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Evaluation of the "condition correction factor" method of estimating theophylline clearance.

The predictive ability of the "condition correction factor" method of estimating total body theophylline clearance as proposed by Powell et al. was evaluated in 22 acutely ill hospitalized patients. Actual theophylline clearance was calculated while the patient was on a constant infusion of aminophylline with serum theophylline concentrations obtained at steady-state conditions. Independently, theophylline clearance was estimated for each patient using condition correction factors. The relationship between actual and estimated total body theophylline clearance was evaluated using multiple regression analysis and correlation testing. The data failed to demonstrate any significant positive correlation between actual and estimated theophylline clearance data. Because of this poor correlation, the use of one of the clearance estimation methods incorporating two serum theophylline concentrations obtained early in therapy is preferable, although less convenient. All estimates of clearance must be considered only as guides for individualization of therapy. Serum concentration monitoring and clinical response of the patient must be considered prior to adjustment of dosage.

Adult↗

Comments on "a mathematical description of the functionality of correction factors used in allometry for predicting human drug clearance".

In a recent paper, Tang and Mayersohn [(2005) Drug Metab Dispos 33:1294-1296] mathematically described the functionality of the correction factors (CFs), maximum life-span potential (MLP), and brain weight (BrW) used in allometric scaling for the prediction of human drug clearance. They found that there is an intrinsic defect in using correction factors because different combinations of species will produce different prediction results. Analysis with real examples reveals that different predicted clearance values observed with different combinations of animal species, with or without CFs, are not due to the intrinsic defect of the correction factors; rather, it is the effect of the species, observed clearance values in the species, and the range of the body weights. Even if one does not use the CF, the predicted clearance by the simple allometry will still vary by severalfold, depending on the species used in the scaling.

Animals↗

Simultaneous dual-isotope technetium-99m/thallium-201 cardiac SPET imaging using a projection-dependent spilldown correction factor.

A spilldown correction method is proposed for the thallium-201 window image in simultaneous dual-isotope technetium-99m/thallium-201 single-photon emission tomographic (SPET) imaging based on a single acquisition into three energy windows. In this method, images are simultaneously acquired in two standard energy windows over the 99mTc and 201Tl photopeak regions and a third spilldown window adjacent to the 201Tl window. Using a Monte Carlo simulation of SPET, the fractional amount of 99mTc and 201Tl spilldown in the 201Tl window with respect to the total counts from the spilldown window, k12, was calculated for simulated images of point sources at varying depths within a water-filled elliptical tub phantom. When applied to experimental acquisitions, k12, multiplied by the total counts from the spilldown window, is then subtracted from the 201Tl window image to produce the corrected image. However, for successful applications in SPET, k12 must be determined on a projection-by-projection basis since k12 is depth dependent. Thus, a regression relation was obtained between k12 and the total count ratio of the spilldown to 99mTc windows, k23. The spilldown correction method was applied to 201Tl photopeak images of an extended source distribution in uniform and nonuniform attenuating media with dual-isotope 99mTc/201Tl and single-isotope 201Tl. A marked improvement in image contrast was observed between the corrected and uncorrected 201Tl window images. The average count ratio of uncorrected dual-isotope 201Tl/single-isotope 201Tl was 3.08 for uniform and 2.99 for non-uniform attenuating media.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart↗

Total perturbation correction factor for PTW and NACP plane parallel chambers in electron beams.

The international protocols of electron dosimetry published by the Nordic Association of Clinical Physics and the Sociedad Española de Física Médica recommend the use of a total perturbation correction factor pu, pp which is constant for all plane parallel chambers. In this work we have compared the dose measured with the PTW-Markus and NACP plane parallel chambers in respect to a cylindrical one. The obtained results indicate that for the ionization chamber NACP the value of pu, pp = 1.000 +/- 0.005 is adequate while for the ionization chamber PTW the observed difference is explained by considering an individual total perturbation correction factor variable with the mean energy at depth z, Ez, as the fluence perturbation correction factor pf is usually given for cylindrical chambers.

Humans↗

An evaluation of correction factors applied to dose-area product meter readings for the use of sinus cones.

