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PubMed1999

Sensitivity of concentration and risk predictions in the PRESTO and MMSOILS multimedia models: regression technique assessment.

This paper describes the application of two multimedia models, PRESTO and MMSOILS, to predict contaminant migration from a landfill that contains an organic chemical (methylene chloride) and a radionuclide (uranium-238). Exposure point concentrations and human health risks are predicted, and distributions of those predictions are generated using Monte Carlo techniques. Analysis of exposure point concentrations shows that predictions of uranium-238 in groundwater differ by more than one order of magnitude between models. These differences occur mainly because PRESTO simulates uranium-238 transport through the groundwater using a one-dimensional algorithm and vertically mixes the plume over an effective mixing depth, whereas MMSOILS uses a three-dimensional algorithm and simulates a plume that resides near the surface of the aquifer. A sensitivity analysis, using stepwise multiple linear regression, is performed to evaluate which of the random variables are most important in producing the predicted distributions of exposure point concentrations and health risks. The sensitivity analysis shows that the predicted distributions can be accurately reproduced using a small subset of the random variables. Simple regression techniques are applied, for comparison, to the same scenarios, and results are similar. The practical implication of this analysis is the ability to distinguish between important versus unimportant random variables in terms of their sensitivity to selected endpoints.

Algorithms↗

PubMed2006

Correlating material properties with tissue composition in enzymatically digested bovine annulus fibrosus and nucleus pulposus tissue.

Aging and degeneration of the intervertebral disk are accompanied by decreases in water and proteoglycan contents, and structural alterations. The aim of this study was to determine the impact of compositional changes on the material properties of intervertebral disk tissues. Confined compression stress-relaxation experiments were applied to bovine caudal annulus fibrosus and nucleus pulposus tissue specimens that were separated into three experimental groups: in situ, free-swelling control (PBS), and digestion (chondroitinase-ABC). Measurements of glycosaminoglycan (GAG) and water content, as well as nonlinear finite deformation biphasic theory and multiple linear regression analyses were performed. The compressive modulus HA0 and permeability k0 of in situ specimens were 0.37+/-0.06 MPa and 0.49+/-0.08x10(-15) m4 N-1 s-1 for nucleus, and 0.74+/-0.13 MPa and 0.42+/-0.05x10(-15) m4 N-1 s-1 for annulus, respectively. There was a larger effect of swelling and digestion on the material properties and biochemical composition of nucleus pulposus than for annulus fibrosus. Alterations in proteoglycan and water content affected the compressive modulus and permeability, although the permeability was somewhat more strongly affected by water content than by proteoglycan content. Correlation coefficients r<or=0.75 for the multiple regression indicated water and GAG content can moderately predict material properties, however other compositional and structural factors must be considered.

Animals↗

PubMed2006

Performance of multicomponent self-organizing regression (MCSOR) in QSAR, QSPR, and multivariate calibration: comparison with partial least-squares (PLS) and validation with large external data sets.

A novel method for underdetermined regression problems, multicomponent self-organizing regression (MCSOR), has been recently introduced. Here, its performance is compared with partial least-squares (PLS), which is perhaps the most widely adopted multivariate method in chemometrics. A potpourri of models is presented, and MCSOR appears to provide highly predictive models that are comparable with or better than the corresponding PLS models in large internal (leave-one-out, LOO) and pseudo-external (leave-many-out, LMO) validation tests. The "blind" external predictive ability of MCSOR and PLS is demonstrated employing large melting point, factor Xa, log P and log S data sets. In a nutshell, MCSOR is fast, conceptually simple (employing multiple linear regression, MLR, as a statistical tool), and applicable to all kinds of multivariate problems with single Y-variable.

Algorithms↗

PubMed1992

The clinical assessment of "Obscure Auditory Dysfunction" (OAD) 2. Case control analysis of determining factors.

