed1994

Chance-corrected measures of the validity of a binary diagnostic test.

Chance-corrected measures of the validity of diagnostic tests can be a valuable supplement to traditional measures which do not take chance-agreement between diagnostic test and true disease status into account. Recently, several authors have propagated chance-corrected measures of sensitivity and specificity, the most commonly employed indices of validity of binary diagnostic tests. A major limitation of these measures is their dependence on disease prevalence. In this paper, we propose simple alternative chance-corrected measures of sensitivity and specificity which do not share this limitation. The chance-corrected measure of sensitivity can be expressed as 1--negative likelihood ratio, and the chance-corrected measure of specificity can be expressed as 1--inverse of the positive likelihood ratio. The properties of the proposed measures are described and graphically illustrated, and formulas are given for point and interval estimation of the measures.

Models, Theoretical↗
PubMed1994

A ventilator with an integrated gas-exchange monitoring function.

OBJECTIVE: To evaluate in the laboratory a new ventilator with a built-in monitoring function for gas exchange. DESIGN: Prospective laboratory evaluation of a new mechanical ventilator. SETTING: Gas exchange was simulated by injecting nitrogen and CO2 at a respiratory exchange ratio close to 1. SUBJECTS: Different settings of controlled-mode ventilation were simulated by the gas-injection model, which permitted an independent adjustment of variables. INTERVENTIONS: The influence of respiratory variables on oxygen consumption (VO2) and the CO2 production (VCO2) agreement with a reference method was investigated. MEASUREMENTS AND MAIN RESULTS: Independent variables, which may influence the accuracy and precision of the tested device, were adjusted systematically within the following ranges and resulted in 71 different combinations: FIO2 0.21 to 0.59; FIO2-mixed FEO2 0.02 to 0.05; mixed FECO2 0.02 to 0.05; inspiratory flow rate 25 to 120 L/min; inspiratory minute volume 4200 to 11,200 mL/min; tidal volume 420 to 1120 mL; respiratory rate 6 to 16 breaths/min; airway pressure 5 to 30 cm H2O. The resulting range for both VO2 and VCO2 was 140 to 390 mL/min. For each test situation, two reference measurements were taken by mass spectrometry and wet gas spirometry. Twelve measurements were taken by the gas-exchange measurement function of the tested ventilator. The two-fold standard deviation (SD) for repeated measurement differences was chosen to quantify the repeatability within each method. This repeatability coefficient gave 5.9 (4.7) mL/min for VO2 (VCO2) within the gas-exchange measurement function, compared with 3.6 (3.1) mL/min within the reference method measurements. The mean intermethod difference (test monitor--reference method) for VCO2 over all test situations was 4.1 +/- 10.7 (2 SD)%. The respective mean VO2 difference was 7.8 +/- 12.2 (2 SD)%. Eliminating test situations with inspiratory flow rates < 50 L/min (remaining n = 46) reduced the mean VO2 difference and variability by one third to 5.4 +/- 8.0 (2 SD)%. CONCLUSIONS: Assuming that limits of agreement for intermethod differences of +/- 20% are clinically acceptable, the VCO2 measurement indicates an acceptable accuracy and precision under controlled ventilation. The respective agreement for the VO2 measurement is lower, but still within the acceptable range. The systematic difference of the VO2 and the VCO2 is mainly influenced by a +8% bias in the inspiratory minute volume measurement, which seems especially susceptible to ventilator settings with inspiratory flow rates of < 50 L/min. An improvement of the minute volume detection would be desirable.

Analysis of Variance↗
PubMed1994

How to correct for chance agreement in the estimation of sensitivity and specificity of diagnostic tests.

The traditional concept of describing the validity of a diagnostic test neglects the presence of chance agreement between test result and true (disease) status. Sensitivity and specificity, as the fundamental measures of validity, can thus only be considered in conjunction with each other to provide an appropriate basis for the evaluation of the capacity of the test to discriminate truly diseased from truly undiseased subjects. In this paper, chance-corrected analogues of sensitivity and specificity are presented as supplemental measures of validity, which pay attention to the problem of chance agreement and offer the opportunity to be interpreted separately. While recent proposals of chance-correction techniques, suggested by several authors in this context, lead to measures which are dependent on disease prevalence, our method does not share this major disadvantage. We discuss the extension of the conventional ROC-curve approach to chance-corrected measures of sensitivity and specificity. Furthermore, point and asymptotic interval estimates of the parameters of interest are derived under different sampling frameworks for validation studies. The small sample behavior of the estimates is investigated in a simulation study, leading to a logarithmic modification of the interval estimate in order to hold the nominal confidence level for small samples.

Diagnostic Tests, Routine↗
PubMed1993

Use of the positive predictive value to correct for disease misclassification in epidemiologic studies.

Misclassification problems of the disease status often arise in large epidemiologic cohort studies in which the outcome is classified on the basis of record linkage with routinely collected error-prone data sources, such as cancer registries or mortality statistics. If the misclassification is nondifferential, i.e., independent of the exposure status, this leads to bias toward the null in estimates of relative risk. A variety of methods have been proposed to correct for this bias. Most approaches are based on estimates of the sensitivity and specificity of disease classification from validation studies, which typically require invasive and time-consuming diagnostic procedures. For ethical and practical reasons, such procedures may often not be applied on individuals classified as not having the disease, in which case estimates of sensitivity and specificity cannot be obtained. In this paper, an alternative correction method is proposed based on estimates of the positive predictive value, which requires validation of the diagnosis among samples of individuals classified as having the disease only. The method is applicable in situations with either differential or nondifferential specificity of disease classification as long as the sensitivity is nondifferential. Point estimates and large-sample interval estimates of the corrected relative risk are algebraically derived. The performance of the method is assessed by extensive simulations and found to be satisfactory even for small sample sizes.