As a result of the refurbishment of a dedicated skull radiography unit (Siemens Orbix) a dose-area product (DAP) meter was fitted into the light beam diaphragm/X-ray collimating system. Following calibration of the DAP system for X-ray beams defined by the unit's integral rectangular and octagonal iris diaphragms, DAP correction factors were obtained for the clinical use of externally fitted sinus cones. Correction factors can be derived from a simple ratio of coned to unconed beam areas, and these agree well with measured correction factors. The simple ratio of areas factor may be used in clinical practice to reduce potential errors.

Evaluation Studies as Topic↗

Sensitivity and specificity of MMPI-2 neurologic correction factors: receiver operating characteristic analysis.

A number of Minnesota Multiphasic Personality Inventory-2 (MMPI-2) items have been hypothesized to reflect neurologic symptomatology, rather than psychopathology, among closed-head-injury (CHI) patients. Some investigators have proposed a correction factor interpretive approach, which involves the deletion of such items from the MMPI-2 profile, as a method of reducing the probability of artificial clinical scale elevations due to the symptoms of CHI. The present study employed receiver operating characteristic (ROC) analysis to evaluate the sensitivity and specificity of three correction factors. All three factors demonstrated strong sensitivity when discriminating CHI patients from normal individuals but demonstrated poor specificity when discriminating CHI patients from psychiatric patients. These findings suggest that caution should be applied in using MMPI-2 neurologic correction factors, particularly with patients who might have comorbid psychiatric conditions.

Adult↗

The perturbation correction factor of ionisation chambers in beta-radiation fields.

In determining the absorbed dose in a solid medium by means of gas-filled ionisation chambers, the perturbation of the radiation field by the chamber needs to be taken into account. So far, an appropriate correction factor has neither been calculated nor measured for beta-radiation. This work describes its experimental determination for an extrapolation chamber and beta-radiation fields of 147Pm, 204Tl, and 90Sr + 90Y. The results show that the correction factor may be assumed to be the product of a shield factor and a scatter factor the magnitudes of which depend on the chamber geometry and the radiation field. The change of the perturbation correction factor with phantom depth is important for the measurement of depth dose curves. This is demonstrated by an example.

Electrons↗

Pseudophakic correction factors for optical biometry.

INTRODUCTION: The IOLMaster of Carl Zeiss Jena, which has recently become available, is a combined instrument for biometry and intraocular lens (IOL) planning for cataract surgery utilizing partial coherence interferometry for measuring axial length. Whereas measurement data from classical ultrasound biometry, e.g. in pseudophakic eyes, need to be corrected by +0.4 to -0.8 mm--depending on the lens material--smaller corrections are expected to be necessary in optical biometry. Correction factors for various modern IOL materials were estimated theoretically and checked in first clinical measurements. METHODS: Starting from the dispersion relation of PMMA and manufacturers' phase refractive index data at 546 nm, the group refractive indices of different IOL materials were estimated for the IOLMaster wavelength of lambda=780 nm. Then, for an average eye of 23.48 mm, the center thicknesses of emmetropizing lenses of different material were calculated. Finally, comparing the pseudophakic optical axial lengths thus deduced with the respective phakic value, individual material-specific correction factors were obtained. RESULTS: Expressing the true axial length ALtrue by the length ALphak measured in phakic mode and a correction factor delta (ALtrue=Alphak+delta), we obtained values of delta=0.12+/-0.01 mm for all IOL materials considered (PMMA, silicone, collamer, AcrySof, MemoryLens). For aphakic eyes, delta=0.20 mm was deduced. DISCUSSION: The calculations suffered from the fact that hardly any information relating to optical material specifications of IOLs is available from lens manufacturers. Therefore, calculations had to be based on--nevertheless realistic--assumptions. Early clinical results support our theoretical findings. Thus, optical biometry seems to be more reliable and forgiving in pseudophakic eyes than classical ultrasound.

Acrylic Resins↗

The effect of hearing loss on ABR interpretation: use of a correction factor.