Obscure Auditory Dysfunction (OAD) is defined as a clinical referral for self-reported auditory disability with no audiometric abnormality by stringent criteria. In stage 2 of a case control study of OAD, we have confirmed the general finding of stage 1 that OAD is multifactorial; compared with controls, patients as a group have a genuine performance deficit for understanding speech in noise, accompanied by personality-related factors. Paired logistic regression analysis optimally differentiated the 50 patients from their 50 matched controls on the basis of variables from three different domains: masked thresholds (psychoacoustic domain), dichotic listening ability (central/cognitive domain), and underestimation of own hearing ability (personality domain). A further and influential contributing variable was understanding of speech in noise supplementing the variables in both the psychoacoustic and the cognitive domains. With this model, 82.7% of the total group deviance was explained (i.e., the binary variable of case/control). A corresponding discriminant function analysis correctly classified 80% of patients and 90% of controls. When factors underlying the performance and personality-related variables were investigated with multiple linear regression within the two groups separately, relatively little of the within-group variance among OADs was explained. This is consistent with the multifactorial nature of OAD, in that the combinations of factors leading to OAD status differ between individuals. The research findings have been used to design a clinical test package to provide diagnostic information on the basis of OAD in individuals.

Adult↗

PubMed2005

Estimated risk score for spine fracture in the specific bending activity of normal Taiwanese men and women.

OBJECTIVE: To investigate the effects of biologic age, as well as chronologic age, on the vertebral ultimate load (strength) and risk score of vertebral fracture (Phi) between the genders. SUMMARY OF BACKGROUND DATA: Previous studies have shown a good correlation between the biomechanical strength of vertebral bodies and measured bone mineral parameters, whereas other factors also contribute to the bone strength and risk of fractures. Combining multiple factors into a single assessment may provide more comprehensive and individualized estimations of the fracture risk. In this study, we applied the measured bone mineral content (BMC) and bone projection area of the second through the fourth lumbar vertebrae (L2-L4) to assess the biomechanical strength of lumbar vertebrae. In addition, we used the body segment model to estimate the load of the L3 vertebral body during a bending-forward activity, to then estimate the risk score (Phi) of vertebral compression fracture in healthy Chinese volunteers in Taiwan, and to analyze the effects of gender and age on the risk score (Phi). METHODS: A total of 611 females and 235 males aged 22-80 years were included in this study. The anteroposterior BMC and projection area of lumbar spine were measured by a Norland XR-26 dual energy radiograph absorptiometer (Norland Corp., Ft. Atkinson, WI). The estimated ultimate strength (L) of lumbar spine was calculated from the regression equation using anteroposterior lumbar BMC and bone area according to Bassman et al (Paper presented at: 39th Annual Meeting of Orthopedic Research Society; February 1993; San Francisco, CA). The estimated spinal load (F) for a person bending over with back horizontal, either with hand free (F0), lifting a 20 kg weight (F20), or a 30 kg weight (F30), was calculated from a force diagram according to William and Lissner. Risk score (Phi) was defined as the quotient of F/L. RESULTS: The results showed an age-related decrease of bone mineral density (P < 0.001) in both genders corrected for weight and height. Using the multiple linear regression analysis and analysis of covariance, Phi for F0, F20, and F30 increased significantly, with increasing age only in females (P < 0.0001), especially after menopause, but not in males. The Phi of postmenopausal females was significantly larger than those of younger females (i.e., F0 (Phi) 0.533 +/- 0.075 vs. 0.458 +/- 0.064, P < 0.001; F20 (Phi) 0.903 +/- 0.101 vs. 0.789 +/- 0.080, P < 0.001; and F30 (Phi) 1.087 +/- 0.117 vs. 0.954 +/- 0.090, respectively, P < 0.001). In females, the ultimate load of the spine and Phi began to decrease to a significant level since the fifth decade, whereas in the males, the similar trends occurred since the sixth decade. Comparing both genders, the F0 (Phi) was slightly yet significantly larger in the young males (< 50 years) than the premenopausal females with similar ages (P < 0.001), but older females had higher F0 (Phi) values than males older than 60 years. Moreover, the Phi increased more prominently in the postmenopausal females with the weight lifted. As a result, both F20 (Phi) and F30 (Phi) were significantly larger in females older than 50 years as compared to males with the similar ages (P < 0.001). CONCLUSIONS: Our findings emphasize the importance of Phi, which considers BMC, bone size, body weight, body height, and weight lifted, for evaluating a more individualized risk of spine fracture in elderly men and postmenopausal women. The Phi increased more prominently with lifting weight and increased with aging only in the early postmenopausal females. The study showed that a combination of bone mass and anthropometric parameters provides a more individualized assessment of fracture risk than bone mineral density alone.