Bias↗
PubMed1993

The effects of joint misclassification of exposure and disease on epidemiologic measures of association.

This paper addresses the effects of simultaneous misclassification of both exposure and disease on epidemiologic measures of association. If misclassification of a dichotomous exposure is independent of a dichotomous disease status and vice versa (non-differential misclassification), and misclassification of exposure is independent of misclassification of disease, then the bias is always toward the null. In practice, however, errors in exposure and disease ascertainment may often be correlated. In this case, the observed exposure-disease association may be strongly biased in any direction even with non-differential misclassification. As an important corollary, the assertion commonly made in the discussion of epidemiologic study results that the observed measures of association can only be biased toward the null due to presumedly non-differential misclassification has to be viewed as inadequate unless the assertion that exposure and disease misclassification are independent is also justified. Inferences regarding the degree and direction of bias due to misclassification of exposure and disease should consider plausible degrees of correlation in classification errors in addition to the overall misclassification rates. Whenever possible, sensitivity analyses should be performed to provide a quantitative basis for such inferences.

Bias↗
PubMed1993

Risk and rate advancement periods as measures of exposure impact on the occurrence of chronic diseases.

The predominant epidemiologic measures of risk factor impact have been various concepts of the "attributable fraction." For many chronic diseases, however, risk factors merely advance the occurrence of disease, and traditional concepts of the attributable fraction do not convey information on the time dimension of premature disease occurrence. Measures of years of disease-free life lost have been proposed to reflect this time dimension but are not always estimable without special assumptions. In this paper, we examine two alternative measures, the risk and rate advancement periods, which are the time periods by which the risk or rate of disease is advanced among exposed subjects conditional on disease-free survival to some baseline age. These measures are applicable for risk factors that promote progression of chronic diseases whose rates increase with age. Point and interval estimates of these measures are easily derived from the output of standard modeling analyses. The measures are illustrated with examples from the literature. The uses and limitations of risk and rate advancement periods are critically discussed.

Adult↗
PubMed1993

The misuse of attributable and prevented fractions in the evaluation of screening in case-control studies.

Methodological problems of evaluating screening programs in case-control studies have been the subjects of controversial discussion in recent years. The increasing number of published papers presenting results of case-control studies on the evaluation of cancer screening during the last few years demonstrate that this design has rapidly gained popularity in cancer epidemiology, although the methodological criticism has not been solved yet and is usually not reflected in the interpretation of the study results. A new development in this area has been the incorporation into the evaluation of some measure of the population impact of screening programs. This paper discusses the application of these measures (attributable and prevented fractions) to screening situations. The implicit assumptions required for their valid interpretation are delineated. Primarily, it is our intention to raise the flag of caution against the naive practical application and overoptimistic interpretation of attributable and prevented fraction estimates derived from case-control studies on the evaluation of screening.

Case-Control Studies↗
PubMed1993

Neutrophil elastase and acute pulmonary damage in neonates with severe respiratory distress syndrome.

This study evaluated possible acute effects of neutrophil elastase on neonatal pulmonary morbidity. The activity of free elastase and alpha 1-proteinase inhibitor as well as concentrations of elastase-alpha 1-proteinase inhibitor in tracheal aspirate fluid of neonates with severe respiratory distress syndrome (fraction of inspired oxygen > 0.6, mechanical ventilation) were analyzed between 6 and 36 hours after surfactant replacement therapy. One hundred forty neonates were included in this prospective study. Characteristics, disease severity, and ventilatory requirements were nearly identical in both groups. All patients were treated with natural porcine surfactant (Curosurf) at an age of 2 to 15 hours. In 42 neonates (30%) considerable activities of free elastase were detected (805 micrograms/L; 100 to 1850 [median, 25th to 75th percentile]); in 98 neonates (70%) who had protective levels of alpha 1-proteinase inhibitor, no elastase activity was detected. The average concentrations of elastase-alpha 1-proteinase inhibitor were significantly increased in patients with free elastase activity when compared with those of the nonelastase group. In logistic regression analyses, 28-day outcome data showed a pronounced increase in risk of pulmonary interstitial emphysema for patients with free elastase activity in tracheal aspirate fluid. The incidence of other pulmonary and nonpulmonary complications was very similar in both groups. It is concluded that elastolytic damage and barotrauma may both contribute to acute pulmonary injury in the early stages of respiratory distress syndrome.

Female↗
PubMed1992

Comparison of adjusted attributable risk estimators.

The estimation of attributable risk in the presence of confounding and effect modification is studied in this paper. Different adjustment methods for the attributable risk are reviewed. The results of a stimulation study comparing these methods under the unrestricted multinomial sampling model are reported. From the study it is concluded that the maximum likelihood estimator resulting from the 'case load weighting' of the stratum-specific attributable risk estimates will be the best overall choice in all practical situations with relatively large sample sizes. Other adjusted attributable risk estimators depend heavily on the underlying structure of the multinomial model.

Humans↗