Patients suspected of retrocochlear disorders often have abnormal ABRs in the presence of high-frequency hearing loss, making clinical decisions difficult. In a retrospective study of the ABR test results of 1539 patients, the false-positive and false-negative rates for ABR are presented as a function of hearing loss at 4000 Hz, both before and after using Selters and Brackmann's correction factor for hearing loss. For patients with more than 50 db HL at 4000 Hz the false-positive and false-negative rates, uncorrected for hearing loss, were 25.0% and 2.9% respectively, and when the correction factor was used were 12.5% and 5.8%. When hearing loss at 4000 Hz was over 90 dB the ABR was abnormal in 75% of nontumor patients. Conclusions are that a correction factor for hearing loss is helpful with reservations, and that ABR is not a useful test when 4000 Hz hearing loss is greater than 90 dB HL and 2000 Hz is greater than 75 dB HL.

Adolescent↗

Rectal temperature time of death nomogram: dependence of corrective factors on the body weight under stronger thermic insulation conditions.

Ninety-eight test coolings were made under various cooling conditions (moving air, two types of both clothing and covering) on dummies of real masses of 1, 3.3, 9.9, 24.5 and 33.4 kg, respectively, which cool under standard conditions (unclothed, uncovered, still air) like human bodies of 14, 33, 41, 83 and 104 kg, respectively. The results provide evidence of a non-linear dependence of corrective factors of body weight upon the body weight. The dynamics of the dependence increases with the thickness of thermic insulation. Transferred to the use of the nomogram method on bodies, cooling conditions requiring corrective factors between 0.75 (moving air) and 1.3 (rather thin clothing/covering), known from experience on bodies of an average weight, can be used as in the past, independent of the body weight. According to experience the dependence of corrective factors on the body weight must be taken into account in bodies of a very high or low body weight. For that purpose both a simplified table and a formula for computing is given.

Bedding and Linens↗

Monte Carlo study of thermal flux profiles and body correction factors for body protein measurements of obese subjects.

In previous calculations for Total Body Nitrogen measurements of children, the anterior/posterior thermal neutron flux profile with depth was found to be fairly flat after an initial rise. However, for obese adults significant variations are found in the flux profile with the central flux value being as low as 20% of the peak value. The significance of these flux variations is examined. Correction factors are calculated for the varying attenuation of the nitrogen and hydrogen photons by a range of obese bodies. The calculations included the effect of the thermal flux profile as well as that of an outer layer of low nitrogen content adipose tissue. The bodies are assumed to have a homogeneous hydrogen content. A study of four obese body models with varying sex and fat content shows that the correction factors do not vary much between males and females. This is surprising since the female models are assumed to have a surface fat layer twice as thick as for the male models. The correction factors are found to be only slightly sensitive to the thermal flux variations with depth.

Adipose Tissue↗

An experimental method for measuring the mean length of cerebellar parallel fibers: validation and derivation of a correction factor by computational simulation and probability analysis.

The length of cerebellar parallel fibers is important for information integration by the Purkinje cells. Based on the Copernican principle for analyzing the length of stochastic events, we have recently devised a stochastic method to estimate the mean length of parallel fibers within a given cerebellar region. The purpose of the present report is to provide validation of this methodology via computational simulations. We create virtual parallel fibers with known lengths and program each step of our stochastic method for computational simulation. We then compare the observed mean length obtained from our computational simulation with the known mean length of the virtual parallel fibers. In particular, we investigate the effect of cutting parallel fibers into segments during histological sectioning. Our computational results reveal an over-estimation factor ranging from 1.0 (no correction is necessary) to 2.0 as the parallel fiber segmentation becomes increasingly severe. Based on probability theory considerations, we have confirmed the existence of this over-estimation. We have further determined the cause of this over-estimation to be an artificial consequence of one of the sampling steps in our stochastic method. These results provide validation of our methodology, as well as a correction factor, which can be derived directly from the experimentally measured parameters and used to obtain the true mean length of parallel fibers. Potential applications of the stochastic method include a comparative analysis of the length of parallel fibers as an approach to gain clues about cerebellar circuit principles and function. In addition, the stochastic method may also find promising applications in other functionally important axonal systems in the brain.

Cerebellar Cortex↗

Determination of the recombination correction factor kS for some specific plane-parallel and cylindrical ionization chambers in pulsed photon and electron beams.