Adult↗

PubMed2000

Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights.

Aging is associated with changes in plasma levels of several hormones. There are conflicting reports on whether circulating leptin levels change during aging, the possible explanation for which is that alterations in adiposity and body mass index (BMI) also occur. In this study we measured plasma leptin and other hormonal parameters known to influence leptin in 150 men and 320 women of a wide age (18-77 yr) and BMI (18.5-61.1 kg/m2) range. Subjects of each gender were separated into 2 groups of similar BMI, i.e. nonobese (BMI, <30) and obese (BMI, >30), and treated separately. Statistical analysis was performed, treating each group of subjects as a whole population or divided into age groups (<30, 30-50, and >50 yr). BMI-adjusted leptin levels were progressively lower with increasing age in women, with a consistent fall after menopause (-21%; P < 0.001); in men, leptin levels also tended to be lower in subjects more than 50 yr of age, but the reduction was not significant. Multiple linear regression analysis, performed on subjects treated either as a whole population or divided into obese and nonobese, showed that in both genders BMI and age were independent contributors of leptin levels, and there was an inverse relationship between leptin and age in both obese (standardized coefficient beta = -0.25 in women and -0.23 in men; P < 0.01) and nonobese (-0.22 in women and -0.20 in men; P < 0.05) subjects. The correlation of leptin and age with plasma levels of sex and thyroid hormones, GH, insulin-like growth factor I, PRL, and insulin was also evaluated. The variables that correlated with leptin were included in a multiple regression model that included BMI and age. Testosterone in men (-0.43 in nonobese and -0.19 in obese; P < 0.05) and estradiol in women (0.22 in nonobese and 0.24 in obese; P < 0.05) were important contributors to leptin levels; also, dehydroepiandrosterone sulfate in obese women (-0.16) and sex hormone-binding globulin in obese subjects of both genders (0.15 in women and 0.19 in men) were significant determinants in the model. However, none of the hormonal parameters abolished the negative correlation between leptin and age or the gender difference in leptin levels. In conclusion, our data show that in adult humans of different body weight, serum leptin gradually declines during aging; leptin reduction is higher in women than in men, but it is independent from BMI and other age-related endocrine changes.

Adolescent↗

PubMed2004

Testing a conceptual framework for diabetes self-care management.

Diabetes is a major source of morbidity, mortality, and economic expense in the United States. The majority of researchers and clinicians believe that diabetes is a self-care management disease, and that patients should be reliable, capable, and sufficiently responsible to take care of themselves. However, individuals with diabetes may or may not have diabetes knowledge, social support, self-care agency (an individual's capability to perform self-care actions), and self-efficacy (an individual's beliefs in his or her capability to perform self-care actions) that would help them to engage in diabetes self-care management. Therefore, this study examined the relationship among those factors using a cross-sectional model testing design. A convenient sample of 141 insulin-requiring individuals with either diabetes type 1 or type 2, 21 years old and over, was recruited from an outpatient diabetes care center located in a Southeast region of the United States. Simple linear regression, multiple standard regression, and multiple hierarchical regression were used to analyze the data. Individuals with greater diabetes knowledge had greater self-care agency and self-efficacy. Those with a higher score in social support had greater self-care agency and better diabetes self-care management, and those with greater self-efficacy had better diabetes self-care management. In addition, self-care agency mediated the effects of diabetes knowledge on self-efficacy and the effects of social support on diabetes self-care management. Self-efficacy mediated the effects of self-care agency on diabetes self-care management. Furthermore, the linear combination of diabetes knowledge, social support, self-care agency, and self-efficacy, taken together, positively affected diabetes self-care management. Enhancing an individual's diabetes knowledge, social support, self-care agency, and self-efficacy may be a strategy which can promote better engagement in diabetes self-care.

Adult↗

PubMed1996

Influence of hypertension on early renal insufficiency in autosomal dominant polycystic kidney disease.

To determine the potential effect of hypertension on early renal function deterioration, 30 patients (13 normotensive and 17 hypertensive) with autosomal dominant polycystic kidney disease and initially normal renal function were retrospectively analyzed. The decline in renal function was estimated by the slope of the linear regression of creatinine clearance versus time. Analysis was made in terms of standardized slope (slope divided by its standard deviation, i.e., measured in standard deviation units). In the hypertensive group the mean standardized slope was significantly higher than in the normotensive group (-10.89 and -4.98, respectively; p < 0.001). The average mean arterial pressure was significantly lower in the normotensive group with respect to the hypertensive one (95 and 109 mm Hg, respectively; p < 0.0001). There was a significant negative linear relationship between the average values of systolic, diastolic, and mean arterial pressures and standardized slopes. The best prediction equation for renal function deterioration was obtained using a multiple linear regression model in which independent variables were maximum and average diastolic pressures. Therefore, prior to renal insufficiency, a high arterial pressure had a significant contribution to renal function deterioration.

Adult↗

PubMed2001

Effects of a community-based lifestyle-modification program on cardiovascular risk factors in middle-aged women.

We investigate the effectiveness of a community-based lifestyle-modification program for reducing blood pressure and other cardiovascular risk factors in sedentary Japanese middle-aged women. Among an initial cohort of 210 middle-aged sedentary women, 195 subjects completed a community-based 12-week lifestyle-modification program for reducing cardiovascular risk factors. Blood pressure, body weight and the serum lipid profile were measured both at baseline and at the end of the 12-week lifestyle-modification program. The program consisted of mild aerobic exercise and a mild hypocaloric diet. After the 12-week program, both systolic and diastolic blood pressure were significantly reduced, especially in subjects who were hypertensive at baseline. Desirable changes in body weight and the serum lipid profile were also found after the 12-week program. Multiple linear regression analysis revealed that, in obese subjects, the decrease in systolic blood pressure was correlated with both the initial systolic blood pressure and the change in estimated maximum oxygen consumption. In addition, the decrease in diastolic blood pressure was correlated with the initial diastolic blood pressure and the change in body weight. On the other hand, in non-obese subjects, the decrease in blood pressure was correlated with the initial blood pressure and the change in salt intake. A community-based lifestyle-modification program that consisted of mild aerobic exercise and a mild hypocaloric diet was considered to be practically effective for reducing multiple cardiovascular risk factors. Individuals who already have one or more mild cardiovascular risk factors still could be good candidates for a community-based lifestyle-modification program.

Blood Pressure↗

PubMed1991

Platelet monoamine oxidase and plasma dopamine-beta-hydroxylase activities in patients with multiple sclerosis.

Platelet monoamine oxidase (MAO) and plasma dopamine-beta-hydroxylase (DBH) activities were determined in a large group of multiple sclerose patients in relapse (49 patients) and in remission (28 patients), and compared with an age- and sex-matched control group (52 normal subjects). The activities of both enzymes did not differ from normal in both patient groups. Women had higher MAO activities both in normal and in patient groups. Multiple linear regression analysis revealed an association of low platelet MAO to the score in the mental subscale in the Kurtzke Disability Status Scale. Both male and female patients with mental symptomatology had significantly (p = 0.02) lower platelet MAO activities compared to the patients without. The possibility of a relationship between MAO activity and psychiatric vulnerability in MS is considered.

Adult↗

PubMed2005

Prediction of DXA-determined whole body fat from skinfolds: importance of including skinfolds from the thigh and calf in young, healthy men and women.