It has been shown from an evaluation of the inverse reading of the dosemeter (1/M) against the inverse of the polarizing voltage (1/V), obtained with a number of commercially available ionization chambers, using dose per pulse values between 0.16 and 5 mGy, that a linear relationship between the recombination correction factor kS and dose per pulse (DPP) can be found. At dose per pulse values above 1 mGy the method of a general equation with coefficients dependent on the chamber type gives more accurate results than the Boag method. This method was already proposed by Burns and McEwen (1998, Phys. Med. Biol. 43 2033) and avoids comprehensive and time-consuming measurements of Jaffé plots which are a prerequisite for the application of the multi-voltage analysis (MVA) or the two-voltage analysis (TVA). We evaluated and verified the response of ionization chambers on the recombination effect in pulsed accelerator beams for both photons and electrons. Our main conclusions are: (1) The correction factor k(S) depends only on the DPP and the chamber type. There is no influence of radiation type and energy. (2) For all the chambers investigated there is a linear relationship between kS and DPP up to 5 mGy/pulse, and for two chambers we could show linearity up to 40 mGy/pulse. (3) A general formalism, such as that of Boag, characterizes chambers exclusively by the distance of the electrodes and gives a trend for the correction factor, and therefore (4) a general formalism has to reflect the influence of the chamber construction on the recombination by the introduction of chamber-type dependent coefficients.

Biophysics↗

A comprehensive analysis of the role of correction factors in the allometric predictivity of clearance from rat, dog, and monkey to humans.

This study was conducted to comprehensively evaluate the performance of various allometric scaling methods for the prediction of human clearance. Allometric scaling was used to predict clearance for 103 compounds, for which clearance data in the rat, dog, monkey, and humans were available. Allometry was performed using all three preclinical species and with combinations of any two species. The methods employed included standard allometry and various correction factors, including brain weight, maximum lifespan potential, and glomerular filtration. Scaling was performed on all compounds universally and on segregated subsets based on allometric exponent, clearance, physicochemical property, or route of elimination. 776 allometric combinations with 27,313 individual outcomes were performed. A predicted-to-observed clearance ratio of 0.5 to twofold was preselected as the criterion for predictive success. The success rate of allometric scaling ranged from 18 to 53%; none of the correction factors resulted in substantially improved predictivity. Furthermore, none of the methods attempted in this study achieved a success rate greater than that observed by simply estimating human clearance based on monkey hepatic extraction. Prospective allometric scaling, with or without correction factors, represents a suboptimal technique for estimating human clearance based on in vivo preclinical data.

Animals↗

Calculation of perturbation correction factors for some reference dosimeters in high-energy photon beams with the Monte Carlo code PENELOPE.

The BNM-LNHB (formerly BNM-LPRI, the French national standard laboratory for ionizing radiation) is equipped with a SATURNE 43 linear accelerator (GE Medical Systems) dedicated to establishing national references of absorbed dose to water for high-energy photon and electron beams. These standards are derived from a dose measurement with a graphite calorimeter and a transfer procedure to water using Fricke dosimeters. This method has already been used to obtain the reference of absorbed dose to water for cobalt-60 beams. The correction factors rising from the perturbations generated by the dosimeters were determined by Monte Carlo calculations. To meet these applications, the Monte Carlo code PENELOPE was used and user codes were specially developed. The first step consisted of simulating the electron and photon showers produced by primary electrons within the accelerator head to determine the characteristics of the resulting photon beams and absorbed dose distributions in a water phantom. These preliminary computations were described in a previous paper. The second step, described in this paper, deals with the calculation of the perturbation correction factors of the graphite calorimeter and of Fricke dosimeters. To point out possible systematic biases, these correction factors were calculated with another Monte Carlo code, EGS4, widely used for years in the field of dose metrology applications. Comparison of the results showed no significant bias. When they were possible, experimental verifications confirmed the calculated values.

Computer Simulation↗

Recombination correction factors for an ionization chamber exposed to discrete patterned pulsed swept beams.