OBJECTIVE: To investigate the relationship of percent body fat (%fat), assessed by dual energy-X-ray absorptiometry (DXA) or a four-compartment model, with upper body and lower limb skinfolds. DESIGN: Cross-sectional design involving forward stepwise and hierarchical multiple regression analyses to assess the relationship of %fat with skinfolds and a combination of four commonly used upper body skinfolds (biceps, triceps, subscapular and iliac crest) with the calf and thigh skinfolds. SETTING: University research laboratory. SUBJECTS: In all, 31 females, mean age 20.9 (+/-2.0) y, and 21 males, mean age 22.3 (+/-5.5) y volunteered for this study, which was approved by the Ethics Committee of the School of Sport, Health and Exercise Sciences, University of Wales, Bangor. MEASUREMENTS: %fat from DXA in both groups, and %fat from a four-compartment (water, bone mineral mass, fat and residual) model (%fat4C) in females only. Skinfolds were measured at the abdomen, iliac crest, biceps, triceps, subscapular, calf and thigh. RESULTS: All skinfolds were positively associated with DXA estimates of %fat (P < 0.01). In males and females, the thigh skinfold had the highest correlation with %fat. This was also observed when %fat4C was used as the criterion in females. Stepwise multiple regression analysis using %fatDXA as the criterion selected the thigh (R(2) = 0.82), calf (R(2) change 0.04) and iliac crest (R(2) change = 0.03) for females, and the thigh (R(2) = 0.79), iliac crest (R(2) change = 0.11) and abdomen (R(2) change = 0.03) for males (all P < 0.01). When %fat4C was used as the criterion in the females, only the thigh was selected as a significant predictor (R(2) = 0.76). Independent prediction factors were created from the sum of biceps, triceps, subscapular and iliac crest (sigma4skf) and from the sum of the thigh and calf (sigmathigh + calf). These factors were then entered into a hierarchical multiple linear regression analysis to predict percent fat. Order of entry was varied to allow the assessment of unique variance accounted for by each predictor. The sum of the thigh and calf explained more variance in %fatDXA than that explained by the sigma4skf alone, irrespective of the order of entry in both males and females. This was also observed when %fat4C was used as the criterion in the females. CONCLUSIONS: The results of this study confirm that lower body skinfolds are highly related to percent body fat in fit and healthy young men and women, and uphold current recommendations by the British Olympic Association to include the thigh skinfold with sigma4skf. Conventional use of the sigma4skf to estimate percent body fat is significantly enhanced by the inclusion of the thigh and calf skinfolds, either independently or in combination. In this group of males and females, the sum of the thigh and calf skinfolds accounted for the most variance in percent fat.

Absorptiometry, Photon↗

PubMed2006

Resting energy expenditure and fuel metabolism following laparoscopic adjustable gastric banding in severely obese women: relationships with excess weight lost.

BACKGROUND: Although adjustable gastric banding is increasingly proposed for massively obese patients, little is known about the modifications of resting metabolic rate and substrate oxidation or about metabolic determinants of weight loss following this type of bariatric surgery. OBJECTIVES: To evaluate the relationships between excess weight loss, resting metabolic rate (RMR) and substrate oxidation, and to identify metabolic predictive factors of weight loss after adjustable gastric banding. SUBJECTS: Seventy-three obese nondiabetic women aged 39.1+/-10.4 years (18.4-64.8). DESIGN: Resting metabolic rate and substrate oxidation (indirect calorimetry), body composition (bio-impedance), lipid profile and insulin sensitivity indexes were assessed before and after (13.3+/-6.0 months, range 6.0-31.1) adjustable gastric banding. Patients were classified according to postsurgery time: group A (6-12 months, n=39); group B (12-18 months, n=21); group C (>18 months, n=13). Metabolic parameters associated with the percentage of excess weight lost (EWL) 1 year after surgery were analyzed in univariate and multivariate regressions. RESULTS: Mean weight loss was 26.2+/-11.4 kg. Mean fat mass loss was 17.3+/-8.1 kg. All biological parameters associated with excess weight improved after surgery. Excess weight lost at 1 year was 45.9+/-17.1% in group A, 47.4+/-17.1% in group B and 51.4+/-18.5% in group C (P=NS). Resting metabolic rate/fat-free mass (FFM) slightly decreased (28.9+/-3.26 vs 30.3+/-2.8, P<0.00001) and RMR/body weight slightly increased (18.5+/-2.8 vs 17.3+/-1.9, P<0.00001) after surgery. Respiratory quotient (0.81+/-0.06 vs 0.82+/-0.05) and FFM-adjusted lipid oxidation (1.10+/-0.41 vs 1.05+/-0.33 mg/min/kg FFM) were not significantly modified after surgery. In multiple linear regression analysis, difference in RMR/body weight, difference in energy sparing, baseline BMI and postsurgery time, were significantly and independently correlated with EWL (total R2=72.5%). CONCLUSIONS: Adjustable gastric banding promotes gradual but sustained weight loss and is associated with long-term conservation of lipid oxidation and energy expenditure. The individual variability in energy sparing mechanisms predicts weight loss during the first year after surgery.

Adolescent↗

PubMed2005

Cross-sectional study of complement C3 as a coronary risk factor among men and women.

In the present study, we examined (i) whether C3 (complement C3) was an independent marker of prevalent CHD (coronary heart disease), and (ii) which preferential associations existed between C3 and some cardiovascular risk factors when jointly analysed with CRP (C-reactive protein) and fibrinogen. In a cohort of 756 unselected adults, 39% of whom had the metabolic syndrome, C3 and other risk variables were evaluated in a cross-sectional manner. In a logistic regression model for the likelihood of CHD, a significant OR (odds ratio) of 3.5 [95% CI (confidence intervals), 1.27 and 9.62)] for C3 was obtained after adjustment for smoking status, TC (total cholesterol) and usage of statins. A similar model, also comprising systolic blood pressure, with a cut-off point of >or=1.6 g/l C3 exhibited a 1.9-fold risk (95% CI, 1.01 and 3.58) compared with individuals below the cut-off point. Both analyses displayed an adjusted OR of 1.37 for each S.D. increment in C3. The significant relationship of C3 with a likelihood of CHD also proved to be independent of CRP. In multiple linear regression models, associations were tested for each acute-phase protein with measures of obesity, fasting insulin, triacylglycerols (triglycerides), TC, HDL (high-density lipoprotein)-cholesterol, physical activity, smoking status, diagnosis of metabolic syndrome and family income. When both genders were combined, C3 was independently associated with serum triacylglycerols, waist circumference, BMI (body mass index) and TC. CRP was independently associated with waist circumference, TC, family income (inversely) and physical activity, and fibrinogen with BMI, TC, smoking status and metabolic syndrome. In summary, elevated levels of complement C3 are associated with an increased likelihood of CHD independent of standard risk factors and regardless of the presence of acute coronary events, suggesting that C3 might be actively involved in coronary atherothrombosis. Unlike CRP and fibrinogen, C3 was preferentially associated with waist girth and serum triacylglycerols.

Adult↗

PubMed1999

Noninvasive assessment of left atrial maximum dP/dt by a combination of transmitral and pulmonary venous flow.

OBJECTIVES: The study assessed whether hemodynamic parameters of left atrial (LA) systolic function could be estimated noninvasively using Doppler echocardiography. BACKGROUND: Left atrial systolic function is an important aspect of cardiac function. Doppler echocardiography can measure changes in LA volume, but has not been shown to relate to hemodynamic parameters such as the maximal value of the first derivative of the pressure (LA dP/dt(max)). METHODS: Eighteen patients in sinus rhythm were studied immediately before and after open heart surgery using simultaneous LA pressure measurements and intraoperative transesophageal echocardiography. Left atrial pressure was measured with a micromanometer catheter, and LA dP/dt(max) during atrial contraction was obtained. Transmitral and pulmonary venous flow were recorded by pulsed Doppler echocardiography. Peak velocity, and mean acceleration and deceleration, and the time-velocity integral of each flow during atrial contraction was measured. The initial eight patients served as the study group to derive a multilinear regression equation to estimate LA dP/dt(max) from Doppler parameters, and the latter 10 patients served as the test group to validate the equation. A previously validated numeric model was used to confirm these results. RESULTS: In the study group, LA dP/dt(max) showed a linear relation with LA pressure before atrial contraction (r = 0.80, p < 0.005), confirming the presence of the Frank-Starling mechanism in the LA. Among transmitral flow parameters, mean acceleration showed the strongest correlation with LA dP/dt(max) (r = 0.78, p < 0.001). Among pulmonary venous flow parameters, no single parameter was sufficient to estimate LA dP/dt(max) with an r2 > 0.30. By stepwise and multiple linear regression analysis, LA dP/dt(max) was best described as follows: LA dP/dt(max) = 0.1 M-AC +/- 1.8 P-V - 4.1; r = 0.88, p < 0.0001, where M-AC is the mean acceleration of transmitral flow and P-V is the peak velocity of pulmonary venous flow during atrial contraction. This equation was tested in the latter 10 patients of the test group. Predicted and measured LA dP/dt(max) correlated well (r = 0.90, p < 0.0001). Numerical simulation verified that this relationship held across a wide range of atrial elastance, ventricular relaxation and systolic function, with LA dP/dt(max) predicted by the above equation with r = 0.94. CONCLUSIONS: A combination of transmitral and pulmonary venous flow parameters can provide a hemodynamic assessment of LA systolic function.