An equation for a recombination correction factor for a pulsed swept beam of electrons was derived by Boag. This equation is based on an integration technique, which assumes that a large number of spot beams cover the radiation field, that the field size is much larger than the spot beam size, and that the spot beam size is much larger than the chamber size. However, for computer-controlled pulsed swept beams of electrons, the spot beam pattern can be altered, may not cover all of the field area, and the locations are reproducible. In this report, a summation method is proposed for this type of beam. Calculations for two such beams are demonstrated with the chamber located in the center of the field, and with the chamber half-way to and at the edge of the field for a linear accelerator. The results lie between the integration pulsed swept and pulsed beam curves. Moving the ionization chamber from the center toward the edge of the field produces curves closer to the pulsed swept beam curve. Increasing spot beam size produces curves closer to the pulsed beam curves. It is therefore concluded that the pulsed swept beam cannot be characterized by a single recombination correction factor curve. The actual curve will be bounded by the integration pulsed swept and pulsed beam curves.

Electrons↗

Temperature correction factors derived from normal subjects may be invalid in demyelinating neuropathies.

This study investigates the temperature effect on motor nerve conduction velocity (MNCV) in patients with neuropathic processes. Fourteen subjects, ages 18-77 yr old, with a diagnosis of uremic polyneuropathies (UPN, n = 5), diabetic polyneuropathies (DPN, n = 6) or carpal tunnel syndrome (CTS, n = 3) and ten normal controls were studied. After limb cooling in a cold water bath for 30 min, skin temperatures were sequentially obtained from the volar midwrist. Motor conduction velocities were obtained at 2-3 degrees increments between 22 and 33 degrees C. Results indicated a large individual variability; 0.1 to 1.8 in the median and 0.8 to 2.0 m/s/degrees C in the ulnar nerve when all three groups are considered together. There was a significant difference between the correction factors for control v DPN and control v CTS. A significant difference was also present for UPN v DPN and UPN v CTS (p < 0.05). There was a positive correlation (r = 0.746, p = 0.0001) between the baseline conduction velocities and the size of the correction factors in all the subjects. The effect of temperature on MNCV appears to be inversely correlated with the severity of conduction slowing or demyelination. These findings suggest that the use of a correction factor may be invalid when studying a demyelinated nerve, and that the extremity should be warmed to a specific temperature before an electrodiagnostic study.

Adolescent↗

Performance analysis and determination of the p(wall) correction factor for 60Co gamma-ray beams for Wellhöfer Roos-type plane-parallel chambers.

The wall perturbation correction factor p(wall) in 60Co for Wellhöfer Roos-type plane-parallel ionization chambers is determined experimentally and compared with the results of a previous study using PTW-Roos chambers (Palm et al 2000 Phys. Med. Biol. 45 971-81). Five ionization chambers of the type Wellhöfer PPC-35 (or its equivalent PPC-40) are used for the analysis. Wall perturbation correction factors are obtained by assuming N(D,air) chamber factors determined by cross-calibration in a high-energy electron and in a 60Co gamma-ray beam to be equal, and by assigning any differences to the wall perturbation factor. The procedure yields a p(wall) value of 1.018 (u(c) = 0.010), which is slightly higher than the value 1.014 (u(c) = 0.010) formerly obtained for the PTW-Roos chambers using the N(D,air) method. The chamber-to-chamber variation in p(wall) for the Wellhöfer-Roos chambers is found to be very small, with a maximum difference of 0.3%. The effect of using new p(cav) values for graphite-walled Farmer-type chambers used in water in electron beams is to decrease p(wall) by approximately 0.5%. The long- and short-term stability of the Roos-type chambers manufactured by Wellhöfer is investigated by measurements at the IAEA Dosimetry Laboratory in Vienna, Austria, and at the Sahlgrenska University Hospital in Göteborg, Sweden. Calibrations made at the IAEA over several months show variations in the N(D,w) calibration factors larger than expected. based on previous experiences with PTW-Roos chambers. Measurements of the short-term stability of the Wellhöfer-Roos chambers show a marked increase in chamber response for the time the chambers are immersed in water, pointing to a possible problem in the chamber design. As a consequence of these findings, Wellhöfer is currently working on a re-design of the chamber to solve the stability problem.

Biophysical Phenomena↗