Adult↗

PubMed1998

Cyclosporine monitoring in patients with renal transplants: two- or three-point methods that estimate area under the curve are superior to trough levels in predicting drug exposure.

The recent introduction of a cyclosporine microemulsion demonstrating less pharmacokinetic variability than the conventional formulation offers the potential for accurately and precisely predicting area under the curve (AUC) with a limited-sampling monitoring strategy. This was studied based on the pharmacokinetic profiles from 55 stable patients with renal transplants who were observed on two occasions at steady state on both formulations. Multiple linear regression analyses were performed on a training dataset from 27 patients, in which combinations of cyclosporine concentrations drawn from 0 to 4 hours postdose were regressed against the full AUC over the dosing interval. Predictor regression equations used concentration combinations ranging from one-point (concentrations at 0, 1, 2, 3, or 4 hours) through five-points (all five concentrations 0 to 4 hours). The predictive performance of these equations was then assessed in the training group with data from a subsequent profiling occasion and in the remaining 28 patients who constituted an independent test group. Prediction bias (mean prediction error) and prediction precision (absolute prediction error) were quantified and compared between formulations. Correlations between predicted and actual AUC were consistently stronger for the microemulsion, suggesting the possibility of more accurate and precise predictions of exposure than from the conventional formulation. For both formulations, the one-point predictors rendered the lowest prediction precision, and predictive performance improved considerably when multiple-point predictors were used. Significantly higher precision and lower variability were observed with the microemulsion for most predictors in the both training and test groups. For the microemulsion, two-point (C0 + C1 or C0 + C2) and three-point (C0 + C1 + C2) predictors yielded relatively unbiased and precise exposure predictions, inasmuch as mean absolute prediction error was less than 10% and 5%, respectively. Hence, a two- or three-point method may provide a clinically important improvement over the use of trough levels in monitoring cyclosporine therapy in patients with renal transplants.

Area Under Curve↗

PubMed2003

[Variations in the use of hospital resources in treating patients with chronic obstructive pulmonary disease].

AIM: To analyze factors associated with the length of stay and pharmaceuticals expense for patients admitted with chronic obstructive pulmonary disease (COPD) and to evaluate whether treatment by different physicians means greater or less use of hospital resources. METHODS: We retrospectively studied a cohort of 1033 COPD patients admitted to the Hospital de Mataró, Catalonia, Spain, during the years 1996 through 1998 in order to analyze factors associated with length of stay and pharmaceuticals use. We used the Minimum Basic Data Set, laboratory databases, and pharmacy single-dose database. We also analyzed the differences among patients treated by different physicians and developed multiple linear regression models to evaluate differences in treatment between one physician and another. RESULTS: The length of stay increased with patient age, the number of times admitted, the presence of atrial fibrillation or respiratory insufficiency, ventilatory alterations, chronicity, a forced expiratory volume in 1 second less than 50% of predicted, and treatment by certain physicians. Medication costs showed a similar pattern. Although the characteristics of patients treated by different physicians were quite homogeneous, the median length of stay varied from 9 to 11 days depending on the physician, while the median cost for medication varied from;43.62 to;54.39 (from $41.07 to $51.21). After removing the effects of several covariables by multiple regression analysis, an effect of physician persisted. CONCLUSIONS: Significant differences in length of hospital stay and consumption of pharmaceuticals are related to attending physician and continue to have an important effect after controlling for the differences in the severity of patient status.

Adult↗

PubMed1994

Availability of amino acids for 10- to 20-kilogram pigs: lysine and threonine in soybean meal.

The availabilities of lysine and threonine in soybean meal for 10- to 20-kg pigs were determined in two experiments using slope-ratio methodology. In the first experiment, a basal diet formulated to contain 6 g of lysine/kg, but adequate in all other amino acids, was supplemented with 1, 2, or 3 g of lysine/kg from either soybean meal or L-lysine-HCl. Each of the seven diets was available on an ad libitum basis to six individually penned pigs (barrows:gilts, 1:1) from an initial weight of 9.9 kg until they reached a live weight of 20.8 kg. Daily feed intake was similar among diets. Common-intercept multiple linear regression of daily live weight gain and gain:feed ratio on dietary lysine level indicate slope ratios (soybean meal:lysine.HCl) of .85 and .88, respectively. In Exp. 2, a basal diet formulated to contain 4 g of threonine/kg was supplemented with .65, 1.30, 1.95, or 2.60 g of threonine/kg from either soybean meal or L-threonine. Each of the nine diets was available on an ad libitum basis to six individually penned pigs (barrows:gilts, 1:1) from 9.9 to 21.0 kg live weight. As in Exp. 1, daily feed intake was similar among the nine diets. The slope ratios (soybean meal:L-threonine) from common-intercept multiple regression analyses were .73 and .78 for daily weight gain and gain:feed ratio, respectively. Thus, the availabilities of lysine and threonine in soybean meal for young pigs were estimated to be 85 to 88% and 73 to 78%, respectively.

Animal Feed↗

PubMed1990

Influence of reflow ventricular fibrillation and electrical defibrillation on infarct size in a canine preparation of myocardial infarction.

STUDY OBJECTIVE - The aim of the study was to investigate the influence of reflow ventricular fibrillation and electrical defibrillation on infarct size in a model of myocardial ischaemia. DESIGN - Myocardial ischaemia was induced in an open chest canine model by occluding the left coronary artery for 2 h. This was followed by 6 h reperfusion. The influence of reflow fibrillation and internal electric defibrillation on infarct size was investigated and compared to dogs which did not develop fibrillation. Infarct size and its major determinants, rate-pressure product (RPP), area at risk (AR), and collateral flow (MBF), were measured and their relationships studied in the two situations, using uni- and multilinear regression analysis. SUBJECTS - 21 adult mongrel dogs of either sex were used in the studies, which were done under pentobarbitone anaesthesia. Two were excluded because they developed ventricular fibrillation soon after coronary occlusion, and one did not survive reflow ventricular fibrillation. Of the remaining 18 dogs, six developed reflow ventricular fibrillation and were compared to the control group of 12 which did not develop fibrillation. MEASUREMENTS and RESULTS - A mean of 70.8(SEM 18.7) joules was required to revive the six dogs with reflow ventricular fibrillation. Difference in mean infarct size in the two groups did not reach significance [49.1(4.4) in fibrillation group v 38(6.2) in the controls]. The multiple linear regression model in the control group accounted for 91% of the variation in infarct size (IS): IS = -3.4 + 0.49 (AR) -21.8 (MBF) + 0.025 (RPP). The equation was not modified by including the reflow fibrillation dogs: IS = -3.1 + 0.52 (AR) - 19 (MBF) + 0.02 (RPP). Ischaemic determinants of infarct size in the reflow fibrillation dogs were computed in the control group equation to compare the infarct size predicted by the model to the measured infarct size in each individual dog in the reflow fibrillation group. There was no significant difference between the means: 12.9(2.9)% (predicted) v 14.9(2.5)% (measured). CONCLUSIONS - In this model of myocardial infarction, reflow ventricular fibrillation and low energy internal electric shocks do not damage the myocardium at risk significantly.

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